Oral Session
O1: Spontaneous Motor Recovery After Cerebrolysin Treatment in a Mouse Model of Stroke
Steven Zeiler
1, Robert Hubbard1, Gabriel Pinilla-Monsalve1, Stefan Winter2, Mahlet Mersha1, Scott DeBoer1
1Johns Hopkins, Baltimore, MD, USA
2EverPharma, Unterach, Austria
Background and Purpose: Most functional upper extremity motor recovery occurs in the first 4 weeks after ischemic stroke in humans and in the first week in rodent models. The majority of functional recovery in humans is spontaneous (ie, occurs as a result of endogenous repair processes rather than rehabilitative interventions). In mouse models of stroke, recovery is impaired when poststroke rehabilitation is delayed and there is very little spontaneous recovery. Cerebrolysin is a polypeptide preparation shown to enhance neuronal plasticity and to promote motor recovery in patients after stroke. In mice, we tested the hypothesis that Cerebrolysin can act early after stroke to enhance spontaneous motor recovery.
Methods: Adult C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance, after which they underwent photocoagulation-induced stroke in the caudal forelimb area (rodent primary motor cortex). The mice were then randomized to receive Cerebrolysin or saline injections beginning either after 1 day or 7 day poststroke delay. Animals were then retrained at the same prehension task by a blinded investigator. Stroke volumes were compared using immunohistochemistry.
Results: We have previously shown that training-associated recovery of prehension is complete if training is initiated after a 1-day delay but incomplete if training is initiated after a 7-day delay, even with additional training days. However, daily Cerebrolysin administration beginning after a 1-day poststroke delay was associated with complete recovery of prehension by day 8, even in the absence of training. To test if delayed Cerebrolysin administration could recover poststroke prehension, even when started days later, we administered daily IP injections of either Cerebrolysin or saline beginning 7 days poststroke. Animals receiving Cerebrolysin displayed improved motor recovery even though both Cerebrolysin administration and rehabilitative training were delayed by 7 days and 8 days, respectively. Stroke volumes were similar across all groups.
Conclusions: We conclude that Cerebrolysin administration can lead to recovery of motor function, even in the absence of motor training. This is one of the first demonstrations of spontaneous motor recovery in a rodent stroke model. Our mouse model, with all of the attendant genetic benefits, should allow us to determine at the cellular and molecular levels how endogenous plasticity and medications like Cerebrolysin interact to mediate recovery.
O2: Effect of Behavioral Practice Targeted at the Premotor-Prefrontal Component of the Motor Network After Stroke
Jill Stewart
1, Allison Lewis1, Jessica Baird1, Stacy Fritz1, Julius Fridriksson1
1University of South Carolina, Columbia, SC, USA
Introduction: Changes in task conditions lead to changes in neural activation that are condition-specific, providing an avenue for creating behavioral practice conditions that target a specific component of the motor network. The addition of action selection demands to movement through abstract, visual cues engages dorsal premotor cortex (PMd). After stroke, bilateral PMd and dorsolateral prefrontal cortices (DLPFC) show changes in activation and connectivity in response to action selection demands; however, the plasticity of this component of the motor network with practice is unknown. The purpose of this study was to determine the response to a period of practice targeted at the PMd-DLPFC component of the motor network after stroke.
Methods: Seventeen individuals poststroke (age: 57.4 ± 10.1 years; months poststroke: 41.9 ± 41.7; UE FM motor score: 43.8 ± 15.4) completed a task that required right or left movement of a joystick with the weaker hand under 2 conditions. In the Execute condition, the individual moved the same direction on every trial. In the Select condition, the individual moved right or left based on an abstract, visual rule. The task was practiced for 4 consecutive days and completed during functional magnetic resonance imaging on days 1 and 4.
Results: On day 1, reaction time (RT) was longer in Select (1.158 ± 0.365 seconds) compared to Execute (0.554 ± 0.201 seconds). This increase in RT during Select corresponded to increased activation in bilateral PMd as well as bilateral DLPFC, supplementary motor area, anterior cingulate and parietal cortices. Over days of practice, Select RT and RT cost (Select RT-Execute RT; represents the relative increase in planning time for the Select condition) decreased (P = .002; RT cost: day1 0.604 ± 0.235; day 4 0.360 ± 0.101). On day 4, the increase in brain activation from the Execute to the Select condition was overall less including in bilateral DLPFC, ipsilesional PMd, and anterior cingulate cortex. No behavioral or brain activation changes were seen with Execute. PMd-M1 and PMd-DLPFC connectivity changed with practice but the direction of change varied, with some individuals showing an increase in connectivity (n = 9) and others showing a decrease (n = 8). Brain-behavior relationships also changed with practice: on day 1, PMd activation had a negative relationship with RT cost (r = −0.594) such that individuals with relatively worse performance (higher cost) had lower activation in PMd, while on day 4, this relationship became positive such that individuals with relatively worse performance had higher activation in PMd (r = 0.476) and DLPFC (r = 0.492).
Conclusion: Behavioral practice targeted at the premotor-prefrontal component of the motor network can change the activation pattern in task-related regions. Changes in brain-behavior relationships over practice suggest that brain activation should be interpreted within the context of behavior. Utilization of structured changes in behavioral practice may allow the targeting of specific components of the motor network during rehabilitation after stroke.
O3: Motor Cortex Inhibition With Somatosensory and Transcranial Direct Current Stimulation: A Metaplasticity Study
John Cirillo
1, Anita Trudgen1, Winston Byblow1
1University of Auckland, Auckland, New Zealand
Priming the brain may provide potential treatment strategies for neurological disorders and stroke. Mesh glove stimulation (MGS) is a type of suprathreshold sensory stimulation that may transiently increase primary motor cortex (M1) excitability. Cathodal transcranial direct current stimulation (c-tDCS) of M1 may transiently decrease corticomotor excitability. We sought to determine if we could prime MGS with c-tDCS to further enhance M1 excitability through homeostatic metaplasticity mechanisms that interact with M1 inhibitory circuits, that is, disinhibition. Sixteen right-handed neurologically healthy individuals (9 female, 19-36 years) participated in a repeated measures crossover study, 9 minutes of sham- or c-tDCS followed by 30 minutes of suprasensory threshold MGS. Corticomotor excitability, intracortical facilitation, short afferent inhibition (SAI), short-interval intracortical inhibition (SICI), SAI with SICI (SAI×SICI), and grooved pegboard performance of the left hand were obtained at baseline, post-tDCS, and immediately, 30 and 60 minutes post-MGS. There was more disinhibition of SAI, and an increase in rest motor threshold and SAI×SICI after c-tDCS primed MGS compared to sham + MGS. There was also a greater improvement in the grooved pegboard times after c-tDCS primed MGS than sham + MGS. Our results indicate a non-homeostatic metaplastic modulation of corticomotor excitability with c-tDCS primed MGS. Consequently, c-tDCS did not modulate corticomotor excitability after MGS, but did improve motor performance. Therefore, c-tDCS may be an effective priming modality to induce non-homeostatic metaplasticity.
O4: Does Cognition Predict Ability to Learn a Novel Walking Pattern in Individuals Poststroke?
Margaret A. French
1, Matthew Cohen1, Darcy S. Reisman1
1University of Delaware, Newark, DE, USA
Background: Rehabilitation outcomes following stroke are highly variable, likely because some individuals respond to interventions while others do not. Physical function measures are unable to identify who does and does not respond favorably during motor learning tasks. Research suggests that cognition may relate to motor learning abilities in healthy adults. Although cognitive deficits are common following stroke, they have largely been ignored in poststroke motor learning. Studies examining the relationship between cognition and motor learning have examined cognition superficially with 1 or 2 tests representing whole cognitive domains. Thus, our aim was to more completely understand the relationship between cognitive deficits observed poststroke and locomotor learning by administering a battery of cognitive tests.
Methods: Chronic stroke survivors between 18 and 85 years old were recruited. Subjects participated in a locomotor learning task (day 1) and cognitive testing (day 2). During day 1, subjects walked on a treadmill for 2 phases: Baseline and Learning. During Baseline, step length (SL) was calculated and the leg with the shorter SL was identified (SSL). During Learning, a bar graph with a target line displayed real-time information about subjects’ SL. Subjects were asked to match the bars to the target line during Learning; however, the SSL bar was distorted resulting in subjects learning a new walking pattern. The primary learning measure was the Absolute Error at the end of Learning (AE), which was the absolute difference between SL of SSL and the target SL. On day 2, a battery of cognitive tests was administered including the Wisconsin Card Sorting Test (WCST), the NIH Cognitive Toolbox, the Weschler Memory Scale, and the Connor’s Continuous Performance Test. Due to the small sample size at this stage, 3 preliminary regressions controlling for age were run with AE as the dependent variable and age-corrected standard scores from cognitive measures the independent variable.
Results: Seven stroke survivors (69 ± 7.6 years, 4 males) are included in these preliminary data. When controlling for age, the number of Perseverative Errors during WCST explained 34% of the variance observed in AE beyond that explained by age. List Sorting Test of Memory only explained 10%, while the Fluid Composite score from the NIH Toolbox explained 22% of the variability.
Conclusion: Based on our preliminary results, some cognitive assessments (such as the WCST) appear better able to identify stroke survivors who are “good learners” than other tests. Additionally, specific measures of cognition may be better able to identify good learners than global measures of cognition. In the future, we will collect additional data and perform a principle component analysis to determine a cognitive “profile” of stroke survivors who are better learners. Understanding the impact of cognition on learning will improve clinicians’ ability to customize post-stroke interventions.
Poster Session I
T1: Effects of TDCS Electrode Size on Motor Cortical Excitability of the Quadriceps Muscles
Aviroop Dutt-Mazumder1, Scott Brown1, Edward Washabaugh1, Aastha Dharia1, Reesha Talati1, Amanda Vogel1, Adam Gardi1,
Chandramouli Krishnan
1
1University of Michigan, Ann Arbor, MI, USA
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that is commonly used for modulating cortical excitability. The tDCS-mediated cortical excitability changes have been shown to vary in a polarity-dependent fashion such that anodal tDCS increases excitability and cathodal tDCS inhibits excitability. Accordingly, the possibility of using tDCS as a therapeutic adjuvant has been investigated in a variety of neurological and neuropsychiatric conditions. Though the results of these studies are encouraging, it appears that the effects of tDCS are highly variable. A number of factors (eg, different devices, electrode montage, electrode size, etc) may contribute to this variability; however, there are not many studies that have systematically evaluated this issue, particularly in large lower-extremity muscle groups, such as the quadriceps. Hence, this study was performed to determine the effect of tDCS electrode size (small [Active area: 7.5-8 cm2] and large [Active area: 15.5-16 cm2]) on motor cortical excitability of the quadriceps muscles. To ensure that the effects are not specific to a particular device, we investigated the effects of tDCS-induced cortical excitability changes using 2 different devices (Empi Dupel Dual Channel Iontophoresis [Isokentics Inc, AR, USA] and Soterix 1x1 [Soterix Medical, NY, USA]) on separate days. Twenty (10 in each group) neurologically intact young adults participated in this study. Subjects in both groups received anodal tDCS over their dominant leg (preferred kicking leg) motor cortex for 15 minutes on 2 different days that were separated by at least 48 hours. All experimental procedures were identical between the groups, except that the electrode size used for the tDCS application varied. Motor cortical excitability of the quadriceps muscle was evaluated both before and after the tDCS by measuring the participant’s recruitment curve generated by stimulating the quadriceps “hotspot” at various intensities (70% to 140% of active motor threshold) using transcranial magnetic stimulation (TMS). The recruitment curve was fitted with a Boltzmann sigmoidal function to determine the parameters relating to motor cortical excitability: (1) maximal MEP torque size (MEPmax), (2) curve slope (k), and (3) stimulus intensity leading to half-maximal MEP torque size (S50). The post-tDCS TMS excitability parameters were normalized to the baseline (ie, pre-tDCS) values and were compared between groups using repeated-measures analysis of variance with device as a within-subjects factor and electrode size as a between-subjects factor. The results indicated no significant differences in MEPmax, slope (k), and S50 between groups, and this finding was consistent between the 2 devices used in this study (P > .05). These results suggest that the electrode size used during tDCS does not significantly affect the modulation of motor cortical excitability in the quadriceps muscles. The findings have meaningful implications for interventions using tDCS as an adjuvant tool for neurorehabilitation.
T2: Evaluation of Motor Cortical Excitability Using Evoked Torque Responses: A New Tool With High Reliability
Aviroop Dutt-Mazumder1, Edward Washabaugh1, Scott Brown1,
Chandramouli Krishnan
1
1University of Michigan, Ann Arbor, MI, USA
Transcranial magnetic stimulation (TMS) is a noninvasive method to quantify cortical excitability in vivo. Typically, motor evoked potentials (MEPs) elicited by TMS are recorded via surface electromyography (EMG). While this approach is suitable for single-headed muscles, it may not be ideal for multi-headed muscles (eg, quadriceps). In this situation, the torque output associated with the MEPs may serve as a reliable measure to study the net effect of TMS-induced motor volleys on the muscle group as a whole. Moreover, unlike EMG responses, torque outputs are inherently stable and may not require conventional normalization procedures. However, this premise has not been verified experimentally. Therefore, this study was performed to evaluate whether TMS-induced MEP torque output is a reliable assessment tool to evaluate cortical excitability. Twenty healthy participants (age: 21.5 ± 4.7) with no prior history of any significant neurological or orthopedic disorders were recruited for this study. Subjects were tested on 2 different days that were separated by at least 48 hours. On both days, the participant was seated on a dynamometer with their dominant lower limb angle fixed at 60° of knee flexion. Surface EMG electrodes were applied over the muscle bellies of vastus medialis, rectus femoris, and vastus lateralis. Testing began by having the subject perform maximum voluntary isometric contractions (MVICs) of their quadriceps muscle. Following which, the motor cortical region that elicited the best MEP at the least threshold (ie, hotspot) was determined using TMS (Magstim 200 stimulator, 110 mm double cone coil). This location was registered and tracked using a frameless stereotactic system (NeuRRoNav). TMS was performed at various intensities (100%, 110%, 120%, 130%, and 140% of active motor threshold [AMT]) while the subject maintained a 5% (of maximum) background contraction of their quadriceps muscles. The experiment was completed by eliciting TMS-evoked peripheral resting twitch torque by stimulating the quadriceps muscles at 100% of maximum stimulator output (MSO). We employed a 2-way mixed intraclass correlation coefficient (ICC) at 95% confidence interval to evaluate the reliability of MEP measures obtained using different normalization procedures (raw MEPtorque, MEPtorque normalized to MVIC torque, MEPtorque normalized to resting twitch torque, raw MEPEMG, MEPEMG normalized to MVICEMG). Reliability analysis indicated that MEPtorque normalized to the resting twitch torque yielded the best ICC scores and raw MEPEMG yielded the lowest ICC scores. In general, MEPtorque (irrespective of the normalization procedure) had excellent reliability (ICC > 0.80 at TMS intensities 110% AMT and above), when compared with MEPEMG from the quadriceps muscles. These results indicate that TMS-induced MEPtorque can reliably substitute MEPEMG and can be used as an assessment tool to measure cortical excitability in the lower extremity.
T3: Critical Appraisal of Telerehabilitation Effectiveness in Poststroke Patients With Residual Motor Deficits
Abhi Jain1,
Jennifer Mao
1
1Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA
Introduction: Stroke is the leading cause of serious long-term disability in the United States, with an annual cost of management of $68.9 billion. Over half of all stroke survivors experience permanent disabilities, most commonly motor and sensory disability. The psychological and physical trauma may lead to clinical depression, which can result in poor functional outcomes. It affects not only the patient, but it also increases stress and demand of their caretakers or family members. Additionally, poststroke rehabilitation faces additional barriers such as high cost, dependence on caregivers, lack of rehabilitation programs, low health professional to patient ratio in rural settings, challenges with transportation, and high costs. To combat these challenges, telerehabilitation (TR) has emerged as a promising modality to remotely supervise, administer, and motivating various forms of physical, occupational, speech, and other forms of therapies.
Objectives: A critical appraisal of selected articles was done to evaluate whether TR is more effective than standard physical therapy in improving poststroke residual deficits, activities of daily living (ADLY), psychologic and cognition, health status, and satisfaction. As a secondary aim, create a list of measures used to assess outcomes after TR interventions.
Methods: A literature review was done by searching relevant terms in 3 databases. Articles were screened based on predefined inclusion and exclusion criteria.
Results: Database search yielded 259 articles. After screening titles 55 full text articles remained. Eleven articles were included in qualitative review, which included 511 patients. This included 6 randomized controlled trials (RCTs) and 4 cohort studies. Two studies involved analysis of the same dataset and were not double counted. The 2 most popular types of TR are home based (4 studies; 121 patients) and robot assisted therapy (3 articles, 2 data sets; 109 patients). Two RCTs have been done with a focus on VR-based TR. In home-based, telecommunication devices (phone, videophone) are used to provide support directly to a disabled person’s home. The greatest used outcomes were classified as motor function (96%), disability, (36%), and psychologic and cognitive (36%). The Wolf Motor Function test (38.5%) and Functional Independence Measure (30.8%) were used as the most common measure of motor function and degree of disability, respectively.
Conclusions: Telerehabilitation is equivocal to conventional rehabilitation procedures irrespective of devices adopted or location (home or clinic) of delivered treatment. TR may be an even better than traditional in-clinic rehabilitation in the improvement of motor functions, depression assessment, and caregiver stress. Patients found TR equally user friendly and motivating. While increasing access, TR may decrease costs. It can increase flexibility, health care worker to patient ratio, and provide access to underserved regions, thus making TR a valuable alternative.
T4: Lower Limb Transcranial Magnetic Stimulation Measures in the Ipsilesional Hemisphere After Stroke: Reliability and Relationship With Lower Limb Motor Function
Hui-Ting Goh
1, Kendall Connolly1, Jenna Hardy1, Delaina Walker-Batson1,2
1Texas Woman’s University, Dallas, TX, USA
2The Stroke Center-Dallas, Dallas, TX, USA
Background and Purpose: Transcranial magnetic stimulation (TMS) has been used extensively to investigate neuroplastic changes associated with upper limb motor recovery in individuals poststroke. The use of TMS for lower limb motor function is relatively understudied. The purpose of this secondary analysis was to examine the test-retest reliability of the lower limb TMS measures in the ipsilesional hemisphere among individuals with chronic stroke and to explore the relationship between TMS measures and lower limb motor impairment and gait speed.
Methods: Twelve individuals with chronic stroke (3 females and 9 males, mean age = 57.8 years, mean duration poststroke = 26.5 months) participated in a larger study investigating the effect of repetitive TMS on dual-task walking. Ipsilesional corticospinal excitability of each participant was assessed 3 times with the test-retest interval set at 1 week. Single-pulse TMS was delivered to the ipsilesional primary motor cortex by a double-cone coil, and the electromyographic (EMG) activity was recorded at the contralateral tibialis anterior (TA) muscle. TMS intensity was set at 120% of resting motor threshold and 10 stimulations were delivered at each session. Three TMS measures were acquired at each session: motor evoked potential (MEP) amplitude, MEP latency, and MEP area. Motor impairment was quantified using Fugl-Meyer Motor Assessment-Lower Extremity (FMA-LE) scale and gait speed was recorded using a GaitRite walkway. Test-retest reliability of each TMS measure was examined using Intraclass correlation coefficient (ICC). Relationship between TMS measures and FMA-LE and gait speed was assessed using Spearman correlation coefficients (ρ).
Results: Ipsilesional MEPs were absent in 5 out of 12 participants. Test-retest reliability of TMS measures was moderate (MEP amplitude ICC = 0.52; MEP latency ICC = 0.67; MEP area ICC = 0.57). Neither TMS measures correlated with FMA-LE (all P > .05), whereas MEP amplitude had a strong positive correlation with gait speed (ρ = 0.79, P = .04).
Conclusion: Lower limb TMS measures can be reliably measured in the ipsilesional hemisphere among individuals with chronic stroke. Individuals with a greater ipsilesional MEP amplitude had a faster gait speed. Future research will include more participants and explore the use of paired pulse TMS measures in investigating lower limb corticospinal excitability.
T5: Task Practice Intensity Estimation in Individuals With Traumatic Brain Injury
Sandeep Subramanian
1, Jericho Barela1, Laura Landry1, Bryan Sheffield1, Esequiel Salcedo1, Patricia Rivera1, Elizabeth Koyle1, Jesse Neeley1, Ramesh Grandhi1
1UT Health San Antonio, San Antonio, TX, USA
Traumatic brain injury (TBI) is one the leading causes of mortality and morbidity in the United States. Individuals sustaining a TBI often have motor impairments involving the lower limb (LL) and upper limb (UL), with lower levels of improvement seen in the UL compared to the LL. These factors may continue to limit UL involvement in performance of functional activities of daily living, well after cessation of rehabilitation. UL motor improvement after a TBI is attributable in part to adaptive neuroplasticity and motor learning, with the intensity of task-practice representing a key influence. Intensity of task-practice has many definitions, including the time spent in therapy and the number of repetitions employed in a single session. There is a growing consensus that the numbers of repetitions used in a session may be the better choice. The minimum number of repetitions per session of therapy for optimal levels of UL motor improvement in people with TBI is currently unknown. One potential solution, used previously in individuals who sustained a stroke, is to estimate the number of repetitions necessary to achieve a plateau in the performance of a motor task (pointing to a target) using kinematic analysis. Our study objective was to estimate the minimal number of repetitions to achieve an asymptote in a UL pointing task in individuals with TBI. We recruited TBI patients with UL hemiparesis along with age-matched controls. The TBI group was further subdivided into participants having mild and moderate severity of injuries (based on 12-hour postinjury Glasgow Coma Scale scores). Both groups of participants were seated. They pointed repeatedly to a target placed in front of them at a distance equal to their UL length. We aligned the target to their sternal notch and placed it at a height of 90° of shoulder flexion. The trial duration was 3 to 5 seconds and recording frequency was 100 Hz. The primary outcome was the number of trials necessary to achieve an asymptote in the endpoint error during pointing movements. The root mean squared error between the endpoint position and the center of the target at the end of the movement quantified the endpoint error. Secondary outcomes included movement speed and ranges of motion of UL joints (elbow, shoulder) and trunk. Preliminary results indicate that compared to controls, individuals with TBI needed more trials to reach an asymptote in the performance of the pointing movement. In addition, the TBI group had slower movements and used less shoulder horizontal adduction range of motion. Results of this study will help in providing information on the minimal number of repetitions necessary to achieve optimal UL motor improvement in individuals with TBI.
T6: Predicting Lower Extremity Motor Recovery After Stroke: Imaging Biomarker Improves Motor Score Predictions
Fanny Munsch1,2, Thomas Tourdias3,4, Igor Sibon3,4, Vincent Dousset3,4,
Gottfried Schlaug
1,2
1BIDMC, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3CHU Bordeaux, Bordeaux, France; 4Bordeaux University, Bordeaux, France
Background and Purpose: Motor impairment assessed in the acute stroke phase (as measured by the Fugl-Meyer [FM] assessment) is a strong predictor of lower extremity (LE) motor impairment at 3 months poststroke. The predictive value of measures of motor tract integrity as well as lesion size and location is not known. For our analysis we combined 2 motor tracts that might be particularly important in the control of proximal leg muscles to create a canonical tract of the corticospinal tract proper (CST) and the corticorubrospinal tract (CRST). In previous work we have shown that weighted CST Lesion Load (a combined variable of lesion size and location) is a significant predictor of 3-month outcome for the upper extremity (UE). Our hypothesis is that weighted CST/CRST Lesion Load (wCST/CRST-LL) can improve the FM-based predictions of LE motor outcome.
Methods: Ischemic stroke patients with a UE paresis (UEFM < 66) and a LE paresis (LEFM < 34) were assessed between 24 and 72 hours and at 3 months poststroke with the FM scale. Lesion maps drawn on diffusion-weighted images were used to calculate lesion loads of a combined CST-CRST probabilistic tract derived from matched elderly healthy control subjects. Then, we tested whether baseline LEFM and wCST/CRST-LL are independent variables and whether adding wCST/CRST-LL to baseline LEFM improves the model accuracy. Finally, we replicated the same analyses on a subgroup of more severely impaired patients (LEFM ⩽13).
Results: Both baseline and 3-month follow-up were available for 187 patients for the derivation sample (Bordeaux cohort) and 66 patients for the validation sample (Boston cohort). Initial motor impairment (LEFM) and wCST/CRST-LL were independent strong predictors of LE motor outcome (respectively P < .001 for the derivation sample and P ⩽ .01 for the validation sample). Combining initial motor impairment and wCST/CRST-LL was a much better model than LEFM by itself (respectively R2 = 0.58 vs R2 = 0.53 and R2 = 0.63 vs R2 = 0.59). Finally, for the subgroups of more severely impaired patients, the wCST/CRST-LL was able to predict LE motor outcome (respectively P < .001 and P = .05) where the LEFM could not.
Conclusion: wCST/CRST-LL, a combined measure of lesion size and location, adds significant power to a combined model with initial LEFM, but is also a strong predictor of LE motor outcome by itself.
T7: The Kinect Motion Capture Reachable Workspace as an Assessment for Stroke Recovery
Vicky Chan
1, Gregorij Kurillo1, Maya Hatch1, Jay Han1
1University of California, Irvine, CA, USA
Background and Purpose: Stroke remains a leading cause of disability in the United States. There is a strong consensus among rehabilitation experts that well focused repetitive practice is the most important element in any rehabilitation program. Traditional physical therapy emphasizes in-clinic therapy as well as in-home exercise to maximize recovery for the patient. Telerehabilitation is becoming more common in stroke rehabilitation and recovery. Currently, assessment of improvement in function requires a therapist to perform validated measures to track patient progress. Telerehabilitation is limited in objective measures of improvement. The purpose of this case report is to compare the Kinect Motion Capture Reachable Workspace to standard clinical outcome measures.
Case Description: A 64-year-old female who suffered from an ischemic stroke was admitted to the acute rehabilitation unit. The patient received standard therapy including physical, occupational, and speech therapy for a 4-week period. Standard clinical outcome measures including Fugl-Meyer Motor Assessment and Functional Independence Measures along with Kinect Motion Capture Reachable Workspace were assessed on admission, weekly and at discharge. The Kinect Motion Capture Reachable Workspace is designed to measure the range of motion of the upper extremities. The study participant is seated in front of a television to follow the movement protocol as the Kinect Motion Capture System records range of motion.
Outcomes: In an attempt to compare the Kinect Motion Capture Reachable Workspace as an assessment of overall upper extremity range of motion to standardized clinical measures, we calculated the percentage of change in clinical measures including Fugl-Meyer Motor Assessment–Upper Extremity (FMA-UE) and Functional Independence Measures–Self Care (FIM-SC) at various time points compared to baseline. There was a direct correlation in the percentage of improvement between FMA-UE, FIM-SC, and Kinect Motion Capture Reachable Workspace at week 1, week 2, discharge, and at the 1-month follow-up. The patient FMA-UE score improved 34%, 46%, 64%, and 74%. The patient FIM-SC score improved 41%, 50%, 58%, and 69%. The Kinect Motion Capture Reachable Workspace assessment showed a strong correlation to FMA-UE and FIM-SC with improvements of upper extremity range of motion over the same time period of 34%, 42%, 59%, and 68% in this patient.
Conclusion: This case report suggests that there may be a meaningful correlation between Kinect Motion Capture Reachable Workspace and standard clinical outcome measures in stroke recovery. This correlation may give meaningful objective data in patients receiving telerehabilitation. Further clinical studies need to be performed to see if there is a true correlation.
T8: Paired Brain and Spinal Cord Stimulation Strengthens Spared Spinal Circuits After Injury
Ajay Pal
1, Aldo Garcia-Sandoval2, Shivakeshavan Ratnadurai-Giridharan1, Qi Yang1, Thelma Bethea1, Aditya Ramamurthy1, Tong-Chun Wen1, Walter Voit2, Jason Carmel1,3
1Burke Neurological Institute, White Plains, NY, USA
2The University of Texas at Dallas, Richardson, TX, USA
3Weill Cornell Medicine, New York, NY, USA
Using the principles of associative learning, we have developed a neuromodulation paradigm that augments sensorimotor excitability in the spinal cord. We pair suprathreshold motor cortex stimulation with subthreshold spinal cord stimulation using a timing that causes the stimuli to arrive synchronously in the spinal cord. This paired stimulation strongly augments motor evoked potentials (MEPs) at the time that they are delivered. When pairing is performed repeatedly for 5 minutes, there is lasting and robust increase in MEPs. The present study tests the efficacy of paired stimulation in rats with injury of the sensorimotor system. We hypothesized that the tissue spared by spinal cord injury (SCI) would be sufficient to enable the lasting effects of paired stimulation. We further hypothesized that repeated sessions of paired stimulation would produce cumulative effects on spinal excitability. To test paired stimulation, we implanted 3 sets of electrodes: epidural screw electrodes over each motor cortex, EMG electrodes in each biceps muscle, and spinal epidural electrodes. The spinal electrodes are printed using photolithography, allowing them to be very thin (<100 mm). In addition, the electrodes are patterned on a softening polymer, which is stiff at room temperature making them easy to insert into the epidural space. It becomes supple after implantation, which protects the cervical spinal cord. A moderate C4 contusion injury was performed, and electrode arrays were inserted over C5-C6. Two weeks later, repetitive stimulation was performed. We measured biceps MEPs produced by cortical and spinal cord stimulation. Both cortical and spinal MEPs were augmented by ~75% and this lasted for over 60 minutes. We also measured H-reflexes in the forelimb. Rats with SCI were hyperreflexic, as demonstrated by the rate-dependent suppression of the H-reflex. Paired stimulation restored the measure of hyperreflexia close to the values of uninjured rats. Finally, we measured the effects of paired stimulation 5 minutes every day for 10 days in rats with a cut injury to the corticospinal tract from one hemisphere. Over the 10 days of pairing, the effects increased from ~75% change to more than 250%. This suggests that there can be a cumulative effect of repeated pairing after injury. Thus, the circuits spared by CST lesions were sufficient to augment MEPs with paired stimulation, which enhanced spinal excitability while decreasing hyperreflexia.
T9: Motor Function as Predictor of Inpatient Length of Stay and Discharge Destination in Stroke Rehabilitation
Martje Tazelaar
1, Martine Eckhardt1, Irene Ploeg1, Majanka Heijenbrok1, Gerard Ribbers1
1Rijndam Rehabilitation Centre, Rotterdam, Netherlands
Introduction: Prediction of length of stay (LOS) and discharge destination (home vs nursing facility) in inpatient stroke rehabilitation is important for setting attainable treatment goals, discharge planning, informing patients and caregivers, and lowering costs.
Objective: To examine whether motor function, measured by Berg Balance Scale (BBS), Functional Ambulation Category Scale (FAC), and Brunnstrom Fugl-Meyer assessment (BFM) on admission, is predictive for LOS and discharge destination in stroke rehabilitation adjusted for patient and stroke-specific factors.
Patients and Methods: Univariable and multivariable linear and logistic regression analyses were performed on data prospectively collected between July 2011 and January 2016 from 715 adult patients (mean age 59 [SD = 10.9] years, 59.4% men) within 21 days poststroke, to assess the predictive value of motor function on LOS and discharge destination respectively.
Results: Mean LOS was 56.5 (SD = 36.9) days and 666 (94.2%) patients were discharged home. BBS, BFM, and FAC were independently predictive for LOS, adjusted for living situation, cognition, current smoking, and days poststroke (R2 = 0.41). Interim hospitalization (odds ratio = 5.0; P < .001), and smoking (odds ratio = 2.0; P < .05) showed the highest predictive value for being discharged to a nursing facility.
Discussion and Conclusions: We found motor function, predominantly BBS, to be predictive for inpatient LOS, but not for discharge destination, in stroke rehabilitation. In contrast, stroke-specific factors did not influence any of these outcomes.
Clinical Message: Early assessment of motor function, especially balance, at admission is important for discharge planning in inpatient stroke rehabilitation.
T10: Pupillary Response to Dual-Tasking in Parkinson’s Disease: A Proof-of-Concept Study
Melike Kahya
1, Kelly Lyons1, Rajesh Pahwa1, Abiodun Akinwuntan1, Hannes Devos1
1University of Kansas Medical Center, Kansas City, KS, USA
Introduction: Most activities of daily living require performing dual-tasking (DT). Individuals with Parkinson’s disease (PD) seem to be highly affected by DT due to the competition of limited cognitive resources. Pupillary response has been used as a neurophysiological measure of cognitive workload during cognitive tasks in individuals with PD. However, it is not known whether pupillary response can be used to evaluate cognitive workload during DT conditions in individuals with PD. The purpose of this study was to establish the proof-of-concept that pupillary response can also be used to evaluate cognitive workload during in DT conditions in individuals with PD.
Subjects: Six individuals with PD (age: 66.1 ± 5.6, sex: 3 female, Hoehn and Yahr stage II-III while ON medication), and 10 age- and sex-matched healthy controls (age: 67 ± 5.7, sex: 6 female) were recruited.
Materials/Methods: All subjects tested at the University of Kansas Medical Center. Subjects were asked to wear eye-tracking glasses (SensoMotoric Instruments) in order to record the pupillary response across 4 conditions: (1) single postural control task with eyes open; (2) single postural control task with eyes occluded; (3) DT condition with eyes open; (4) DT condition with eyes occluded. During the single postural control task, subjects were asked to stand on the balance platform (Advanced Mechanical Technology, Inc) for 60 seconds with eyes open and eyes occluded. The DT conditions involved standing on the balance platform while performing the auditory Stroop test. The cognitive workload, indexed by pupillary response, was transformed on a continuous scale ranging from 0 to 1, was the main outcome variable. The center of pressure (CoP) displacement was the secondary outcome variable. Two-way repeated measures analysis of variance (ANOVA) was employed to compare pupillary response and CoP displacement across the 4 conditions and between the groups.
Results: The results demonstrated that the pupillary response in both groups increased with more challenging postural conditions (P = .03). The pupillary response in PD was higher than in controls across conditions, yet reached borderline significance (P = .05). No interaction effect was observed (P = .63). The balance platform results demonstrated an increased COP sway on the x-axis with increased postural demand within groups (P = .03), but not a between-group difference (P = .82). For the CoP on the y-axis, there was no significant within (P = .29) or between group effect (P = .60).
Conclusion: Our data showed that pupillary response can be potentially used to evaluate cognitive workload during postural control and DT conditions in individuals with PD. Pupillary response is perhaps even more sensitive than traditional measures of postural control during DT. Future studies are warranted to investigate whether pupillary response may predict postural control and DT impairments in individuals with PD before they emerge in balance tests.
T11: History of Depression and Antidepressant Use at Stroke Onset and Posttroke Post-Acute Rehabilitation Care: The Brain Attack Surveillance in Corpus Christi (BASIC) Project
Eric Stulberg
1,2, Liming Dong1, Alexander Zheutlin1, Sehee Kim1, Edward Claflin1, Lesli Skolarus1, Lewis Morgenstern1, Lynda Lisabeth1
1University of Michigan, Ann Arbor, MI, USA2Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Background: Prestroke depression status and post-acute rehabilitation care (PARC) are determinants of poststroke depression and function. Both outcomes likely affect each other. However, treatment of poststroke depression does not appear to improve functional outcomes. Little is known on how prestroke depression status affects PARC, a possible pathway for upstream intervention. We examined how prestroke depression status affects PARC in a population-based study.
Methods: Incident ischemic stroke cases were from the Brain Attack Surveillance in Corpus Christi Project from 2008 to 2012. Prestroke depression status was self-reported and categorized as never depressed, history of depression without antidepressant use at stroke onset, or antidepressant use at stroke onset. PARC included home, skilled nursing facility (SNF), or inpatient rehabilitation facility (IRF). Confounder-adjusted multinomial regression models were used to examine the association between prestroke depression status and PARC. We accounted for missing data using inverse probability weighting and multiple imputation. Multiple sensitivity analyses were conducted to assess the robustness of our findings.
Results: There were 548 stroke survivors (mean age 65.3 years, 48.3% female, 62.6% Mexican-American). Fully adjusted odds ratios (ORs) comparing home discharge to SNF were 2.19 (95% confidence interval [CI]: 0.95-5.11) for those with a history of depression and 2.03 (95% CI: 0.85-4.83) for those using an antidepressant at stroke onset, relative to those never depressed. When withholding adjustment for stroke severity, the association between antidepressant use at stroke onset and home discharge relative to SNF increased (OR 2.55, 95% CI: 1.11-5.83), but the association between history of depression and home discharge relative to SNF was attenuated (OR 1.88, 95% CI: 0.86-4.11). Fully adjusted odds ratios comparing IRF to SNF were 0.99 (95% CI: 0.32-3.01) and 2.56 (95% CI: 0.94-7.00) for those with a history of depression and using an antidepressant at stroke onset, respectively, relative to those never depressed. When withholding adjustment for stroke severity, the association between antidepressant use at stroke onset and IRF discharge relative to SNF increased (OR 3.28, 95% CI:1.24-8.67), and the association between history of depression and IRF discharge relative to SNF had a qualitative change in direction (OR 1.17, 95% CI: 0.40-3.42). The sensitivity analyses results were largely consistent with our primary analyses with respect to the direction of effects, though at times attenuated in size.
Conclusions: Antidepressant use at stroke onset use may provide medical-functional protection, increasing odds of home and IRF discharge over SNF discharge, with evidence of possible mediation by stroke severity. History of depression may increase odds of home discharge over SNF. We encourage research investigating the causal pathway from prestroke SSRI use to stroke severity and PARC placement, as well as how poststroke resiliency and social support vary by depression status and affect subsequent outcomes.
T12: Interlimb Differences During Bimanual Aiming After Stroke: Effect of Target Distance
Rini Varghese
1, Robert Sainburg2, James Gordon1, Carolee Winstein1
1University of Southern California, Los Angeles, CA, USA
2Pennsylvania State University, College Station, PA, USA
Previous studies suggest that when the 2 hands move toward independent target goals, there is a strong tendency to synchronize movement times. Do the 2 hands achieve this high degree of temporal synchrony by adopting similar movement trajectories? In this study, we examined the effect of manipulating target distance on movement time and directional error during bimanual aiming movements in non-disabled adults (ND) and chronic stroke survivors. Six right-hand dominant non-disabled young adults and 2 chronic stroke survivors—1 left- (LHD) and 1 right-hemisphere damaged (RHD)—performed bimanual aiming movements to 2 visual targets in a frictionless 2D workspace, without vision of their hands. Visual feedback of hand position was not given during movements, but was available at the end of each trial. Additionally, performance feedback was given in the form of a numeric score. In 5 experimental conditions, target distance was manipulated symmetrically (6-6, 10-10, and 14-14 cm), and then asymmetrically (ie, 6-10, 6-14 for the right hand, or 10-6 and 14-6 for the left hand). We quantified movement time (T) and directional error at peak acceleration (DE-PA) and movement end (DE-ME) for the 2 hands and compared them across conditions in ND and stroke. Compared to ND, both LHD and RHD cases show a significant increase in T, DE-PA, and DE-ME (Wilcox P < .0001). We summarize and focus here on our findings for ND. First, as distance increases symmetrically (10-10, 14-14), ND showed a significant increase in T and DE-PA, especially for the farthest target (14-14 compared to 6-6), but only for the right hand (P < .01). DE-ME did not change across symmetric conditions. Second, for asymmetric-right conditions (6-10 and 6-14) T was longer for both hands (P < .001), and DE-PA were smaller but only for the right hand. Again, DE-ME did not change across asymmetric-right conditions. Third, for asymmetric-left conditions (10-6, 14-6), T was longer only for the left hand. As distance increased, DE-PA were smaller for the left hand, but larger for the right hand. DE-ME was significantly larger for the left hand (P < .001) but did not change for the right hand. Findings suggest that movement time synchrony is modified by target distance, particularly for the right hand. When present, such temporal synchrony is achieved through different movement trajectories by the 2 hands, as indicated by interlimb differences in directional error. Directional errors were also modified by target distance, and may provide insight into the locus of movement time asynchronies. Preliminary analyses of stroke cases suggest that bimanual movement deficits may differ between LHD and RHD.
T13: Effects of the Aerobic Exercise With Limbs Compression and Body Cooling on Individuals With Post-Concussion Syndrome
Yi-Ning Wu
1, Jessica Gravel2, Matthew White2, Josh Avery2, Terrie Enis2, Caroline Stark1, Robert Cantu2
1University of Massachusetts Lowell, Lowell, MA, USA2Emerson Hospital, Concord, MA, USA
Introduction: Post-concussion syndrome (PCS) is a complex disorder in which concussion symptoms last for weeks, months, and rarely years. Recent research has shown that exercise can improve post-concussion symptoms. The leading theory supporting this is that human growth hormone released in response to increased lactate production from exercise enhances the brain function and recovery. Blood flow restriction and cooling are thought to trigger physiological responses at a relatively low intensity that might be beneficial to people with PCS. This study aimed to examine the outcomes of limbs compression and body cooling.
Methods: Twenty-three individuals who were diagnosed with PCS due to a concussive event within a year, and with modified Somatic Perceptions Questionnaire score less than 10, were recruited and randomly assigned to the aerobic exercise (control) or aerobic exercise with limbs compression and body cooling (experimental) groups. Vasper system (Vasper, Mountain View, CA) consists of a recumbent elliptical (NuStep) and a cooling table was used for exercise. All participants rode the NuStep for 21 minutes at 60% of the predicted maximum heart rate twice a week for 6 consecutive weeks followed by 6 weeks of no intervention. In addition to the aerobic exercise, each participant received the standardized physical therapy as part of the 6-week intervention. A post-concussion symptoms checklist was filled daily by the participants over the period of the 12-week study. To examine the severity changes, the variance of checklist scores for each participant during the 6-week intervention period and 6 weeks after the intervention ended were calculated. The changes in health-related quality of life were captured using QOLIBRI and PedsQL when it was appropriate. Mann-Whitney U test was used to test the group differences in symptom reductions.
Results: The results showed that variability of the overall symptom severity was significantly less in the experimental group (P = .01) during the intervention period. The number of symptoms remained significantly more stable in the experimental group (P = .02). Grouped data showed that people underwent the aerobic exercise with cooling and limbs compression had relatively larger improvement in the quality of life compared to the group without.
Discussion: The results of this study have demonstrated that aerobic exercise with limbs compression and cooling enhances the recovery of PCS. The effect caused by limbs compression and cooling maintains and stays more stable after the intervention ends compared to regular aerobic exercise at the same intensity. Aerobic exercise with limbs compression and body cooling did not exacerbate the post-concussion symptoms.
Conclusion: Aerobic exercise alleviates the post-concussion symptoms of individuals with PCS. More stable recovery was found in the individuals who exercised under limbs compression and body cooling as compared to the individuals without body cooling and limbs compression.
T14: Repeated AbobotulinumtoxinA Injections Benefit Walking Speed, Step Length, and Cadence in Adults With Spastic Hemiparesis due to Stroke or Traumatic Brain Injury
Alberto Esquenazi1, Allison Brashear2, Thierry Deltombe3,
Brian Carlson
4, Anne-Sophie Grandoulier5, Claire Vilain5, Philippe Picaut5, Jean-Michel Gracies6
1MossRehab Gait and Motion Analysis Laboratory, Elkins Park, PA, USA
2Wake Forest School of Medicine, Winston-Salem, NC, USA
3Centre Hospitalier Universitaire UCL Namur site Mont-Godinne, Yvoir, Belgium
4Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA
5Ipsen Pharma, Les Ulis, France
6Université Paris-Est, Hospital Albert Chenevier-Henri Mondor, Service de Rééducation Neurolocomotrice, Créteil, France
Background and Aims: Patients with chronic hemiparesis following stroke or traumatic brain injury (TBI) often experience restricted walking performance. Our previous double-blind (DB) trial of 388 patients demonstrated that abobotulinumtoxinA (aboBoNT-A) treatment improves muscle tone and functional outcomes in adults with lower limb spastic paresis. This subanalysis from the open-label (OL) study extension phase assesses changes in walking speed (WS), step length (SL), and cadence in these patients.
Methods: A phase 3, prospective, multicenter, DB, randomized study of a single injection of aboBoNT-A (1000 U or 1500 U or placebo; NCT01249404), followed by an OL study extension (⩽4 cycles of aboBoNT-A 1000 U or 1500 U; NCT01251367). Participants were ambulatory adults with spastic hemiparesis causing gait dysfunction, comfortable barefoot WS 0.1 to 0.8 m/s in 10-meter WS test without walking aids, and stroke or TBI ⩾6 months before study enrollment. Patients receiving either aboBoNT-A dose were assessed relative to DB baseline for WS, SL, and cadence using 10-meter WS tests under 4 different conditions (maximal and comfortable WS, barefoot, and with shoes).
Results: Relative to baseline, improvements in WS, SL, and cadence by OL Cycle 3 Week 12 were observed under all 4 test conditions. Mean change from baseline in WS (m/s [SD], %) was the following: comfortable barefoot WS +0.09 (0.14), 23.6%; comfortable WS with shoes +0.08 (0.15), 22.6%; maximal WS barefoot +0.10 (0.19), 22.9%; and maximal WS with shoes +0.10 (0.20), 19.7%. Mean change from baseline in step length (m/step [SD], %) for each WS test by Cycle 3 of the OL study was as follows: comfortable barefoot WS +0.04 (0.08), 13.8%; comfortable WS with shoes +0.04 (0.09), 13.2%; maximal barefoot WS +0.04 (0.09), 11.2%; and maximal WS with shoes +0.03 (0.10), 9.4%. Mean change from baseline in cadence (steps/s [SD], %) for comfortable barefoot WS was +0.08 (0.21), 8.4%; comfortable WS with shoes was +0.06 (0.21), 7.2%; maximal barefoot WS was +0.10 (0.25), 9.7%; and maximal WS with shoes was +0.10 (0.26), 8.6%.
Conclusions: Substantial improvements in WS, SL, and cadence were achieved over time in hemiparetic adults with repeated administration of aboBoNT-A. The highest mean percentage improvements were at comfortable barefoot WS for WS and SL, and at maximal barefoot WS for cadence. The least improvements from DB baseline were observed under test conditions with shoes compared with barefoot, across all categories.
T15: The Natural Trajectory of Upper Limb Performance in Daily Life Over the First 12 Weeks After Stroke
Kimberly Waddell
1, Michael Strube1, Rachel Tabak1, Catherine Lang1
1Washington University, Saint Louis, MO, USA
Background: Upper limb capacity, defined as what the limb is capable of doing, can improve both early (⩽6 months) and later (>6 months) after stroke. Clinicians and researchers often assume improved UL capacity directly translates to increased UL performance, defined as what a person actually does in daily life. Recent research does not support the direct link between UL capacity and UL performance. Indeed, UL performance in daily life is a unique and complex construct of recovery and may not be a direct consequence of improved UL capacity. Other aspects, such as self-perceived barriers to use and psychosocial factors, may influence UL performance after stroke. Given that UL performance does not appear to change ⩾6 months after stroke, the next critical step is to investigate if and how UL performance changes early (<12 weeks) after stroke. The first 12 weeks are when majority of neurological recovery occurs and rehabilitation services are provided. Additionally, characterizing the relationship between self-perceived barriers, psychosocial factors (eg, belief, confidence, motivation), and UL performance will provide additional insights into how nonmotor characteristics may affect UL performance in daily life.
Objective: The purpose of this study was to quantify the natural trajectory of upper limb performance over the first 12 weeks following a stroke. The secondary purpose was to evaluate the potential influence of self-perceived barriers and psychosocial factors on UL performance.
Methods: This was a prospective, longitudinal cohort study. Participants (n = 25) were enrolled within 2 weeks of a first ever ischemic or hemorrhagic stroke with documented UL weakness within the first 48 hours of stroke onset. A battery of assessments was administered at 2, 4, 6, 8, and 12 weeks poststroke. The Action Research Arm Test measured UL capacity and bilateral, wrist-worn accelerometers quantified UL performance. The accelerometers were worn for 24 hours at each assessment time point. A survey measured self-perceived barriers and psychosocial factors related to UL performance. Final analyses are pending at this time but will use hierarchical linear modeling. The primary outcome of interest is change in UL performance over time (ie, growth curve) of 5 primary accelerometry-derived variables. The potential moderating effects of self-perceived barriers and psychosocial factors will be evaluated as part of the final analyses.
Results: Final results are pending.
Conclusions: Characterizing the natural trajectory of UL performance, a unique and separate construct of UL rehabilitation, provides important insight for future UL interventions. Driving change on a performance level is likely a product of several factors, including but not limited to UL capacity. This is the first study to characterize the dynamic relationship between UL performance and psychosocial factors, such as self-perceived barriers and belief, confidence, and motivation to improve UL performance in daily life.
T16: Variability of Leg Movements Across 7 Days During Early Infancy
Weiyang Deng
1, Beth Smith1
1University of Southern California, Los Angeles, CA, USA
Background: Infants with or at risk of developmental disabilities tend to have different movement patterns and characteristics. Early intervention aims to provide beneficial motor experience for infants at risk and promote neuromotor development. To detect infants’ typical movement patterns in the natural environment, we are using wearable sensors to measure the characteristics of leg movements infants produce across days and relate movement experience to skill development.
Purpose: To determine whether 1 day is sufficient to represent an infant’s typical performance, or more days are needed.
Methods: We used wearable sensors to collect 7 consecutive days of full-day leg movement activity, 7 to 13 hours per day, from 10 infants with typical development between the ages of 1 and 5 months. We identified each leg movement’s average acceleration, peak acceleration, and duration.
Results: Absolute difference between the average of first 2 days and the standards (average of 7 days) of average acceleration, peak acceleration, and duration dropped below 5% of the standard (3.8%, 4.4%, and 3.3%). Wilcoxon signed rank test shows there is no significant different between the average of first 2 days and standards across all measurements (P = .508, .799, .878).
Conclusions: The variability of leg movement kinematic data across 7 days is visually within a limited range in infants with typical development. The results suggest it is better to collect data for 2 consecutive days. Our results will inform the clinical measurement of full-day infant leg movement for neuromotor assessment and outcome measurement purposes.
T17: Development and Validation of Virtual Prism Adaptation Therapy in Subacute Stroke Patients With Hemispatial Neglect
Won-Seok Kim
1, Sungmin Cho1, Jihong Park1, Seo Hyun Park1, Nam-Jong Paik1
1Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
Background: Hemispatial neglect is common after stroke and associated with poor functional recovery and social return. Among various possible treatments for neglect, prism adaptation therapy has been known to be effective to promote the recovery from neglect. However, the conventional prism therapy using a prism glass and real object has a few shortcomings. Prism lens has to be changed to adjust the degree of deviation by the prism and the hand trajectory has to be masked during therapy. To solve these problems in conventional prism therapy, we developed virtual prism adaptation therapy using immersive virtual reality and depth-sense camera.
Methods: The developed system was applied to 10 subacute stroke patients with hemispatial neglect (60.3 ± 10.1 years, male–female = 6:4). The experiment consisted of 4 phases, which were non-prism, 5-minute-prism (10° deviation), 5-minute-prism (20° deviation), and 5-minute-non-prism (post-adaptation). The median values of pointing deviations for 30-second-block in each phase were plotted. The cortical activation pattern was analyzed in each condition using the functional near-infrared spectroscopy with the block design. The most significantly activated channel during the pointing in each last 3 conditions in contrast to the pointing in non-prism condition was investigated.
Results: The pointing error in the first block of pointing during the 20° deviation mode was significantly higher (7.9 ± 3.2) than that in the non-prism mode (1.4 ± 7.3) (P = .046). The pointing error in the first block of pointing during the post-adaptation phase was changed to the negative direction (−6.5 ± 4.4) compared to the non-prism mode (P = .028). The most significantly activated area during the last 3 phases in contrast to the non-prism phase was the area around the right premotor cortex (Brodmann area 6).
Conclusion: The virtual prism adaptation therapy could be a feasible system to solve the problems of conventional prism adaptation therapy. Further clinical trial to investigate the efficacy of this system on hemispatial neglect is required in stroke patients.
T18: Contralesional Hindlimb Motor Response Induced by Unilateral Brain Injury: Evidence for Extra Spinal Mechanism
Nikolay Lukoyanov1, Liliana Carvalho1, Hiroyuki Watanabe2, Mengliang Zhang3, Daniil Sarkisyan2, Olga Kononenko2, Igor Bazov2, Tatiana Yakovleva2, Jens Schouenborg4,
Georgy Bakalkin
2
1Universidade do Porto, Porto, Portugal
2Uppsala University, Uppsala, Sweden
3University of Southern Denmark, Odense, Denmark
4Lund University, Lund, Sweden
Background: The neurological dogma states that motor deficits secondary to traumatic brain injury and stroke arise due to the aberrant activity of neural pathways descending from injured brain to the spinal cord. We tested this dogma by analyzing hindlimb motor response to unilateral brain injury in rats with completely transected spinal cord.
Methods: The spinal cord was first transected at T2/T3 levels, and then the cortical hindlimb representation area was unilaterally ablated. Motor outputs were analyzed under pentobarbital anesthesia during 3 to 4 hours. Formation of hindlimb postural asymmetry was assessed as differences between the contra- and ipsilesional legs in (1) their position; (2) hip, knee, and ankle joint angles; and (3) stretch forces. The nociceptive withdrawal reflexes, quantified as EMG responses evoked by electrical stimulation of the digits and heel, were compared between the ipsi- and contralesional hindlimb muscles. Expression of plastic genes was analyzed by qRT-PCR in the lumbar spinal cord, that is, below the transection level.
Results: Behavioral, electrophysiological, and molecular evidence demonstrated the development of the contralesional-side specific response to the unilateral brain injury. The rats, which received unilateral cortical ablation but not sham operation after complete spinal transection, developed asymmetric hindlimb posture with flexion of the contralesional leg. The hindlimb withdrawal reflexes of the flexor muscles (the extensor digitorum longus and semitendinosus) were enhanced on the contralesional side while extensor muscle (the interosseous) on the ipsilesional side. Unilateral cortical ablation in spinal rats produced robust changes in the expression of neuroplastic genes in the lumbar spinal cord. mRNA levels were elevated mostly on the ipsilesional side resulting in the asymmetric expression patterns. Unilateral brain injury failed to induce postural asymmetry in the hypophysectomized spinal rats.
Conclusions: These results demonstrate that, in parallel with neural pathways, signals elicited by injured brain are transmitted to the lumbar spinal cord by alternative, likely endocrine mechanism. Spinal plastic and hindlimb motor responses induced by these signals are side specific.
T19: Effects of Remote Limb Ischemic Conditioning on Motor Learning and Muscle Strength in Healthy Young Adults: Phase I Randomized Controlled Trial
Swati Surkar
1, Anna Mattlage1, Marghuretta Bland1, Jeff Gidday2, Ling Chen1, Tamara Hershey1, Jin-Moo Lee1, Catherine Lang1
1Washington University School of Medicine, St. Louis, MO, USA2LSU School of Medicine, New Orleans, LA, USA
Background: Remote ischemic conditioning (IC) is the phenomenon in which brief organ ischemia induces endogenous response such that a different (remote) organ is protected against subsequent ischemia. A clinically feasible method for this is remote limb ischemic conditioning (RLIC), where episodes of ischemia and perfusion are induced with a blood pressure (BP) cuff placed on the arm. The cardioprotective effects of RLIC have been demonstrated for quite some time; however, only recently clinical trials began to evaluate the neuroprotective effects. The overall goal of this research is to investigate if the effects of RLIC extend into motor learning and muscle performance. The purpose of this study is to determine if RLIC can enhance learning of a motor (balance) task and increase skeletal muscle strength in neurologically-intact young adults as compared to sham conditioning.
Methods: Sixteen participants (RLIC = 7, age = 27.5 ± 3.7 years; Sham = 9, age = 27.8 ± 5.2 years) were randomly assigned to RLIC (BP cuff inflation 20 mm Hg above systolic BP, which causes transient sublethal ischemia) or Sham conditioning (BP cuff inflation 10 mm Hg below diastolic BP, which does not cause ischemia) group. The study consists of a total of 9 visits. Both groups, which were blinded to the group assignment, received conditioning on visits 1 to 8 with 5 cycles of 5 minutes BP cuff inflation followed by alternating 5 minutes deflation on the dominant arm. Visits 3 to 8 additionally involved training on balance (15 trials of 30 seconds each on a stability platform) and non-dominant wrist extensors strength training (standard American College of Sports Medicine Guidelines for frequency, intensity, progression, etc). Outcomes were balance (average time (seconds) of 5 trials of 30 seconds each) and strength (1 repetition maximum [1 RM] in lbs), measured on visits 1 and 9 for pre- and postassessment, respectively. Results were analyzed using mixed model ANOVA (Group × Time).
Results: Preliminary results are presented in this abstract with final results pending. A total of 40 participants (80% power for strength) are anticipated to complete the study in November 2018. Both groups significantly improved (P = .01) in balance over time, but the RLIC group showed greater improvements from pre to post compared to sham group. Similarly, both groups significantly improved (P = .03) in strength with the RLIC group having greater gains in 1 RM compared to the sham group.
Conclusions: RLIC combined with training appears to have potential to enhance both motor learning and muscle strength in healthy young adults.
Clinical Relevance: This inexpensive and clinically feasible paradigm may serve as a promising agent to enhance motor learning and strength in patients with neurological injuries, such as individuals with stroke.
T20: Stroke Recovery and the Effects of Intermittent Theta Burst Stimulation on Interhemispheric Inhibition
Rose Melchers
1, Mariana Leriche Vazquez1, John Reynolds1
1Otago University, Dunedin, New Zealand
Poor recovery from motor cortex (M1) stroke has been shown to be associated with an increase in interhemispheric inhibition (IHI) initiated by the unlesioned cortex. Previously we showed using intracellular recordings from single neurons that intermittent theta-burst stimulation (iTBS; bursts of 3 pulses at 50 Hz at 5 Hz) delivered to the contralateral M1 acutely reduced IHI in normal rats. Additionally, we showed that this stimulation improved motor recovery subacutely following stroke. The present study aimed to determine whether iTBS modifies IHI subacutely in the rat. To study effects of stroke and iTBS, lesions were induced by injecting Endothelin-1 into M1 and subcortex and electrodes implanted to measure IHI in freely moving animals. Sham stimulation or iTBS was delivered for 15 days, followed by 3 weeks of no stimulation. Behavior was recorded throughout, using grid walking and pasta handling tasks. Baseline IHI was 17.0 ± 4.9% and was increased to 31.5 ± 6.3% 1 week following lesion induction (paired t test: P < .05; n = 21). In the final week of the study, animals receiving iTBS showed a reduction in foot faults from their poststroke grid walking performances of 43.9 ± 8.5% (n = 12), compared with 8.40 ± 22.3% (n = 8) worsening of performance in the sham group (P < .05). In addition, delivery of iTBS reduced IHI to a greater degree than the spontaneous reduction observed in the sham group (linear mixed model: P < .05), both in the weeks during and following stimulation. Our results show that IHI and behavioral recovery are modified by iTBS stimulation and suggest that IHI reduction is associated with recovery following iTBS stimulation.
T21: A Systematic Review Exploring Brain Activity to Index Neural Activity in Relation to Sensorimotor Upper Limb Impairment and Activities After Stroke
Lisa Tedesco Triccas
1, Sarah Meyer1, Kenneth Camilleri2, Dante Mantini1, Tracey Camilleri2, Geert Verheyden1
1KU Leuven, Leuven, Belgium2University of Malta, Msida, Malta
Purpose: At 6 months poststroke, 33% to 66% do not present with full recovery of upper limb function. Predicting sensorimotor upper limb outcome receives continued attention. Measures by electroencephalography (EEG) and magnetoencephalography (MEG) could be neurophysiological predictors for sensorimotor upper limb recovery. Recently, a systematic review exploring the evidence and determining which neurological biomarker(s) meet the high evidence quality criteria for use in predicting motor recovery was conducted. However, only biomarkers using imaging and transcranial magnetic stimulation were included. Therefore, we conducted a systematic review to (1) evaluate high-quality evidence for EEG/MEG-based measures to index neural activity after stroke and their relationships with abnormal neural activity related to sensorimotor upper limb impairment and activities in the acute, subacute, and chronic stages and (2) determine if such measures could predict sensorimotor upper limb recovery.
Methods: Relevant papers from databases EMBASE, CINHAL, MEDLINE, and PubMed were identified. Methodological quality of selected studies was assessed with the Modified Downs and Black form. Data collected were reported descriptively.
Results: From 2616 related titles, 646 abstracts were screened and 96 full-text papers were assessed for eligibility from which 49 were then excluded. Low-quality papers (<65% of total Modified Downs and Black score) (n = 30) were also removed. As a result, 17 papers were included in the review where 13 used EEG and 4 used MEG methodologies. Findings showed that (1) an interhemispheric imbalance of cortical oscillatory signals was associated with upper limb impairment; (2) the presence of median nerve somatosensory evoked potentials in the acute stage are related to better outcome of upper limb motor impairment and activities from 10 weeks to 6 months poststroke; and (3) predictive models including beta oscillatory cortical signal factors with corticospinal integrity and clinical measures measured in the subacute and chronic stages enhance upper limb motor prognosis.
Conclusions: Alterations in neural activity including cortical oscillations and sensory evoked potentials by means of EEG and MEG are demonstrated from the early poststroke stage onwards, and are related to sensorimotor upper limb impairment and activities. Future work exploring cortical oscillatory signals during movement of the impaired upper limb and different modalities of sensory evoked potentials in the acute stage could provide further insight about prediction of upper limb sensorimotor recovery at 3 to 6 months poststroke.
T22: Is Cerebral Blood Flow a Potential Marker of Transcranial Direct Current Stimulation Induced Cortical Modulation in Chronic Stroke Survivors?
Pooja Iyer
1, Sangeetha Madhavan1
1University of Illinois at Chicago, Chicago, IL, USA
Background: Transcranial direct current stimulation (tDCS) is emerging as a promising therapeutic adjuvant for stroke rehabilitation to promote task-specific functional recovery. However, the effectiveness of tDCS is inhibited by its high interindividual variability limiting clinical application. There is a critical need to examine neurophysiological biomarkers that can identify responsiveness to tDCS. Transcranial Doppler (TCD) is a widely accepted clinical diagnostic tool that measures changes in cerebral blood flow velocity (CBFv) during neural activation paradigms. Various TCD studies have revealed the close association of neural activity with CBFv during motor and cognitive task performance in healthy and stroke populations. However, the relationship between CBFv and tDCS-induced corticomotor excitability has not been studied in stroke. To determine if CBFv, measured with TCD, can be used as a biomarker of tDCS-induced changes in corticomotor excitability, we asked the following questions: Does tDCS modulate CBFv in chronic stroke survivors? Do changes in CBFv correlate with changes in corticomotor excitability after tDCS? Can CBFv differentiate between responders and non-responders to tDCS?
Methods: The study included 14 chronic stroke survivors who participated in 3 sessions. In the first session, TMS testing was performed before and after anodal tDCS to measure changes in corticomotor excitability, and to identify responders and nonresponders to tDCS. In the second and third sessions, CBFv was measured with continuous recording of TCD before and after anodal or sham tDCS. Anodal tDCS involved 1 mA of current delivered to the lower limb motor cortex (M1) for 15 minutes.
Results: Out of 14 participants, 60% responded to tDCS demonstrating ~83% increase in the excitability of the lesioned M1, while nonresponders showed an insignificant 20% decrease in corticomotor excitability after anodal tDCS. Measures of CBFv did not change after anodal tDCS for all participants or for responders and nonresponders. There was no strong association between changes in CBFv and changes in corticomotor excitability.
Conclusion: This is the first study to examine changes in CBFv after anodal tDCS of the lower limb M1. We observed no modulation in CBFv after tDCS in our sample of participants. Future studies are needed to examine tDCS influences on CBFv in a larger cohort of participants that includes other dosages of tDCS in order to determine the applicability of TCD as a biomarker of neuromodulation.
T23: High-Intensity Speed-Based Treadmill Training Enables Walking Capacity and Neural Plasticity in Chronic Stroke Survivors
Hyosok Lim
1, Sivaramakrishnan Anjali1, Pooja Iyer1, Sangeetha Madhavan1
1University of Illinois at Chicago, Chicago, IL, USA
Background and Purpose: High-intensity treadmill training demonstrates superior health outcomes when compared to moderate-intensity training in stroke survivors. However, feasibility, efficacy, and long-term neurophysiological effects remain unclear. This study aimed to determine whether a 4-week high-intensity speed-based treadmill training (HISTT) is feasible for chronic stroke survivors, and we also examined its effectiveness on locomotor performance, corticomotor excitability (CME), and long-term retention of functional change.
Methods: Sixteen individuals poststroke participated in the study (10 males/6 females; mean age 57.4 ± 9.7 years; average 6.3 ± 4.5 years poststroke). Forty minutes of HISTT was conducted for 4 weeks at a frequency of 3 sessions per week. Walking speed was measured using the 10-meter walk test and endurance was measured using the 6-minute walk test, at baseline, posttraining, and at 3-month follow-up. CME of paretic and nonparetic tibialis anterior muscles were measured at baseline and posttraining using transcranial magnetic stimulation (TMS).
Results: All participants were able to tolerate the 4-week HISTT without any adverse events. Participants increased fastest walking speed by 19% (1.04 to 1.18 m/s), self-selected walking speed by 18% (0.80 to 0.91 m/s), walking endurance by 12% (299.08 to 326.43 m) after the training (all P < .05). Although significance was not found, CME of the paretic side increased by 41% and nonparetic side increased by 3% after the training. Improvements in clinical measures were maintained for 3 months after the intervention (fastest walking speed = 1.16 m/s; self-selected walking speed = 0.94 m/s; walking endurance = 327.44 m).
Conclusion: Our results indicate that the 4-week HISTT program provides a feasible and effective gait training option for individuals with stroke. Moreover, HISTT demonstrated the potential to balance interhemispheric asymmetry of CME. Further studies are recommended to better understand the effectiveness of this protocol in combination with other physical therapy interventions for promoting functional recovery and neuroplasticity after stroke.
T24: Recovery of Gait Speeds Is Not Associated With TMS-Induced Lower Limb Corticomotor Responses
Anjali Sivaramakrishnan
1, Sangeetha Madhavan1
1University of Illinois at Chicago, Chicago, IL, USA
Background: Stroke is known to cause long-term adult-onset disability, and most stroke survivors do not achieve independent community ambulation. Gait speed is an important measure for characterizing walking recovery and can be influenced by descending corticomotor control among numerous other factors. Transcranial magnetic stimulation (TMS) is one way to noninvasively measure the functional integrity of the corticospinal tracts via motor evoked potentials (MEPs), and it is used to characterize changes in cortical reorganization after a stroke. Findings from several upper extremity studies have shown a relationship between the presence of MEPs and functional recovery. However, the relationship of MEPs to walking speed and lower extremity recovery is still unclear. In this study we determined (1) whether the presence of TMS-induced ipsilesional MEPs in the lower extremity muscles was associated with gait speeds in chronic stroke and (2) examined the contribution of the contralesional hemisphere to walking recovery.
Methods: This is a retrospective study that included data from 61 individuals with chronic stroke. We used single-pulse TMS to quantify contralateral and ipsilateral responses from the contralesional and ipsilesional hemispheres. We assessed walking recovery with gait speeds as measured by the 10-meter walk test (self-selected and fast speeds), cardiovascular endurance as measured by the 6-minute walk distance (6MWD), dynamic balance as measured with the timed up and go test (TUG), motor recovery with the lower limb Fugl Meyer (FMLE) scale, and lower limb strength using a dynamometer.
Results: Our participants were classified based on the presence (MEP+ group [n = 28]) or absence (MEP− group [n = 33]) of MEPs in the paretic lower limb muscles (tibialis anterior and rectus femoris). There were no significant differences between the MEP+ and MEP− groups for gait speed, 6MWD, or TUG measures. Participants with MEPs showed significantly higher FMLE (P < .001) and ankle dorsiflexor strength (P = .004). There was no difference in ipsilateral conductivity from the contralesional hemisphere between the 2 groups. Last, MEP parameters did not predict gait speeds in participants with MEPs.
Conclusion: This study examined the diagnostic value of a TMS-induced MEP for examining walking recovery in stroke survivors. Findings from our study showed that MEPs may not explain gait recovery in chronic stroke. Future studies with larger heterogeneous samples with stronger comprehensive models are warranted to establish the factors influencing gait recovery.
T25: Exercise-Dependent Upregulation of Angiogenic Proteins and Motor Function Recovery after Photothrombotic Stroke in Mice
Abdullah Al Shoyaib
1, Faisal F. Alamri1, Abbie Biggers1, Srinidhi Jayaraman1, Fakhrul Ahsan1, Taslim A. Al-Hilal1, Vardan T. Karamyan1
1Texas Tech University Health Sciences Center, Amarillo, TX, USA
Exercise-induced angiogenesis is one of the pivotal neurorestorative events, along with neurogenesis and synaptic plasticity that promote functional recovery after stroke. However, the role of platelet-derived growth factor receptor beta (PDGFR-β) and doppel (Dpl) in exercise-induced motor function recovery after photothrombotic stroke is unknown. The aim of this study was to understand the correlation of motor function recovery with the extent of exercise and the expression of PDGFR-β, Dpl, and VEGFR-2 in the motor cortex after photothrombotic stroke in mice. In the first set of experiments, 3- to 4-month-old CD1 male mice were randomly assigned to sham, stroke, and stroke plus overnight running groups, whereas in the second set of experiments mice which were subjected to stroke run only 5 hours. Running, which started on day 7 poststroke and lasted until day 21, comprised voluntary running on a wheel (overnight, 6 pm to 8 am; 5 hours, 6 pm to 11 pm). Motor function was evaluated by 2 well-established behavioral tests known as gridwalk and cylinder tests. Expression level of the above-mentioned proteins in the ipsilateral and contralateral motor cortex of the experimental animals was carried out on day 21 poststroke using Western Blotting. Our results indicate significant improvement of the motor function by day 21 poststroke in both overnight and 5-hour running groups compared to stroke only groups. In addition, significant upregulation of VEGFR-2, PDGFR-β, and Dpl proteins in ischemic and healthy cortex of overnight running group but not in 5-hour running group was observed. These findings indicate that there is a dose-dependent relationship between the extent of voluntary exercise and VEGFR-2, PDGFR-β, and Dpl levels in brain cortex after photothrombotic stroke in mice.
T26: Transcranial Direct Current Stimulation Plus Concurrent Activity May Influence Task Prioritization During Walking in People With Parkinson’s Disease
Jyutika Mehta1, Christina Criminger2,
Chad Swank
1, Sattam Alumutairi1
1Texas Woman’s University, Dallas, TX, USA2Winston-Salem State University, Winston-Salem, NC, USA
Background and Objective: Progressive deterioration of cognitive and motor function is characteristic in Parkinson’s disease (PD). Walking for people with PD degrades during motor-cognitive interplay (ie, dual-task conditions). Current management of people with PD improves motor symptoms but inadequately benefits cognitive function, indicating a necessity for novel treatment approaches. Transcranial direct current stimulation (tDCS) may have therapeutic potential as it has demonstrated isolated facilitation of motor and cognitive processing in people with PD. Our purpose was to identify if application of bilateral brain hemisphere tDCS with concurrent activity improved dual task walking in people with PD.
Design: Four sessions of tDCS protocol (tDCSsitting, tDCSaerobic, tDCSWii, tDCSsham) during medication “ON” times each separated by 7 days. tDCS protocols were randomized and sham blinded to participants. Following each tDCS protocol, participants performed single- and dual-task walking. Walking conditions were randomized. Friedman’s 2-way analysis of variance by ranks test was used to compare within-subject performance differences of tDCS sessions on single- and dual-task TUG conditions and dual-task cost, where significant, pairwise comparisons differentiated between conditions.
Setting: Texas Woman’s University Human Neurophysiology laboratory.
Participants: Convenience sample of twenty people with PD age 44 to 83 years.
Interventions: Three 20-minute session of bilateral tDCS (dorsolateral prefrontal cortex; left = anode, right = cathode) at 2 mA and one sham session. tDCS protocols were sitting alone, playing Wii golf, and pedaling a recumbent bicycle at moderate intensity.
Main Outcome Measures: Participants assessed at baseline for disease severity (United Parkinson Disease Rating Scale [UPDRS]) and executive function (Repeatable Battery for the Assessment of Neuropsychological Status [RBANS]). Immediately following each tDCS condition, participants performed Timed Up and Go (TUG) single- and dual-task conditions (TUGalone, TUGmotor, TUGcognitive).
Results: Participants (UPDRS x = 42.40 [range = 14-70], RBANS x = 83.25 [13%ile]) showed no significant differences on TUG conditions between tDCS protocols. However, dual-task cost for TUGcognitive mobility task velocity was significantly different between tDCS protocols (Friedman test P = .023) with tDCSWii significantly greater associated dual-task cost than tDCSaerobic (P = .012). Mobility task velocity dual-task cost for TUGmotor was 14.45% (tDCSsitting), 16.74% (tDCSaerobic), 14.98% (tDCSWii)), 17.27% (tDCSsham); for TUGcognitive was 19.03% (tDCSsitting), 19.93% (tDCSaerobic), 28.45% (tDCSWii), 18.92% (tDCSsham). Cognitive dual task cost for TUGcognitive was 26.26% (tDCSsitting), 8.51% (tDCSaerobic), 7.02% (tDCSWii), 20.54% (tDCSsham).
Conclusions: When paired with a concurrent activity (Wii golf vs recumbent cycling), tDCS may deliver a task-specific value rather than overall walking benefits. That is, tDCS paired with concurrent activity may influence task prioritization. Further investigation with a larger sample size is warranted.
T27: Flexion Synergy-Dependent Cortical Activity and Associated White Matter Changes During Attempted Paretic Hand Opening in Moderate to Severe Chronic Stroke
Kevin Wilkins
1, Jun Yao1, Meriel Owen1, Carson Ingo1, Julius Dewald1
1Northwestern University, Chicago, IL, USA
Hand opening is often significantly impaired following a stroke, particularly in moderate to severely impaired individuals. These individuals tend to have weakness in the paretic hand, which has been shown to be associated with damage to the contralateral corticofugal tracts. Unfortunately, lifting the arm at the shoulder, a crucial component of many activities of daily living, further reduces hand opening ability in this population. This is a consequence of involuntary abnormal coupling between shoulder abductors and elbow, wrist, and finger flexors termed the “flexion synergy.” Evidence from primates and diffusion imaging in humans implicates increased reliance on the ipsilateral cortico-reticulospinal (CRS) pathway, possibly via callosal interactions, as a potential reason for this synergy-related impairment. However, evidence connecting functional activity related to the arm/hand and underlying white matter structure, particularly in the ipsilateral hemisphere, is currently missing. To fill the above gap, we recruited 16 individuals with moderate to severe chronic hemiparetic stroke and 10 healthy age-matched controls. All the individuals participated in a high-density EEG experiment in which subjects performed 2 tasks on an ACT3D robot: (1) hand opening and (2) hand opening while lifting against 50% maximum shoulder abduction (SABD) force, using the paretic (stroke) or dominant (control) hand. Furthermore, stroke individuals also took part in an magnetic resonance imaging scan, including structural T1-weighted and diffusion-weighted images. We then quantified the following: (1) cortical activity related to hand opening with or without lifting; (2) fractional anisotropy (FA) of the ipsilateral reticular formation and body of the corpus callosum. The addition of lifting caused a significantly greater reliance on the ipsilateral hemisphere in stroke, but not controls (P < .05). This was driven by a decrease in activity in the contralateral primary sensorimotor cortex, and an increase in activity in ipsilateral secondary motor areas during the lifting and opening condition compared to opening in isolation. Furthermore, data from stroke participants demonstrated that use of the ipsilateral hemisphere was positively associated with higher FA, a potential indicator of white matter integrity, in the ipsilateral reticulospinal tract and body of the corpus callosum (P < .05). These findings suggest that greater functional reliance on the ipsilateral hemisphere may be resulting in changes in white matter structural integrity in the ipsilateral hemisphere.
T28: The Cellular Effects of rTMS in Healthy and Stroke-Damaged Brains: An In Vivo Intracellular Electrophysiological Study in the Rat
Natalie Matheson
1, Simon Fisher1, Jon Shemmell1, John Reynolds1
1University of Otago, Dunedin, New Zealand
Transcranial magnetic stimulation (TMS) is a form of noninvasive brain stimulation. A magnetic field is pulsed through the skull and into the brain where it induces electrical currents in underlying tissue and activates neural elements. Applying pulses of TMS repeatedly (repetitive TMS [rTMS]) over a period of time has been shown to cause lasting changes in neural activity. Many attempts have been made to harness these long-term changes induced by rTMS to provide a potential treatment option for a wide range of neurological disorders. In the field of stroke rehabilitation, it is hypothesized that rTMS may be effective in enhancing plasticity of tissue surrounding the stroke core and therefore facilitating the ability for peri-infarct areas to take on the function of neurons that have died. Numerous clinical trials have tried different approaches to applying rTMS, but to date there is little evidence that rTMS provides any additional benefit in poststroke rehabilitation compared to physiotherapy alone. We believe this is because the mechanisms of TMS are not well understood at a single neuron level and therefore TMS cannot be applied in the most effective manner to patients poststroke. To gain insight into the mechanism of action, we used a transpharyngeal recording approach to make in vivo intracellular electrophysiological recordings with TMS applied to the outside of the scalp, in order to determine changes in neural excitability and synaptic efficacy. In naïve animals, application of an intermittent theta burst (iTBS) stimulation protocol led to a transient facilitation of the strength of corticocortical synapses made within the ipsilateral cortex, and a significant increase in excitability in recorded neurons. Stimulation with a continuous theta burst (cTBS) protocol had no effect on synaptic efficacy; however, several measures of excitability were reduced. A second train of iTBS delivered 20 minutes following the first rTMS train led to significant depression of synaptic efficacy in animals that had received iTBS first. In animals that received cTBS first, no change in synaptic efficacy was observed following the second iTBS protocol; however, responses of individual animals were variable. In order to determine the effects of TMS in the brain following stroke damage, in vivo recordings were made in brains of animals 3 weeks poststroke induction, using the endothelin-1 stroke model. Preliminary data suggest that the efficacy of corticocortical synapses within a hemisphere made with the recorded neurons and their intrinsic excitability can be modulated in a lasting manner by rTMS, differentially in stroked or sham animals. This work provides new insights into the design of rTMS protocols where rTMS is used as a means of priming neural tissue for subsequent induction of long-term neural plasticity.
T30: AbobotulinumtoxinA Using 2-mL Dilution Maintains Durable Functional Improvements Across Multiple Treatment Cycles
Khashayar Dashtipour
1, Gustavo Suarez2, Pascal Maisonobe3, Laxman Bahroo4, Daniel Truong5, Richard Trosch6
1Loma Linda University, Loma Linda, CA, USA
2Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA
3Ipsen Pharma, Boulogne-Billancourt, France
4Georgetown University Hospital Pasquerilla Healthcare Center, Washington, DC
5The Parkinson and Movement Disorder Institute, Fountain Valley, CA, USA
6Parkinson’s and Movement Disorders Center, Farmington Hills, MI, USA
Background: Cervical dystonia (CD) is a chronic neurological movement disorder characterized by sustained involuntary contractions of the neck muscles, leading to an abnormal posture. In a 12-week, phase 3b, randomized trial, a 500-U, 2-mL dilution of abobotulinumtoxinA significantly improved symptoms in patients with CD. Here, we evaluate the long-term functional benefits of repeat treatment cycles of abobotulinumtoxinA using 2-mL dilution from a prospective open-label extension (OLE; NCT01753336) of the 12-week lead-in study.
Methods: Adults (aged ⩾18 years) with a primary diagnosis of idiopathic CD who completed the lead-in week 12 (Wk12) visit or whose Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score between lead-in Wk4 and Wk8 was reduced by ⩽15% from baseline were invited to participate in this OLE. The OLE involved ⩽3 treatment cycles, with re-treatment occurring every 12 to 16 weeks based on clinical judgment. For OLE Cycle 1 (C1), patients who were toxin-naïve at lead-in baseline received 500 U/2 mL in ⩾2 affected neck muscles and non-naïve patients received 250 to 500 U/2 mL (2.5:1, abobotulinumtoxinA–previous onabotulinumtoxinA dose) into previously injected muscles. For C2/C3, dose adjustments were determined by the investigator, with increments and decrements limited to ⩽250 U/cycle and maximal total dose limited to 1000 U/cycle. Effectiveness was evaluated by TWSTRS total and subscale scores. Safety was assessed by treatment-emergent adverse events (TEAEs).
Results: A total of 112 patients were enrolled and treated, and 92 (82.1%) completed the Wk36 visit (C3-Wk12). Median time since symptom onset was 10 years (range: 0-55). Mean TWSTRS total score was 42.2 (±10.3) at pretreatment baseline (before first abobotulinumtoxinA administration). Mean TWSTRS total score decreased from 37.7 on C1-Day 1 (D1) to 30.1 at C3-Wk12 (n = 92), with a total change from pretreatment baseline of −11.7 at C3-Wk12. For each cycle, TWSTRS total and subscale scores decreased from D1 to Wk4 and increased between Wk4 and Wk12, though the Wk12 scores remained lower than D1 scores. The mean TWSTRS scores at Wk4 and Wk12 were primarily lower for each successive cycle, with no worsening to baseline. A total of 220 TEAEs were reported for 70 patients (62.5%). Dysphagia, muscular weakness, and neck pain were the most frequent TEAEs (10.7% each). Most TEAEs (n = 156) were not considered by the investigators to be treatment-related. Seven patients reported 8 serious TEAEs. None of the TEAEs led to study withdrawal or death.
Conclusions: AbobotulinumtoxinA injected at approved doses using an injection volume of 2 mL provided sustained improvements within and across treatment cycles in CD patients. Consistent with abobotulinumtoxinA pharmacological effect, 12-week efficacy was numerically higher than 4-week efficacy for each cycle. Results were consistent with the lead-in and showed that abobotulinumtoxinA using a 2-mL injection volume remained effective and well tolerated over 4 treatment cycles.
Funding: Ipsen Biopharmaceuticals, Inc (Basking Ridge, NJ).
T31: Can Paired Associative Stimulation Be Used to Modulate Resting-State Intracortical Connectivity?
Andrew Hooyman
1, Alex Garbin1, Beth Fisher1, Jason Kutch1, Carolee Winstein1
1University of Southern California, Los Angeles, CA, USA
Intracortical connectivity measured by resting state electroencephalography (rs-EEG) has been shown to be a robust and highly accurate predictor of motor skill learning, as well as stroke recovery. However, what if we could modulate connectivity between specific cortical areas to thereby improve learning or recovery? Theoretically, interneuron communication can be driven through the neural mechanism of Spike Timing Dependent Plasticity (STDP). Earlier work has used transcranial magnetic stimulation (TMS) to drive STDP to facilitate connectivity between a target brain area and a specific muscle through paired associative stimulation (PAS). PAS is the process of delivering repeated bouts of specifically timed paired pulses to either facilitate or inhibit connectivity between different regions of the nervous system. Although previous PAS methods were only capable of modulating connectivity to the peripheral nervous system, with recent innovations in EEG technology it is now plausible for a combined TMS/EEG approach to measure modulatory effects of PAS in resting state intracortical connectivity. The overall purpose of this experiment is to examine the feasibility of using PAS to increase intracortical connectivity and to measure that change using rs-EEG. Ten young healthy adults were recruited into the experiment (mean age 26.4 years). Each participant underwent both a true PAS and sham PAS condition in a counterbalanced fashion. The lead PAS pulse was applied over the right frontal cortex and the proceeding pulse was applied to the right motor cortex. PAS for both conditions was delivered at 120% of resting motor threshold (RMT) of the abductor pollicus muscle of the dominant hand. RMT was used as a baseline for stimulator output with the capability to reliably depolarize cortical neurons. Depending on condition order participants received either 100 pulses of real PAS with a 5 ms interstimulus delay (PAS+5) and then 100 sham PAS pulses with a 500 ms interstimulus delay (PAS+500) or vice versa. To determine the effect of PAS, rs-EEG data were collected pre and post both PAS conditions, baseline corrected, and then analyzed. PAS+5 significantly increased intracortical connectivity compared to PAS+500 (P < .05). Preliminary results thus far demonstrate that the application of PAS+5 can feasibly modulate specific resting state intracortical connectivity. Given that the PAS+5 condition was superior to the PAS+500 condition, STDP as the mechanism of action is supported. For generalizability, this effect will need a larger sample size and comparison with different sham protocols to better understand the effect of PAS on intracortical connectivity.
T33: Chronic Stroke Patients Using a Brain-Computer Interface for Motor Rehabilitation: A Group Study
Christoph Guger1,2,3, Fan Cao1,3,
Katrin Mayr
1, Günter Edlinger1,2,3
1Guger Technologies OG, Graz, Austria2g.tec medical engineering GmbH, Schiedlberg, Austria3g.tec neurotechnology Inc, Albany, NY, USA
A brain-computer interface (BCI) detects the neuronal activity of patients’ motor intention and controls external devices to provide appropriate sensory feedback via peripheral nervous system to central nervous system (CNS). When the feedback is timely sent to CNS according to the motor intention with multiple training sessions, the neuronal network in the brain is reorganized due to the neuroplasticity. In this current study, a BCI controlled an avatar and functional electrical stimulation (FES) to provide the visual and proprioceptive feedback, respectively. The expected task was to imagine either left or right wrist dorsiflexion according to the instructions in randomized sequences. Then, the linear discriminant analysis and common spatial filter classified the brain activity acquired by EEG. The avatar and FES were triggered only on correct classification. The avatar of forearms was presented to patients in the first-person point of view, and FES produced a smooth passive dorsiflexion of the patient’s wrist. The training was designed to have 25 sessions (240 trials of either left or right motor imagery) of BCI feedback sessions over 13 weeks. Two days before and 2 days after the BCI training intervention, clinical measures were used to observe any motor improvement. The primary measure was upper extremity Fugl Meyer assessment (UE-FMA), which evaluates the motor impairment. Four secondary measures were also performed to examine the spasm (modified Ashworth scale [MAS]), tremor (Fahn tremor rating scale [FTRS]), and level of daily activity (Barthel index [BI]). In 27 chronic stroke patients the study showed an average improvement of the UE-FMA of 8 points (P < .0001). Furthermore, spasticity and tremor were significantly reduced and the Barthel index increase significantly. Therefore, the BCI-based motor rehabilitation is a very effective way of treatment in chronic stroke patients. In the future the protocol will be extended to treat lower limb movements with the BCI system.
T34: Exploring the Use of Visuospatial Tests to Predict Motor Learning Capacity in Older Adults
Jennapher Lingo VanGilder
1, Keith Lohse2, Sydney Schaefer1
1Arizona State University, Tempe, AZ, USA2University of Utah, Salt Lake City, UT, USA
Background: Recent data suggest that age-related declines in motor learning may be related to declines in visuospatial function, regardless of baseline motor function or other cognitive impairments. Thus, visuospatial tests may be useful for evaluating older patients’ motor learning capacity prior to therapy. The purpose of this study was to identify which visuospatial test is most predictive of motor learning within an older cohort.
Methods: A convenience sample of 33 participants (mean ± SD age = 70.8 ± 6.0 years) completed a battery of 6 visuospatial tests: visual perception (Line Orientation), visual construction (Rey-Osterrieth Complex Figure Copy), visual memory (Rey-Osterrieth Complex Figure Recall), visual attention (Visual Puzzles), visual abstraction (Block Design), and executive function (Matrix Reasoning). All are standardized and available for clinical use, with higher scores indicating better function. Other neuropsychological tests evaluated additional cognitive domains as control variables. Participants then completed 3 weekly training sessions on a functional upper-extremity motor task (ie, task-specific training), and were retested 1 month later on both the trained and another untrained motor task to test the durability and generalizability of motor learning, respectively. Both motor tasks were measured as movement time, with lower values indicating better performance. Principal components (PCs) analysis was used to reduce the dimensions of the visuospatial battery for inclusion in the regression models. PCs with Eigenvalues >1.00 were included. Subsequent least-square regressions predicted 1-month follow-up performance on both the trained and untrained tasks, as a function of baseline performance and the PCs of the visuospatial battery. Separate regressions were conducted for the trained and untrained tasks.
Results: The 6 visuospatial tests loaded on 2 PCs with Eigenvalues >1.00. Block Design and Matrix Reasoning loaded most heavily on PC1 (r > 0.80), whereas Figure Copy and Figure Recall loaded most heavily on PC2 (r > 0.75). Both PCs were therefore included as covariates in the regression models. For the trained task, participants improved by a mean of 19.71% (13 seconds) from baseline to 1-month follow-up (P < .001), with follow-up being positively related to baseline performance (β = 0.44,P < .001), but not PC1 (β = −0.17, P = .87), nor PC2 (β = −0.61, P = .58). The untrained task also significantly improved by 11.2% (6.9 seconds), despite no training (P < .001). One-month follow-up on the untrained task was positively related to its baseline performance (β = 0.50, P < .001), but unrelated to PC1 (β = 0.24, P = .84). It may, however, be negatively related to PC2 (β = −2.03, P = .09), controlling for other variables.
Discussion: Motor learning capacity may be evaluated using the Rey-Osterrieth test, which could be administered prior to any motor training and may relate to risk of nonresponsiveness in therapy. Results also suggest that the pathways underlying visuospatial construction and memory are necessary for the generalizability of motor learning, rather than its durability in response to extensive training.
T35: Convergence of Biological and Artificial Learning: Electroencephalography-Informed Adaptation of Neurorehabilitation Robots to Maximize Cognitive Engagement
Neelesh Kumar1, Nick Georgiou1,2,
Konstantinos Michmizos
1
1Rutgers University, Piscataway, NJ, USA
2University of Virginia, Charlottesville, VA, USA
Despite the significant improvements achieved by the use of neurorehabilitation robots (NR), the crucial aspect of cognitive engagement (CE) during therapy is partially incorporated into the current adaptation strategies. The reason for this is that the CE approximation relies on (1) self-reports, which cannot be used in real time and are limited by the patient’s self-perception capabilities; (2) robot-derived metrics of motor performance, which is anyway compromised by the disease itself; and (3) physiological signals, such as cardiovascular or skin responses, which could be easily distorted by inaccurate sensor placements or by the interference of other functions that the autonomic nervous system controls, such as homeostasis, effort, and emotions. These implicit measurements of CE offer limited insights on motor recovery and impede our efforts to harness and nurture brain plasticity. Herein, we present the first fruits of our ongoing efforts to develop a computational framework that objectively measures CE and drives NR adaptation. Our approach involves on the one hand a data-analytic component that assesses CE explicitly and, on the other hand, a CE-informed rehabilitation environment that adapts its therapeutic strategy to achieve maximum CE. For data analysis, we are developing comprehensive representations of CE by combing (1) electroencephalography (EEG) signals associated with attention; (2) facial signs of cognitive fatigue; and (3) motor behavior metrics of gameplay performance. We are employing state-of-the art deep networks initially trained on the open-access 64-channel EEG dataset PhysioNet for classifying hand movement versus no movement (10 subjects, 4-layered ReLU convolutional neural network, 8500 EEG epochs, partitioned randomly into 70% training set and 30% test set, 85% testing accuracy). For the rehabilitation component, we are developing a Go/No-Go paradigm that continuously challenges the levels of CE over time. We will further employ this framework in our Bionik InMotion Arm robot, informed by our 128-channel Biosemi Active2 EEG recording system, and conduct an institutional review board–approved pilot study on human subjects. Overall, our approach aims to elucidate the underlying neurophysiological mechanisms of motor learning and inform the design of new NRs, with a “built-in” adaptability. Furthermore, the development of data-rich computational models is expected to optimally drive therapeutic robots as they interact with brain dysfunction to steer it toward normalcy.
T37: Noninvasive Cervical Root Stimulation for Spinal Cord Injury
Jonah Levine
1, Yu-Kuang Wu1,2, Sana Saeed1, James LiMonta1, Matthew Maher1, Eric Bailey1, Jaclyn Wecht1, Noam Y. Harel1,2
1James J Peters VAMC, New York, NY, USA
2Icahn School of Medicine, New York, NY, USA
Introduction: Electromagnetic stimulation facilitates activation of spared neural circuits after cervical spinal cord injury (SCI). With this goal in mind, we apply a novel method of noninvasive cervical electrical stimulation (CES) that activates nerve roots across multiple myotomes in both upper extremities simultaneously. To understand CES circuit interactions, we measured the effects of CES delivered alone or paired with transcranial magnetic stimulation (TMS), peripheral nerve stimulation (PNS), or volitional movement.
Methods: Transcutaneous stimulation is delivered via 5 × 10 cm electrodes placed over the ~C4-C5 levels anteriorly and ~T2-T4 levels posteriorly. Preliminary experiments involved optimizing CES waveform and titrating intensity to selectively activate either sensory afferent or motor efferent nerve roots. Subsequent experiments are measuring the acute electromyographic responses of hand muscles to CES paired with TMS, PNS, or volitional movement at varying intensities and timing. Safety is monitored via blood pressure, heart rate, oxygenation, vital capacity, and subjective tolerance.
Results: To date, 22 able-bodied volunteers and 17 incomplete cervical SCI subjects have undergone >250 CES sessions without major safety or tolerability issues. A cathode-posterior, 2 ms biphasic waveform provides optimal stimulation characteristics. At subthreshold and perithreshold intensity, CES activates sensory afferents susceptible to homosynaptic depression. At intensities approaching 200% of motor threshold, CES tends to activate motor efferents not susceptible to homosynaptic depression. When paired with TMS, subthreshold CES pulses facilitate motor evoked potentials in intrinsic hand muscles in timing-dependent fashion in both SCI and nondisabled individuals. Facilitation is over 200% when the TMS pulse is timed to arrive at cervical synapses less than 5 ms prior to CES pulse arrival. Experiments are now underway to assess whether CES can acutely facilitate concurrent volitional hand and wrist movements. To date, we have observed that suprathreshold CES pulses delivered during volitional muscle contraction can induce a relative “spinal silent period.” Results of subthreshold CES circuit interactions with volitional movement as well as peripheral nerve stimulation (F-responses and H-reflexes) will be presented.
Conclusion: Our novel approach to transcutaneous cervical electrical stimulation provides both mechanistic insight and potential therapeutic application toward upper extremity muscles after SCI. The ability of subthreshold CES to facilitate response to TMS raises the possibility that it may also be able to enhance responses to physical rehabilitation by facilitating volitional movements.
Support: New York State DOH C30599; New York State DOH C31291; Craig H. Neilsen Foundation 457648.
T38: Simultaneous tDCS and Gait Rehabilitation in Chronic Stroke: A Pilot Study
Jessica McCabe1, Margaret Skelly1, Elizabeth Hardin1, Marom Bikson2,
Svetlana Pundik
1,3
1Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA2The City College of New York of the City University of New York, New York, NY, USA3Case Western Reserve University, Cleveland, OH, USA
Purpose: Gait deficits are prevalent and frequently persistent after stroke. However, effective and cost-efficient interventions are limited. Noninvasive brain stimulation is a promising adjunct to peripherally administered rehabilitation therapies but has not been extensively explored for gait rehabilitation after stroke. The purpose of this pilot study was to assess feasibility of simultaneous transcranial direct current stimulation (tDCS) and task-specific gait training in a relatively short 10-session intervention protocol.
Methods: Stroke survivors (>6 months post; n = 5) with gait deficits participated in 10 treatment sessions that consisted of simultaneous tDCS and gait training. Based on current density modeling, a bihemispheric montage with anode over the ipsilesional motor region and cathode over the contralesional region was selected for delivery of the stimulation. Gait therapy was performed using a virtual reality environment and training emphasized weight bearing during stance phase on the stroke-affected limb. Over-ground exercises to reinforce training were also included. Outcome measures included gait speed, Timed Up and Go (TUG), Fugl-Meyer for lower extremity (FM), Functional Gait assessment (FGA), and spatiotemporal gait characteristics. Testing was done at baseline, mid-treatment, posttreatment, and 3-week follow-up. Changes in outcomes were calculated as difference from baseline, that is, mid-treatment minus baseline, posttreatment minus baseline, and 3-week follow-up minus baseline. Findings are reported as descriptive statistics (median [interquartile range]), and results of the Friedman test (nonparametric test for repeated measures).
Results: Subjects were 58.6 (7.8) years old, 68 (53) months after stroke, 80% left-hemispheric lesion and 100% male. tDCS current modeling confirmed a desired current distribution through the bilateral lower extremity primary motor cortex regions. Baseline gait characteristics were as follows: gait speed 1.02 (0.3) m/s, FM 22 (6.5) points, TUG 11.9 (6.4) seconds, FGA 14 (6) points, and involved leg single limb stance percent of gait cycle 21% (6.5%). There were changes at mid-treatment, posttreatment, and 3 week follow-up, as follows: (1) increased gait speed by 0.11 (0.27), 0.27 (0.23), and 0.27 (0.13) m/s, respectively (Friedman P = .0194); (2) improved FM by 4 (4.5), 5 (4), and 4 (3) points, respectively (Friedman P = .0198); (3) improved TUG by 0.85 (2.4), 2.7 (2.2), and 3.6 (0.98) seconds, respectively (Friedman P = .019); (4) improved FGA score by 3 (1.5), 4 (2.3), and 4 (1) points, respectively (Friedman P = .017); and (5) increased single limb stance by 0.82% (2.4%), 2.88% (3.81%), and 1.55% (2.52%), respectively (Friedman P = .2). Post hoc analysis showed that for all measures, the greatest change from baseline was seen at 3 weeks of follow-up.
Conclusion: A 10-session intervention combining bihemispheric tDCS and task-specific targeted gait rehabilitation produces lasting improvements in lower limb function in patients with chronic gait deficits after stroke.
T40: Surface EMG-Triggered Closed Loop Stimulation for Individuals With Spinal Cord Injury: A Case Report
Yu-Kuang Wu
1,2, Jonah Levine1, Jaclyn Wecht1, James Limonta1, Matthew Maher1, Eric Bailey1, Sana Saeed1, Noam Harel1,2
1Bronx Veterans Medical Research Foundation, Bronx, NY, USA
2Icahn School of Medicine at Mount Sinai, New York, NY, USA
Background: Noninvasive paired stimulation has been demonstrated to temporarily strengthen synaptic efficacy after spinal cord injury (SCI). Stimulation over motor cortex via transcranial magnetic stimulation (TMS) and over a peripheral nerve via electrical stimulation (PNS) may be timed to arrive at cortical or spinal synapses synchronically to facilitate and enhance transmission. Our group targets cervical spine synapses with this paired approach. The potential results also encourage the idea of closed-loop stimulation, which utilizes subjects’ endogenous signals to trigger external stimulation. Results of other groups in an incomplete SCI rat model showed that EMG-triggered spinal stimulation plus physical retraining led to greater motor recovery than nontriggered stimulation (open-loop) or physical training alone. For this reason, we have developed a noninvasive EMG-triggered closed-loop stimulation system to improve hand functions for humans with cervical SCI. We report the preliminary results from one chronic cervical SCI participant.
Methods: A 56-year-old male with chronic C4 neurological level SCI (ASIA Impairment Scale C) has completed testing. In order to target the C8-T1 synapses, TMS was targeted at the optimal scalp location for hand M1 and PNS was delivered over the median nerve at the wrist. Abductor pollicis brevis (APB) muscle EMG activity was used to trigger the stimulation devices (15% maximal voluntary contraction). The participant went through 5 sessions of repetitive pinch movements including EMG-triggered TMS alone, PNS alone, paired stimulation (TMS+PNS) and no stimulation. We also compare to nontriggered passive paired stimulation. Each session includes baseline measurement, 20-minute stimulation, and poststimulation measurement at 0-, 20-, 40-, and 60-minute time points. Our primary outcome is Peak-to-Peak Amplitude of Motor Evoked Potentials at 120% intensity of resting motor threshold (MEP120).
Results: In this case study, the most improvement of MEP120 was after repetitive pinch exercise without additional stimulation (relative changes to baseline [RR]: 0: 204.13 ± 121.10%, 20: 197.14 ± 84.23%, 40: 59.32 ± 77.71%, 60: 252.49 ± 146.02%), followed by passive paired stimulation (RR: 0: 91 ± 75.15%, 20: 22.57 ± 46.66%, 40: 41.71 ± 75.06%, 60: 76.29 ± 50.25%) and EMG-triggered PNS alone (RR: 0: 96.37 ± 75.90%, 20: 19.98 ± 48.52%, 40: 7.80 ± 26.08%, 60: 31.78 ± 58.17%). The MEP120 slightly decreased at some time points in the EMG-triggered TMS (RR: 0: −39.17 ± 18.30%, 20: −12.85 ± 66.08%, 40: 25.49 ± 49.35%, 60: 28.39 ± 65.17%) and EMG-triggered paired stimulation (RR: 0: −29.00 ± 27.61%, 20: 20.90 ± 24.12%, 40: 4.58 ± 16.06%, 60: −24.33 ± 31.72%).
Discussion: The data from the single SCI participant shows some interesting results. First, the EMG-triggered stimulation compared to no stimulation did not reinforce the improvement of MEP120 and somewhat decrease the MEP120. Second, the MEP120 were lower than baseline in those EMG-triggered stimulation including TMS. These 2 findings might indicate the importance of stimulation delivery timing and whether external stimulation might possibly interfere with endogenous signals that travel over the corticospinal pathway. However, more participants are needed to confirm these findings.
T41: Inpatient Cognitive Rehabilitation Following Traumatic Brain Injury: Main Effects and Patient by Therapy Interactions Using Causal Inference Models
Keith Lohse
1, Tianyu Zheng1, Tom Greene1, Jacob Kean1, Angela Presson1, Jincheng Shen1
1University of Utah, Salt Lake City, UT, USA
Background: Previous studies have associated better cognitive recovery with more challenging therapeutic activities following traumatic brain injury (TBI). However, past results are confounded by indication; that is, patients who are recovering more quickly are also more likely to receive challenging therapy earlier, making causality difficult to establish. To address this limitation, we used advanced Causal Inference Models (CIMs) to derive causal inferences from observational data.
Method: This secondary analysis used the TBI–Practice-Based Evidence database (TBI-PBE). Data were collected from 10 participating rehabilitation centers in the United States and Canada, totaling 2130 participants (586 females). Participants were ⩾14 years of age with a primary diagnosis of TBI. Our primary dependent measure was participants’ Rasch-scaled cognitive subscale score on the Functional Independence Measure (FIM) at 3 months postadmission. Importantly, the TBI-PBE database not only contains FIM scores (including the FIM motor subscale) but also detailed longitudinal data about the amount/type of therapy delivered. In these initial analyses, we simplified the multidimensional nature of treatment into a dichotomous variable: Tx1 = ⩾5 hours of cognitive therapy per week; Tx0 = <5 hours of cognitive therapy per week, during the first 4 weeks of inpatient therapy. Using CIM, we can control for time-varying patient (eg, improvement from week-to-week) and treatment (eg, physical therapy hours) factors to establish the causal-effect of treatment on cognitive-FIM status at 3 months.
Selection of Covariates: The strength of the causal inference from observational data is dependent on the validity of covariate adjustment. Models controlled for time-dependent changes in FIM status and hours spent in cognitive and physical therapy. Other baseline covariates included age at admission, years of education, type of insurance, time from injury to admission, occurrence of a previous TBI, the Glasgow Coma Scale, and agitation. Missing covariates (including FIM scores) during inpatient rehabilitation were estimated using multiple imputation (12.1% of the data were imputed).
Results: We have obtained preliminary estimates of the average causal effect using inverse probability weighting with stabilized weights under marginal structural models. Controlling for confounding factors, we found evidence for a causal effect of treatment on cognitive-FIM scores at 3 months (P = .008). Furthermore, there was evidence that treatment efficacy was moderated by admission cognitive-FIM status, but not admission motor-FIM status.
Discussion: From these observational data, we were able to draw a strong causal inference that receiving ⩾5 hours of cognitive therapy per week during inpatient rehabilitation led to statistically significant cognitive recovery at 3 months postadmission. However, this effect was also moderated by initial level of cognitive impairment, such that more impaired participants showed a greater benefit from therapy. Future work will examine the treatment variable multidimensionally and extend these models to motor rehabilitation and recovery.
T42: Identifying the Optimal Resistance to Increase Unilateral Propulsion Force With a Novel Mechanical Gait Training Device
Krista Fjeld
1, Terence Thomas1, Siyao Hu2,3, Katherine Kuchenbecker3,4
1SUNY Stony Brook, Stony Brook, NY, USA
2Schlumberger-Doll Research Center, Cambridge, MA, USA
3University of Pennsylvania, Philadelphia, PA, USA
4Max Planck Institute for Intelligent Systems, Stuttgart, Germany
The gait propulsion trainer (GPT) is a novel device designed to train paretic leg propulsion force. Paretic leg propulsion (the anterior component of anterior-posterior ground reaction force) is the force that propels us forward while walking, and is positively correlated with walking speed after stroke. Deficits in paretic leg propulsion stem from unilateral impairments in strength, range of motion, and voluntary control that are frequent consequences of stroke. It is likely that poor paretic leg propulsion contributes to hemiparetic gait patterns and reduced walking function. The GPT is an inexpensive mechanical device, composed of 3 parts: a waist harness worn by the participant, a cable that attaches to the waist harness, and a stationary unit that houses a cable spool and a brake. When the participant is in the appropriate phase of gait, the brake turns on and resists forward motion, thus requiring an increase of propulsion force to maintain forward movement. The GPT is unique in its design to resist forward movement of only one leg during mid-to-late stance phase (the propulsion force generating phase of gait). The objective of this study was to determine whether the GPT is capable of unilaterally increasing leg propulsion in adults without stroke. Our secondary objective was to determine the optimal resistance for increasing unilateral leg propulsion. Adults without stroke participated in a 1-day study, during which 4 different magnitudes of resistance were applied to a randomly selected leg. All walking trials were completed over the ground along a 10-meter pathway, which contained 4 imbedded force plates to capture ground reaction forces. Baseline trials were completed without GPT resistance. During baseline trials, baseline levels of propulsive force were recorded and averaged. From this value, the magnitudes of resistance were calculated. Four magnitudes of resistance were tested: 20%, 30%, 40%, and 50% of peak propulsion force during baseline. Posttest trials were collected without GPT resistance to monitor acute differences in propulsion. Future research will include people with stroke in a similar paradigm, with resistance to only the paretic leg. This research contributes to the development of the GPT, a device that is being designed to be an effective, portable, and affordable gait training device for people after stroke.
T43: Cortical Inhibitory/Excitatory Balance During Dynamic Plantarflexion Scales With Walking Speed
Caitlin Banks
1,2, Virginia Little2, Qian Ding2,3, Carolynn Patten1,2,3
1University of California, Davis, Davis, CA, USA; 2VA Northern California Healthcare System, Martinez, CA, USA; 3University of California, Davis, Sacramento, CA, USA
Short-interval intracortical inhibition (SICI) is a GABAA-mediated phenomenon often used to probe inhibitory brain circuits related to motor control. Similarly, intracortical facilitation (ICF) probes excitatory circuits putatively mediated by glutamate. These paradigms are typically measured at rest or during isometric contractions; thus, it is unknown how SICI and ICF are modulated with respect to each other during dynamic contractions, particularly in the lower extremity. Here, we investigated task-dependent differences in lower extremity inhibitory/excitatory (I/E) balance in individuals with stroke and healthy individuals. Twenty individuals with chronic stroke (age: 62 ± 9 years, chronicity: 83 ± 61 months) and 14 healthy controls (age: 65 ± 9 years) performed isolated isometric (ISO) and dynamic (DYN) plantarflexor contractions against a dynamometer. Motor evoked responses (MEPs) were recorded from the paretic medial gastrocnemius (MG) and soleus (SOL). SICI was induced using paired-pulse transcranial magnetic stimulation (TMS) by conditioning the test MEP at 0.7*active motor threshold (aMT) with an interstimulus interval (ISI) of 0.25 ms, while ICF used a conditioning pulse of 0.9*aMT and an ISI of 1.5 ms. Test pulses were invoked at stimulator intensity producing an MEP of 1 mV peak-to-peak. Inhibitory/excitatory balance was calculated as the ratio of the conditioned MEPs evoked during SICI and ICF, respectively. I/E balance was similar across the control and stroke groups in the ISO condition for both the MG (P = .14) and SOL (P = .40). In the DYN condition, I/E balance in stroke and control groups was similar in MG (P = .33), but higher in controls than stroke in SOL (P = .008). I/E balance increased between ISO and DYN conditions in healthy controls in both MG (P = .03) and SOL (P = .0008), while in the stroke group, I/E balance increased significantly between ISO and DYN for MG (P = .004) but not SOL (P = .06). DYN I/E balance in the MG correlated positively with self-selected walking speed (P = .006, r = 0.43) across both control and stroke groups, and with Dynamic Gait Index score (P = .02, r = 0.44) in the stroke group. To our knowledge, this is the first reported study of dynamic cortical inhibitory/excitatory balance in the lower extremity. Increased I/E balance during dynamic, relative to isometric, plantarflexion suggests dynamic force production is mediated via disinhibition, rather than facilitation. Associations between I/E balance and gait function, combined with absence of modulation in SOL in the stroke group, suggests dynamic I/E balance may be indicative of functional outcomes following stroke.
T45: Astrocytic Mechanisms of Neuronal Synchronization and Local Plasticity in Motor Learning: A Computational Study
Ioannis Polykretis1, Vladimir Ivanov1,
Konstantinos Michmizos
1
1Rutgers University, Piscataway, NJ, USA
Compared with neurons, the role of glial cells in brain disorders and rehabilitation has been so far weakly targeted and sparsely understood. Therefore, further explaining the role of astrocytes, the most abundant yet long-neglected glial cells, in health and disease is a nascent challenge promising immense rewards to impairment recovery. Of particular interest to this study is the functional relation between neuronal activity and astrocytic calcium waves, which are altered in most brain diseases and significantly increase in ischemic stroke. However, there is scarcity of studies on the cellular neuromodulatory mechanisms, linking astrocytic calcium waves to neural repair. To address this vacuum, we have developed a biophysically realistic model of neural-astrocytic networks where astrocytes preserve the spatial allocation of their distinct subcellular compartments and communicate with neurons through tripartite synapses. Our model preserves the distinctive stellate structure of astrocytes, comprising functionally independent building blocks named microdomains, and the spatial allocation of their subcellular functional organelles as well as the distinct intracellular calcium stores such as IP3-sensitive and calcium-sensitive calcium release mechanisms. Our modeling results suggest that astrocytes, via a calcium cascade mechanism, encode the synchronization of neuronal activity into the extent of their intracellular calcium waves. These calcium fluctuations are known to modulate glio-transmitter release, which in their turn impose synchronization in postsynaptic neurons through slow-inward currents (SIC). Rhythmic neural synchrony is known to decrease reaction time and enhance information processing and communication speed between distinct groups of neurons. This proposed astrocytic-induced facilitation of neural synchronization is a possible microscopic (cellular) mechanism for the macroscopic (behavioral) changes observed in motor learning. In addition to imposing neural synchronization, our model suggested that astrocytes might be also implicated in the emergence of spatially organized functional groups of dendritic spines. The spread of the emulated calcium waves extended from highly localized activity in the vicinity of synapses, to microdomain-wide calcium waves and global calcium fluctuations that reach the cell’s soma. Inside an astrocytic microdomain, a local calcium wave emerging from the high activity of a small number of synapses introduced SICs into the nearby inactive synapses, spatially restricting neuroplasticity inside the microdomain and shaping new synaptic groups. With local plasticity being a known mechanism for motor learning, we speculate that this microdomain-wide calcium wave might be a decisive mechanism for the the long-observed implication of astrocytes to neuroplasticity and the recently reported organization of nearby synapses into functional groups. Overall, our comprehensive computational model is used as a test bed for verifying and further hypothesizing on the possible astrocytic mechanisms associated with neuronal synchronization and plasticity. The modeling results could further our understanding on neurorehabilitation and guide future studies on alternative therapeutic avenues, including new drugs targeting impaired astrocytic functions.
T46: A 3-Dimensional Quantitative Model of Finger and Hand Kinematics During Functional Tasks
Tomas Oppenheim1, Jenny Trieu2,
Adelyn Tu-Chan
2, Karunesh Ganguly2
1California State University Maritime Academy, Vallejo, CA, USA
2University of California San Francisco, San Francisco, CA, USA
Introduction: Impaired hand dexterity caused by stroke contributes significantly to the poor functional use of the upper limb. While interventions in chronic stroke patients can result in observed gains, it is increasingly hypothesized to be due to compensatory behaviors as opposed to driving true recovery (ie, reducing impairments). However, the kinematic underpinnings of compensatory behaviors are not fully understood. Importantly, few instruments, in our experience, are capable of precisely and reliably measuring the complex 3-dimensional movements of the finger joints affected by motor dysfunction. We have pursued the development of a quantitative model of finger dexterity using an electromagnetic sensor system to address this core need.
Methods: A healthy control cohort was examined and compared with a stroke cohort. All participants performed 2 sets of tasks, the Action Research Arm Test (ARAT) and the Range of Motion Test (ROM). To track both gross and fine upper limb movements, we used an electromagnetic sensor system called trakSTAR. Sensors were mounted on the hand and arm to monitor upper limb movements. Each sensor tracked 6 degrees of freedom, yielding information regarding 3-dimensional spatial position (x, y, and z) and angle orientation (azimuth, elevation, and roll) at a sampling rate of 80 Hz. Joint angles of the upper limb were calculated using the sensor measurements. Joint angle measurements were validated at each joint with a goniometer. Heat maps of finger and hand movement were created from both the ARAT and ROM tests.
Results: The accuracy of the sensors was 1.4 mm root mean square (RMS) for position and 0.5 RMS for angle measurements. For both the ARAT and ROM tests, the absolute position and orientation of the research participant’s index finger and thumb were plotted throughout the test. These plots precisely and efficiently quantified the kinematic differences in fine and gross hand movements between the stroke and control groups.
Conclusion: A glove-based electromagnetic sensor system mounted on the hand and fingers was determined to be a feasible, convenient, and reliable instrument for kinematic monitoring of finger and hand movements in chronic stroke and healthy control cohorts. A quantitative model using this system was successfully developed to analyze fine and gross finger and hand movements during simple range of motion and complex functional tasks. This model can potentially provide the opportunity for researchers and clinicians to more precisely delineate recovery versus compensatory behaviors.
T47: Changes in Corticomotor Excitability Associated With Successful Recovery of Upper Extremity Motor Function Poststroke
Shashwati Geed
1,2, Farhanaz Nowshin2, Jessica Barth2, Michelle Harris-Love3, Peter Lum4, Alexander Dromerick1,2
1Georgetown University Medical Center, Washington, DC, USA
2MedStar National Rehabilitation Hospital, Washington, DC, USA
3George Mason University, Fairfax, VA, USA
4The Catholic University of America, Washington, DC, USA
Introduction: Upper extremity (UE) impairment affects 88% of stroke survivors due to dysfunctional shoulder-hand coordination. Patients may be able to grasp with the arm at rest but unable to grasp in a functional context because shoulder use elicits involuntary hand muscle activity. Additionally, much research is directed at unsuccessful (incomplete) recovery but little toward patients with successful clinical recovery of UE function even though these patients attain the desired rehabilitation outcome. We examined the neurophysiological trajectory of successful compared to unsuccessful poststroke recovery in the context of functional UE movements.
Methods: We enrolled 3 groups: (1) mildly impaired patients with the National Institutes of Health Stroke Scale (NIHSS) motor arm score ⩽1, representing those who will show successful poststroke recovery, tested Early, at <17, 30, 90, and 180 days after stroke; (2) moderately impaired patients with NIHSS motor arm score = 2 or 3, representing those with persistent impairment and incomplete recovery, tested once, in the Chronic stage (>6 months post); and (3) age-matched healthy Controls. Using transcranial magnetic stimulation in participants, we tested whether shoulder position influences corticomotor excitability and intracortical inhibition of hand muscles involved in grasp (first dorsal interosseous [FDI], flexor pollicis brevis [FPB], extensor digitorum [EDC], and flexor digitorum [FDS]).
Experimental Setup: Participants were seated with back support in front of a waist-height workstation. The impaired or nonimpaired UE was fully supported with the shoulder in horizontal adduction (0°) or abduction (90°), elbow flexion (90°), forearm in pronation and digits extended and at rest in a wrist-support brace. UE motor function was measured using the UE Fugl-Meyer, Jebsen-Taylor hand function test, and Stroke Impact Scale Hand-arm subscale. Activity Card Sort test was used to measure participation at the 30-, 90-, and 180-day time points. Data collection is underway.
Preliminary Findings: Age-matched controls show that horizontal shoulder adduction or abduction differentially influences corticomotor excitability of hand muscles involved in grasp. Data from 10 mildly impaired participants in Early group (mean time to testing poststroke = 12.6 ± 2 days) show differences in peak-to-peak average waveform (uV), % facilitation, and motor evoked potential (MEP) area at 90%, 110%, 130%, and 150% resting motor threshold (RMT) for the same hand muscles between (1) impaired and nonimpaired UE and between (2) shoulder adduction compared to abduction. Mean Jebsen-Taylor hand function test scores for impaired and nonimpaired UE were 149.1 ± 79 seconds and 102.3 ± 37 seconds, respectively, in this group. Data collection and analysis is currently underway and will be presented.
Conclusion: We hypothesize that this shoulder-hand coupling may be centrally facilitated, and is dysfunctional after stroke resulting in involuntary coactivation of UE muscles leading to persistent impairment. These findings will help distinguish the neurophysiology of successful from unsuccessful UE recovery following stroke, leading to effective, mechanism-based interventions for UE dysfunction.
T48: Home-Based Daily Exercises Using Wearable Motion Sensors for Community Dwelling Stroke Survivors With Hemiparesis
Jeremy Fidock
1,
Marissa Wuennemann
1, Avrielle Rykman Peltz1, Dylan Edwards1
1Burke Neurological Institute, White Plains, NY, USA
Background: Telerehabilitation is a novel form of therapy that may be a practical and feasible method to increase and/or maintain function after stroke. A portable device capable of delivering therapy in a home setting may provide a paradigm shift for rehabilitation in the chronic stroke population.
Objective: To determine the feasibility and functional benefits of using wearable motion sensors to complete an at-home upper limb exercise program for chronic stroke survivors with hemiparesis.
Methods: We conducted a single-arm, pre-post, feasibility study with 6 stroke survivors who had moderate to mild motor impairments according to individual Fugl-Meyer scores (FM > 20). Each participant was provided with a 4D Motion device, as well as an accompanying application for their Apple devices. Active range of motion (AROM) was assessed using the 4D Motion kit as well as a goniometer, and goals were individually customized such that each participant performed exercises that achieved 90% of their baseline AROM. Participants performed up to 1 hour of upper extremity exercise for 4 weeks by completing repetitive movements of 4 prescribed exercises (Shoulder Flexion, Shoulder Abduction, Elbow Extension, Shoulder External Rotation). Participants were monitored remotely on a weekly basis by a clinician. Outcome measures included participant compliance and changes in AROM, Fugl-Meyer, Physical Activity Enjoyment Scale (PACES), and a System Usability Scale (SUS).
Results: On average, study participants were 66.0 ± 19.7 years old (mean ± SD), 6.50 ± 3.34 years poststroke, and 3 (60%) were male. Compliance was high on average, 81.4 ± 14.2%. On average, participants experienced increases in AROM for Shoulder Abduction and Shoulder Flexion and there was a significant increase in AROM for Elbow Flexion/Extension, 9.60 ± 7.30 (P = .04). A clinician-measured AROM using a goniometer while measurements made with the 4D Motion device were compared to this number to assess the fidelity of the sensors’ angle measurements. There was a significant change in the average scores from baseline to 4 weeks postintervention in the Fugl-Meyer, 2.00 ± 0.71 (P < .01).
Conclusion: At-home therapy using a wearable device was feasible and functionally beneficial for the hemiparetic chronic stroke population as demonstrated by a high level of compliance, improvements in Fugl-Meyer scores, and AROM measurements. These results warrant further, randomized experiments with an increased number of participants to determine efficacy of the intervention.
T49: Concurrent Reorganization in Cortex and Striatum During Motor Recovery After Stroke
Ling Guo
1,2, Seok-Joon Won2, Karunesh Ganguly1,2
1University of California, San Francisco, San Francisco, CA, USA
2San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA
Many stroke patients suffer chronic upper limb motor impairments. There is a lack of effective treatments, hampered by a limited understanding of brain reorganization after stroke, especially at the network level. Past research has focused on the role of the perilesional cortex (PLC), the area of cortex directly adjacent of the stroke site, in motor recovery. However, executing a skilled motor action requires coordinated activity of both cortical and subcortical motor areas. Particularly, the dorsal lateral striatum (DLS) is involved in motor learning and execution in healthy individuals and loses input projections after a motor cortical stroke. However, its role in motor recovery after stroke remains unknown. To understand the dynamic changes in the motor cortex and striatum during the stroke recovery process, we first trained Long Evans rats on a reach-to-grasp task that assesses skilled forelimb motor function. Next, we induced a photothrombotic stroke over the forelimb motor cortex of the rats, and then implanted electrodes in the PLC and DLS. We recorded single unit and local field potential data while rats undergo physical rehabilitation in the same task. We also recorded neural activity in a separate group of healthy rats performing the same task for comparison. We found that rats were significantly impaired in the reach-to-grasp task after stroke, and partially recovered after several weeks of rehabilitation. The proportion of neurons with significant firing rate modulation during the task increased with recovery, in both PLC and DLS. The low-frequency local field potential power also showed concurrent increases in both regions. The results show that the DLS, a previously understudied area in the context of stroke, is also functionally affected by a motor cortical stroke and that patterns of neural activity in DLS during motor actions are reorganized with recovery.
T50: Corticospinal Tract Wiring and Brain Lesion Characteristics in Unilateral Cerebral Palsy: Determinants of Upper Limb Motor and Sensory Function
Cristina Simon-Martinez
1, Ellen Jaspers2, Lisa Mailleux1, Els Ortibus1, Katrijn Klingels1,3, Nicole Wenderoth2, Hilde Feys1
1KU Leuven, Leuven, Belgium
2ETH Zurich, Zurich, Switzerland
3Hasselt University, Hasselt, Belgium
Background: Brain lesion characteristics (timing, location, and extent) and the type of corticospinal tract (CST) wiring have been proposed as determinants of upper limb (UL) motor function in unilateral cerebral palsy (uCP), yet an investigation of the relative combined impact of these factors on both motor and sensory function is still lacking. Here, we first investigated whether structural brain lesion characteristics could predict the underlying type of CST wiring, and we explored the role of CST wiring and brain lesion characteristics on UL motor and sensory function in uCP.
Methods: Fifty-two participants with uCP (mean age [SD]: 11 years 3 months [3 years 10 months]) underwent a single-pulse transcranial magnetic stimulation session to determine CST wiring between the motor cortex and the more affected hand (n = 17 contralateral; n = 19 ipsilateral; n = 16 bilateral) and an MRI (magnetic resonance imaging) to determine lesion timing (n = 34 periventricular [PV] lesion; n = 18 cortico-subcortical [CSC] lesion), location, and extent. Lesion location and extent were evaluated with a semiquantitative scale. A standardized protocol included UL motor (grip strength, unimanual capacity, bimanual performance) and sensory measures. Linear discriminant analysis was used to determine CST wiring group membership based on the brain lesion characteristics. Multiple (linear, ordinal, or logistic) regression analyses were conducted to predict UL motor and sensory deficits based on the type of CST wiring and lesion timing, location, and extent. Statistical analysis was carried out with SPSS 24.0 and α was set at 0.05.
Results: A combination of lesion locations (damage to the PLIC and frontal lobe) significantly contributed to differentiate between the CST wiring groups, reclassifying the participants in their original group with 57% of accuracy. Although motor and sensory function were influenced by the brain lesion characteristics and the type of CST wiring (P < .05) in a simple linear regression analysis, the multiple regression identified the main significant predictors. Motor function was mostly predicted (R2 [range] = 0.46-0.60) by the type of CST wiring (more preserved in individuals with contralateral CST wiring; P < .01), the lesion extent, and the damage to the basal ganglia and thalamus. Sensory function seemed to be best predicted by the combination of a large and later lesion, and an ipsilateral or bilateral CST wiring, which led to increased sensory deficits (P < .05).
Discussion and Conclusion: Brain lesion characteristics do not seem to provide with accurate information to predict the type of CST wiring. Motor function deficits seemed to be best predicted by the type of CST wiring, although lesion extent and damage to the basal ganglia and thalamus further add to the model. In contrast, sensory function seems to be mainly determined by lesion extent and timing. These novel insights contribute to a better understanding of the underlying pathophysiology of UL motor and sensory function and may be useful to delineate individualized treatment strategies.
T51: Case Study: The Effect of the Use of an EMG-Driven FES Device for Finger Extension on the Expression of the Flexion Synergy in an Individual With Severe Hemiparetic Stroke
Dylan Fitzsimons
1, Carolina Carmona1, Kevin B. Wilkins1, Justin Drogos1, Julius P. A. Dewald1, Jun Yao1
1Northwestern University, Chicago, IL, USA
Introduction: Many activities of daily living (ADLs) require the coordination of the arm and hand. However, a loss of independent joint control in the upper extremity (UE), resulting in coupling between shoulder abduction with elbow/wrist and finger flexion, or the flexion synergy, commonly affects joint individuation in individuals with moderate to severe chronic stroke. Due to the above-mentioned motor impairment, more impaired stroke survivors are largely excluded from intervention programs that require some residual hand function. To reengage this population back to a more functional use of their paretic upper limb, we have developed the ReIn-Hand device. This is an EMG-driven functional electrical stimulation (FES) device that facilitates hand opening, even in the presence of flexion synergy, and can be used alongside a robotic device capable of modulating shoulder abduction loading. In this study, we explored if this multifaceted intervention can reduce the expression of the flexion synergy seen in chronic stroke, while simultaneously improving hand opening, and lead to significant functional improvements in the paretic limb.
Subject: One individual with severe chronic stroke (Upper Extremity Fugl-Meyer Motor Assessment [UEFMA] = 23/66, year poststroke = 11) was recruited to participate in a 24-session intervention (4 sessions per week for 6 weeks).
Methods: During each session, the participant was fitted with the ReIn-Hand device and seated and secured in a Biodex chair. Maximal passive hand opening using FES was found with the arm supported by the robot and then found again while actively abducting the shoulder against the ACT3D robot. Shoulder abduction loading was adjusted such that the participant’s FES-generated hand opening was 70% that of hand opening measured while the arm was fully supported and was then maintained throughout that day’s trials. The participant completed 20 to 25 trials (per session), which involved lifting and reaching for an object, opening the hand, grasping and retrieving it, and then releasing the object. EMG recording during the opening/releasing phases triggered the ReIn-Hand stimulation of the extensor muscles. Pre- and posttest assessment included the Box and Blocks test (BBT).
Results: At posttest, the subject demonstrated improved score on the BBT (from 0 to 6), attaining the MCD for the test.
Conclusion: These results indicate the therapeutic benefits of combining progressive shoulder abduction loading with the ReIn-Hand induced hand opening. Further research is needed to assess the effectiveness of the combination of these 2 approaches in a larger sample size.
T52: Brain Source Analysis of Motor Planning for Initiating Stepping in Individuals With Subacute Stroke: A Case Series
Sue Peters
1, S Jayne Garland2, Bimal Lakhani1, Anthony Herdman1, Lara Boyd1
1University of British Columbia, Vancouver, Canada2Western University, London, Canada
Background: Electroencephalography (EEG) recorded from Cz in individuals with subacute stroke has revealed that, despite the lesion, some measures during step planning are similar between legs. This finding suggested that elements of motor planning may be symmetrical. Interestingly, differences were found when stepping speed was factored in; individuals who stepped slowly with the paretic leg had greater cognitive effort to plan a step. This suggested that after stroke, motor planning differences between legs may be present, but difficult to quantify with a single electrode approach. While multiple brain regions contribute to motor planning, EEG experiments involving the leg provide a challenge identifying these brain regions. Bilateral activations of medial motor cortices for stepping tasks generate overlapping EEG scalp activities from volume conduction, and make interpreting scalp-based EEG activity difficult. Source modeling methods that apply algorithms to find the location of neural activity may be helpful. Recently, Herdman et al validated a Multi-step Iterative Approach (MIA) beamformer with simulated and real EEG data in healthy adults. Critically, MIA was found to have better localization precision than 2 other approaches. The benefit of MIA is that the iterative algorithm finds multiple sources without a priori assumptions about source locations and orientations, which are limitations in other dipole modeling procedures, like Brain Electrical Source Analysis (BESA). Since medial bilateral motor regions are difficult to localize, the study’s aim was to compare MIA and BESA approaches.
Methods: Ten individuals with subacute stroke (70.9 ± 7.7 years old; 6 males, 4 females, 3.9 ± 1.5 months poststroke) performed self-initiated stepping resulting in 2 conditions: paretic and nonparetic stepping. Custom MATLAB scripts preprocessed the 64-channel EEG data. We used the MIA beamformer to localize brain sources of the readiness potential within the prestepping interval. For comparison, we used BESA to localize this same interval by adding and fitting single dipoles until residual variances were <20% for each participant. We compared source locations and waveforms between MIA and BESA.
Results (Pending): Preliminary results (n = 4) showed that MIA and BESA found medial sources within the motor cortices; BESA modeling had greater variability of the number and locations of sources. Because of inherent source mixing using BESA, the medial motor source waveforms were difficult to differentiate between hemispheres, whereas MIA showed separation of interhemispheric source activities.
Discussion: This work used a new source modeling approach (MIA beamformer) to separate interhemispheric neural activations during motor planning of stepping in individuals with subacute stroke. Thus, MIA could be useful in identifying the spatial-temporal dynamics of stepping after stroke. Better understanding of brain sources during motor planning may advance the field and further elucidate the extent to which planning deficits limit stepping performance poststroke.
T53: Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke
Joshua Silverstein
1, Mar Cortes1, Katherine Tsagaris1, Alejandra Climent1,2, Linda Gerber3, Clara Oromendia3, Pasquale Fonzetti3,4, Rajiv Ratan1,3, Tomoko Kitago1,3, Marco Iacoboni5,6, Allan Wu6,7, Bruce Dobkin8,9, Dylan Edwards1,3
1Burke Neurological Institute, White Plains, NY, USA
2Sant Joan de Deu Hospital, Barcelona, Spain
3Weill Cornell Medical College, New York, NY, USA
4Burke Rehabilitation Hospital, White Plains, NY, USA
5UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA
6Ahmanson-Lovelace Brain Mapping Center, Los Angeles, CA, USA
7University of California, Los Angeles, CA, USA
8Geffen School of Medicine, Los Angeles, CA, USA
9Reed Neurologic Research Center, Los Angeles, CA, USA
Background and Purpose: The potential for adaptive plasticity in the poststroke brain is difficult to estimate, as is the target engagement of promising drugs that might facilitate recovery. We set out to determine if paired associative stimulation (PAS) can (1) be used as an assay of plasticity in chronic stroke and (2) test target engagement by memantine, which has potential plasticity-modulating effects for use in motor recovery following stroke.
Methods: We examined the effect of PAS in 14 participants with chronic hemiparetic stroke at 5 time points in a within-subjects repeated-measures design: baseline off-drug, and following a week of orally administered memantine at doses of 5, 10, 15, and 20 mg. Each week, MEP amplitude pre- and post-PAS was assessed in the contralesional hemisphere as a marker of enhanced or diminished plasticity. Strength and dexterity were recorded each week to monitor motor-specific clinical status across the study period.
Results: Relative to baseline, (1) post-PAS MEP amplitude was significantly elevated in the absence of memantine and (2) no increase in MEP amplitude was observed in the memantine condition post-PAS, at any dose. Strength and dexterity were unaffected by memantine.
Conclusions: PAS successfully induced motor system excitability enhancement in chronic stroke subjects, yet was suppressed by memantine at all doses tested, indicative of target engagement. Response to PAS off-drug does not occur in all patients, and could be an important stratification for future PAS-drug studies.
T54: Severity of Impairment Is Important When Exploring Biomarkers of Upper Limb Outcome Poststroke
Kate Hayward
1,2, Jennifer Ferris2, Keith Lohse3, Michael Borich4, Steve Cramer5, Alexandra Borstad6,7, Jill Stewart8, Sean Dukelow9, Jessica Cassidy5, Sonja Findlater9, Jason Neva2, Lara Boyd2
1Florey Institute of Neuroscience and Mental Health, Melbourne, Australia2University of British Columbia, Vancouver, Canada3University of Utah, Salt Lake City, UT, USA4Emory University, Atlanta, GA, USA5University of California, Irvine, CA, USA6College of St. Scholastica, Duluth, MN, USA7Ohio State University, Columbus, OH, USA8University of South Carolina, Columbia, SC, USA9University of Calgary, Calgary, Canada
Background: The First Stroke Rehabilitation and Recovery Roundtable concluded that trials need to base participant eligibility on more than presence of stroke, or behavioral status, and include appropriate biomarkers. Diffusion tensor imaging (DTI) is frequently used to capture biomarker information, but individual studies often include small samples of people with severe upper limb (UL) impairment.
Aim: We built a mega-data set to determine if candidate DTI biomarkers can differentiate: (1) individuals with mild-moderate from severe and (2 within individuals with severe UL impairment poststroke. We hypothesized that corticospinal tract (CST) integrity could differentiate individuals with mild-moderate from severe, but corpus callosum (CC) integrity could differentiate within individuals with severe UL impairment.
Methods: Seven sites in Canada and the United States contributed individual DTI and motor impairment (Fugl Meyer-UL, FM-UL) data. Hand-drawn regions-of-interest were used to reconstruct CST (ipsilesional, contralesional) and CC (prefrontal/premotor/motor/sensory/posterior) tracts. Mean fractional anisotropy was extracted. Linear mixed-effect regression models were performed, with a random-effect of study group (ie, dependent sets of participants nested together).
Results: We collated data from 114 individuals (84 severe, 30 mild-moderate) from 9 independent study groups. Analysis of FM-UL data found that (1) CST integrity distinguished between individuals with mild-moderate (n = 30) from severe (n = 84) UL impairment (P < .001); (2) prefrontal (P = .001) and posterior (P < .001) CC tracts distinguished between individuals with severe UL impairment (n = 84), accounting for unique variance beyond CST integrity; (3) stronger prefrontal CC to FM-UL relationship was observed that nonlinearly related to increased poststroke duration for prefrontal CC (P = .004).
Conclusions: Our data suggest biomarkers of upper limb outcome are not “one-size-fits-all”; severity, time poststroke, and distinct neuroimaging biomarkers are all important variables for consideration. These data focused on the relationship between several distinct biomarkers and initial UL impairment following stroke. Given the robust pattern of results, a longitudinal study exploring the multifaceted nature of recovery in these subgroups is warranted.
T55: The Importance of Edinburgh Handedness Inventory Short Form to Determine Handedness in 17 Indonesian Stroke Patients: A Case Series
Widjajalaksmi Kusumaningsih
1, Herry Hong1
1University of Indonesia, Ciptomangunkusumo Hospital, Jakarta, Indonesia
Background: Handedness has an important role in motor skill function of the upper extremity, which is important for a person’s daily activities. Handedness in stroke patients may change due to a lesion in the brain hemisphere. Edinburgh Handedness Inventory–Short Form (EHI-SF) is one of the tools that can be used to determine handedness in stroke patients.
Objectives: The aim is to determine whether there is any change in handedness between pre- and poststroke patients. Determination of handedness in stroke patients is important before providing hand rehabilitation programs.
Methods: Stroke patients from all 3 stroke phases, acute, subacute, and chronic, were evaluated to find out which hands are dominant using EHI-SF twice, before (by interview) and after. EHI-SF consist of 4 activities that should be done by subjects. Those were writing, throwing, using toothbrush, and spoon. Each activities was scored by 5 categories, which are always right (score 100), usually right (50), both equally (0), usually left (−50), and always left (−100). To calculate the Laterality Quotient (LQ) score, sum the scores of the 4 activities and divide by 4. Laterality Quotient (LQ) score classified handedness into Left Handed (−100 to 61), Mixed Handed (−60 to 60), and Right Handed (61 to 100).
Results: Seventeen subjects, ages from 28 to 75, 11 males (64.7%), 6 females (35.2%). Three stroke phases, 2 acute (11.7%), 7 subacute (41.2%), and 8 chronic (47.1%). Prestroke handedness, 16 Right Handed (RH) (94.1%) and 1 Mixed Handed (MH) (5.9%), Zero Left Handed. Twelve patients (70.5%) with the LQ score and category were not changed between pre- and poststroke, 4 patients (23.5%) whose LQ scores were changed but still in the same category and there was only one chronic phase patient (5,9%) whose LQ scores and category changed from RH to LH. Four of 5 patients (80%) whose LQ scores were changed are RH who has right hemiparesis.
Conclusions: This study shows that hemiparesis can influence the changes of LQ scores in stroke patients, over 80% of patients whose LQ scores changed are right handed before stroke who has right hemiparesis. From 5 patients whose LQ scores changed, only 1 patient (5.9%) experienced a major change from RH to LH. Several things can affect this result including dominant hand impairment, onset of stroke, and adaptive mechanisms. This study indicates that evaluation using EHI-SF is important to know the LQ score in stroke patients to determine their handedness before giving hand exercises in rehabilitation programs.
Poster Session II
F1: How Anticipatory Postural Adjustments Affect Protective Steps: A Step-by-Step Multilevel Analysis
Daniel Peterson1,
Keith Lohse
2, Martina Mancini3
1Arizona State University, Tempe, AZ, USA2University of Utah, Salt Lake City, UT, USA3Oregon Health Sciences University, Portland, OR, USA
Background: Effective protective steps are critical for fall prevention, and anticipatory postural adjustments (APAs) prior to steps can both negatively and positively affect step performance. APAs prior to protective steps seem to be too big in people with Parkinson’s disease (PD), and it is unknown whether they contribute to better or worse stepping. Understanding how APAs relate to protective step performance will inform therapies aimed at improving postural adjustments and preventing falls.
Objective: Characterize the relationship between APAs’ magnitude and several aspects of the subsequent protective step in people with PD.
Methods: Twenty-eight individuals with PD completed 25 forward and 25 backward protective steps (pseudo-randomly ordered) in response to discrete support surface translations. Anterior-posterior APAs and step characteristics were measured via force platform and motion analysis. Multilevel linear models related APAs size to step outcomes for each trial, controlling for sequential effects.
Results: During forward protective stepping, APA size predicted delayed (P < .001), but larger (P = .004) steps. Larger APAs also predicted smaller mediolateral, but larger anterior-posterior center of mass movement at foot off (P < .001 for both). During backward stepping, larger postural adjustments predicted later steps (P < .001), and smaller anterior-posterior margin of stability at first foot contact (P < .001). Several effects were also complicated by interactions between APA and freezing of gate (FOG) status. These interactions showed that APAs were predictive of certain step characteristic for FOG− participants, but these relationships were attenuated (or even reversed) for FOG+ participants.
Conclusions: During forward protective stepping, larger APAs were related to larger but later protective steps, suggesting APAs may have mixed effects on the subsequent protective step. During backward stepping, larger APAs predicted worse stepping, as characterized by later steps and smaller anterior-posterior margin of stability at first foot contact. Interventions aimed at improving APA size in PD should monitor both spatial and temporal protective step outcomes to ensure that treatment does not negatively impact protective steps, particularly for forward protective stepping.
F2: Asymmetric Hindlimb Posture and Withdraw Reflexes Induced by Unilateral Brain Injury Are Encoded in Spinal Cord
Mengliang Zhang1, Hiroyuki Watanabe2, Daniil Sarkisyan2, Jonas Thelin3, Jens Schouenborg3,
Georgy Bakalkin
2
1University of Southern Denmark, Odense, Denmark
2Uppsala University, Uppsala, Sweden
3Lund University, Lund, Sweden
Introduction: Spinal plasticity induced by brain trauma or stroke may underlie pathological changes in motor reflexes and locomotion or contribute to recovery of motor functions. Knowledge on the intrinsic spinal plasticity induced by brain injuries is limited.
Objective: To establish a rat model of the brain injury–induced spinal plasticity underlying formation of asymmetric posture and asymmetric cutaneous reflexes that allows analysis of neurobiological mechanisms and effects of pharmacological substances.
Methods: Cortical hindlimb representation area was unilaterally ablated by aspiration in the rats. Formation of hind limb postural asymmetry was assessed as differences in limb position; and differences in hip, knee and ankle joint angles, and stretch force between the ipsilesional and contralesional legs before and after complete spinal transection at T7 level performed at 3- to 21-day time points after the injury. Withdrawal reflex analyzed as electromyographic (EMG) activity evoked by electrical stimulation was compared between ipsilesional and contralesional hindlimb muscles in spinalized decerebrate rats.
Results: Visual and electrophysiological examination revealed development of the contralesional-side specific response to the unilateral brain injury evident before and after spinalization. Most rats received the injury developed flexion of the contralateral hindlimb; the ankle joint angle was smaller on the contralateral than on the ipsilateral side; stretch force was larger on the contralateral side when legs were stretched to the same level. Hindlimb withdrawal reflex was asymmetric in the rats received brain injury but not sham operation; EMG activities of flexor muscles extensor digitorum longus, biceps posterior, and semitendinosus were elevated on the contralateral side. In response to stretching, EMG activity of the semitendinosus was much stronger on the contralateral side than that on the ipsilateral side. Sham-operated spinal rats showed no differences between contralesional and ipsilesional hindlimbs.
Conclusion: The results indicate that (1) the unilateral brain injury–induced hindlimb postural asymmetry is encoded at the spinal level; (2) the visually recorded differences in the hindlimb position correlate with differences in joint angles and stretch force; and (3) contralesional versus ipsilesional side-specific changes in nociceptive withdrawal reflexes are developed due to plastic changes in the spinal cord induced by unilateral brain injury.
F3: Assessing Task Execution Abilities for Communication of Patients With Unresponsive Wakefulness Syndrome Using a Vibrotactile P300 Brain-Computer Interface
Christoph Guger1,2, Rossella Spataro3,
Katrin Mayr
1, Günter Edlinger1,2
1Guger Technologies OG, Graz, Austria
2g.tec medical engineering GmbH, Schiedlberg, Austria
3University of Palermo, Palermo, Italy
Persons diagnosed with disorders of consciousness (DOC) might suffer from motor disabilities, and thus assessing their spared cognitive abilities can be difficult. Recent research from several groups has shown that noninvasive brain-computer interface (BCI) technology can provide assessments of these patients’ cognitive function that can supplement information provided through conventional behavioral assessment methods. In rare cases, BCIs may provide a binary communication mechanism. Here, we present results from a vibrotactile BCI assessment aiming at detecting command-following and communication in 12 unresponsive wakefulness syndrome (UWS) patients. Two different paradigms were administered at least once for every patient: (1) VT2 with 2 vibrotactile stimulators fixed on the patient’s left and right wrists and (2) VT3 with 3 vibrotactile stimulators fixed on both wrists and on the back. The patients were instructed to mentally count either the stimuli on the left or right wrist, which elicits a robust P300 for the target wrist only. The EEG data around each stimulus were extracted and subdivided into 8 averages. These data were classified with linear discriminant analysis and used to calibrate a brain-computer interface to test YES/NO communication abilities. The grand average VT2 accuracy was 38.3% and the VT3 accuracy 26.3%. Two patients achieved a VT3 accuracy ⩾80% and went through communication testing (one answered 4 out of 5 questions correctly in session 1, whereas the other could answer 6/10 and 7/10 questions correctly in sessions 2 and 4). In 6 other patients, the VT2 or VT3 accuracy was above the significance threshold of 23% for at least one run, while in 4 patients the accuracy was always below this threshold. The study highlights the importance of repeating EEG assessments to increase the chance of detecting command-following in patients with severe brain injury. Furthermore, the study shows that BCI technology can be useful to test command following in chronic UWS patients and can allow patients to answer YES/NO questions. Beside UWS patients, the principle can be used in locked-in/completely locked in and minimal consciousness patients for assessment and communication.
F4: Treatment Frequency for Long-Term Efficacy of AbobotulinumtoxinA Injections: A Phase 3 Study in Patients With Upper Limb Spasticity Following Stroke or Traumatic Brain Injury
Jean-Michel Gracies1, Allison Brashear2, Svetlana Khatkova3,
Brian Carlson
4, Anne-Sophie Grandoulier5, Philippe Picaut5
1EA 7377 BIOTN, Université Paris-Est, Hospital Albert Chenevier-Henri Mondor, Service de Rééducation Neurolocomotrice, Créteil, France
2Wake Forest School of Medicine, Winston-Salem, NC, USA
3Center of Ministry of Health and Social Development of Russian Federation, Moscow, Russian Federation
4Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA
5Ipsen Pharma, Les Ulis, France
Introduction and Background: Long-term safety and efficacy of repeated abobotulinumtoxinA (aboBoNT-A) injections in patients with upper limb spasticity (ULS) after stroke or traumatic brain injury have been described in an open-label study. Continuous improvements in active movements, and perceived and active function were reported, with no unexpected safety signals identified. Here, we describe the frequency of repeated aboBoNT-A injections over the open-label study.
Material and Method: A phase 3, international, double-blind, single-treatment study (NCT01313299) of aboBoNT-A in the hemiparetic upper limb, followed by a 12-month open-label extension study (NCT01313312) with up to 4 additional treatment cycles, at least 12 weeks apart. Retreatment was per investigator’s clinical judgement, based on muscle tone, spasticity measures, and other findings. Patients not requiring re-treatment completed the study.
Results: A total of 254 patients entered in open-label Cycle 1. In Cycle 1, 14/254 (5.5%) patients withdrew and 240 (94.5%) completed the cycle. After Cycle 1, 10 patients completed the study without subsequent aboBoNT-A injections. In Cycle 2, 219/229 (95.6%) patients completed the cycle (10 [4.4%] withdrew) and 44 did not require subsequent injections. Of 175 patients who entered Cycle 3, 6 (3.4%) withdrew and 169 (96.6%) completed the cycle, 88 of whom did not require subsequent injections. Overall, 55.9% (n = 142) of patients required 3 or fewer injections of aboBoNT-A over the course of the 12-month study, 21.6% required 2 or fewer injections, and 3.9% required 1 injection.
Conclusion: Over half of the patients (55.9%) enrolled in this phase 3 study required 3 or fewer injections of aboBoNT-A over the course of a year, based on physician clinical assessment. This decreased injection frequency, with respect to usual practice, may reduce the burden associated with botulinum toxin treatment for patients and their caregivers/families.
F5: Effect of the Gait Imagery Related Supplementary Motor Area Facilitation Using Functional Near-Infrared Spectroscopy Mediated Neurofeedback on Poststroke Balance and Upper Limb Function
Masahito Mihara
1,2, Hiroaki Fujimoto2,3, Hironori Otomune2,3, Noriaki Hattori2,3, Yoshiyuki Watanabe2, Teiji Kawano3, Megumi Hatakenaka3, Hajime Yagura3, Ichiro Miyai3, Hideki Mochizuki2
1Kawaqsaki Medical School, Kurashiki, Japan; 2Osaka University, Suita, Japan; 3Morinomiya Hospital, Osaka, Japan
Background: Neurofeedback is a novel neuromodulative technique and several studies suggested its therapeutic effect on motor recovery after stroke. We have developed functional near-infrared spectroscopy (fNIRS) mediated neurofeedback system and revealed its therapeutic effect on upper limb function when it applied for lateral premotor activation during motor imagery. We also revealed that neurofeedback facilitation of the supplementary motor area (SMA) has beneficial effect on balance ability in healthy subjects. Considering that the SMA suggested to be involved in various motor tasks including complex finger task, proximal arm movement, and postural control, it is not clear that the SMA facilitation can augment functional recovery of balance ability and/or upper limb function.
Objectives: To investigate the therapeutic effect of neurofeedback facilitation of the SMA on balance and upper limb function.
Methods: We have conducted the double-blinded randomized control study for poststroke gait and balance function using fNIRS-mediated neurofeedback (UMIN000010723). In this study, the target for neurofeedback facilitation is the SMA activation during motor imagery. Subacute 43 subcortical stroke patients (59.8 ± 11.3 years, 115.0 days from onset) participated. Besides the usual rehabilitation up to 180 min/day, they participated in 6 sessions of motor imagery training of balance task concurrent with SMA neurofeedback. Clinical measures including Berg Balance Scale (BBS), 3-m Timed Up-and-Go test (TUG), and Fugl-Meyer motor assessment score (FMA) were assessed. Subjects are randomly assigned to REAL and SHAM groups. For upper limb functional recovery, we also compared these data with previous pilot randomized control trials investigating the effect of the lateral premotor facilitation by fNIRS-mediated neurofeedback.
Results: Baseline clinical characteristics were comparable. There was significant interaction between gait and balance measures including BBS and TUG with significant improvement in the REAL group. But there was no significant interaction for FMA upper score. Only the REAL group showed significant increase of imagery related SMA activation. There was significant difference between the FMA upper limb score gain between the REAL group data of this study and the REAL group of the previous study.
Conclusion: Our findings confirmed the feasibility and efficacy of fNIRS-NFB on poststroke gait and balance recovery, but not on upper limb function. In addition to the neuromodulation effect, it is possible that fNIRS-mediated neurofeedback might enhance the efficacy of the concurrent mental practice-based intervention.
F6: Transcranial Direct Current Stimulation Effects on Cerebral Blood Flow and Motor Learning
Anant Shinde
1,2, Fanny Munsch1,2, David Alsop1,2, Gottfried Schlaug1,2
1Harvard Medical School, Boston, MA, USA
2Beth Israel Deaconess Medical Center, Boston, MA, USA
Reports have shown that anodal stimulation leads to an increase in cortical excitability in targeted brain regions. Modulation in cortical excitability seems to covary with changes in regional cerebral blood flow. Our aim was to determine whether transcranially applied direct current stimulation (DCS) would lead to local and remote changes in regional cerebral blood flow, which would establish rCBF as a surrogate marker of tDCS’ modulatory effects. We are reporting the results of ongoing studies to characterize brain imaging and associated behavioral motor learning effects varying dose and electrode montage of tDCS. Twelve healthy right-handed subjects (5 females and 7 males) have participated in the experiments so far. For the behavioral as well as for the imaging studies, we used 3 different dose levels (Sham, 2 mA, and 4 mA corresponding current densities: 0 mA/cm2, 0.156 mA/cm2, and 0.318 mA/cm2) and 2 different electrode montages (unihemispheric or bihemispheric) to examine tDCS effects on a finger sequence learning task and on regional cerebral blood flow (using Arterial Spin Labeling as a Blood Flow MR sequence) and an MR compatible NeuroConn DCMC stimulator. An anodal electrode (diameter 4 cm) was placed over the right motor region (C4) while the cathodal electrode (diameter 5 cm) was either placed over the left supraorbital region (unihemispheric montage) or over the left motor region (C3; bihemispheric montage). The resulting images were analyzed with SPM12 and its toolbox CAT12. First and second level analyses were performed in an OFF-ON-OFF (6 min-10 min-8 min) paradigm. A significant difference (P < .05 unc) in cerebral blood flow between ON and OFF conditions was seen for the group in a region of interest including the perirolandic region on the right (targeted with anodal stimulation) showing a linear increase in rCBF between sham, 2 mA, and 4 mA. There was also a minimal effect in the left hemisphere for the 2 mA and 4 mA conditions. In general, the bihemispheric montages showed stronger bihemispheric effects than the unihemispheric montages. In the finger sequence learning task, subjects were asked to type a randomly chosen sequence of 7 digits with digits 2 to 5 of each hand several times before and immediately after the 10-minute stimulation. Numbers of correct sequences typed by participant were counted before and after stimulation, and percentage change in the correct number of sequences is calculated. Repeated-measures ANOVA with the percentage change data for right-hand stimulation showed a significant effect on the left-hand performance after stimulation. Furthermore, for both electrode montages, left-hand performance shows a positive trend in performance improvements with increasing stimulation current. Overall, we hope to demonstrate that increasing doses of tDCS (up to 4 mA) is safe and tolerable and reveals linear effects in response when compared to 2 mA and Sham condition in both the regional blood flow response and the finger sequence learning effect.
F7: Toward Real-Time Prediction of Freezing of Gait in Parkinson’s Disease Using Spectral and Temporal Features From Acceleration of Lower-Body Segments
Nader Naghavi
1, Eric Wade1
1University of Tennessee, Knoxville, TN, USA
Parkinson’s disease (PD) is the most common form of parkinsonism and results from a progressive loss of dopaminergic neurons degenerating the nervous system of a patient over time. Freezing of gate (FoG), a form of akinesia, is sudden and transient loss of voluntary movement, and is the main risk factor for falling, negatively affecting mobility and independence, and resulting in emotional stresses and reduced quality of life. The current study tests a new hypothesis for prediction of FoG episodes during activities of daily living. The prediction results can be used to trigger stimuli to prevent FoG occurrence. Frequency Index (FI) and mean of wavelet transform coefficients (WT) have shown to be able to discriminate between walking and freezing. In this study, we also used the number of peaks (NP) in a window of the acceleration signal that can be related to higher frequency harmonics. We hypothesized that changes in the values of spectral and temporal features over successive sliding windows of recorded signals can reflect FoG occurrence. In this method, the starting point of a window is marked as FoG onset if there is a statistically significant difference, as determined by one-way ANOVA, between the 2N preceding windows (2 groups of N samples). The system was required to identify FoG in the range of 1 second before (predict FoG) to 1 second after (detect FoG) the actual FoG onset in order to report it as a correct recognized FoG event. We validated the proposed approach on the public available DAPHNet data set, which contains data collected from 8 PD patients who experienced FoG during the experiment. Data were recorded using three 3D accelerometers attached to the shank, thigh, and lower back. Subjects completed 3 walking tasks: (1) walking in a straight line including several 180-degrees turns; (2) random walking with a series of 360-degrees turns; (3) walking simulating real-world activities. The DAPHNet data set contains 237 FoG episodes labeled by physiotherapists using synchronized video recordings. The duration of FoG episodes ranged from 0.5 to 40.5 seconds (mean 7.3 seconds, SD 6.7 seconds). The results obtained for window length of 2 seconds, update time of 0.25 seconds, and total number of windows (2N) of 6 showed the strongest agreement with the physicians using NP of the vertical axis of the sensor at hip (73.4% sensitivity, 84.8% specificity), majority voting of FI from the vertical axis of the 3 sensors (82.7% sensitivity, 84.5% specificity), and majority voting of WT from the frontal axis of the 3 sensors (81.4% sensitivity, 80.5% specificity). The system also predicted 75%, 71%, and 71% of events before FoG occurrence, respectively. The results suggest that real-time prediction of FoG may be realized by using analysis of variance of gait features over successive windows of data.
F8: Increased Resting Motor Network Connectivity Is Associated With Positive Outcomes in Chronic Stroke
Daniel Lench
1, Akash Mishra1, Colleen Hanlon1
1Medical University of South Carolina, Charleston, SC, USA
Introduction: Functional outcomes for patients with chronic stroke are highly variable. While there are many health factors that contribute to this variance, one of the primary factors may be differences in neural reorganization of the motor network. The purpose of this study was to evaluate the impact of chronic stroke on motor network reorganization in patients with upper extremity impairment and age-matched controls. Consistent with previous theories regarding cortical compensation poststroke, we tested the hypothesis that better upper extremity Fugl-Meyer Scores would be associated with higher levels of functional connectivity within stroke participants, even when adjusting for stroke volume.
Methods: Resting state functional connectivity was collected from 53 individuals (36 chronic stroke patients with upper extremity motor deficits and 17 age-matched controls [with risk factors for stroke]). Lesions were manually defined (MRIcron) for each individual on a high-resolution T1 scan acquired immediately before the resting state fMRI data. Strong test-retest reliability of lesion volume between raters was determined using an interclass correlation coefficient. Functional connectivity analysis within the motor network (eg, primary motor cortex, SMA, pre-SMA, and pre-motor cortex [PMd/PMv]) was performed using Matlab-based software (CONN and SPM12). BOLD (blood oxygen level dependent) time course correlation coefficients between motor network ROI pairs were converted to Fisher z-scores and then averaged to obtain an overall motor network connectivity score for each participant. Pearson correlations between connectivity and motor performance were performed using SPSS Statistics (v24).
Results: Overall, there was no significant difference in average corticomotor network connectivity between the controls and the chronic stroke patients. Laterality analysis demonstrated that stroke patients had significantly less cross-hemisphere motor network connectivity (t = 4.828, P < .001). Among stroke patients, higher overall motor network connectivity (within and between hemisphere) was correlated with higher Fugl-Meyer score (r = 0.44, P < .05). Additionally, greater Fugl-Meyer score was correlated with greater connectivity between left and right SMA (P < .05), M1 and PMv (P < .05), and PMd and SMA (P < .05).
Conclusions: These results demonstrate that, while between-hemisphere connectivity is decreased in chronic stroke patients, overall there is no significant difference in resting state corticomotor connectivity in these upper extremity patients relative to controls. Furthermore, those individuals with the best functional motor outcomes appear to have the highest levels of connectivity. In aggregate these data support a body of evidence that suggests that stroke disrupts the ability for the left and right motor network to communicate properly and that overall motor network connectivity during rest may reflect the degree of motor impairment. Ultimately, these results indicate that resting state connectivity within the cortical motor network may be a useful neurobiological outcome measure to evaluate therapeutic interventions in chronic stroke.
F9: Predictors of Recovery From Acute Aphasia
Julius Kernbach1, Andrea Norton2, Karen Chenausky3, Sarah Marchina1,
Gottfried Schlaug
1
1Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA2Beth Israel Deaconess Medical Center, Boston, MA, USA3Boston University, Boston, MA, USA
Making accurate predictions about a stroke patient’s language/speech-motor outcome and recovery potential is a challenge. We previously showed that a combined variable of lesion site and size pertinent to relevant white matter language structures, the Arcuate Fasciculus lesion load (AF-LL), correlated highly with measures of speech fluency in chronic aphasic patients. Studies in motor recovery and other domains have shown that behavioral measures in the acute stroke phase might be equal or even better predictors of recovery than lesion measures. Thus, the aim of our study was to determine whether lesions measures (eg, the AF-LL) or structural and functional assessments of the unimpaired right hemisphere would add to language/speech motor assessments in the acute stroke phase in predicting recovery and outcome of language functions. Over a period of several years, patients presenting with acute aphasia were evaluated using a bedside version of the Western Aphasia Battery (WAB) complemented by picture naming tests, automatic speech measures, and a custom-made test assessing words/phrases in a spoken and sung mode. A total of 100 acute patients were assessed of which 60 were followed-up at 3 months for outcome assessments. Lesion maps drawn on diffusion-weighted images were used to calculate lesion loads of probabilistic language/speech-motor tracts (eg, Arcuate Fasciculus [AF], Extreme Capsule Fiber Tract [EMC], Uncinate Fasciculus [UF], and Frontal Aslant Tract [FAT]). Analyses included correlations between recovery potential and actual recovery and other predictors of 3 months outcome. Confounding measures, including lesion size, time between the onset of stroke and follow-up, and patients’ age, were removed by linearly regressing out their effects from all analyses. We used a 10-fold cross-validation to validate and assess the algorithm’s prediction performance. For this purpose, the sample was randomly divided into 90% training data for model fitting and 10% testing data for empirical model evaluation. The acute WAB score was a very good predictor of chronic WAB score at 3 months explaining about 50% of the in-sample and 40% of the out-of-sample variance. This predictor was improved when any of the lesion-load measures were added to the model with the AF-lesion load adding the most improvement. Further model improvements were achieved when a structural measure of right hemisphere tract integrity (the right hemisphere FA values of the AF), and a measure of right hemisphere function, the speaking-singing dissociation score, were added to the model. Language and speech-motor outcome after stroke can be predicted by a multivariate model using structural and functional information from both the lesional and contralesional hemisphere obtained in the acute stroke phase. These models can explain more than 80% of the out-of-sample variance in outcome at 3 months.
F10: Clinical Translation of Early Clinical and Neuroimaging Biomarkers to Predict Upper Extremity Stroke Motor Recovery
David Lin
1, Alison Cloutier1, Samuel Snider1, Fabio Giatsidis1, Jessica Ranford1, Kristin Parlman1, Susan Fasoli2, Teresa Kimberley2, Steven Cramer3, Seth Finklestein1, Leigh Hochberg1
1Massachusetts General Hospital, MA, Boston, USA2MGH Institute of Health Professions, Boston, MA, USA3University of California Irvine, Irvine, CA, USA
Background: Recovery of upper extremity motor impairment is critical for functional independence after stroke. Clinical, neuroimaging (ie, magnetic resonance imaging [MRI]), and neurophysiological (ie, transcranial magnetic stimulation [TMS]) assessments are being developed to provide predictions of upper extremity motor recovery after stroke. However, not all clinical centers have access to the technology required, and unpredictable length of stay and follow-up in the current post-acute care continuum make validation of these predictors challenging. More detailed, longitudinal predictors of upper extremity motor impairment, as well as an understanding of how recovery generalizes across International Classification of Functioning (ICF) domains, are needed to accurately capture stroke outcomes and better personalize rehabilitation. Here our aim is to define robust and clinically translatable predictors of motor recovery before discharge from the acute stroke admission and to understand how upper extremity motor recovery generalizes across ICF Domains in the first 3 months after ischemic stroke.
Methods: We enrolled 50 participants (n = 50) with unilateral arm weakness after an ischemic stroke in an ongoing single-center, prospective, observational cohort study at an academic tertiary care center in Boston, Massachusetts. Assessments were performed during the acute stroke hospitalization, as well as in follow-up at 6 weeks and 3 months. These spanned WHO ICF domains for loss of body structure-function (arm impairment—grip strength and Fugl-Meyer arm motor assessment [FMA-UE]; globally, NIH stroke scale [NIHSS]), activity limitations (arm impairment, Box and Blocks, 9 Hole Peg; globally, Barthel Index and modified Rankin Scale), and participation restrictions (Stroke Impact Scale and PROMIS-10). Neuroimaging (MRI and CT images), acquired as part of the clinical standard of care, were analyzed for lesion mapping.
Results: Preliminary results demonstrate that participants with mild-moderate initial impairment (FMA-UE > 22) recover to approximately 70% of their available recovery at 3 months, confirming the proportional recovery rule of stroke motor impairment. In participants with severe initial impairment (ie, baseline FMA-UE < 22), pre-discharge NIHSS (t-test, P < .05) and injury to the corticospinal tract (t-test, P < .01) independently distinguished those who recover proportionally from those who do not. Proportional recovery generalized to measures of Grip Strength as well as activity measures (Box and Blocks and 9-Hole Peg) but not to measures of participation. In n = 32 participants with follow-up data at both 6 weeks and 3 months, 98% of the variance in motor impairment and activity measures at 3 months could be explained at 6 weeks.
Conclusions: Our findings suggest that clinical assessments and neuroimaging performed before discharge from the acute stroke hospitalization can predict upper extremity motor recovery at 3 months. Proportional recovery of motor impairment generalized to activity domains of the ICF. The majority of spontaneous motor recovery occurred within the first 6 weeks, calling into question traditional time points for stroke recovery trials.
F11: Grey Matter Hypertrophy in the Right Hemisphere Explains Variance in Speech-Motor Outcomes in Chronic Aphasia
Sebastien Paquette
1, Andrea Norton1, Gottfried Schlaug1
1Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
Although the specific neural mechanisms underlying poststroke recovery of speech-motor function have yet to be empirically defined, 2 prominent hypotheses inform our current understanding: (1) the perilesional hypothesis suggesting recruitment of healthy perilesional cortex forms a new network of regions in the affected hemisphere and (2) the “right-shift” hypothesis proposing engagement of homotopic regions in the undamaged right hemisphere facilitate recovery of speech-motor function, or a combination of the two. The right-shift hypothesis is based on the neural redundancy theory that both hemispheres are capable of supporting speech-motor function; however, the degree to which this right-hemisphere shift occurs after damage to the left depends on specific factors (eg, size, extent, and site of lesions). Some studies have suggested that right-hemisphere involvement in recovery is actually maladaptive or ineffective. Using voxel-based morphometry, we aimed to test the notion that gray matter volume in the right hemisphere is significantly associated with speech outcomes in chronic aphasia, and thus, provide further evidence for beneficial right-shift adaptations. An initial sample of 48 left-hemisphere stroke patients with aphasia underwent speech assessments using an adapted version of the Western Aphasia Battery and the Boston Naming Test. T1-weighted images were acquired for all patients and voxel-based morphometry (as implemented in CAT12) was used to determine whether local gray matter volume in the right hemisphere explained variance in speech outcomes. The effects of specific treatments (ie, Melodic Intonation Therapy and Speech Repetition Therapy) on gray matter volume were also evaluated in subsamples of the group. After controlling for demographic factors, gray matter volumes in portions of the right inferior parietal cortex and right middle/superior temporal gyrus, as well as portions of the superior cerebellum on the left more than the right side positively correlated with a speech fluency measure derived from picture descriptions (as measured by Correct Information Units), and scores on the Boston Naming Test. These findings suggest that right-hemisphere gray matter structures can be utilized to support speech-motor function in patients with chronic aphasia. Although it is possible that the premorbid natural development or hypertrophy of these structures may facilitate poststroke aphasia recovery, it is highly probable that intense therapy and practice after a left hemisphere stroke might lead to structural adaptation in right-hemisphere homotopic structures as well as in the cerebellum on both sides to support functions of speech production. Ongoing longitudinal research examines whether or not the detected right hemisphere gray matter differences in the current cross-sectional analysis are indeed the result of intense poststroke therapy.
F12: Differential Effects of Low-Frequency rTMS on Cortical Excitability and Inhibition in Aged Healthy Participants
Lauren Edwards
1, Miles Wischnewski1, Deborah Barany1, Isabelle Vernon1, Daniel Drake2, Gerry Hobbs3, Cathrin Buetefisch1
1Emory University, Atlanta, GA, USA
2Columbia University, New York, NY, USA
3West Virginia University, WV, Morgantown
Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of the primary motor cortex (M1) alone, or when combined with training, induces functional changes at both the stimulated location and in remotely connected cortical areas. Level B evidence supports the use of LF-rTMS over the contralesional M1 for the treatment of hemiparesis in stroke patients, an effect that may be mediated through interhemispheric connections with the nonstimulated (ipsilesional) M1. However, the results are variable and the biological substrate underlying these therapeutic effects remains controversial. Furthermore, the majority of current evidence is limited by the young age of the studied populations, the restriction of studying effects in either the stimulated M1 or nonstimulated M1, and the small number of studies investigating interhemispheric interactions. The objective of the present study is to determine the effects of LF-rTMS on both the stimulated and nonstimulated M1’s excitability and interhemispheric inhibition (IHI) in an older healthy population. Nineteen right-handed healthy older adults (59.6 ± 6.3 years old, 13 women) with normal cognition and brain structure participated. All participants underwent 3 LF-rTMS experiments where rTMS was applied at 1 Hz (15 minutes, 900 pulses) over their left M1. rTMS intensity was 1 of 3 conditions: sham stimulation using a placebo coil, rTMS at 80% of resting motor threshold (RMT), or rTMS at 90% of RMT. Motor evoked potentials (MEPs) were collected using electromyography from both the left and right extensor carpi ulnaris muscles. We used single- and paired-pulse TMS to assess cortical excitability and intracortical inhibition pre and post LF-rTMS. Stimulus response curves (SRC) were collected, plotted, and the Boltzmann function was fitted to the curves with the following parameters extracted: maximum MEP amplitude, the inflection point, and growth rate parameters. To measure short-interval intracortical inhibition (SICI), a test stimulus (TS) of 120% of RMT was preceded by a conditioning stimulus (CS) at either 60% or 80% RMT with an interstimulus interval (ISI) of 2 ms. SICI was expressed as the ratio of conditioned to unconditioned TS pulses. For IHI, a suprathreshold CS was applied to one M1 followed by a second suprathreshold TS applied to the other M1 at an ISI of 10 ms. IHI was expressed as the ratio of conditioned to unconditioned TS. Preliminary results demonstrate differential effects of LF-rTMS depending on its intensity and stimulation site (stimulated vs nonstimulated M1) for the 3 SRC curve parameters. Analysis of SICI and IHI show no significant differences of either LF-rTMS intensity when compared to sham. These preliminary results suggest that small differences in the intensity of LF-rTMS affect the input/output function of the stimulated and nonstimulated M1s differently but do not change interhemispheric inhibition between both M1s.
F13: A Novel Method for Quantifying Interlimb Coordination in Persons With Hemiparesis Poststroke
Susan Duff
1, Aaron Miller2, Lori Quinn3, Lauri Bishop3, Gregory Youdan3, Heather Ruthrauff4, Eric Wade2
1Chapman University, Irvine, CA, USA
2University of Tennessee, Knoxville, TN, USA
3Teachers College, Columbia University, New York, NY, USA
4Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Background: Upper extremity (UE) interlimb coordination is essential to the successful performance of daily tasks. Individuals with hemiparesis poststroke often have difficulty performing these tasks due to limb weakness and motor control impairments. The purpose of this study was to develop a quantitative measure of UE interlimb coordination capable of discriminating between unimanual (U), bimanual symmetric (BS), and bimanual asymmetric (BA) task performance. Our long-term goal is to use this method of analysis to accurately measure recovery and change with intervention in persons with hemiparesis poststroke.
Methods: Twenty adults poststroke and 20 age-matched controls performed 6 seated manual tasks twice while wearing 5 APDM Opal inertial sensors (Portland, OR) on the wrists, upper arms, and chest. Raw sensor data measuring acceleration, angular rate of change, and magnetism were compared across 3 metrics (peak-to-peak amplitude, time, and frequency), then combined to create one similarity metric. A novel algorithm examined similarity based on sensor location for each task type and group. In our preliminary analysis we focused on 3 of 10 comparisons between sensor locations: wrist to sternum; wrist to upper arm; and primary to secondary upper arms. We compared outputs for these comparisons based on sensor location for controls across task type using a one-way Friedman test followed by a post hoc Wilcoxon signed rank test. We looked for differences between persons poststroke and controls for the 3 comparisons based on task type, using Mann-Whitney U tests.
Results: For controls, significant differences were noted between the 3 task types for comparisons between the wrist to sternum (χ2(2) = 12.1,P = .002), the wrist to upper arm (χ2(2) = 46.3, P < .001), and between the 2 upper arms (χ2(2) = 24.2, P < .001). Significant differences were found between controls and persons poststroke for comparisons between the wrist to sternum for unimanual tasks (U: P < .001, BA: P = .68, BS: P = .70); the wrist to upper arm for unimanual and bimanual symmetric tasks (U, BS: P < .004, BA: P = .075), and between the upper arms for unimanual and bimanual symmetric tasks (U: P = .03, BA: P = .075, BS: P = .012).
Discussion and Conclusion: Findings indicate that this assessment and data processing algorithm quantitatively discriminates between tasks based on 3 comparisons of sensor location among controls and differentiated task performance between controls and persons poststroke. Expansion of our analysis to 10 sensor locations should allow accurate assessment of features of interlimb coordination in persons with hemiparesis poststroke, often viewed as compensatory such as greater trunk involvement and reduced amplitude of motion. The strength of this approach will be evident when we use all sensor locations and compare the similarity metric to clinical outcome measures in a larger sample.
F14: Proprioception After Stroke: Examining Diffusion Properties in Sensory and Motor Pathways
Sonja Findlater
1, Erin Mazzerole1, G. Bruce Pike1, Sean Dukelow1
1University of Calgary, Calgary, Canada
Proprioception, the awareness of limb position and movement, underpins coordinated, timely, and efficient movement. Proprioceptive deficits are present in 50% to 70% of stroke survivors. These deficits have been associated with increased time in hospital and poor motor recovery. Unlike the motor system, however, where a relationship between lower fractional anisotropy (FA) of the corticospinal tract (CST) and poor motor performance has been established, little is known about proprioceptive deficits and FA of the sensory tract. We hypothesized that lower FA in the dorsal column medial lemniscus tract (DCML) would be associated with poorer proprioception. To address this question, subjects with primarily subcortical stroke (n = 17) were assessed at 1 and 6 months poststroke. We examined proprioception with 2 mirror-matching tasks conducted in an exoskeleton robot. With the subject’s vision occluded, a position matching task assessed static arm position sense and a kinesthetic matching task assessed awareness of arm movement. Motor performance was quantified using a center-out visually guided reaching task (VGR). Within 1 week of the robotic assessment, subjects underwent MRI scans during which a 90-direction diffusion sequence was collected (b-value = 1000). FSL software was used for preprocessing and probabilistic tractography. The DCML was tracked between an atlas-based postcentral gyrus seed and a manually defined medial lemniscus seed. The CST was tracked between an atlas-based precentral gyrus seed and a manually defined seed in the anterior pons. In each subject, mean FA for the affected hemisphere was calculated for both tracts. Preliminary results reveal that 70%, 53%, and 65% of subjects had position matching, kinesthetic matching, and reaching deficits, respectively, at 1-month poststroke. This improved to 35%, 23%, and 58%, respectively, at 6 months poststroke. Lower CST FA values at 1-month correlated with poorer 1-month and 6-month motor scores (r = −0.69, P < .05; r = −0.51, P < .05). While lower FA values corresponded to poor performance on the robotic proprioceptive tasks in the majority of subjects, a subset of individuals (n = 4) with average to above average (for the sample) DCML FA and poor proprioception scores was identified. Each of these subjects had lesions that overlapped with Heschl’s gyrus and 2 had lesions that also overlapped with the supramarginal gyrus, areas previously identified as important for proprioceptive processing. Our findings indicate that the relationship between lower DCML FA and proprioception may not be as straightforward as that observed between CST FA and motor performance poststroke. This supports the concept that a distributed network of brain areas is required to process sensory percepts like proprioception. These findings have implications for prognosis and treatment of proprioceptive deficits poststroke.
F15: Alterations in Cortical Excitability and Motor Skill Practice Following a 3-Month Aerobic Exercise Program in Individuals With Parkinson’s Disease
Jason Neva
1, Bimal Lakhani1, Matthew Sacheli2, Nicole Nielson2, Jassamyn McKenzie2, A. Jonathan Stoessl2, Lara Boyd1
1University of British Columbia, Vancouver, Canada2Parkinson’s Research Center, Vancouver, Canada
Purpose: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by several clinical symptoms. Individuals with PD show diminished motor function, neuroplasticity-like responses, and altered cortical excitability. Aerobic exercise (AEX) can improve PD-related symptoms like bradykinesia, impaired balance, and increased cognition function. In young healthy people, acute AEX enhances motor skill learning, enhances response to paired-associative stimulation (PAS)-induced plasticity, and modulates intracortical excitability. Currently, it is not known whether participation in an AEX program improves clinical symptoms, motor skill learning, response to PAS, and modulates intracortical excitability in individuals with PD. Here, we aimed to determine the effects of a 3-month AEX program on motor skill practice, response to PAS-induced plasticity, and intracortical excitability compared to a stretching control (CTRL) program.
Methods: Twenty-four participants with mild to moderate PD (pre-mean ± SD Unified Parkinson’s Disease Rating Scale [UPDRS] = 24.8 ± 6.9) took part in the study (AEX n = 13, CTRL n = 11). Participants underwent clinical assessment (UPDRS), motor skill practice of a continuous tracking task (CTT), and measures of corticospinal and intracortical excitability using transcranial magnetic stimulation (TMS) before and after the AEX or CTRL intervention. Corticospinal and intracortical excitability was assessed with TMS over the less affected primary motor cortex (M1) before and after PAS. PAS consisted of 200 paired stimuli over the median nerve followed by a TMS pulse over M1 25 ms later. CTT practice was performed with the less affected thumb for 25 minutes, and involved repeated and random sequences to distinguish sequence-specific skill acquisition and non–sequence-specific motor control. Motor evoked potentials were measured from 90% to 140% (10% increments) of resting motor threshold. Short-interval intracortical inhibition (SICI) and intracortical facilitation measured inhibition and facilitation, respectively.
Results: Individuals in the AEX intervention performed better at the CTT for random sequence motor control (P = .03), with no difference between AEX and CTRL for the repeated sequence. We found greater corticospinal excitability following PAS (P = .046) in both groups, with no difference after the 3-month AEX or CTRL programs. We noted a trend toward greater corticospinal excitability following the AEX intervention (P = .07). Interestingly, SICI decreased following the AEX program (P = .02), but not following the CTRL (P = .33). Finally, decreased SICI was associated with improved performance at the CTT following AEX (r = −0.622, P = .04) but not the CTRL intervention. No significant change was observed in UPDRS.
Conclusions: These findings suggest that a 3-month AEX program can enhance motor control performance of a skilled motor task, maintain corticospinal excitability, and decrease intracortical inhibition. These findings have potential implications for improving clinical symptoms and the altered cortical excitability associated with PD. However, further analysis is required to understand the neurophysiological and structural mechanisms underpinning the potential benefits of AEX for individuals with PD.
F16: Effects of Different Transcranial Direct Current Stimulation Devices on Motor Cortical Excitability
Aviroop Dutt-Mazumder
1, Scott Brown1, Aastha Dharia1, Amanda Vogel1, Reesha Talati1, Adam Gardi1,
Chandramouli Krishnan
1
1University of Michigan, Ann Arbor, MI, USA
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique in which low-amplitude electric currents are delivered to the brain via specific sites on the scalp. This electric current is purported to alter neuronal resting membrane potential and subsequently modulate cortical excitability. Over time, researchers have found numerous applications for tDCS including treatment of various neurological (eg, stroke, cerebral palsy, etc) and neuropsychiatric (eg, depression, anxiety, etc) disorders. However, a number of researchers have also shown that responses to tDCS are highly variable. It is possible that the differences in devices used in these studies could explain some of the observed variability. Hence, this study aimed at determining the effect of 2 different tDCS devices (Empi Dupel Dual Channel Iontophoresis; Isokentics Inc, AR, USA) and Soterix 1x1 (Soterix Medical, NY, USA) on motor cortical excitability of the quadriceps muscles. Twenty neurologically intact young adults participated in this crossover study. Subjects received anodal tDCS over their dominant leg (preferred kicking leg) motor cortex for 15 minutes on 2 different days that were separated by at least 48 hours. The tDCS devices were interchanged during these testing sessions and the device order was randomized. Motor cortical excitability of the quadriceps muscle was evaluated both before and after the tDCS by measuring the participant’s recruitment curve (ie, the relationship between stimulus intensity and the evoked MEP torque) generated by stimulating the quadriceps “hotspot” at various intensities (70% to 140% of active motor threshold) using transcranial magnetic stimulation (TMS). The recruitment curve was fitted with a Boltzmann sigmoidal function (Levenberg-Marquardt algorithm in LabVIEW) to determine the parameters relating to motor cortical excitability: (1) maximal MEP torque size (MEPmax), (2) curve slope (k), and (3) stimulus intensity leading to half-maximal MEP torque size (S50). The results indicated that there were no changes in MEPmax, slope (k), and S50 before and after tDCS for both tDCS devices (P > .05). These results suggest that variability in tDCS-induced motor cortical excitability changes are not explained by the differences in the tDCS units. The findings of this study have meaningful implications for interventions using tDCS as an adjuvant tool for neurorehabilitation.
F17: The Potential of Exercise Combined With an Exercise Mimetic Drug to Promote Functional Recovery Following Hindlimb Stroke
Matthew McDonald
1,2, Anthony Carter2, Angela Dykes1,2, Matthew Jeffers1,2, Florance Franko1, Baptiste Lacoste1,2,3, Dale Corbett1,2
1University of Ottawa, Ottawa, Canada2Canadian Partnership for Stroke Recovery, Ottawa, Canada3Ottawa Hospital Research Institute, Ottawa, Canada
Many stroke survivors have gait deficits that greatly limit activities of daily living, yet most preclinical research to date has predominantly targeted forelimb impairments. A major barrier to intensive rehabilitation, such as aerobic exercise, is the rapid deterioration in cardiovascular fitness and muscle strength that occurs following stroke. Currently, exercise guidelines for stroke survivors suggest combining aerobic exercise with resistance exercise to circumvent muscular atrophy. Resveratrol (Resv), a naturally occurring exercise mimetic commonly found in a variety of foods (ie, grapes, blueberries, peanuts, and red wine), is known to exert similar benefits as exercise (ie, attenuate deconditioning, decrease inflammation, promote vascular plasticity, etc). Using a cold light photothrombotic stroke model, we investigated whether a combination of aerobic and resistance exercise, similar to what is prescribed clinically, with/without Resv, could restore physical fitness levels and promote recovery of hindlimb deficits. First, we developed a photothrombotic stroke model that produced consistent hindlimb deficits and abnormal gait in Sprague-Dawley rats. Additionally, within mixed-glycolytic skeletal muscle in the affected hindlimb, we found selective atrophy of oxidative muscle fibers. Next, to assess the efficacy of the combination exercise regime and Resv treatment, 40 female Sprague-Dawley rats were given a photothrombotic stroke targeting the hindlimb representation of the motor cortex. Resv or vehicle was delivered daily for 3 weeks (5 mg/kg ip), beginning 24 hours poststroke. Exercise rehabilitation was initiated 10 days poststroke and occurred for 5 weeks. The exercise rehabilitation consisted of progressive treadmill exercise and a weighted ladder climbing task, designed to model resistance exercise in humans. Functional recovery following stroke was assessed using a beam walking task, kinematic assessment of gait, and peak oxygen consumption (VO2) during a maximal exercise test. Infarct volume was similar across experimental groups, as measured by magnetic resonance imaging (MRI). Rats that received the Resv regime showed reduced forelimb and hindlimb impairments on the beam walking task 1 week poststroke and throughout recovery. Furthermore, rats that received the exercise rehabilitation showed significantly greater recovery on the beam walking task than rats that remained sedentary throughout their recovery. Peak VO2 levels on a progressive exercise test continually decreased over time poststroke, suggesting cardiovascular and skeletal muscle deconditioning. However, rats that received the exercise rehabilitation were able to attenuate further decreases in peak VO2 during the maximal exercise test and ran greater distances until exhaustion. Both Resv and the exercise rehabilitation had unique advantages, with Resv reducing immediate poststroke impairments and exercise producing a greater degree of functional recovery. Additionally, the potential role of vascular plasticity in facilitating these benefits was investigated. This proposed experimental approach has a high translational potential to significantly increase both the rate and level of motor recovery in stroke patients.
F18: Proportional Recovery: How It Arises and Implications for Stroke Rehabilitation
Merav Rachel Senesh1,
David J. Reinkensmeyer
1
1University of California Irvine, Irvine, CA, USA
The Proportional Recovery (PR) Rule was first observed for upper extremity (UE) movement recovery measured with the Fugl-Meyer (FM) Score. Stroke patients evaluated at 1 week and a long-term follow-up recovered ~75% of the difference between their baseline and the maximum FM score. The finding of such regularity is suspicious. How can PR be interpreted, does it constrain what’s possible with an individual’s recovery, and what does PR mean for rehabilitation? Here, we describe insights into PR gained by analyzing it in terms of how the FM score is constructed—as a sum of subscores on test items. From this perspective, we show that the slope of the PR relationship is the mean probability of scoring on test items at follow-up (ie, if the slope is 0.75, there is a 75% chance of scoring on an item, on average, across remaining items). One can thus see that the slope relates to decisions made during scale design about how difficult items should be (and will vary somewhat with rater strictness). Furthermore, PR arises robustly when data are analyzed with global linear regression because of the smoothing properties of summed subscore type scales. If data are analyzed with local linear regression, the local slope estimate varies substantially away from 0.75. In fact, the global slope estimate is apparently “pegged” to be 0.75 by the data of less-impaired patients, which are less variable because such patients are closer to the FM ceiling of 66. To summarize, PR exists largely because higher level subjects have about a 75% chance of scoring on remaining test items at follow-up. What about “non-fitters”? We show that if a subject cannot score on a subset of test items, they will not follow PR and will become a non-fitter. We further show that these “non-fitters” are simply individuals who cannot score on items requiring hand function. If this is how fitters and non-fitters to PR arise, what does it mean for rehabilitation? First, we estimate that ~40% of all patients vary by more than the Minimal Clinically Important Difference (MCID = 5 patients) from the PR prediction (these are people with baseline FM scores < 30), leaving room for a rehabilitation effect. Second, we analyzed a set of UE chronic phase rehabilitation trials (robotic and conventional therapy) recently reported in a systematic review. Counterintuitively, the better-recovered non-fitters (FM chronic score [21-44], ~12% of patients) exhibited significantly enhanced response to rehabilitation, at a level above the UE FM MCID. We suggest that PR is interpretable in terms of scale construction, is not exactly proportional, breaks down when the hand does not recover, leaves clinically significant levels of variability unexplained, and has unexpected utility for identifying a select group of hyperresponders to UE rehabilitation.
F19: Cortical-Cerebellar Excitability Changes During Visuomotor Adaptation in Individuals With Middle Cerebral Artery Stroke and Healthy Older Individuals
Samantha Feldman
1, Katlyn Brown2, Julia Schmidt1,3, Jennifer Ma1, Jason Neva1, Lara Boyd1
1University of British Columbia, Vancouver, Canada
2University College London, London, UK
3La Trobe University, Melbourne, Australia
Introduction: The acquisition of complex motor skills shapes our behavior and ability to adapt to new and challenging environments in everyday life. Primary motor cortex (M1)-cerebellar circuitry is important in signaling errors, making it critical for sensorimotor adaptation and motor learning. M1-cerebellar circuitry can be indexed using a dual-coil transcranial magnetic stimulation (TMS) paradigm known as cerebellar inhibition (CBI), which has been shown to be sensitive to motor learning–related changes. In young healthy individuals, CBI is reduced during the early stages of practicing a visuomotor adaptation task (VMA), but returns to baseline following further VMA practice. Given the relevance of CBI to sensorimotor adaptation, M1-cerebellar excitability may be particularly relevant as an alternate neural pathway that assists with complex motor skill adaptation and learning in neuropathological populations, such as individuals poststroke. Therefore, we aimed to evaluate the impact of chronic stroke on M1-cerebellar excitability at baseline, as well as throughout a VMA task. Furthermore, we sought to understand the impact of chronic stroke on performance of the VMA task. We hypothesized that CBI would be decreased in those with MCA stroke at baseline and change less over the course of adaptation relative to healthy controls. Furthermore, we hypothesized that individuals with chronic MCA stroke would adapt to the VMA task to a lesser extent compared to healthy older controls.
Methods: Individuals with stroke (n = 14) and healthy older individuals (n = 15) completed 2 lab sessions: one session that examined CBI changes before, during, and after practicing reaching to visual targets with rotated visual feedback (VMA task) and a second session assessing savings and readaptation on the VMA task 24 hours later.
Results: For CBI, although there was no difference between groups at baseline, there was a significant reduction in CBI during VMA practice in both groups (P = .03). Interestingly, although there were no between group differences in neurophysiology, there were differences in behavior on the VMA task. Individuals with chronic MCA stroke adapted to a lesser extent on the VMA task when compared to healthy older individuals (P = .01).
Discussion: This study demonstrates that within the current sample, individuals with MCA stroke have similar changes in cortical-cerebellar excitability during VMA as healthy older individuals. The presence of cortical-cerebellar excitability changes during adaptation suggests that it may be a candidate pathway for TMS to modulate motor related networks. It would be of interest to investigate whether repetitive TMS over the cerebellum enhances motor adaptation in individuals with chronic MCA stroke.
F20: Using Exploratory Learning to Encourage Selective Hip-Knee Joint Movement in Infants Born Full-Term and Preterm
Jeongah Kim
1, Barbara Sargent1, Linda Fetters1
1University of Southern California, Los Angeles, CA, USA
Purpose: Infants born preterm (PT) are at high risk for brain damage, which may result in cerebral palsy. A primary impairment in cerebral palsy is impaired selective joint movement. Selective joint movement is the ability to isolate the movement of one joint from the movement of the other joints within the limb. Previous research shows that infants born full-term (FT), but not PT, generate more selective leg movement when playing with an infant kicking-activated mobile. To encourage infants born PT to exhibit selective leg movement, we scaffolded the kicking-activated mobile task. Our aims are to determine (1) if infants born FT and PT learn the association between their leg movement and mobile activation and (2) if infants who learn the association generate more selective hip-knee movement.
Methods: Six infants born FT and 6 infants born PT (<32 weeks gestation) participated at 4 months of age, corrected for prematurity. Each infant participated in a 10-min Scaffolded Mobile Task for 2 or 3 consecutive days. Day 1 consisted of a 2-minute Baseline “spontaneous kicking” followed by an 8-minute Mobile condition, during which the musical mobile rotated when the infant lifted either foot over an individualized threshold. Days 2 and 3 consisted of a 10-minute Mobile condition, during which the height of the threshold was systematically increased. Learning was quantified as mobile active time (MAT) ratio, the ratio of time that the infant activated the mobile during the Mobile condition on their last participation day, compared to the time that the infant would have activated the mobile during the Baseline condition. Selective hip-knee movement was quantified as the hip and knee joint angle correlation coefficient (Hip-Knee CC) of each leg movement. Mixed regression models were used to test differences in MAT ratios and Hip-Knee CCs between groups.
Results: Learning: Both the FT group and PT group demonstrated learning based on a significant increase in MAT ratio (P = .01, P = .04, respectively). Each infant was then classified as a “Learner” or “Non-Learner” based on individual learning criteria. Selective hip-knee movement: The Learner group (5 FT, 4 PT), but not the Non-Learner group (1 FT, 2 PT), demonstrated more selective movement based on a significant decrease in the Hip-Knee CC of their leg movements during the Mobile condition on their last participation day, compared to their Baseline condition (P = .002, P = .12).
Conclusions: These findings are consistent with our hypotheses that infants born FT and PT can learn the Scaffolded Mobile Task, and that infants who learn the task generate more selective hip-knee movement. Our data inform how to structure tasks to support infants born PT to generate more selective movement. This provides foundational knowledge for developing early, child-active therapeutic interventions.
F21: A Mouse Model of Perinatal Stroke That Produces Targeted Injury in Sensorimotor Cortex and Contralateral Impairments in Forelimb Function
Isabelle Takoff1, Mariana Gomez-Smith1, Julian Pitney1,
Greg Silasi
1
1University of Ottawa, Ottawa, Canada
Perinatal stroke affects approximately 1 in 1500 newborns and is the leading cause of hemiplegic cerebral palsy. The majority of cases result from ischemia and produce damage in motor centers. Given that the motor system undergoes significant postnatal development, the mechanisms and time course of impairments after perinatal stroke likely differ from adult stroke. To better understand such differences, preclinical models are needed where both functional and structural changes can be assessed longitudinally. We induced a photothrombotic stroke in the sensorimotor cortex of 7-day-old C57BL/6 pups. Infarct volume was assessed 24 hours after stroke using a 7T small animal MRI. Sensorimotor function was evaluated at 2 time points: when mice were 3 weeks old (weaned from dam) and 2 months old (adulthood). Behavioral tasks included cylinder, DigiGait, horizontal ladder, and adhesive tape removal. A mean infarct volume of 25.4 ± 2.3 mm3 produced long-term contralateral deficits when mice were assessed in adulthood. Specifically, the stroke produced significant asymmetry in spontaneous forepaw use in the cylinder task (stroke: 35.6 ± 16.8%, sham: 59.0 ± 11.0%) and PT mice took significantly longer to contact the tape on the contralateral forepaw in the adhesive tape removal task (stroke: 8.4 ± 4.5 seconds, sham: 2.6 ± 0.96 seconds) suggesting impaired sensory processing. We did not find any deficits on skilled walking in the horizontal ladder task or gait analysis. These data establish postnatal day-7 photothrombosis as an effective model for inducing targeted strokes within the sensorimotor system, thus mimicking the impairments present in children with perinatal stroke.
F22: Neural Correlate of Movement Proficiency in Infants Learning Prone Locomotion
Thubi H. A. Kolobe
1, Andrew H. Fagg2, David P. Miller2, Lei Ding2
1University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA2University of Oklahoma, Norman, OK, USA
Objective: Infants with brain insult such as cerebral palsy (CP) show early developmental delays that negatively affect later skill acquisition and learning. While research suggests that interventions that produce sustained gains tend to be those that also show changes in brain structure and functioning, the brain-behavior relationship during infant learning of complex motor skills is poorly understood. We compared changes between movement proficiency during the development of prone locomotion and brain activity in infants who are expected to show skill retention.
Methods: We used a repeated measure design with ten 4- to 5-month-old infants who were typically developing and were a part of a larger study on prone locomotion using the Self-initiated Prone Progression Crawler (SIPPC) robotic system. The study protocol involved weekly baseline recording of the infants’ brain activity for 5 minutes using a high-density EEG (124 channels) followed by videotaped training in prone locomotion on the SIPPC for 15 minutes and up to12 weeks. Movement proficiency scores were coded from the weekly videotaped performance using the Movement Observation Coding System (MOCS). The MOCS assesses postural control, arm and leg movements, and goal directed movement. Data analysis: We used repeated-measures ANOVA to analyze weekly MOCS scores and EEG power densities. The power densities were plotted spectrally and spatially. The weekly scores were averaged monthly for a longitudinal comparison.
Results: The mean MOCS motor proficiency scores increased from 28 at the beginning of the study (5 months), 50 at 6 months, 54 at 7 months to 70 by the end of the study at 8 months (P < .05). The peak frequency of the alpha band shifted toward higher frequency range. The total power within the 6 to 9 Hz range increased from 5 to 7 months (P < .05); however, the mean change between 5 and 6 or between 6 and 7 months were not statistically significant (P > .05). The frequency within the alpha band increased from 6.6 Hz at 5 months to 7.3 Hz at 7 to 8 months, despite the weekly fluctuations, suggesting that the emergence of mu rhythm peak began around 5 months of age.
F24: Acoustic Stimulation During a Daytime Nap to Enhance Sensorimotor Skill Performance in Older Adults With and Without a History of Stroke
Brian Johnson
1, Kelly Westlake1
1University of Maryland, Baltimore, MD, USA
Introduction: While neural replay during sleep enhances consolidation of individual memories, this process becomes altered during aging. Classical conditioning of an auditory cue paired with task performance followed by repetitive cue replay during sleep, known as targeted memory reactivation (TMR), has been used to enhance sleep-based consolidation in healthy young adults. We have previously demonstrated that TMR throughout overnight sleep or a daytime nap, but not daytime wake, enhanced nondominant arm throwing accuracy in healthy young adults. The purpose of the current study was to determine whether TMR throughout a daytime nap can also enhance sensorimotor performance of older healthy adults and individuals with stroke using the nondominant arm and nonaffected arm, respectively.
Method: Participants were asked to perform repetitive throwing to unique visuospatial targets, with novel auditory cues distinctively paired with each target. The primary outcome of absolute throwing error distance change score ratio was collected at 4 time points (baseline, post initial training session, post 1-hour sleep interval, and post second training session). Participants were divided into groups based on the use of TMR during the intertraining interval and history of stroke: Stroke+NoTMR (n = 4), Stroke+TMR (n = 5), NoStroke+NoTMR (n = 5), NoStroke+TMR (n = 4).
Results: Preliminary findings indicate that absolute throwing error distance remained unchanged from baseline to post second training session in both Stroke+NoTMR (absolute error change score ratio: 0.011) and NoStroke+NoTMR (0.088) groups, while there was a decrease in both Stroke+TMR (−0.285) and NoStroke+TMR (−0.167) groups.
Conclusion: Both Stroke+TMR and NoStroke+TMR groups demonstrated an overall decrease in throwing error from baseline to post second training session. These findings suggest that TMR during sleep may be able to be used to counteract age-related declines to sleep-based memory consolidation. Further data collection is underway, and future analyses will investigate sleep quality and quantity.
F25: Functional Neuroimaging Predicts Motor Recovery in Early Stroke Rehabilitation
Jessica M. Cassidy
1, Kiranjot Kaur1, Ashley K. Masuda1, Ramesh Srinivasan1, Steven C. Cramer1
1University of California, Irvine, Irvine, CA, USA
The development of valid, reliable biomarkers in stroke rehabilitation is a high priority. Since biomarkers convey underlying mechanisms driving neural repair and subsequent behavioral recovery, these measurements have the potential to benefit clinicians and researchers alike by enhancing prognostic determination for spontaneous recovery, treatment response prediction, and stratification in clinical trial settings. Biomarkers derived from structural neuroimaging, for example, percent injury to corticospinal tract (CST), are well-established and widely reported. However, biomarkers based on functional neuroimaging require additional investigation. The purpose of this study was to predict motor recovery in early stroke rehabilitation using a portable, dense-array electroencephalography (EEG) system. We hypothesized that functional EEG measurements, particularly in delta and beta frequency ranges, would significantly predict motor recovery from acute rehabilitation unit (ARU) admission to discharge and from ARU admission to 90-days poststroke. Additionally, we hypothesized that combining functional and structural (percent CST injury) measurements would best predict motor recovery in these 2 timeframes. Individuals with recent ischemic or hemorrhagic stroke admitted to an ARU completed a 3-minute resting-state EEG recording, an MRI, and a behavioral assessment involving the Functional Independence Measurement motor subscale (FIM-motor) and Upper Extremity Fugl-Meyer (UEFM). Subjects completed another EEG recording and behavioral assessment at 90 days poststroke. EEG relative power and coherence (connectivity) measures in delta (1-3 Hz) and beta (20-30 Hz) frequency bands were computed from electrodes overlying ipsilesional and contralesional primary motor (iM1 and cM1) and dorsal premotor (iPMd and cPMd) cortices and supplementary motor area (SMA). Linear regression procedures were done to assess the predictive performance of EEG alone and in combination with CST injury. Twenty-seven subjects with stroke (20 males, age 58.3 ± 14.6 years, 14.7 ± 12.8 days poststroke) participated. A subset of these individuals (n = 17) also completed a 90-day follow-up visit. Beta ipsilesional M1 coherence in electrodes overlying SMA predicted a significant percentage of FIM-motor change (R2 = 19%, P = .024). Adding a measure of CST injury to the model boosted prediction (R2 = 32%, P = .032). Beta ipsilesional M1 coherence in electrodes overlying cPMd predicted a significant percentage of UEFM change from ARU admission to 90 days poststroke (R2 = 24%, P = .048). Addition of CST injury to the model enhanced prediction (R2 = 46%, P = .033). Both beta coherence measurements outperformed a baseline measure of stroke severity (NIH Stroke Scale) (R2 < 1-6%, P > .05) and did not vary according to baseline motor impairment level, age, and time poststroke. These findings demonstrate the utility of functional neuroimaging in early stroke rehabilitation and underscore the performance of dense-array EEG in motor recovery prediction especially when combined with a motor-specific structural measure. The coherence of high-frequency neural oscillations involving ipsilesional M1 with secondary motor regions are relevant across the recovery timeframe and may represent potential treatment targets in early stroke rehabilitation.
F26: Chronic Stroke and Force: A Novel Assessment Tool
Berkenesh Gebrekristos
1, Daniel Neumaier2, Adelyn Tu-Chan1, Karunesh Ganguly1
1University of California, San Francisco, San Francisco, CA, USA; 2California State University, Maritime Academy, Vallejo, CA, USA
Background: The highly specialized use of the upper extremity necessitates multiple body systems to properly integrate. The inability to generate force is a hallmark of impaired motor function but force control and modulation is less understood. Sensory input is thought to be a critical aspect of proper force direction and control during fine motor task execution as well as the ability to individuate digits. It is thus important to develop quantitative frameworks to measure the role of impaired sensation on motor function recovery and any compensatory use of other digits in a defined task. We therefore created a new force modulation task using a custom-made grip device with embedded load sensors that measures forces exerted by each finger. Our system is referred to as the Individuated Grip Gauge Interface (IGGI). The IGGI resembles a quantitative dynamometer with 4 sensors that allow precise measurements of forces at the fingertips; we aim to use it to determine the role of sensory deficits on force modulation after stroke.
Objective: The primary goal is to understand how stereotypical forces are generated, maintained, and learned in a cohort of stroke subjects by comparing their affected and unaffected arms. We aim to better parse out the force dynamics necessary for successful execution of a motor task, like a power pinch or grasp.
Methods: Specifically, we conducted a feasibility study in 5 chronic stroke subjects with unilateral upper limb deficits and examined each subject’s ability to replicate and learn a small set of displayed patterns of forces with their index finger. The accuracy of force modulation was determined with and without visual feedback during this period of skill acquisition.
Results: There was a statistically significant increase in error of force generated when comparing subjects’ affected and unaffected arms. For lower force level tasks in the unaffected and affected arms, the RMSE is .04 (.03) and .07 (.06), P = .001 (95% CI −.05 to −.01), respectively. The RMSE is .09 (.08) and .14 (.11), P = .008 (95% CI −.08 to .01) for higher force level tasks in the unaffected and affected arms, respectively. Additionally, removal of visual feedback resulted in increased error. Interestingly, when analyzing the use of the middle digit during an index finger precision task, participants showed more coupling with their affected arm for all iterations of the IGGI task.
Discussion/Significance of Impact: We ultimately hope that the IGGI framework will allow us to determine the role of impaired sensation after stroke on motor disability.
F27: Severity-Specific Brain Stimulation for Promoting Paretic Upper Limb Motor Function in Chronic Stroke Patients
Yin-Liang Lin1, Kelsey Potter-Baker1,2, Vishwanath Sankarasubramanian3, David Cunningham2,4,5, Adriana Conforto6, Nicole Varnerin1, Xiaofeng Wang1, Ken Sakaie1, Jayme Knutson4,7, Andre Machado1,
Ela Plow
1
1Cleveland Clinic, Cleveland, OH, USA
2Louis Stokes Cleveland Department of Veteran’s Affairs, Cleveland, OH, USA
3University of Michigan, Ann Arbor, MI, USA
4Case Western Reserve University, Cleveland, OH, USA
5MetroHealth Medical Center, Cleveland, OH, USA
6Sao Paulo University, Sao Paulo, Brazil
7MetroHealth Rehabilitation Institute, Cleveland, OH, USA
Brain stimulation is conventionally delivered in patients with stroke to facilitate excitability of the ipsilesional primary motor cortex (iM1) and suppress excitability of the intact, contralesional motor cortices based on the belief that iM1 makes functionally relevant contributions to movement of the paretic upper limb, while the intact contralesional motor cortices exert persistent interhemispheric inhibition (IHI). However, outcomes of this conventional approach are favorable mainly in less-affected patients, not the severely affected. Damage to ipsilesional corticospinal pathways prevents gains in excitability necessary to achieve functional restoration. Recent evidence has suggested that severe patients can rely on undamaged contralesional motor cortices such as the contralesional dorsal premotor cortex (cPMd) for recovery. Here, we investigated whether facilitating cPMd promotes greater improvement in paretic limb movement control than conventional stimulation in severe patients, and whether this effect is opposite of that seen in less-affected patients, a finding we believed would establish severity-specific protocols of brain stimulation. Twenty-four patients with mild to severe impairment (upper extremity Fugl Meyer [UEFM] score ranging between 7 and 64) received repetitive transcranial magnetic stimulation (rTMS) to facilitate cPMd, inhibit contralesional M1 (conventional approach), and apply sham at intervals ⩾1 week. Before and after each session, patients completed tests of movement speed (reaching time or RT) and neurophysiology assessed using TMS. Eleven patients were categorized as less affected, while 13 were classified as severely affected based on cutoffs derived from our previous study. Less-affected patients showed maximum improvement in RT with conventional stimulation (P = .001), whereas severely affected patients demonstrated the greatest gains with cPMd facilitation (P = .039). Less-affected patients experienced anticipated facilitation in ipsilesional excitability with conventional stimulation (P = .027), whereas severely affected patients tended to experience gain in ipsilesional excitability with facilitation of cPMd (P = .078). cPMd facilitation reduced IHI imposed on weak iM1 in severely affected patients who failed to show any excitable response to TMS (P = .001) (indicative of near-complete damage). Improvement in RT seen with cPMd facilitation versus conventional stimulation was higher in patients with worse UEFM (r = −0.41, P = .049), poor ipsilesional active motor threshold (r = 0.49, P = .042), and weak structural integrity of pathways (r = 0.66, P = .001). These relationships were evident especially in patients with subcortical than cortical injury ([n = 17, r = −0.80, P < .001] vs [n = 7, r = −0.02, P = .975]). Therefore, we have revealed that a new approach of brain stimulation targeting the intact hemisphere can promote recovery in patients with severe deficit who fail to respond to the conventional approach. Our new approach augments inherent functional contributions made by the undamaged hemisphere. A unique finding is that facilitation of the intact hemisphere is beneficial specifically for severe patients, whereas the conventional approach is favorable mainly for the less affected. Our results carry important implications for designing clinical trials of targeted stimulation in less severe and more severe patients.
F28: Assessing the Clinical- and Laboratory-Based Criterion Validity of Four Methods for Flexion Synergy Quantification
Grace C. Bellinger
1, Michael D. Ellis1
1Northwestern University, Chicago, IL, USA
Volitional movement following stroke is often characterized by abnormal muscle activation patterns. A coupling pattern that limits reaching function is flexion synergy that manifests as the pairing of shoulder abduction with elbow, wrist, and finger flexion. Flexion synergy is quantified using kinematic/kinetic measurements, which offer direct high-resolution evaluation. Such outcomes are ideal for interventions designed to restore reaching function through the amelioration of flexion synergy. Various measurements have resulted from experimental protocols involving different limitations and therefore require evidence supporting their validity. The current study evaluated the validity of 4 previously reported measurements of flexion synergy using both a clinical and laboratory-based criterion measure. The standard clinical/rehabilitation research assessment is the Fugl-Meyer Motor Assessment (FMA), which measures movement ability in and out of synergy. The laboratory-based metric specifically measures the ability to move outside of flexion synergy by measuring reaching distance under standardized abduction loading in a robotic device. Twenty-one chronic stroke survivors (58.02 ± 10.34 years old, 7 females) participated and the cohort was 11.00 ± 6.89 years poststroke with a mean FMA score of 28.24 ± 7.80. The protocol began with the measurement of isometric maximum shoulder abduction (SABD) and elbow flexion (EF) strength in a standardized position of 90° of abduction and 40° of horizontal adduction with the elbow in 90° of flexion. The first measure of flexion synergy was the abnormal EF torque that occurred during SABD. Next, dynamic testing was completed in a robotic device where participants performed reaches against 50% maximum SABD from the standardized position. The reaching target required an additional 30° of horizontal adduction and 80° of elbow extension. Endpoint reaching distance was calculated from kinematic data and normalized by distance to the target. A physiological quantification of flexion synergy was measured from the same dynamics data as the biceps EMG occurring 25 milliseconds preceding movement onset. The final measures were the flexion synergy emergence and takeover thresholds representing the highest SABD loads at which the participant can still lift and reach to a far and close target, respectively. The emergence threshold is the load at which flexion synergy begins to affect reaching function, whereas the takeover threshold is the load that overtakes reaching function. The 4 laboratory-based metrics are abnormal EF-coupling, onset biceps EMG, emergence threshold, and takeover threshold. The 2 criterion metrics were significantly correlated with each other (r = 0.466, P = .033). Two laboratory-based metrics significantly correlated with FMA: emergence threshold (r = 0.569, P = .022) and abnormal EF-coupling (r = −0.458, P = .042). Only emergence threshold significantly correlated with reaching distance (r = 0.843, P < .001), though abnormal EF-coupling was approaching significance (r = −0.443, P = .050). The study provides evidence in support of the concurrent validity of the emergence threshold and abnormal EF-coupling as measurements of flexion synergy-related impairment.
F29: Patterns of Behavioral Impairment and Recovery Differ Based on Regionalization of Cortical Infarcts in Rats
Matthew Jeffers
1,2, Gillian Lahey3, Boris Touvykine4, Numa Dancause4, Dale Corbett1,2
1University of Ottawa, Ottawa, Canada2Canadian Partnership for Stroke Recovery, Ottawa, Canada3Carleton University, Ottawa, Canada4Université de Montréal, Montréal, Canada
Background: Lesion location is a critical component of the type and severity of impairments that result from stroke. Likewise, the perilesional cortex has previously been shown to be an important contributor to stroke recovery. However, the pattern of poststroke reorganization of different motor functions around the site of stroke injury is not fully understood.
Objective: To evaluate the effect of variable stroke size and location within the motor cortex on impairment and recovery of motor function.
Methods: Male Sprague Dawley rats (N = 41) were trained and tested on a battery of motor tasks: the Montoya staircase (grasping), beam traversal (balance/limb placement), and cylinder (spontaneous limb use for exploration/weight bearing). Rats were split into 4 groups that received varying sizes of photothrombotic stroke: Sham (n = 5), small (2.5 × 2.5 mm window, n = 12), medium (3.0 × 5.0 mm window, n = 12), or large (5.0 × 7.5 mm window, n = 12). The severity of impairment and change in performance across time on the battery of motor tasks was monitored biweekly for 7 weeks. Probabilistic motor maps of the caudal forelimb area (CFA), rostral forelimb area (RFA), and hindlimb (HL) representations were generated from a group of age-matched control rats (n = 10) using intracranial microstimulation. The volume and location of each rat’s stroke was quantified using MRI and the proportion of injured CFA, RFA, and HL cortex was calculated using a voxel-based analysis. Multiple linear regression was used to determine the groups of voxels and motor regions that were most predictive of both impairment and recovery on each behavioral task.
Results: Larger photothrombotic windows corresponded to larger stroke injury and more severe impairments across all tasks. However, different groups of voxels appeared to be predictive of the severity of impairment for each type of task. Voxels in the CFA region best predicted impairment on the Montoya staircase, voxels in the HL region were most predictive of impairment on beam traversal, and voxels in the RFA and medial to the CFA were most predictive of contralesional limb use in the cylinder. Interestingly, an entirely different set of voxels was related to recovery of function on each task. The degree of individualized staircase recovery was related to voxels spared from injury in the region anterior to CFA. Beam recovery was linked to regions anterior and medial to HL, and cylinder recovery was related to the proportion of the CFA that was spared from injury.
Conclusions: In all cases, perilesional regions were related to recovery from cortical photothrombotic stroke. However, the exact group of voxels linked to recovery varied based on behavioral task. This study demonstrates the importance of using multiple behavioral tasks for quantifying stroke impairment and recovery. The degree to which individual motor functions spontaneously recover may depend on the regions that are injured following stroke.
F30: Using Multichannel Visual Feedback to Learn a New Walking Pattern
Kevin Day
1,2, Amy Bastian1,2
1Johns Hopkins Medical Institute, Baltimore, MD, USA
2Kennedy Krieger Institute, Baltimore, MD, USA
Learning a new walking pattern involves the adjustment of multiple joint-level kinematics. Paretic gait following stroke is often characterized by multiple kinematic abnormalities (eg, circumducted gait, decreased knee flexion, abnormal plantar flexion, etc) that contribute to a global deficit (eg, limping). While adaptive gait training has been shown to improve global deficits such as step length asymmetry following stroke, it does not necessarily address the individual abnormalities that contribute to the larger deficit. For example, walking with symmetric step lengths may not be the most functional or even aesthetic pattern for the patient. Here, we investigate if we can use visual feedback to simultaneously teach participants multiple facets of a new walking pattern. We have created a novel feedback system that uses principal component analysis to weight multiple channels of kinematic information and display the participant’s performance as a simple 1-dimensional “summary” of their walking pattern relative to a prescribed goal pattern. For this proof-of-concept study, we focused on sagittal ankle trajectories such that participants had to alter their kinematics along the anteroposterior and vertical axes within each stride in order to match the goal stride. Therefore, participants received 1-dimensional visual feedback that contained 4 dimensions of information (ie, 2 dimensions—anteroposterior and vertical position—for each ankle). We compared the performance using the multichannel visual feedback to participants who received 4 concurrent streams of 1-dimensional visual feedback (ie, one for each dimension) to learn the same goal pattern. We found that healthy, young participants could use the multichannel visual feedback to learn a prescribed goal pattern at a faster rate than those who received concurrent feedback of all dimensions. Furthermore, participants were able to use the multichannel feedback to achieve the same kinematics by the end of a single session of training as those who received feedback of each dimension. These results suggest that this novel multichannel visual feedback can be used as a straightforward summary of walking performance that enables us to alter multiple aspects of gait toward a given goal pattern. We now aim to use this form of visual feedback as a way to rapidly and intuitively teach persons poststroke how to simultaneously correct multiple gait abnormalities.
F31: Evidence of Altered Interhemispheric Communication in Pediatric Mild Traumatic Brain Injury
Julia Schmidt
1,2, Katlyn E. Brown2,3, Samantha J. Feldman2, Shelina Babul2,4, Jill G. Zwicker2,4, Lara A. Boyd2
1La Trobe University, Melbourne, Australia
2University of British Columbia, Vancouver, Canada
3University College London, London, UK
4BC Children’s Hospital, Vancouver, Canada
Introduction: Pediatric mild traumatic brain injury (mTBI) is common, but recovery is poorly understood. Most return-to-activity management plans rely on symptom-based measures as the underlying mechanism of brain injury is not known and thus it is not evident when the brain is recovered. As such, individuals may return to activity prematurely or be unnecessarily held back from activity. This inappropriate timing of returning to activity could place an individual at risk for further damage or could initiate negative psychosocial effects (eg, depression, anxiety). Transcranial magnetic stimulation (TMS) is a form of noninvasive brain stimulation that can quantify neurophysiological circuitry contributing to corticospinal excitability and interhemispheric communication. As such, TMS may provide unique insight into the neurophysiological impact of mTBI, enabling investigation into potential markers of injury and recovery. The identification of such a marker, in conjunction with an understanding of the relationship between neurophysiological and clinical measures, is necessary to inform clinical decision making.
Objectives: (1) To explore the neurophysiological impact of mTBI in children/adolescents with a recent mTBI compared to matched healthy controls and (2) to establish the relationship between the neurophysiology underlying mTBI, indexed by TMS and clinical outcomes (eg, symptom-report, cognitive and physical outcomes).
Methods: In this cross-sectional controlled cohort study, 11 children aged 11 to 17 years within 1 month after mTBI were compared to 14 healthy matched controls. Neurophysiological measures using TMS included indices of (1) cortical excitability (eg, short- and long-latency interval intracortical inhibition, intracortical facilitation); (2) sensorimotor integration afferent stimulation (eg, short- and long-latency interval afferent inhibition, afferent facilitation); and (3) interhemispheric communication via the corpus callosum (eg, transcallosal inhibition of the motor cortex and dorsolateral prefrontal cortex). Clinical outcomes were collected using symptom scales, brain injury–specific cognitive measures, and physical assessments (eg, balance and visual-ocular-motor).
Results: Preliminary analysis identified 3 key findings. First, there were no differences in measures of cortical excitability or sensorimotor integration between groups (P > .05). Second, the participants with a recent concussion had a significantly shorter duration of transcallosal inhibition (t(22) = 3.24, P < .01) and longer time for onset of transcallosal inhibition (t(22) = 2.42, P < .01), indicating altered interhemispheric communication. Finally, there was no correlation between neurophysiological measures and clinical outcomes, indicating a disconnect between neurophysiological and clinical outcomes. Results of the full sample (n = 15 per group) are currently being analyzed and will be reported during the presentation at the conference.
Conclusions: Our early results demonstrate that pediatric mTBI affects interhemispheric communication. These data serve as a critical first step in the future development of neurobiological and evidence-based outcome measures and interventions.
F32: Does Matching Task Challenge to Patient Ability during Stroke Rehabilitation Promote Greater Poststroke Arm Motor Recovery Than Usual Care? The MAtching Task CHallenge (MATCH) Trial
Michelle Woodbury
1, Scott Hutchison1, Christian Finetto1, Andrew Fortune1, Kelly Anderson1, Abigail Lauer-Kelly1, Viswanathan Ramakrishnan1
1Medical University of South Carolina, Charleston, SC, USA
Background: During stroke rehabilitation, the challenge level of tasks practiced should match the patient ability level so that the tasks practiced are neither too easy nor too difficult. Optimally challenging task-practice promotes motor skill relearning because errors/successes drive problem-solving to establish new motor strategies. Previously, we conducted Rasch analyses of Fugl-Meyer Assessment of the Upper Extremity (FMAUE) data from a large poststroke sample and published a progression of easy-to-challenging arm movements called a “recovery map.” We demonstrated a method to locate patients’ FMAUE item ratings on the map thereby matching patients’ ability level to arm movements having a corresponding challenge level. We suggested that these ability-matched movements should be targeted during task-practice.
Objective: Test the hypothesis that matching patient ability to task challenge level during task practice would elicit greater motor recovery when compared to task practice without an explicit focus on challenge level.
Methods: Patient and assessor blinded phase II stroke rehabilitation randomized controlled trian with randomized block design, intent-to-treat analysis, and powered to detect between-group FMAUE differences. Subjects with moderate-mild arm hemiparesis from ischemic or hemorrhagic stroke ⩾3 months to ⩽5 years were included and randomized to 2 well-defined rehabilitation groups: (1) MATCH versus (2) Usual Care (UC). Groups had equivalent dose and duration (4 weeks, 3 sessions/week, 200 movement repetitions/session) but separate therapists. MATCH: The recovery map was used to link each subject’s FMAUE item ratings to optimally challenging arm motions targeted during functional task practice. UC: The therapist and subject collaborated to choose functional tasks for practice, then altered task challenge level as needed based on therapist observation of patient response. Outcome measures: Impairment (FMA-UE), motor function (Wolf Motor Function Test [WMFT]), and self-reported paretic hand use (Stroke Impact Scale–Hand [SIS-H]).
Results: N = 103 subjects provided informed consent and were randomized. N = 90 (87%) completed all sessions. Subjects were 19 to 84 years of age and averaged 27 months post ischemic (73%) or hemorrhagic (27%) stroke. Pre- to postintervention change scores (mean, SD) for the FMAUE, WMFT, and SIS-H were small for MATCH (4.08 [4.39], −4.81 [8.40], and 0.67 [0.68]) and UC (2.45 [4.34], −6.51 [18.85], and 0.36 [0.74]). Repeated-measures ANOVA showed that both groups demonstrated similar impairment reduction (FMA-UE: time P < .001, group P = .912) and gains in motor function (WMFT: time P = .003, group P = .996), but the MATCH group showed reduced perceived difficulty of hand use (SIS-H: time, P < .001, group P = .048).
Discussion: Consistent with the literature, different therapy approaches yielded similar benefits when equally dosed. Results suggest that either challenge level is not a critical element of stroke rehabilitation or the “recovery map” method is not superior to usual care. MATCH subjects reported less paretic hand use difficulty suggesting that an explicit identification of optimally challenging arm motions during task-practice may impact subjects’ perception of arm use in the home.
F33: Dual-Tasking During Initial Learning Interferes With Savings of a Novel Walking Pattern
Kristan Leech
1,2, Amy Bastian1,2
1Kennedy Krieger Institute, Baltimore, MD, USA
2Johns Hopkins University, Baltimore, MD, USA
Savings, or faster relearning after initial learning, is a phenomenon observed across motor adaptation paradigms (eg, reaching, walking). Recent evidence suggests that cognitive learning processes interact with error-based learning to account for savings in arm and hand movements. For example, savings of an adapted reaching movement has been attributed to the use of cognitive aiming strategies. That is, after re-exposure to a large perturbation in reach angle, participants change their behavior quickly by aiming their reaches toward the previously learned target location. Though it is unlikely that an aiming strategy accounts for savings during a more automatic task like walking, we have previously demonstrated that savings during walking relies on being able to explicitly recall the perturbation. Yet the contribution of cognitive learning processes to savings during walking remains unclear. Here we investigated how cognitive engagement in a secondary cognitive task while learning a new walking pattern may influence relearning. We collected data from young healthy participants while they walked on a split-belt treadmill. All participants initially adapted to a split-belt perturbation where the belts moved at different speeds (adaptation), de-adapted with the belt speeds tied, and adapted again to the same split-perturbation (re-adaptation). To investigate the effects of an increased cognitive load on savings during walking, we tested 2 groups, one that performed the split-belt paradigm alone (Single Task) and one that simultaneously completed an auditory 3-back task during initial adaptation (Dual Task). We found that dual-task performance did not change initial learning behavior. Despite simultaneously engaging in a cognitive task, participants in the Dual Task group learned the new walking pattern at a similar rate as the Single Task group. While both groups learned similarly initially, we found that savings of the walking pattern was much stronger in the Single Task group. These findings show that the engagement of cognitive processes in a separate task during initial motor learning interferes with the formation of a motor memory during walking. These findings may be important when considering the utility of adaptation-based learning in people with deficits in cognitive function.
F34: A Preliminary Study on Fatigue Severity Scale in Subacute and Chronic Poststroke Patients Using 2-Minute Walking Test: The Indonesian Experience
Widjajalaksmi Kusumaningsih
1, Teinny Suryadi1
1University of Indonesia, Ciptomangunkusumo Hospital, Jakarta, Indonesia
Background: Fatigue is a common symptom after stroke that contributes to a decline in quality of life in stroke patients. The 9-item Fatigue Severity Scale (FSS) is a reliable and valid method to measure poststroke fatigue based on self-report questionnaires. This study aimed to assess the severity of fatigue in stroke patients using the FSS with the 2-minute walking test.
Objectives: To evaluate poststroke fatigue by using the FSS with the 2-minute walking test.
Methods: Analytic study of 35 subjects, men (30) and women (5). Subjects were outpatient clinic patients, aged between 28 and 75, and expressed experiencing fatigue when the FSS score was ⩾4.
Results: Mean value of FSS was 2.92 (±1.43). Two-minute walking test shows no correlation between FSS with distance (r = −0.063, P = .718) and no correlation between FSS with walking speed (r = −0.068, P = .700).
Conclusion: The study shows the 2-minute walking test showed no fatigue. It is a safe tool for stroke patients, chronic and subacute. Further studies are needed to improve the quality of life in poststroke patients and to study brain neuroplasticity.
F35: Neuroplasticity Following Interlimb Training With a Prosthesis Simulator in Intact Participants
Bennett Alterman
1, Shuo Wang1, James Kling1, Lewis Wheaton1
1Georgia Institute of Technology, Atlanta, GA, USA
After amputation surgery, there exists a time window during which the fitting of a prosthesis yields higher acceptance rates. As most patients are not able to be fitted within this window, oftentimes, benefit is lost. This study examines interlimb transfer, seeking to evaluate whether a prosthesis training paradigm using the unaffected limb will increase functional outcomes of prosthesis use on the affected limb. Here, healthy, intact participants underwent 3 days of prosthesis training on their nondominant side between testing sessions on their dominant side. Testing sessions consisted of a prescribed number of repetitions of 4 reach, grasp, and manipulation tasks. Training sessions involved 4 different tasks, and participants were asked to complete as many repetitions as they could within 8 minutes. Total training time using the nondominant limb was 96 minutes. A control group performed only a pretest and follow-up test on day 5 using their dominant side. We used a 58-channel electroencephalography (EEG) setup to provide a quantitative neural signal for associated improvements in qualitative movement performance. We hypothesized that participants undergoing interlimb training would show increases in bihemispheric coherence, particularly between motor cortices. Preliminary data analysis of the beta band during motor execution revealed that training tends to cause a decrease in the overall amount of coherence from the pretest to posttest, which may be indicative of motor learning. Significant coherence was observed between bilateral frontal and parietal electrodes, as well as interhemispheric parietofrontal coherence. As task difficulty increases, we observed increased communication in frontal neural regions in the pretest, which tends to shift to a more posterior parietooccipital coherence in the posttest. These patterns may be representative of a shift in learning to use the prosthesis (which requires increased executive functioning), to visually guided feedback of motor performance. Contrary to our hypothesis, we see little evidence of bihemispheric motor cortex coherence changes. This work will form the foundation for research in patients with amputation to examine clinically significant effects of interlimb training in motor rehabilitation.
F36: MoTaStim-Foot, a Randomized, Single-Blinded, Mixed-Methods, Feasibility Study Exploring Sensory Stimulation of the Foot and Ankle Early Poststroke
Alison M. Aries
1, Valerie M. Pomeroy2, Julius Sim1, Sue Read1, Susan M. Hunter1
1Keele University, Keele, Staffordshire, UK
2University of East Anglia, Norwich, UK
Introduction: It is not known whether increasing somatosensation of the foot could improve walking recovery after stroke. This study was undertaken to investigate the feasibility of conducting a future randomized controlled trial (RCT) to determine whether the effect of task-specific gait training is enhanced more with mobilization and tactile stimulation or by wearing textured insoles. The objectives of the present feasibility study were to (1) explore recruitment methods and monitor attrition; (2) explore acceptability of interventions; (3) investigate feasibility, cost, and acceptability of a battery of outcome measures; (4) explore responses to intervention over time informing future dose; (5) investigate suitability of daily diaries and focus groups for exploring stroke survivors’ experiences; and (6) generate participant information, that is, demographics, clinical characteristics, including time since stroke, type of stroke, and comorbidities.
Methods: Design: Randomized, single-blinded, mixed-methods feasibility study. Setting: Rehabilitation ward and community. Participants: Thirty-four people aged 18+ years, 42 to 112 days poststroke who provided informed consent (IRAS No.: 171968/REC Ref 16/WM/0080). Intervention: Participants were randomly allocated to either 30 to 60 minutes mobilization and tactile stimulation or unlimited textured insole wearing. All participants also received 20 sessions of task-specific gait training over the 6-week intervention phase. Outcomes: Lower limb sensorimotor impairment was measured before randomization, after the 6-week intervention phase, and 1 month thereafter (follow-up). Adherence to the allocated intervention and the number/length of sessions were documented. Participants recorded their trial experiences during the intervention period in daily diaries and participated in focus groups exploring acceptability of interventions and overall trial experience, on completion of interventions (Objective 2). Analysis: Recruitment, attrition, and adherence rates (Objective 1) were calculated with descriptive statistics. The magnitude and variance of within-group changes in potential outcome measures (Objectives 3 and 4) were calculated. Thematic analysis of the diaries and focus groups was undertaken (Objectives 2 and 5).
Results: Thirty-four stroke survivors were recruited. Recruitment, attrition, and adherence rates were 48.8%, 5.9%, and 97.9%, respectively, on trial completion (Objective 1). The magnitude of within-group change was statistically significant for both groups for the 5-m walk test, Functional Ambulation Classification, modified Rivermead Mobility Index, and the Lower Extremity Motricity Index (P < .01) (Objective 4). Participants described diaries as “simple” and “valuable” (Objective 5). Quotations from the focus groups indicated acceptability and that the trial experience was positive, for example: “It [the trial] was no trouble at all” and “the treatment’s given me the ability to walk.”
Conclusion: Feasibility of delivering and acceptability of the interventions and outcome measures was established. The results indicate that a subsequent RCT of mobilization and tactile stimulation + task-specific gait training and wearing of textured insoles + task-specific gait training is feasible. The variance of the outcome measures will inform the sample size calculation for a subsequent RCT.
F37: Using a Novel Lever-Drive Wheelchair to Increase Arm Movement Practice Early After Stroke: Preliminary Results of a Randomized Controlled Trial
Joan Lobo Prat1, Daniel K. Zondervan2, Christopher Lew1, Brendan W. Smith3,
Vicky Chan
1, Cathy Chou1, Susan Shaw4, David J. Reinkensmeyer1, Steven C. Cramer1
1University of California, Irvine, Irvine, CA, USA
2Flint Rehabilitation Devices, LLC, Irvine, CA, USA
3Loyola Marymount University, Los Angeles, CA, USA
4Rancho Los Amigos National Rehabilitation Center, Downey, CA, USA
Intensive rehabilitation reduces long-term arm impairment especially when performed early after stroke. Unfortunately, therapy time is limited and individuals lack tools to increase arm movement practice, particularly when they have severe arm impairment. To address this problem, we developed LARA (Lever-Actuated Rehabilitation and Ambulation), a novel lever drive wheelchair that has 2 modes of exercise: (1) playing videogames in a stationary mode using the sensorized levers as a joystick and (2) ambulating overground by bimanually propelling the wheelchair using the levers. We found previously that people with severe arm impairment in the chronic phase of stroke could learn to independently ambulate with LARA. Here we tested if subacute patients could learn to drive LARA, achieving a skill that could allow them to avoid compensatory wheelchair propulsion (ie, 1-arm/1-leg propulsion) that contributes to arm disuse early after stroke. A total of 23 patients with subacute stroke were recruited and randomized to receive 30 minutes of extra arm movement practice each day (for 17.18 ± 8.57 days) while admitted to inpatient rehabilitation or were outpatients waiting to be enrolled in outpatient therapy. Participants were randomized to train with the LARA wheelchair (n = 12) or conventional exercises with a rehabilitation therapist (n = 9; 2 subjects dropped out). The primary outcome measure was the Upper-Extremity Fugl-Meyer (FM) score, evaluated at enrollment, discharge, and at a 3-month follow-up (which is not reported here as data are still accruing). Secondary outcome measures included Box and Blocks, Grip Strength, Visual Analog Pain Scale, and modified Ashworth Spasticity Scale. Participants were 17.5 ± 13.4 (mean ± SD) days poststroke at enrollment with a FM of 22.9 ± 12.8 out of 66 and groups were balanced at baseline according to their FM score. Based on data from sensors mounted on LARA’s levers, participants completed 7.3 ± 4.7 exercise sessions that lasted 25.4 ± 23.7 minutes. Overground ambulation with LARA accounted for approximately two thirds of each of these sessions’ duration. The increases in FM score at discharge were 13.8 ± 10.3 and 7.2 ± 4.1 for the LARA and conventional groups, respectively. Both improvements were significant (paired t-test, P < .001), and the improvement was significantly greater for the LARA group than for the conventional group (one-sided t-test, P = .043). These improvements occurred even though only 3 of the 10 participants in the LARA group became skillful at overground ambulation. No significant changes in arm pain, arm spasticity, Box and Blocks, or Grip Strength were found at discharge between the 2 groups. These preliminary results indicate that practicing arm movement with the LARA wheelchair was feasible early after stroke and may lead to a significantly greater reduction of arm impairment compared to a matched amount of conventional therapy without increasing arm pain or spasticity.
F38: Using the Manumeter for Continuous Feedback on Hand Activity After Stroke: Preliminary Results
Diogo S. de Lucena
1,2, Justin B. Rowe3, Vicky Chan1, Steven C. Cramer1, David J. Reinkensmeyer1
1University of California, Irvine, Irvine, CA, USA
2CAPES Foundation, Ministry of Education of Brazil, Brasilia, Brazil
3Flint Rehabilitation Devices, LLC, Irvine, CA, USA
Quantitative continuous feedback can modulate health-related activity; for example, pedometers are effective in increasing walking activity and overall health. Here, we report on initial testing of a “Pedometer for the Fingers”—the Manumeter—designed for home use by people with stroke. The Manumeter is a wristwatch-like device that senses the magnetic field of a small magnet ring worn on the index finger. We describe for the first time here a calibration-free, computationally simple algorithm that uses the direction of the magnetic field to count hand movements, enabling a continuous feedback on the number of hand movements using a built-in display. To validate the hand movement-counting algorithm, unimpaired adults (n = 8) performed 50 hand-only and 200 arm-only exercises (with the hand and wrist constrained in a splint) while wearing the Manumeter. The Manumeter counted 53.9 ± 5.7 hand movements for the hand-only exercise (expected 50) and 7.9 ± 9.5 (expected 0) for the arm-only exercise. In ongoing work, we are testing whether the Manumeter can help people with a chronic stroke increase hand use at home. Six (of an expected total of 22) participants have worn the Manumeter for 1 day (baseline, no feedback) and then for 3 weeks (with or without feedback). Three subjects randomized to the experimental group received a daily goal based on their baseline Box-and-Blocks Test (BBT) score and continuous feedback on the number of hand movements performed while wearing the device. Meanwhile, the 3 subjects in the control group used the device as a wristwatch. Both groups also received a book of exercises tailored by a blinded physical therapist and were asked to perform the exercises for 15 minutes every day. When compared to their baseline hand movement counts obtained with no device feedback, the participants in the experimental group performed, on average, an additional 88 movements per hour during the 3-week therapy period versus 33 for the control group. With an average wearing time of 8.2 ± 2.1 hours per day, the experimental group performed an additional 717 hand movements per day and 15 060 hand movements over the 3 weeks of the study versus 271 per day and 5696 over the 3 weeks for the control group. The BBT score increased by 4.7 ± 3.8 blocks for the experimental group and by 1.0 ± 2.9 blocks for the control group. The Manumeter algorithm presented here correctly counts hand movements in the laboratory with about 92% accuracy, differentiating hand movements from gross arm movements with about 4% cross-talk. For the first 3 subjects of an ongoing randomized control trial, continuous feedback of hand activity increased hand activity at home, as well as a clinical measure of hand function.
F39: A Novel Method of Producing Asymmetric Propulsive-Force Generation During Walking Using Differential Fore-Aft Resistance in Nonimpaired Individuals
Avantika Naidu
1, David Brown1
1University of Alabama at Birmingham, Birmingham, AL, USA
Purpose: Symmetric interlimb generation of fore-aft forces, that is, braking and propulsive forces are required to maintain speed and forward progression during walking. In stroke survivors, hemiparesis impairs the paretic limb’s propulsive force generation ability, which causes the nonparetic limb to produce the majority of propulsive forces needed to maintain walking speed. The resulting interlimb propulsion asymmetry produces disrupted, slow, and inefficient walking patterns that increase fall risk. To help improve interlimb propulsion symmetry in individuals poststroke, we examined a novel method of applying different amounts of fore-aft resistance (differential resistance) during split-belt walking. As proof of concept, in this study, we explore if differential forces can produce interlimb propulsion asymmetry in nonimpaired individuals during split-belt walking. We hypothesized that with greater differential resistance, the slower limb will increase its propulsive-force relative to the moving faster-limb due to increased proprioceptive load-feedback.
Methods: We used a novel split-belt treadmill-interface to provide differential resistance at the pelvis during a walking task. We automatically controlled (AC mode) speed of the dominant (D) limb at 0.5 m/s using the treadmill-software, while speed of the nondominant (ND) limb belt was self-driven (SD) at 1 m/s by the participant walking inside the interface by overcoming a set fore-aft resistance at the pelvis using a programmed force-velocity relationship. We provided visual feedback to participants to maintain belt-speed of the SD limb, and incrementally increased fore-aft resistance equivalent to 6%, 9%, 12%, 15%, 18%, and 21% vertical body weight to the ND limb. Each trial was 60 seconds long. We collected data for D an ND limb belt speeds and kinetic parameters for each trial. We primarily assessed mean propulsive impulse (nPI) normalized to participants body weight (BW) in newtons for each limb separately.
Results: To date we have analyzed data of 7 NI individuals (mean = 28 years [SD = 3.9], right dominant = 6). All participants maintained their mean ND limb speed at 1 m/s (SD = 0.02) m/s for all trials. At 6% resistance mean nPI of the D limb was 4.1% BW (SE = 0.5) while ND limb mean nPI was 4.8% BW (SE = 1). We observed asymmetrical increased in propulsion at 21% resistance, with the D limb mean nPI increasing to 15.2% BW (SE = 0.8) compared to 9.6% BW (SE = 0.8) of the ND limb. The D limb also had a higher slope (2.07) and R2 (0.99) compared to the ND limb (slope = 0.97, R2 = 0.93).
Conclusion: Differential for-aft resistance applied at the pelvis during split-belt walking generates asymmetrical propulsion that increases with greater resistance applied. This method can be used to test hypotheses about the relative propulsive force generation ability to help improve interlimb propulsion symmetry in individuals poststroke during walking. Potentially, these results can help guide design and testing of new training paradigms for individuals poststroke.
F40: Generalizability of Muscle Synergies During Static and Dynamic Motor Tasks in the Arm Workspace of Stroke Survivors
Christopher Taylor
1, Lei Ma1, Manuel Portilla-Jiménez1, Jinsook Roh1
1Temple University, Philadelphia, PA, USA
Introduction: Novel treatments for deficits in motor coordination have received increased attention. Though human motor control is not limited by an invariant posture in daily activities, many previous studies have limited their investigation to muscle coordination in a single arm position; therefore, the overall workspace required to perform movement tasks remains not extensively explored. Moreover, stroke studies on isometric reaching suggest that the composition of muscle synergies, defined as consistent patterns of muscle activity to produce functional motor behaviors, is altered at a single arm posture. However, it is unclear to what extent synergies produced in one position can be generalized to predict motor coordination in other arm configurations. Furthermore, it is unclear how healthy individuals and individuals with neurological impairment differ in synergies produced. The current study investigated the generalizability of muscle synergies in healthy individuals compared to stroke survivors with motor control deficits in the horizontal plane.
Methods: Electromyographic (EMG) signals of 10 muscles in affected arms of 4 chronic stroke survivors with mild impairment and the dominant arms of 5 healthy age-matched controls were analyzed using non-negative matrix factorization to identify muscle synergies. Participants performed 2 tasks: (1) a simulated reaching task in the horizontal plane using isometric force generation and (2) a dynamic reaching task in the horizontal plane using a robotic end-effector. Both tasks were performed at multiple starting positions, equidistant apart, to observe the generalization of muscle coordination within the same workspace.
Results: Four synergies were most often required to predict the EMG pattern of isometric tasks of controls regardless of the arm position in the workspace. In contrast, stroke survivors exhibited increased number of synergies during the isometric task as the arm was positioned further away from the body. The dynamic reaching task required a greater number of synergies than the isometric force generating task in both groups when the number of targets and the location of the arm in the workspace were matched. Stroke survivors had increased difficulty performing dynamic tasks at distal arm postures, resulting in incomplete trials.
Conclusion: The number and characteristics of muscle synergies observed during isometric tasks were comparable in controls across varying arm locations, while stroke survivors’ synergies during the same tasks were fractionated in distal workspaces. This finding suggests that healthy individuals show greater ability to flexibly change the activation of the same set of muscle synergies to meet the biomechanical needs of reaching at distal locations of the arm. In contrast, stroke survivors may need additional degrees of freedom to perform the same motor task at distal arm positions, leading to fractionation and increase in synergies. Overall, current observations might account for the different motor control schemes in stroke at varying arm locations in the workspace.
F41: Influence of Descending Cortical Projections on Spinal Reflex Excitability in Poststroke Individuals
Alejandro Lopez
1, Jiang Xu1, Steven Eicholtz1, Michael Borich1, Trisha Kesar1
1Emory University, Atlanta, GA, USA
Combining peripheral electrical stimulation with transcranial magnetic stimulation (TMS) at specific inter-stimulus intervals can index descending corticofugal influences on spinal reflex excitability. Subthreshold TMS pulses sent before or after peripheral nerve stimulation modulates the Hoffmann’s reflex (H-reflex). Short-latency facilitation (SLF) of the H-reflex occurs when a TMS pulse is sent 1 to 5 ms after peripheral nerve stimulation, and long-latency facilitation (LLF) occurs when a TMS pulse is delivered before peripheral nerve stimulation. Poststroke individuals have abnormally elevated spinal reflex excitability. However, the influence of descending corticofugal projections on spinal alpha motoneurons for poststroke individuals remains unknown. The purpose of this study was to evaluate the influence of these projections on spinal reflex excitability in poststroke individuals using TMS-conditioned H-reflex responses. Ten neurologically unimpaired, adult participants (8 females, 2 males; 25 ± 3 years old) and 8 poststroke participants (6 females, 2 males; 60 ± 4 years old) completed a single experimental session. The unconditioned (UC) H-reflex was obtained by delivering peripheral nerve stimulation to the posterior tibial nerve at an intensity that elicited an H-reflex amplitude at 20% Mmax in the soleus muscle. Subsequently, SLF and LLF (conditioned H-reflexes) were collected in an analogous manner. For SLF, TMS was delivered over the soleus motor cortex hotspot 1.5 ms following peripheral nerve stimulation. For LLF, TMS was delivered 10 ms before peripheral stimulation. Subthreshold TMS (85% of resting motor threshold) was delivered for both SLF and LLF conditions. For poststroke individuals, compared to UC H-reflex amplitude, conditioned H-reflex amplitude was significantly greater for LLF (P < .005), but not significantly greater for SLF (P > .22). Also, LLF was significantly greater than SLF (P < .01). Stroke survivors showed a significant reduction in SLF compared to able-bodied (P < .03). These results provide the first characterization of SLF and LLF in individuals poststroke. Reduced excitability of direct descending corticofugal projections in individuals poststroke may be related to reduced descending inhibition of spinal segmental reflexes, resulting in heightened spinal reflex excitability. Our future work will aim to determine how the excitability of descending cortical projections onto spinal motoneurons is modulated by rehabilitation interventions.
F42: Predicting Recovery of Upper Limb Function 6 Months After Middle Cerebral Artery Infarction Using Diffusion Tensor Imaging
Doo Young Kim1, Junsoo Noh2, Woo-Suk Tae2,3, Yu Mi Hwang3, Yoonhye Na2,3,
Sung Bom Pyun
2,3
1Catholic Kwandong University International St Mary’s Hospital, Seoul, Republic of Korea
2Korea University, Seoul, Republic of Korea
3Brain Convergence Research Center, Seoul, Republic of Korea
Purpose: The purpose of this study was to predict the upper limb function in patients with middle cerebral artery (MCA) infarction 6 months after stroke using subacute phase diffusion tensor imaging (DTI).
Methods: We retrospectively investigated the database of “Stroke Outcome Prediction” (STOP). Patients with single MCA infarction, who underwent DTI between 14 and 30 days after onset, were enrolled. Upper limb function was evaluated by manual function test 1 month (MFT-i) and 6 months (MFT-f) after onset. Demographic factors, National Institutes of Health Stroke Scale (NIHSS) scores, cognitive function, presence of depression, and DTI-derived parameters of corticospinal tract were collected. Multiple linear regressions were used for analysis.
Results: Finally, 20 patients were included. Mean age was 64.1 ± 14.7 years, and 9 patients (45%) were women. The mean of MFT-i and MFT-f was 13.4 ± 11.8 and 20.5 ± 9.2, respectively. Regression analysis revealed that MFT-i, age, and initial NIHSS were significant predictors when the DTI parameters were not included in the statistical model (adjusted R2 = 0.800, P = .027). In the final model including the DTI parameters, MFT-i, age, and FA asymmetry significantly predicted MFT-f (adjusted R2 = 0.933, P < .001).
Conclusion: In MCA stroke patients, precise prediction of upper limb function after 6 months is possible using clinical and neuroimaging parameters. Also, FA asymmetry may be the best predictor among subacute phase DTI parameters.
F43: Understanding the Determinants of Reactive Step Choice in Parkinson’s Disease
Niveditha Muthukrishnan
1, Daniel S. Peterson1
1Arizona State University, Tempe, AZ, USA
Background: People with Parkinson’s disease (PD) exhibit frequent falls, and protective steps after a loss of balance can reduce the incidence of falls. However, our knowledge of protective stepping is incomplete. For example, the factors that predict which foot people use to step with are unknown. PD symptoms often presents asymmetrically; however, whether this asymmetry affects stepping foot choice is unknown. Understanding the factors that contribute to stepping foot choice could improve therapists’ ability to design individualized protective step training regimes emphasizing step stability. The primary objective of this study is to determine whether disease severity or limb dominance are related to stepping foot choice. Our second objective was to determine whether step effectiveness (measured by margin of stability [MOS]) was related to stepping foot choice.
Materials and Methods: Twenty-eight participants (age: 66.4 ± 8.5) diagnosed with PD (Unified Parkinson’s Disease Rating Scale: 26.8 ± 13.4) were presented with ground perturbations in the forward and backward directions using hydraulically driven force-plate, resulting in a protective step. The dependent variable used in the study is stepping ratio. This outcome, calculated for each stepping direction, indicated the number of steps taken using left and right leg. For aim 1, we related stepping ratio to UPDRS asymmetry score (taking items 20, 26, and 32 of the scale). Footedness (ie, limb dominance) was also included in the model. For objective 2, stepping ratio was related to anterioposterior MOS. MOS is a measure of step effectiveness, and it is the distance between the center of mass and base of support at the moment of first foot contact. Again, footedness was included in the model to study its effect on step stability.
Results: Multivariate analyses indicated that both UPDRS asymmetry score and footedness predicted step ratio for backward stepping (P = .05 and P = .07, respectively), but not for forward stepping (P > .05 for all). UPDRS asymmetry score was inversely correlated with the step ratio, such that people more frequently stepped with their less affected side. Footedness was positively correlated with the step ratio, such that people typically stepped with their dominant limb. Analysis performed for the secondary objective between anterioposterior MOS (P = .02 for backward and P = .35 for forward) and footedness (P = .11 and P = .33, respectively) was positive but nonsignificantly related to stepping ratio.
Conclusion: During backward protective stepping, people with PD typically step with their least effected leg. Results on step stability need to be further analyzed with larger data as the given set of data did not provide sufficient indication on the relationship between anterioposterior MOS and choice of stepping limb. These results provide preliminary evidence regarding the natural choice of protective stepping limb in people with PD and may inform step training programs aimed to reduce falls in this population.
F44: Effects of Visual Feedback on the Coordination of Pointing With a Prosthesis
Daniela Junckes da Silva Mattos1,
Scott Frey
1
1University of Missouri, Columbia, MO, USA
Introduction: Goal-directed tasks involve integration of multisensory feedback. Most of the commercial prosthetic devices provide limited proprioceptive information. As a result, there is a common sense that vision compensates for the deficits in sensation. We tested the hypothesis that prosthetic users rely on limb visual feedback to perform pointing tasks.
Methods: Our study included 9 upper-limb prosthetic users (2 females, 1 left-handed, mean age: 60.00 ± 8.60 years, age range: 50-76 years) and 9 controls (57.44 ± 9.55 years, age range: 44-75 years) matched by age and sex. Optotrack cameras tracked the position of infrared markers attached to the terminal device of prosthetic users and to the tip of the index fingers of controls. The subjects reached and pointed to the top of a 2 cm3 wooden block placed either on the same side or on the contralateral side of the limb; random target perturbations were introduced in two thirds of the trials. The experiment was performed in 2 conditions of visual feedback: inside of an illuminated and of a darkened room (that reduced the limb visual feedback).
Results: Pointing with prosthesis was characterized by prolonged movement time (P = .018), smaller peak velocity (P = .008), peak acceleration (P = .046), and peak deceleration (P = .006), and an earlier time to peak deceleration (P = .035) than controls. The reaction time (P = .037), index of curvature (P = .224), and variable error at movement termination (P = .229) were not different between prosthetic users and controls. Without limb visual feedback, pointing performed by both groups had larger movement time (P = .001) and reaction time (P = .037), and was less accurate (P < .0001). None of the kinematics variables were altered by the manipulation of visual feedback (all P > .1).
Conclusions: These findings suggest that the prosthetic limb is successfully incorporated into the amputee’s body schema. The prolonged movement time accompanied by kinematics changes might be the strategy used by the amputees to preserve normal levels of performance.
F45: Prediction of Aphasia Severity in Early and Later Subacute Phase of Stroke
Sekwang Lee1, Yoonhye Na1, Woo Suk Tae1,2,
Sung Bom Pyun
1,2
1Korea University, Seoul, Republic of Korea2Brain Convergence Research Center, Seoul, Republic of Korea
Background: Approximately 35% to 40% of adults admitted to the hospital with stroke are diagnosed with aphasia. Many demographical, neurological, and treatment-related factors have been reported as predictors of aphasia recovery. Recently developed neuroimaging techniques, such as diffusion tensor imaging (DTI), voxel-based lesion-symptom mapping (VLSM), functional magnetic resonance imaging (fMRI), may provide more information regarding the relationship between the severity of aphasia and the characteristics of brain lesions after stroke. Also, DTI is a useful technique for investigation about the subcortical white matter, especially for arcuate fasciculus (AF) in aphasia.
Objective: This study was designed to identify the predictors of severity of poststroke aphasia in 2 time points (1 month and 3 months after onset) using brain DTI parameters and brain lesion volume measurement in addition to traditional clinical variables.
Methods: Left hemispheric stroke patients were enrolled for the study from the STOP (STroke Outcome Prediction) database of Korea University Anam Hospital. Demographical, clinical, and neuroimaging data were collected for analysis. Aphasia was evaluated by Western Aphasia Battery, and aphasia quotient (AQ) score was used for the single dependent variable of aphasia severity. DTI parameters scanned by 3.0-T MRI included measuring fractional anisotropy (FA), fiber number, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), and brain lesion volume. Laterality index, LI = (Left − Right)/(Left + Right), was used for analysis and patients were stratified into 4 groups according to the severity of left AF injury. A multivariate linear regression analysis was performed to find out predictors of AQ at 1 month (AQ1, n = 70) and 3 months (AQ2, n = 21) after onset of stroke.
Results: Mean AQ1 and AQ2 scores were 49.0 and 65.8 points out of 100, respectively. In AQ1, the stroke lesion volume and FA laterality index were the significant predictors (adjusted R2 = 0.316) and they were also significant predictors of fluency, repetition, and naming scores. Age and FA laterality index were significant predictors of comprehension score. In AQ2, initial aphasia severity, age, and depression were the significant predictors (adjusted R2 = 0.782) and DTI parameters of AF and lesion volumes were not significant predictors for AQ2 and other subdomain language scores.
Conclusions: In this study, neuroanatomical factors from DTI and lesion volumes were more associated with aphasia severity of early subacute phase of stroke. However, initial severity of aphasia and patient-related factors (age and depression) are more important for prediction of aphasia score in 3 months after onset of stroke.
F46: Leveraging Visual Search Patterns in the Trail-Making Task to Understand Cognitive Impairments in Stroke Patients
Christopher Perry
1, Adam Harrison1, Troy Herter1
1University of South Carolina, Columbia, SC, USA
Efficient patterns of eye movements and fixations (visual search) are needed to accurately perform visuomotor skills such as driving a car. Visual search collects task relevant information from the environment in order to make accurate decisions about future motor actions (eg, stopping for pedestrians). Inefficient patterns of eye movements have shown association with poor visuomotor performance and increases in the number of task errors. Survivors of a cerebral stroke will often exhibit altered visual search patterns and make more errors when performing visuomotor tasks. However, it is not known if the visual search patterns associated with task errors differ from the visual search patterns associated with non-error performances in those with stroke. To investigate this, a total of 32 participants with chronic stroke were recruited to perform a virtual trail making task. Participants were seated in a height-adjustable chair at an upper limb kinematic apparatus with an integrated eye tracking system. To perform the trail making task, participants grasped a manipulandum with their least affected hand. They were then instructed to use the white circle on the workspace (representative of their hand position) to accurately and quickly connect labeled targets in the correct order while alternating alphabetical and numerical sequences (trail making part B). Participants that made at least one error while performing the trail-making task (n = 19) were included for data analysis. Analysis of intraparticipant eye movements was performed on the visual search patterns between error and non-error trials. Error trials were further divided into 2 primary error types in the task: (1) “non-switch” errors which were classified as a failure to alternate alphanumeric sequences and (2) “switch” errors which were classified as successful alternate alphanumeric sequences, but still resulted in an error. Results show that during non-switch error trials, participants exhibited fewer fixations (P < .001) and shorter foveation durations of their destination target (P < .001) compared to non-error trials. In addition, non-switch error trials were uniquely characterized by indiscriminate foveation durations of all visual stimuli. During switch error trials, participants exhibited visual search patterns similar to that of non-error trials. Based on these results, it can be inferred that non-switch and switch errors are likely the result of impairments of 2 distinct neural processes involved in task performance. This experiment provides evidence that visual search patterns can provide new insights into the impairments that underlie visuomotor errors in those with stroke.
F47: Nonparetic Hand Exercise to Task-Failure Increases Functional Connectivity to Paretic Hand in Chronic Stroke
Qian Ding
1,2, Theresa McGuirk1,2, Elliott Perry1,2, Carolynn Patten1,2
1University of California, Davis, Davis, CA, USA2Northern California VA Healthcare System, Davis, CA, USA
We previously observed acute neural adaptations in the ipsilesional hemisphere of chronic stroke survivors in response to nonparetic hand exercise to task failure (ETF). These robust adaptations were sustained for up to 4 hours and accompanied by improved paretic hand dexterity and maximal voluntary contraction (MVC) facilitation. Here we sought to determine the locus of these adaptations and how ETF affects functional connectivity between the central nervous system and nonexercised paretic limb. We calculated intermuscular coherence (IMC), a method used to assess the strength of functional connectivity between the central nervous system and effector muscles. IMC activity in specific frequency bands is argued to arise from different neural loci (eg, alpha [range 8-12 Hz]: spinal and reflexes; beta [range 15-30 Hz]: corticospinal tract, subcortical and cortical; gamma [range 30-60 Hz]: cortical). We investigated IMC using surface EMG from first dorsal interosseous and opponens pollicis in 12 individuals with chronic stroke (upper extremity Fugl-Meyer assessment: 21-64/66, age: 66 ± 8 [53-79] years, 11 males) who performed ETF with repeated submaximal nonparetic hand isometric power grip. Powergrip MVC, dexterity (Box and Blocks Test [BBT]), and IMC were tested at baseline, immediately post-ETF, and every 45 minutes until 4 hours post-ETF. At baseline IMC in beta and gamma bands was significantly lower in the paretic than nonparetic hand (Ps < .05). Immediately post-ETF IMC in the exercised nonparetic hand increased in alpha, beta, and gamma bands revealing peaks at 0 (alpha) and 45 (beta, gamma) minutes (Ps < .05). In the nonexercised paretic hand, IMC increased significantly only in beta and gamma bands, revealing peaks at 90 and 135 minutes post-ETF, respectively (Ps < .05). In most participants, increased IMC in the nonexercised paretic hand post-ETF lagged changes in the exercised nonparetic hand by 1 to 2 hours. Paretic hand BBT improved (4% to 24%) in 11/12 participants at ⩾1 point post-ETF. The magnitudes of paretic hand facilitation and increased paretic hand beta band IMC were positively correlated (r2 = 0.45, P = .02). These parallel increases in paretic hand beta band IMC and BBT were greater in higher-functioning individuals (Ps < .05). In response to ETF, functional connectivity to the exercised, nonparetic hand increased from all levels of the central nervous system. However, to the nonexercised paretic hand functional connectivity increased primarily from supraspinal levels and was associated with paretic hand behavioral facilitation. The temporal disassociation in increased IMC between the exercised and nonexercised hands indicates that acute changes in functional connectivity to the nonexercised side require 1 to 2 hours to manifest. Our results suggest that nonparetic hand ETF induces acute supraspinal changes in the ipsilesional hemisphere, which may contribute to motor acquisition in the paretic hand and provide evidence regarding the mechanisms of nonparetic hand ETF and how it may be leveraged to promote paretic hand recovery in neurorehabilitation.
F48: Targeted Neuromodulation of Interhemispheric Connectivity After Stroke
Shiyu Lin1, Jacqueline Palmer1,
Michael Borich
1
1Emory University, Atlanta, GA, USA
Introduction: After stroke, atypical interhemispheric connectivity has been observed in stroke survivors with limited motor recovery. The presence of excessive interhemispheric inhibition (IHI) from the contralesional to ipsilesional motor cortex may impede motor recovery. Cortico-cortical paired associative stimulation (ccPAS) is a potentially promising noninvasive brain stimulation approach to target abnormal IHI in stroke. Using repeated pairing of transcranial magnetic stimulation (TMS) pulses applied over 2 distinct but connected cortical sites at a precise interpulse interval (IPI), ccPAS induces systems-level plasticity resembling synaptic spike timing-dependent plasticity (STDP) that modifies the connection strength of the targeted pathways. The purpose of this study was to evaluate the effect of a single session of ccPAS on IHI and motor cortex (M1) excitability in participants with chronic poststroke upper extremity impairment.
Methods: Eight participants (3 male) with ischemic chronic (>6 months) stroke completed 2 separate sessions separated by 1 week. Two different ccPAS conditions were evaluated and order was randomized between sessions: ccPAS8ms (IPI: 8 ms) and ccPAS1ms (IPI: 1 ms). The ccPAS conditions each consisted of 100 paired TMS pulses applied over the contralesional M1 (cM1) prior to ipsilesional M1 (iM1) at the designated ISI. Stimulus pairs were delivered at 0.25 Hz. IHI and M1 excitability were evaluated bilaterally prior to and at 3 time points following ccPAS (POST 0′, POST 30′, POST 24 hours). Electromyography (EMG) of the first dorsal interosseous muscle was collected bilaterally to evaluate motor evoked potential (MEP) amplitudes for both assessments. The 9-hole peg test (NHPT) was performed at the PRE time point to assess manual dexterity.
Results: Prior to ccPAS, significantly greater IHI from iM1-to-cM1 was observed (P = .004) compared to IHI from cM1-to-iM1. Baseline iM1-to-cM1 IHI was positively correlated (r = 0.81, P = .05) with better NHPT performance. Following ccPAS8ms, there was a significant decrease in iM1-to-cM1 IHI (P = .03) at POST 30′ compared to ccPAS1ms. Neither ccPAS condition significantly modulated cM1-to-iM1 IHI or M1 excitability.
Discussion: Preliminary results suggest that greater iM1-to-cM1 IHI may be present in individuals poststroke and associated with manual dexterity, a finding that contrasts the classical interhemispheric competition model of stroke recovery. Results also suggest that ccPAS may reduce iM1-to-cM1 IHI resulting in more balanced IHI between hemispheres. Further analyses are needed to evaluate IHI values in stroke versus matched healthy individuals and to evaluate ccPAS-based neuromodulatory effects on paretic arm motor behavior after stroke.
F49: Backward Locomotor Treadmill Training Combined With Transcutaneous Spinal Direct Current Stimulation in Stroke: A Pilot Feasibility and Safety Study
Oluwole Awosika
1, Saira Matthews1, Emily Staggs1, Christina Zhang1, Nirguna Thalla1, Rohitha Moudgal1, Pierce Boyne1, Kari Dunning1, Daniel Woo1, Brett Kissela1
1University of Cincinnati, Cincinnati, OH, USA
Background: Locomotor impairment after a stroke is due to the loss of adequate lower extremity function and affects nearly 66% of stroke survivors and is a significant cause of disability in the United States. Our recent proof of concept study suggests that transcutaneous spinal direct current stimulation (tsDCS) may enhance the effects of backward locomotor treadmill training (BLT) in healthy controls; however, this training paradigm has not been explored in chronic stroke patients.
Objective: Herein, we investigate the feasibility and safety of BLT+tsDCS in stroke, and present preliminary data on the effects of training on forward over-ground walking.
Methods: Chronic stroke patients (>6 months) with residual gait impairment were recruited to undergo six 30-minute BLT sessions (minimum belt speed >0.3 mph) with concurrent active (2.5 mA) or sham tsDCS, over 2 consecutive weeks (3 sessions/week). A safety harness was used during treadmill training and with over-ground walking. Primary outcomes were recruitment rate, successful protocol completion, and documentation of safety incidences. Additionally, preliminary data on BLT training efficacy (step length, cadence, symmetry) and change in over-ground walking performance (10-meter walk test), and exercise capacity (6-minute walk test) were collected at baseline, posttraining, and at 1 month. Enrollment goal is 36 participants.
Results: Between September 5, 2017, through July 10, 2018, 25 people were screened, and 21 met the criteria for enrollment. Ninety-five percent (20 of 21) enrolled participants successfully completed the study. One dropout occurred on day 1 of 6 of training and was due to excess fatigue. There were no serious adverse events with BLT or tsDCS, and both were well tolerated. All patients reported feeling stronger and more confident in forwarding walking. Posttraining, the mean change in walking speed was +0.27 ± 0.20 m/s and sustained +0.30 ± 0.21 m/s at 1 month. Similarly, there was a 56.2 ± 38.8 M improvement in walking capacity posttraining and 65.5 ± 41.0 M at 1 month.
Conclusion: This pilot study shows the feasibility and safety of BLT+ tsDCS in stroke. Our preliminary findings suggest that our BLT protocol is efficacious in improving over-ground walking speed and exercise capacity in chronic stroke patients. To maintain blinding, between-group comparison (to determine the effect of tsDCS) is deferred until study completion.
F50: A Novel EMG-Based Robotic Control for Restoring Normal Synergies After Stroke
Thomas Augenstein
1, Edward Washabaugh1, Christian Remy1, Chandramouli Krishnan1
1University of Michigan, Ann Arbor, MI, USA
Muscle weakness and loss of independent joint control are the 2 most common neuromotor impairments after stroke. While there are a number of approaches to improve poststroke muscle weakness, there are currently no rehabilitation strategies that directly target a patient’s inability to match and independently activate the normal patterned muscle coordination strategies, or “muscle synergies.” Our goal is to develop an EMG-based controller for retraining healthy muscle synergies in patients with stroke-related disabilities. The controller can be integrated into rehabilitation robots for their ability to structure the robot’s force output based on input EMG activity. However, developing such a controller would require a clear understanding of the relationship between the applied force from a rehabilitation robot and the resulting changes to a patient’s muscle synergies. Therefore, this study was performed to quantify how the muscle synergies of horizontal planar-reaching are affected by direction of an applied force at the end-effector (ie, hand). A 2 DOF, 10 muscle model was developed in MATLAB using parameters obtained from the OpenSim (version 3.3) open source software system. Simulation experiments were then performed in MATLAB to investigate the relationship between the applied force and the resulting muscle synergies. The simulated event was composed of several trials of the same right-handed, planar, multidirectional reaching task from 0° (to the right) to 360°. Each trial applied a different steering force direction at the subject’s hand, varying from −45° to 45° relative to the reaching direction. The simulation trials were also validated by evaluating the EMG patterns of a healthy subject when performing the same reaching task with varying steering force directions. For the 0° steering force trials, the muscle synergies and their activation timings were extracted using nonnegative matrix factorization (NMF). For all other trials, the synergy matrix was fixed and the activation timings were extracted from the product of the EMG of that trial and the pseudo-inverse of the synergy matrix from the 0° steering force trial. By fixing the synergy matrix in the trials with steering forces, we can directly track activation changes of a certain synergy as steering force is varied. For both simulation and experimental trials, circular statistics revealed a linear relationship between changes in steering force direction and principal direction of synergy activation. These results suggest that the activation of a synergy can be controlled directly by the direction of an applied steering force. This has relevant implications in synergy-based controller design because a computer can easily manipulate a patient’s muscle synergies and track the changes while avoiding the computational expense of NMF. In addition, similar analysis could be used to extract the relationship between applied forces and changes in synergies for other types of motion.
F51: Validity of Subjective Sleep Inventories for Assessment of Sleepiness in Inpatient Rehabilitation for Stroke
Heather Johns1, Elaina Cummer2, Ellie Flack3, Sarah Neveux3, Elena Skornyakov3,
Douglas Weeks
4
1University of Washington, Seattle, WA, USA
2Wake Forest University, Winston-Salem, NC, USA
3Eastern Washington University, Spokane, WA, USA
4St. Luke’s Rehabilitation Institute, Spokane, WA, USA
Objective: To study the association between self-report measures of sleepiness and sensor-based objective sleep measures among patients with stroke during inpatient medical rehabilitation.
Design: Patients receiving inpatient rehabilitation for stroke were consecutively approached to participate. Participants were fitted with an actigraph for 4 days and administered 3 subjective measures of sleepiness: Karolinska Sleepiness Scale (KSS), Wits Pictorial Sleepiness Scale (WPSS), and a Fatigue Visual Analog Scale (VAS) on days 2 and 4. Objective sleep metrics derived from the actigraph were minutes of nighttime sleep and minutes of daytime sleep. Setting: Inpatient rehabilitation facility. Participants: Adult male and female patients receiving inpatient rehabilitation services for stroke. Interventions: None. Main Outcome Measures: KSS, WPSS, VAS, minutes of nighttime sleep, and minutes of daytime sleep.
Results: Correlations as measures of criterion-related validity were derived among subjective and objective sleep measures on 16 patients with stroke. The only correlations that were significant were among the KSS and minutes of daytime sleep (r range = .522 to .556). No subjective measures correlated with nighttime sleep (r range = −.472 to .324).
Conclusions: There was poor agreement between subjective measures of nighttime sleep and objective metrics of sleep, suggesting that self-report sleep measures may not accurately represent true sleep status in stroke. The KSS seems to be effective for identifying patients with excessive daytime sleep. Further work is needed to identify subjective sleepiness scales for use in patients with stroke.
F52: Interventions to Augment Upper Extremity Motor Improvement in Individuals With a Traumatic Brain Injury: A Systematic Review
Sandeep Subramanian
1, Melinda Fountain1, Ashley Hood1
1UT Health San Antonio, San Antonio, UT, USA
Traumatic brain injury (TBI) is a leading cause of adult morbidity and mortality in the United States. Individuals who have sustained a TBI have impairments in both cognitive and motor domains. Motor improvements seen after a TBI are attributable to adaptive neuroplasticity and motor learning. Majority of the motor rehabilitation intervention studies in individuals who have sustained a TBI focus on remediation of balance and mobility impairments. Despite lower recovery rates in the upper (UL) compared to lower limbs, few studies have addressed UL issues in these individuals. There is limited understanding on the use of interventions for UL motor improvements in individuals who have sustained a TBI. We examined the evidence regarding the effectiveness of different interventions to augment UL motor improvement in individuals who have sustained a TBI. Using standard methodology, we systematically reviewed the literature published in English language. The quality of the studies was evaluated using modified Down’s and Black checklist scores (total of 28). Based on the range of total scores, we categorized the interventions as “excellent” (24-28), “good” (19-23), “fair” (14-18), and “poor” (⩽13) quality. We retrieved 16 studies that addressed upper limb motor impairment and activity limitations in this population. The interventions used included task-practice using virtual reality gaming (VR; 4 studies); constraint induced movement therapy (CIMT; 3 studies); arm motor ability training (1 study); task-oriented training (1 study); transcranial direct current stimulation (1 study); augmented feedback (1 study); stem-cell transplants (1 study); and strategies to reduce spasticity (serial casting, 1 study; provision of Botox, tizanidine, and acupuncture, 1 study each). Study designs used included randomized controlled trials (5 studies), case series (1 study), and cross-sectional design (10 studies). Six studies assessed only impairment measures, 2 studies assessed limitations in activity performance, and the remaining studies used both motor impairment and activity limitation outcomes. Most commonly used impairment outcomes included Fugl-Meyer Assessment, Modified Ashworth’s Scale, and kinematic outcomes of error, movement straightness, and velocity. Activity limitation outcomes included Wolf Motor Function Test and Motor Activity Log. Only 7 studies included any form of retention testing, with a maximum period of 1 month postintervention. The evidence was excellent for arm motor ability training, good for serial casting, and fair for the other interventions. The results suggest that use of these interventions can reduce motor impairment and improve levels of activity performance in individuals with TBI. Future studies should be designed using comparative efficacy designs with longer-term retention testing.
F53: Does Haptic Feedback Support Motor Learning With a Prosthesis? A Neurobehavioral Evaluation
John Johnson
1, Lewis Wheaton1
1Georgia Institute of Technology, Atlanta, GA, USA
Prosthesis use poses a unique challenge. Following an upper extremity amputation, the patient loses motor, structural, and somatosensory functionality. Technological advances have had negligible impact on clinical outcome measures, and rejection rates of upper extremity prostheses remains high. One technological advance is to provide greater sensory feedback from the prosthetic limb to potentially support improved function. However, the question of whether enhancing sensory feedback from the prosthesis improves motor learning and control remains open. To address this question, we recruited healthy intact subjects (n = 18) to use a prosthesis simulator to perform a repetitive reach-and-grasp task involving 3 differently sized discs. The 3 different disc sizes were used to determine if participants could learn to adapt to the disc size during reach-to-grasp. Participants were supplied with vibrotactile feedback indicative of successfully grasping a disc during half of their trials. Electroencephalographic (EEG) and kinematic data of the arm and prosthesis were gathered during the experiment. Kinematic results during reach show a greatly exaggerated overshoot of maximum aperture relative to all disc sizes. Vibrotactile feedback resulted in negligible benefit to aperture overshoot. These failures of additional information to improve grasp aperture accuracy indicate the vibrotactile sensory information is not being integrated with efferent motor information to drive a prosthesis-specific motor program. Electroencephalographic results show an increase in parietofrontal network activity in the presence of vibrotactile feedback, as well as increases in activity in frontal and left pre-motor cortex. The lack of kinematic effects may indicate the increased neural activity was due to the presence of the stimulus, though the stimulus was ineffective. These results suggest a limitation of tactile feedback to improve motor function with a prosthetic limb. Vibrotactile feedback did not facilitate development of a motor program for prosthesis use, and was shown to be detrimental to grasp aperture accuracy. The provision of vibrotactile feedback seems inconsequential to anticipatory motor learning with a prosthesis.
F54: Development of an Electromyographically Controlled Virtual Arm for Poststroke Motor Rehabilitation
Mingjian Zhang
1, Reza Rawassizadeh2, Ehsan Hoque2, Ania Busza1
1University of Rochester Medical Center, Strong Memorial Hospital, Rochester, NY, USA
2University of Rochester, Rochester, NY, USA
Objective: To develop a surface-electromyography (sEMG)-controlled virtual arm for early poststroke upper extremity motor rehabilitation in patients with moderate to severe arm weakness.
Background: Despite improvements in acute stroke treatment, stroke continues to be the leading cause of adult disability. There are currently several rehabilitation interventions that have been shown to facilitate motor recovery in clinical trials; however, many of these interventions require at least 2/5 strength (on the Medical Research Council [MRC] scale) of the limb for participation in therapy. For patients with more severe weakness, motor imagery and biofeedback may be helpful. New technologies, such as augmented or virtual reality devices, may provide ways to combine motor imagery and biofeedback.
Design and Methods: We have developed a system where sEMG signals recorded from the wrist flexor and extensor muscle groups are used to control the wrist flexion/extension of a virtual arm, which is displayed to the user as part of a game interface to encourage repetitive activation of the paretic arm. First, we evaluated different algorithms for translating sEMG signals into movement of the virtual arm. Four machine learning models were trained with sEMG and wrist position data (with wrist angle measured using a Cyberglove sensor system) from both healthy and weak individuals, and then we compared the predictive accuracies and precision of each model in strong and weak patients. Finally, we developed a simple ball game interface for the arm model that uses wrist movement to push a ball into a goal. We are currently comparing patient subjective experiences using the game in 3 different displays: augmented/mixed reality (using Microsoft HoloLens, a set of goggles that displays holographic images superimposed on the user’s field of view), immersive virtual reality (HTC Vive), and nonimmersive virtual reality (computer screen).
Results: Our results suggest that naive Bayes, linear regression, decision tree, and support vector machine algorithms have similar performance when used to predict wrist movement in both healthy controls and in patients with mild weakness (4/5 on the MRC scale). Work is ongoing assessing the accuracy of our system at interpreting sEMG signals from weaker patients (1/5 to 3/5 on the MRC scale) as well as adding additional game options to boost patient motivation.
Conclusions and Future Work: By using an iterative mixed-methods approach, we plan to continue to modify the system for improved patient subjective experience and increased duration of each practice session with the system. When the majority of patients trying our system are able to engage in 15 to 30 minutes of practice per session, we will transition from our device development phase to a pilot trial assessing efficacy.
F55: Assessment of Reflex and Nonreflex Components of Spasticity in Cerebral Palsy
Dali Xu1, Yi-Ning Wu2, Yupeng Ren3, Deborah Gaebler-Spira4, Fan Gao5, Mauricio Delgado6,
Li-Qun Zhang
1,7
1University of Maryland, Baltimore, Baltimore, MD, USA
2University of Massachusetts Lowell, Lowell, MA, USA
3Rehabtek, Baltimore, MD, USA
4Rehabilitation Institute of Chicago, Chicago, IL, USA
5University of Kentucky, Lexington, KY, USA
6Texas Scottish Rite Hospital for Children, Dallas, TX, USA
7Northwestern University, Chicago, IL, USA
Introduction: The purpose of this study was to compare reflex and nonreflex components of ankle spastic hypertonia in cerebral palsy (CP) to that of typically developing children (TDC). A portable robotic device was employed to quantify reflex and nonreflex components of ankle spasticity in children with CP. Our hypothesis was phasic and tonic stretch-reflex, intrinsic and passive joint stiffness, and viscous damping increased significantly in spastic CP as compared to TDC.
Methods: Seventeen children with CP and 17 typically developing children participated in this study. A robotic device and a surface electromyography (EMG) system were used to examine reflex and nonreflex responses of participants during controlled passive movements. The participant sat with the tested leg strapped to an adjustable leg-support. Surface EMG was measured at the tibialis anterior (TA) and triceps surae. The participant’s ankle was moved at multiple speeds to evaluate elastic stiffness (at 5°/s) and reflex and nonreflex responses 3 times at each of 4 speeds (60°, 90°, 180°, and 210°/s) in a random order. Two-way (2 × 4) repeated-measures ANOVA were used for evaluating stretching responses between 2 groups.
Results: Responses of muscles to stretching: The reflex EMG responses were observed at both soleus and tibialis anterior under passive stretching. The CP group had significantly higher peak values of the SOL-EMG and reflex torques than that in the TDC under each speed of the passive stretching. TA response was significantly greater in the CP patients across each stretching speed too (0.017 ± 0.017 vs 0.006 ± 0.001 at 60°/s [P = .02]; 0.018 ± 0.012 vs 0.007 ± 0.002 at 90°/s [P = .0008]; 0.035 ± 0.027 vs 0.011 ± 0.008 at 180°/s [P = .002]; 0.049 ± 0.049 vs 0.012 ± 0.008 at 210°/s [P = .007]). Evaluating nonreflex components: Normalized ankle stiffness in CP (0.01 ± 0.005) was higher than that of TDC (0.002 ± 0.001, P = .01). The normalized viscous damping in CP was higher than that in TDC across all stretching velocities (P = .006). The average normalized viscous damping at 60°/s were significantly different (0.021 ± 0.01 in CP vs 0.014 ± 0.01 in TDC, P = .02). The averages were 0.026 ± 0.01 in CP and 0.016 ± 0.01 in TDC at 90°/s (P = .02). The averages at 180°/s were 0.031 ± 0.02 in CP and 0.017 ± 0.01 in TDC (P = .02). The averages at 210°/s were 0.0360.02 in CP and 0.0170.01 in TDC (P = .01).
Discussion: Overall, our results showed not only the reflex-mediated reactive torque was higher in children with CP as compared to TDC, but the nonreflex components, stiffness and viscous torques, also contributed to the increased torque significantly higher in CP group. The results suggested that the joint flexibility and control ability was reduced and reflex reciprocal facilitation of antagonist (TA) is suppressed. This assessment may help guide therapeutic treatments.
F56: Effects of Gait Training on Spinal Excitability and Gait Biomechanics in Individuals Poststroke
Jiang Xu
1, Steven Eicholtz1, Justin Liu1, Morgan Trees1, Alejandro Lopez1, Trisha Kesar1
1Emory University, Atlanta, GA, USA
Background: Although neuroplasticity is considered a central mechanism underlying rehabilitation, there are very few comprehensive investigations of neuroplasticity processes underlying gait training. The stroke lesion disrupts descending inhibition, leading to heightened spinal excitability, which can be measured with Hoffman’s reflex (H-reflex). This study investigated plasticity in spinal reflex circuitry induced by a poststroke gait training intervention combining fast treadmill walking and functional electrical stimulation (FastFES) delivered to dorsiflexor and plantarflexor muscles. We tested 3 hypotheses: (1) 3 sessions of either Fast or FastFES training are sufficient to induce a change in spinal reflex excitability; (2) 3 sessions of FastFES training produce greater improvements in spinal excitability compared to Fast training; (3) training-induced changes in spinal excitability correlate with changes in gait biomechanics.
Methods: Ten individuals with poststroke hemiparesis participated in the study (5 females, age 59.7 ± 8.3 years, Fugl Myer-LE score 24 ± 5.1). The study comprised a repeated-measures crossover design with 3 sessions of Fast and 3 sessions of FastFES treadmill training. Soleus spinal excitability was evaluated using the peak H-reflex amplitude normalized to the maximal M-wave response (Hmax/Mmax ratio). Gait biomechanics variables included propulsion (peak anterior ground reaction force), ankle plantarflexor moment, and peak trailing limb angle for the paretic leg. Clinical function was evaluated using the Timed Up and Go and 10-meter walk tests (self-selected and fast speeds).
Results: Three sessions of gait training (Fast or FastFES) were sufficient to induce changes in spinal excitability and gait biomechanics. After 3 Fast sessions, we observed a decrease in Hmax/Mmax. In contrast, after FastFES, we observed a significant increase in Hmax/Mmax (P < .01). Training-induced change in Hmax/Mmax showed a statistical trend for differences between FastFES versus Fast (P = .09). Pearson’s correlation analysis revealed that baseline Hmax/Mmax correlated with training-induced change in paretic pushoff (P = .03). FastFES-induced change in Hmax/Mmax correlated with change in paretic propulsion, such that larger training-induced depression of Hmax/Mmax correlated with improved paretic propulsion (P = .004, r = −0.82).
Discussion: Our findings regarding the effects of Fast and FastFES on spinal reflex circuitry, and relationships between training-induced modulation of spinal excitability and gait biomechanics, can elucidate novel mechanisms underlying the clinical effects of these interventions. Our results suggest that Hmax/Mmax may have potential to serve as a neurophysiologic marker of training response.
