Brain Connectivity

Understanding how brain function and language skills change during early (acute and subacute) stroke phases is critical for maximizing patient recovery, yet functional neuroimaging studies of early aphasia are scarce. In this pilot study, we used functional near-infrared spectroscopy (fNIRS) to investigate how resting-state functional connectivity (rs-FC) in early aphasia differs from neurologically healthy adults and is related to language deficits.

Twenty individuals with aphasia (12 acute and 8 subacute phase) and 15 healthy controls underwent rs-fNIRS imaging with a 46-channel montage centered over bilateral perisylvian language areas. FC was computed using a prewhitening, autoregressive Pearson correlation routine applied to preprocessed oxyhemoglobin (HbO) data. Connections were classified as left intra-, right intra-, or interhemispheric. We then compared rs-FC between groups by connection type and examined Spearman correlations between rs-FC averages and language measures within patients.

Participants in the acute phase had significantly reduced global rs-FC across all HbO-based connections compared to healthy controls. No significant differences were found in rs-FC between controls and patients in the subacute phase. Controlling for days since stroke, stronger right intra- and interhemispheric rs-FC was related to milder aphasia across all patients. Exploratory correlations revealed that relationships between language measures and rs-FC differed between acute and subacute patient groups.

This study provides preliminary evidence that fNIRS-based rs-FC measures may be a viable metric to index the early impacts of stroke in people with aphasia.

Questions regarding the nature of neural recovery in early poststroke aphasia mostly remain unanswered, largely due to the shortage of functional imaging studies in this population. Logistical challenges of magnetic resonance imaging are central barriers to early stroke imaging. Functional near-infrared spectroscopy (fNIRS) is a promising alternative as it is relatively inexpensive and portable. Resting-state functional connectivity (rs-FC) provides an avenue to avoid the confounds of task demands and difficulties inherent in task-based imaging studies. The importance of this pilot study lies in its first-ever application of fNIRS-based rs-FC to investigate brain–behavior relationships in acute and subacute aphasia.

Transcranial direct current stimulation (tDCS) targeting the primary motor cortex is modestly effective for promoting upper-limb motor function following stroke. The premotor cortex (PMC) represents an alternative target based on its higher likelihood of survival and dense motor-network connections.

The objective of this study was to determine whether ipsilesional PMC tDCS affects motor network functional connectivity (FC) in association with reduction in motor impairment, and to determine whether this relationship is influenced by baseline motor severity.

Participants with chronic stroke were randomly assigned to receive active-PMC or sham-tDCS with rehabilitation for 5 weeks. Resting-state functional magnetic resonance imaging was acquired to characterize change in FC across motor-cortical regions.

Our results indicated that moderate-to-severe participants who received active-tDCS had greater increases in PMC-to-PMC interhemispheric FC compared to those who received sham; this increase was correlated with reduction in proximal motor impairment. There was also an increase in intrahemispheric dorsal premotor cortex-primary motor cortex FC across participants regardless of severity or tDCS group assignment; this increase was correlated with a reduction in proximal motor impairment in only the mild participants.

Our findings have significance for developing targeted brain stimulation approaches. While participants with milder impairments may inherently recruit viable substrates within the ipsilesional hemisphere, stimulation of PMC may enhance interhemispheric FC in association with recovery in more impaired participants.

ClinicalTrials.gov Identifier: NCT01539096; Registration date: February 21, 2012.

This study reports that improved post-stroke proximal motor impairment following constraint induced movement therapy is associated with increases (a) inter-hemispheric connectivity in participants with moderate-to-severe impairments, and (b) intra-hemispheric connectivity in participants with mild impairments. As non-invasive brain stimulation of the ipsilesional premotor cortex was shown to enhance inter-hemispheric connectivity between homologous premotor cortex in participants with more severe impairments, we suggest that future studies of non-invasive brain stimulation should aim to personalize stimulation targets based on intrinsic mechanisms of recovery available to patients within different impairment ranges.

To investigate the association between the degree of spatial neglect and the changes of brain system segregation (SyS; i.e., the ratio of the extent to which brain networks interact internally and with each other) after stroke.

A cohort of 20 patients with right hemisphere lesion was submitted to neuropsychological assessment as well as to resting-state functional magnetic resonance imaging session at acute stage after stroke. The severity of spatial neglect was quantified using the Center of Cancellation (CoC) scores of the Bells cancellation test. For each patient, resting-state functional connectivity (FC) matrices were assessed by implementing a brain parcellation of nine networks that included the visual network, dorsal attention network (DAN), ventral attention network (VAN), sensorimotor network (SMN), auditory network, cingulo-opercular network, language network, frontoparietal network, and default mode network (DMN). For each patient and each network, we then computed the SyS derived by subtracting the between-network FC from the within-network FC (normalized by the within-network FC). Finally, for each network, the CoC scores were correlated with the SyS.

The correlational analyses indicated a negative association between CoC and SyS in the DAN, VAN, SMN, and DMN (q < 0.05 false discovery rate [FDR]-corrected). Patients with more severe spatial neglect exhibited lower SyS and vice versa.

The loss of segregation in multiple and specific networks provides a functional framework for the deficits in spatial and nonspatial attention and motor/exploratory ability observed in neglect patients.

In a graph-theoretic framework, we identify a loss of system segregation associative and sensorimotor networks in neglect patients who had suffered from right hemisphere stroke. From a theoretical standpoint, our findings corroborate the working hypothesis that the efficient segregation among brain systems is relevant for executing higher functions such as spatial attention. Clinically, the set of networks that exhibit loss of segregation offers a therapeutic opportunity and can be targets of neuromodulation protocols for neglect rehabilitation.

To identify brain hubs that are behaviorally relevant for neglect after stroke as well as to characterize their functional architecture of communication.

Twenty acute right hemisphere damaged patients underwent neuropsychological and resting-state functional magnetic resonance imaging sessions. Spatial neglect was assessed by means of the Center of Cancellation on the Bells Cancellation Test. For each patient, resting-state functional connectivity matrices were derived by adopting a brain parcellation scheme consisting of 153 nodes. For every node, we extracted its betweenness centrality (BC) defined as the portion of all shortest paths in the connectome involving such node. Then, neglect hubs were identified as those regions showing a high correlation between their BC and neglect scores.

A first set of neglect hubs was identified in multiple systems including dorsal attention and ventral attention, default mode, and frontoparietal executive–control networks within the damaged hemisphere as well as in the posterior and anterior cingulate cortex. Such cortical regions exhibited a loss of BC and increased (i.e., less efficient) weighted shortest path length (WSPL) related to severe neglect. Conversely, a second group of neglect hubs found in visual and motor networks, in the undamaged hemisphere, exhibited a pathological increase of BC and reduction of WSPL associated with severe neglect.

The topological reorganization of the brain in neglect patients might reflect a maladaptive shift in processing spatial information from higher level associative-control systems to lower level visual and sensory–motor processing areas after a right hemisphere lesion.

In this study, by employing the theoretic graph measures of betweenness centrality, we identified a set of neglect hubs, that is a cohort of cortical hubs that are behaviorally relevant for neglect after right hemisphere stroke. Although regions in higher level associative-control systems decreased their centrality and efficacy in communication, lower level visual and sensory–motor processing areas exhibited a dysfunctional increase in centrality. These findings have clinical implications as neglect hubs may be targeted for noninvasive brain stimulation protocols to restore their centrality and in turn to ameliorate the spatial deficit.

Impaired movement after stroke is closely associated with altered brain functions, and thus the investigation on neural substrates of patients with stroke can pave a way for not only understanding the underlying mechanisms of neuropathological traits, but also providing an innovative solution for stroke rehabilitation. The objective of this study was to precisely investigate altered brain functions in terms of power spectral and brain network analyses.

Altered brain function was investigated by using electroencephalography (EEG) measured while 34 patients with chronic stroke performed movement tasks with the affected and unaffected hands. The relationships between functional brain network indices and Fugl-Meyer Assessment (FMA) scores were also investigated.

A stronger low-beta event-related desynchronization was found in the contralesional hemisphere for both affected and unaffected movement tasks compared with that of the ipsilesional hemisphere. More efficient whole-brain networks (increased strength and clustering coefficient, and prolonged path length) in the low-beta frequency band were revealed when moving the unaffected hand compared with when moving the affected hand. In addition, the brain network indices of the contralesional hemisphere indicated higher efficiency and cost-effectiveness than those of the ipsilesional hemisphere in both the alpha and low-beta frequency bands. Moreover, the alpha network indices (strength, clustering coefficient, path length, and small-worldness) were significantly correlated with the FMA scores.

Efficient functional brain network indices are associated with better motor outcomes in patients with stroke and could be useful biomarkers to monitor stroke recovery during rehabilitation.

Even though understanding neuropathological mechanisms in patients with stroke can assist motor rehabilitation, their neuropathological traits have not been fully explored in previous studies. The present study discovered the distinct disruptions of functional brain networks by using electroencephalography data measured during the affected hand movement, and the altered functional networks were significantly correlated with Fugl-Meyer Assessment scores. Our experimental results can provide an in-depth understanding of the neuropathology for patients with stroke, implying that the distinct functional network indices can be potentially used as biomarkers to objectively monitor the degree of motor impairments for patients with stroke during motor rehabilitation.

The primary aim of the research was to compare the impact of postischemic and hemorrhagic stroke on brain connectivity and recovery using resting-state functional magnetic resonance imaging.

We serially imaged 20 stroke patients, 10 with ischemic stroke (IS) and 10 with intracerebral hemorrhage (ICH), at 1, 3, and 12 months (1M, 3M, and 12M) after ictus. Data from 10 healthy volunteers were obtained from a publically available imaging data set. All functional and structural images underwent standard processing for brain extraction, realignment, serial registration, unwrapping, and denoising using SPM12. A seed-based group analysis using CONN software was used to evaluate the default mode network and the sensorimotor network connections by applying bivariate correlation and hemodynamic response function weighting.

In comparison with healthy controls, both IS and ICH exhibited disrupted interactions (decreased connectivity) between these two networks at 1M. Interactions then increased by 12M in each group. Temporally, each group exhibited a minimal increase in connectivity at 3M compared with 12M. Overall, the ICH patients exhibited a greater magnitude of connectivity disruption compared with IS patients, despite a significant intrasubject reduction in hematoma volume. We did not observe any significant correlation between change in connectivity and recovery as measured on the National Institutes of Health Stroke Scale (NIHSS) at any time point.

These findings demonstrate that the largest changes in functional connectivity occur earlier (3M) rather than later (12M) and show subtle differences between IS and ICH during recovery and should be explored further in larger samples.

The primary aim of the serial neuroimaging study was to compare the impact of postischemic and hemorrhagic stroke on brain connectivity and recovery using resting-state functional magnetic resonance imaging. A seed-based connectivity analysis was applied to evaluate the interaction between the default mode network and the sensorimotor network using bivariate correlation and hemodynamic response function weighting. Overall, the intracerebral hemorrhage patients exhibited a greater magnitude of connectivity disruption compared with ischemic stroke patients, despite a significant intrasubject reduction in hematoma volume.

Intracranial atherosclerotic stenosis (ICAS) is a key risk factor for vascular cognitive impairment. Cerebral blood flow (CBF) and the spatial coefficient of variation (sCoV) of CBF images (based on pseudocontinuous arterial spin labeling) are used to explore abnormal cerebral perfusion. We aimed to probe the mechanisms underlying cognitive impairment in patients with nondisabling anterior circulation macrovascular disease.

This study included 47 patients with ICAS or occlusion and 40 controls. All participants underwent global and individual neuropsychology assessments and magnetic resonance imaging scan. The correlations between cognitive function and abnormal perfusion were explored.

The CBF in the ipsilateral middle cerebral artery (MCA) territory of the lesion side decreased significantly, while it increased on the contralateral side. CBF value had a significant correlation with the memory function in the right cerebral artery lesion group. The sCoV in both gray matter (GM) and the ipsilateral MCA territory of the lesion increased significantly. The sCoV value based on the GM territory or MCA territory was significantly correlated with global cognitive function, memory function, and executive function in patients with ICAS.

The cognitive function of patients with severe ICAS or occlusion in anterior circulation was significantly impaired. sCoV could be a better indicator of cognitive impairment than CBF. Interventions to relieve vascular stenosis or occlusion and delay cognitive impairment or improve cognitive function should be actively considered.

Intracranial atherosclerotic stenosis (ICAS) is a key risk factor for stroke and vascular cognitive impairment (VCI). VCI seriously affects the physical and mental health of patients and their caregivers, significantly increasing the social burden. The most direct changes in patients with ICAS are the decrease of cerebral blood flow in the blood supply area and the abnormality of local or whole cerebral perfusion. This study explores the relationship between abnormal cerebral perfusion and cognitive impairment in patients with ICAS, which helps to increase the attention paid to VCI and promote the improvement of diagnosis and treatment measures.