Use of noninvasive brain stimulation and neurorehabilitation devices to enhance poststroke recovery: review of the current evidence and pitfalls

Abstract

Neurorehabilitation devices and technologies are crucial for enhancing stroke recovery. These include noninvasive brain stimulation devices that provide repetitive transcranial magnetic stimulation or transcranial direct current stimulation, which can remodulate an injured brain. Technologies such as robotics, virtual reality, and telerehabilitation are suitable add-ons or complements to physical therapy. However, the appropriate application of these devices and technologies, which target specific deficits and stages, for stroke therapy must be clarified. Accordingly, a literature review was conducted to evaluate the theoretical and practical evidence on the use of neurorehabilitation devices and technologies for stroke therapy. This narrative review provides a practical guide for the use of neurorehabilitation devices and describes the implications of use and potential integration of these devices into healthcare.

Keywords

Neurorehabilitation repetitive transcranial magnetic stimulation transcranial direct current stimulation robotics virtual reality telerehabilitation noninvasive brain stimulation stroke

Introduction

Stroke is a leading cause of adult disability, and involves neurological sequelae such as motor, speech, and cognitive deficits. Stroke prognoses vary considerably, and recovery from stroke is often dependent on the stroke severity and type as well as the brain areas affected. Strokes that involve large lesion sites and multiple deficits are associated with delayed and poor recovery. The conventional approach to stroke recovery is centered around intensive neurorehabilitation, with physical, speech, and occupational therapies aimed at restoring functional and muscle strength.¹ Comorbidities related to stroke increase after COVID 19-infection, which raises further concerns about stroke care and recovery. However, in one study, 85% of patients with stroke exhibited considerable improvements after 3 to 6 months of traditional inpatient therapy.² New technologies that facilitate poststroke neurorecovery through neuromodulation and assistive devices have been developed to increase the efficacy of stroke therapies. Noninvasive brain stimulation (NIBS) is a primary neuromodulation tool that is used to modulate brain excitability. Furthermore, robotics and other technologies such as virtual reality (VR) and telerehabilitation (TR) have been increasingly applied as stroke recovery therapies. The COVID-19 pandemic period provided a unique opportunity for the broad use of TR and VR.

Although these devices can facilitate brain activity in stroke recovery, inconsistent therapeutic effects have been reported. Few studies have addressed whether these devices and techniques have superior therapeutic efficacy to traditional rehabilitation in stroke recovery. The present narrative review aimed to summarize the current application of neurorehabilitation devices to facilitate stroke recovery. NIBS is particularly important for one main reason: because traditional rehabilitation methods cannot alter imbalances in cortical activity directly after stroke. We will therefore highlight the mechanisms of these devices and provide an overview of their modes, types, and clinical uses. Finally, we will discuss the appropriate selection and use of these devices to facilitate neurorecovery in different stages of stroke.

Methodology

The present review explored the existing evidence on the use of neurorehabilitation devices through a literature review, and provided evidence-based suggestions using a narrative review model.³ We reviewed studies that explored neurorehabilitation devices and technologies related to stroke rehabilitation that had been published from inception until July 2022 in the Web of Science and PubMed databases. The following keywords were used in the search: “rTMS” (repetitive transcranial magnetic stimulation), “tDCS” (transcranial direct current stimulation), “robotic rehabilitation,” “virtual reality,” “telerehabilitation,” “stroke rehabilitation,” and “neurorehabilitation.” There were no restrictions on the type of study design. Our inclusion criteria were limited to articles related to neurorehabilitation or neuromodulation of stroke patients. We excluded articles with inaccessible full texts. Two authors then reviewed the selected references. This yielded 124 articles, which were screened based on title/abstract to identify original research and review articles written in English. As a result, 50 articles met the eligibility criteria and were included in the present review.

NIBS for patients with stroke

rTMS

Mechanisms of neuroplasticity

TMS is a noninvasive process that uses magnetic fields to generate a change in cell membrane potential within a nerve cell to stimulate tracts descending to the spinal cord, such as the cortical spinal tract, which descends from the brainstem to the spinal cord.⁴ The repetitive mode, known as rTMS, generates long-term effects on neural potentiation, comprising long-term potentiation (LTP) and long-term depression (LTD). These terms refer to the strengthened and reduced efficacy of synapses, respectively, after persistent excitation or inhibition of a cortical region; the effects depend on stimulation frequency and intensity.⁵ These effects can last from 30 minutes to several days, thus remodulating neuroactivity at the applied site. On the basis of the mechanism of transcallosal inhibition, an imbalance occurs between the ipsilesional and contralesional hemispheres; the contralesional brain becomes overactive and the ipsilesional brain becomes underactive.⁶ The high-frequency (10 to 20 Hz) stimulation mode is applied to the ipsilesional site to provide a facilitatory effect, whereas low-frequency (1 to 5 Hz) stimulation is applied to the contralesional brain to induce inhibition.⁷ High- and low-frequency stimulations induce LTP and LTD, respectively, and can improve motor function through neuromodulation. Modulation effects are also observed outside of the original stimulated cortex through transcortical and interhemispheric connections.

Modes and types

A clinical consideration for mode selection is the risk of stimulation-induced epilepsy; the application of the inhibitory mode to the contralesional cortex is safer than the application of the facilitatory mode to lesion sites. Moreover, different patterns of stimulation protocols, such as theta-burst and quadripulse stimulation, may exert varying effects. Theta-burst stimulation consists of short bursts of stimulation at high frequencies and low stimulation intensities. Compared with standard rTMS, theta-burst stimulation has the advantage of shorter administration durations, and it produces effects comparable to those of standard rTMS.⁸ Quadripulse stimulation serves as an another patterned rTMS protocol, and produces stronger LTP and LTD than theta-burst stimulation⁹ (Table 1).

Table 1.

Characteristics of devices used in neurorehabilitation.

Category	Device	Mechanism	Type/mode	Advantages	Disadvantages
Noninvasive brain stimulation	rTMS	Magnetic fieldSynaptic strength enhancement (i.e., LTP and LTD)	High frequency (10 to 20 Hz): facilitation of lesion siteLow frequency (1 to 5 Hz): inhibition of healthy area	Deep brain lesionsMore persistent Neuroplasticity	Seizure risk
	tDCS	Electrical fieldLTP/LTD	Anodal: facilitatory effectCathodal: inhibitory effect	NeuroplasticityPortable	Less stimulation intensity than rTMSCannot use for speech deficits or depression
Neurorehabilitation devices	Robotics	High-dosageHigh-intensity training	End-effector-typeExoskeletal	High-labored therapy such as gait training	ExpensiveMode setting
	Virtual reality	Exercise repetitionIntensity variationTask-oriented training	Fully immersiveSemi-immersiveNon-immersive	Enjoyable increased adherenceSafe environment	DizzinessHeadacheMotion sickness
	TR	Remote training	Motor training exercisesSpeech therapyVirtual realityRobotic therapyGoal settingGroup exercise	Improved accessibilityPsychological stabilization	TR acceptance, knowledge, skillsTechnical factors

LTD, long-term depression; LTP, long-term potentiation; rTMS, repetitive transcranial magnetic stimulation; tDCS, transcranial direct current stimulation; TR, telerehabilitation.

In addition to stimulating effects, stimulation modes can exert therapeutic effects. In an earlier study, we found that consecutive 1-Hz inhibitory stimulation and theta-burst stimulation had a superior therapeutic effect on the experimental group relative to the control group.¹⁰ This previous study also suggested that preconditioning, in which different types of modulation are combined, produces an add-on effect that facilitates neuronal activation.¹⁰

Clinical use

Although rTMS therapy was initially designed to treat depression, accumulating evidence suggests that it can be used as a stroke therapy. One study reported that inhibitory rTMS application over contralesional sites or facilitatory rTMS application over lesion sites can improve motor function.¹¹ The application of rTMS in stroke is focused mainly on upper extremity motor deficits because the brain area that represents the hand is in the precentral gyrus. In addition, 1-Hz inhibitory stimulation applied to the contralesional cortex can reduce upper extremity spasticity.

The lower extremities are represented in the inner cortex of the central brain, which requires deeper stimulation; rTMS is therefore less effective for treating these regions. By contrast, the application of 1-Hz rTMS modulation to Broca’s area (in the frontal lobe) can improve the naming ability of patients with aphasia. Nevertheless, individuals with concomitant speech disorders and motor deficits typically have more severe brain damage than those without such disorders; rTMS therapy may be less effective for such individuals.¹²

tDCS

Mechanism and clinical use

A tDCS device comprises two electrodes and a stimulator, and is considerably more portable than a magnetic stimulation machine. tDCS devices polarize neurons by creating an electrical field; the anode and cathode exert facilitatory and inhibitory effects, respectively. These devices can also exert a neuroplastic effect on LTD or LTP by modulating the activity of healthy or lesioned brain regions.¹³ Furthermore, both anodal and cathodal stimulation can improve the functional and muscle strength of poststroke hemiplegic limbs, although anodal stimulation of the ipsilesional hemisphere is generally superior to cathodal stimulation of the contralesional hemisphere.¹⁴

The conventional mechanism of tDCS, involving transcortical inhibition through intercallosal interaction, has been challenged by researchers, making it more applicable to all patients. The high cortical excitability of the contralesional hemisphere, which is attributable to imbalanced cortical inhibition, may be compensation for hypoactivity at lesion sites. This phenomenon is more pronounced in patients with chronic or severe damage. The application of facilitatory rather than inhibitory stimulation to the contralesional hemisphere may therefore produce more favorable outcomes. Together, these findings indicate that tDCS protocols must be tailored to stroke stage. Notably, the integration of adjunctive therapies, such as constraint-induced movement therapy, into rehabilitation programs can improve recovery outcomes. Similarly, studies have suggested that a combination of rTMS and tDCS can produce synergistic effects on various therapeutic targets.¹⁵ However, tDCS is ineffective when applied to patients with aphasia,¹⁶ and further investigations are required to clarify the efficacy of tDCS for the treatment of speech and swallowing disorders and poststroke depression.

Limitations and variability

Evidence regarding the therapeutic efficacy of tDCS is inconsistent, likely because of the heterogeneity of clinical data, different tDCS methods used, and varying outcome measurements of previous studies.¹³ These varying findings are also likely caused by differences in tDCS parameters, including electrode size, stimulation intensity, stimulation duration, and attachment positions. For example, current intensity is generally set between 1 and 2 mA, and stimulation duration ranges between 5 and 30 minutes and is believed to influence the duration of poststimulation cortical excitability.¹⁷ Moreover, the electrode position is chosen based on the target brain area.¹⁷ For example, in the dual stimulation method, the electrode is placed bilateral to the motor cortex area, thus providing facilitatory stimulation to one site and inhibitory stimulation to another site. Interestingly, smaller electrodes with more focal positions are reportedly more effective than square sponges for enhancing spatial focality.

Remotely supervised methods

Because of the small size and portability of tDCS devices, they can be used for home-based rehabilitation. Studies have proposed remotely supervised tDCS treatment protocols that include strict dose controls and the monitoring of device preparation and adverse effects.¹⁸ Remotely supervised tDCS has already been implemented in some hospital facilities (e.g., New York University Langone Health) to increase patients’ access to treatments. Studies conducted since 2017 have reported the safety and efficacy of remotely supervised tDCS for treating neurological deficits, such as those associated with multiple sclerosis, stroke, and vascular dementia.¹⁹ Thus, tDCS is considered an alternative therapy to rTMS for maintaining neuromodulation.

Neurorehabilitation devices

Robotics

Robotic devices have been used for decades to assist individuals with disabilities to stand or walk; they are especially helpful for patients with lower limb paraplegia, such as those with spinal cord injury or stroke. A robotic device is a preprogrammed machine with multifunctional manipulators that provides high-dose, high-intensity rehabilitation therapy to patients. Robotic rehabilitation can be classified into assisted and therapeutic rehabilitation, and robotic devices can be used to conduct task-specific training. Robotic rehabilitation can be further classified into end-effector and exoskeletal types depending on the type of robot used. End-effector robots are connected to a patient’s distal limbs and are easy to set up. However, they may result in abnormal movement patterns, which results in limited control of the proximal joints of limbs.²⁰ By contrast, exoskeletal robots can be used to achieve appropriate limb alignment through the precise control of joints; however, these devices are expensive and are more complex than other types of devices.²¹ They also have disadvantages of limited power and ranges of motion.

Exoskeletal robots, such as the Lokomat, play an essential role in lower leg rehabilitation by assisting patients to stand using a control system. Because the main rehabilitation goal is to restore lower limb motor function and normal gait, a normal gait pattern reference is installed in the control system. Exoskeletal devices can also be connected to treadmills in body weight support systems used for gait training, which require less space. In patients with stroke who have hand disabilities, electromyography-driven exoskeletal hand devices are used; these can detect electromyography signals from a single muscle group, such as the triceps or biceps, and generate force and torque at the extremity joint. Moreover, a combination of task-oriented therapy and physiotherapy has been suggested to improve functional recovery in patients with stroke.²²

Robotic rehabilitation is associated with brain reorganization, and its mechanism of action involves increased cortical excitability in the ipsilesional hemisphere, thus generating therapy-induced plasticity.²³ A combination of exoskeletal devices and traditional physiotherapy has been demonstrated to produce superior gait function improvements relative to traditional therapy or exoskeletal robotic rehabilitation alone.²⁴ However, exoskeletal devices alone do not produce superior results to traditional therapy. For example, in one study, the use of robot-assisted gait exercises for the rehabilitation of patients with hemiplegia after primary stroke resulted in significant early improvements in walking ability relative to the control group at 4 weeks, but not at 8 weeks.²⁵ These results suggest that exoskeletal devices cannot fully replace physiotherapy because of their complexity and limitations of mobility.

End-effector devices are effective as adjunctive therapies for the lower extremities. Regarding upper limb and hand function restoration, end-effector devices can produce improvements in activities of daily living that are similar or superior to those achieved with traditional physiotherapy in patients with subacute stroke.²⁶ Furthermore, robotics-assisted, high-intensity training of the upper limbs has been reported to produce improvements, but the effects are not significantly superior to those achieved through physiotherapy.²⁷ In summary, robotic assistance devices can be used as adjunctive rehabilitation therapy to primary therapies (e.g., rTMS) but cannot yet replace traditional physiotherapy.

Robotic rehabilitation has a fundamental potential role in combination with other therapies. A framework of intelligent home rehabilitation systems comprising robotic devices has been developed, wherein “internet of things” technologies and telesupervision create a comprehensive network and database for therapists and patients.²⁸ Such developments highlight the key role of robotic rehabilitation in noncontact and unmanned rehabilitation. For example, one study reported the effectiveness of a combination of TR and affordable robotic devices for home-based upper limb rehabilitation.²⁹ Furthermore, the addition of robotic and VR training to usual care may lead to greater improvements in the early poststroke period relative to usual care alone.

VR

VR involves the use of computer technology to create a simulated environment that can interact with a user who is equipped with VR instruments (e.g., gloves fitted with sensors and head-mounted displays). In terms of the immersion level, VR can be classified as fully immersive, semi-immersive, and non-immersive. Fully immersive simulations provide a complete view of the created content through a headset, whereas semi-immersive simulations incorporate real objects into virtual content through displays.³⁰ VR has several advantages when used for tasks that are repetitive or goal-oriented, as well as for tasks that are unsafe to practice in the real world for patients with stroke. For example, the motion-sensing input device Kinect has sensors that can accurately track a patient’s performance and feedback, and the device can record the kinematic data of a user and control VR interventions.³¹ A randomized study reported that the use of Nintendo’s Wii video game console as an intervention tool for stroke rehabilitation resulted in significantly superior motor function improvements relative to those achieved by recreation therapy;³² this finding indicates that VR devices can be applied for both interventions and precision measurements.

Neuroimaging studies can characterize structural changes related to factors affecting therapeutic efficacy. A functional magnetic resonance imaging study has revealed the activation of various sensory areas (e.g., the angular gyrus, precuneus, and extrastriate body area) in the brain of a VR user when virtual avatars were used as an extension of the user’s own body, suggesting that VR can serve as a disembodied training tool.³³

VR content also plays a crucial role. VR-based therapies that include games that are specifically designed for rehabilitation have been reported to be more efficacious than conventional therapy for improving upper limb function.³⁴ In addition, the most immediate effects of VR-based interventions are greater adherence to therapy and longer exercise sessions because of the enjoyable nature of interactive video games. However, although emerging studies have reported promising results for the use of VR in stroke rehabilitation, VR can still only be used as an adjunctive therapeutic tool for improving upper limb function.³⁵ VR has also been used in posture and balance training in patients with chronic stroke because it can easily create a visual setting for training. For example, one study applied a VR-based postural control program comprising trunk stability, pelvic tilting, pelvis lower extremity, and muscle strengthening exercises for posture training for a patient, and the program implemented visual feedback.³⁶

VR is frequently combined with other therapies to enhance therapeutic efficacy. For example, we recently developed a semi-immersive VR system equipped with multiple body sensors for performing vestibular function analysis and therapy.³⁷ VR has also been combined with other therapies, such as rTMS, tDCS, functional stimulation, robotic rehabilitation, and TR. Simultaneous VR and robot-assisted gait training may enhance functional performance in patients with chronic stroke.³⁸ VR-assisted training should therefore be incorporated into regular training rehabilitation programs.

A topic of particular interest is the creation of a metaverse that combines augmented reality and VR, and thus allows physicians and therapists to treat their patients in a virtual room. Augmented reality has also been used in the fields of neuroscience and neurosurgery—for example, to identify tumors or avoid dangerous structures during an operation.³⁹

TR

TR refers to the delivery of rehabilitation services through electronic communication devices.⁴⁰ This type of rehabilitation incorporates videoconferencing systems and computers that enable therapists to instruct their patients from a remote location. TR can be conducted in real time with therapists and their patients connecting synchronously or asynchronously, such that patients can download therapeutic intervention content in advance and view it offline. TR has the advantages of low costs and high accessibility; it is more cost-effective than traditional therapy and allows patients with severe cognitive deficits and neurogenerative diseases to receive therapy at home without having to travel. A systematic review reported that TR can produce results similar to those of traditional therapy, indicating that TR can serve as an alternative to in-person therapy.⁴¹ A neuroimaging study revealed that TR can not only improve motor performance, but can also increase bilateral motor cortex connectivity in patients with subcortical stroke, thus suggesting that TR enhances cortical plasticity.⁴²

TR has been increasingly applied to deliver stroke rehabilitation services. TR can be synchronous (i.e., the therapist and patients are connected in real time via any device) or asynchronous (i.e., the interventions are given offline). TR systems such as the Rehab@Home framework can automatically execute assessment tests by using instrumented insoles that are wirelessly connected to a computer, and provide the assessment results to therapists remotely.⁴³ The success of TR in patients with stroke depends on a range of factors, including therapist experience, program content, family support, and equipment quality. A Canadian study conducted high-quality, high-intensity TR sessions and reported higher attendance in these sessions than in in-person sessions among patients with chronic stroke. The study also reported that TR sessions resulted in significant improvements in upper limb function and quality of life.⁴⁴ However, high-intensity TR may not be suitable for all patients. Moreover, technical problems related to the inadequate quality of webcam images and program delivery must be addressed. The use of TR for neurorehabilitation thus warrants more evidence and further investigation to identify best practices.

A key therapeutic benefit of TR is that it may alleviate anxiety or depression in patients with stroke (this is important because 50% of patients with stroke experience anxiety or depression).⁴⁵ TR enables patients to receive timely counseling, allowing them to achieve psychological stabilization without visiting a hospital, thus experiencing improved quality of life. Disadvantages of TR include the absence of in-person contact and face-to-face interactions with physicians or therapists. Moreover, because of the lack of a standard legal framework, legal concerns have been raised around patient privacy, insurance coverage, and potential malpractice litigation.⁴⁶

Suggested neurorehabilitation devices for various recovery phases and neurological deficits

The recovery process for patients with stroke is complex and entails considerable expenses, which places both financial and social burdens on patients. Moreover, the rehabilitation prognosis is generally limited by the location or severity of the stroke lesion, the patient’s socioeconomic support, and their access to healthcare. To address these problems, a multidisciplinary strategy incorporating novel healthcare technology should be used that is dependent on stroke severity. For example, patients with subacute or acute stroke can undergo neuromodulation with either rTMS or tDCS to alleviate brain function disruptions caused by stroke. For patients with multiple neurological deficits (including language and swallowing deficits), however, NIBS may be more suitable for rebalancing cortical excitability. Moreover, intensive stroke rehabilitation programs should be emphasized. When intensive rehabilitation through in-person therapy is not possible, TR and VR should be used. Furthermore, considering that alleviating psychosocial problems such as depression and a lack of motivation is crucial to recovery, TR and VR may serve as adjunctive therapies (Figure 1).

Figure 1.

Use of noninvasive brain stimulation and neurorehabilitation devices for improving specific stroke deficits.

Limb spasticity is a common neurological sequela in the subacute to chronic stages of stroke. Inhibitory rTMS can be used to relieve limb spasticity. Additionally, anodal tDCS combined with other neurostimulation techniques, such as robot-assisted therapy, is effective for reducing spasticity.⁴⁷ Robot-assisted therapy is particularly helpful for treating spasticity associated with tasks involving repetition and heavy loads. Moreover, psychosocial problems such as poststroke depression and a lack of motivation considerably influence therapeutic efficacy. Socioeconomic burdens can also affect the motivation of patients to continue rehabilitation therapy. Engaging VR-based rehabilitation programs should therefore be designed to increase the motivation of patients to receive therapy. Such programs should also enable patients to use paretic limbs more frequently, which is essential for recovery. Thus, NIBS is an efficient method for alleviating the aforementioned stroke-related psychosocial issues.

In the chronic stage of stroke, the maintenance of current function and the application of compensatory strategies for performing activities of daily living are the main therapeutic goals. During this period, some patients experience secondary stroke and gradually lose their muscle strength and endurance. At this stage, 1-Hz rTMS may be considered as an adjunctive therapy for improving intracortical plasticity, although associated motor improvements may be subtle. Moreover, NIBS may only be required when a patient has psychosocial problems such as depression or anxiety. VR rehabilitation with Wii or Kinect can be a cost-effective therapeutic option during the chronic stage, and TR may be used to replace regular outpatient follow-ups for full-condition assessments.

Adverse events and limitations of NIBS and neurorehabilitation devices

The use of neurorehabilitation devices has several limitations and adverse effects that should be considered. First, rTMS cannot be applied to patients with implanted electronic devices (e.g., pacemakers and shunt systems) because the magnetic fields generated during rTMS disable these electronic devices. In addition, patients with metal implants in their brains cannot undergo repeated stimulation because the stimulation process increases the temperature of the metal implants. Moreover, for patients with a history of seizures, the intensity and mode of rTMS should be modified to prevent seizure induction during therapy.

Second, tDCS is generally associated with minor risks, such as headache and fatigue, because its stimulation intensity is low.⁴⁸ An intensity of <4 mA for up to 60 minutes per day is considered low.⁴⁷ However, although tDCS has low risks, patients with brain implants or implanted electrical devices should also avoid this therapy because of safety concerns.

Third, the main limitation of robotic systems is their high costs. Adverse events associated with robotic rehabilitation mostly affect the soft tissue or musculoskeletal system as a result of inappropriate contact with a machine or applied force.⁴⁹ Patients with fragile skin or osteoporotic bone should exercise particular caution when undergoing robotic rehabilitation to prevent skin abrasions or lower extremity bone fracture. Furthermore, patients with spasticity may experience abrasions, falls, pressure sores, and fractures after walking for long periods.

Fourth, VR is associated with dizziness, headache, and motion sickness. Full-immersion VR games can also have a negative effect on static balance and cause dizziness and fatigue. This adverse effect can be reduced by switching from a movable background to a fixed background in full-immersion VR games during therapy.⁵⁰ During VR therapies, patients with cerebellar or subcortical stroke can easily develop dizziness or vestibular insufficiency that may lead to falls.

Fifth, the limitations of TR vary depending on human factors, including TR acceptance, knowledge, skills, and awareness. Other factors include organizational factors such as payment schemes, reimbursements, and measures for protecting data privacy. Technical factors relating to the improvement of tangible (i.e., equipment and Internet) and intangible (i.e., technical skills and communications frameworks) e-health resources are also major limitations of TR.⁵¹

Conclusions

Stroke rehabilitation typically entails considerable effort and resources. The role of neurorehabilitation devices and technologies to compensate for reduced in-person therapy is therefore becoming increasingly evident. These devices can help to reorganize brain activity and achieve improved brain activation, thus facilitating the recovery of a flaccid limb, for example. However, although these devices can be fundamental in the recovery process, they must be carefully selected on the basis of the lesion site and stroke stage. Our review indicates that rTMS devices have the widest applicability for almost all stroke stages and lesion sites. tDCS can serve as an alternative therapy to rTMS for neuromodulation owing to its ease of portability and convenience, although it is generally only effective for treating motor deficits. For stroke patients with motor deficits, robotic rehabilitation can provide high practice intensity and early opportunities to stand during the subacute and chronic stages. Nonetheless, the successful administration of robotic rehabilitation depends on the careful setup and wearing of devices. Robotic rehabilitation should be combined with NIBS to enhance neuromodulation, and TR may also be used to deliver required therapies—particularly during the chronic phase, when the condition of patients tends to be stable. Furthermore, VR may be used in combination with therapies that target motor deficits because an immersive environment can help to alleviate psychosocial problems such as poststroke depression. In contrast to traditional in-person therapy, NIBS can directly remodulate brain activity to address the imbalance between contralesional and ipsilesional hemispheres of the brain. Furthermore, the related devices can be used alone or in combination with traditional therapies to treat stroke deficits, and they can serve as key substitute therapies when traditional therapy methods are unavailable. In the present review, rTMS appears to be one of the most suitable NIBS for enhancing rehabilitation in acute stages, whereas tDCS seems most feasible for chronic stroke patients. The concept of multidisciplinary neurorehabilitation therapy with these devices in patients with stroke should be emphasized in future clinical practice.

Footnotes

Author contributions

CCW, YJL, TMH, and CLK contributed substantially to the conception and design of the study. CLC and YCH contributed to the literature search and review. CCW wrote the first draft of the manuscript. CCW and CLK had full access to the data, took responsibility for the content, and guaranteed the integrity and accuracy of the work undertaken. All authors have read and provided critical feedback on intellectual content and approved the final manuscript.

Declaration of conflicting interest

The authors declare that there is no conflict of interest.

Funding

This work was financially supported by the Taipei Veterans General Hospital Yuli Branch (ref:VHYL-113-01).

ORCID iD

Chien-Chih Wang

References

Coleman

Moudgal

Lang

, et al. Early rehabilitation after stroke: a narrative review. Curr Atheroscler Rep 2017; 19: 59.

Studenski

Wallace

Duncan

, et al. Predicting stroke recovery: three- and six-month rates of patient-centered functional outcomes based on the Orpington Prognostic Scale. J Am Geriatr Soc 2001; 49: 308–312.

Ferrari

Writing narrative style literature reviews. Medical Writing 2015; 24: 230–235.

Luo

Yang

Wang

, et al. Cellular mechanism underlying rTMS treatment for the neural plasticity of nervous system in Drosophila brain. Int J Mol Sci 2019; 20: 4625.

Ogiue-Ikeda

Kawato

Ueno

The effect of repetitive transcranial magnetic stimulation on long-term potentiation in rat hippocampus depends on stimulus intensity. Brain Res 2003; 993: 222–226.

Cook

ND.

Callosal inhibition: the key to the brain code. Behav Sci 1984; 29: 98–110.

Speer

Kimbrell

Wassermann

, et al. Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol Psychiatry 2000; 48: 1133–1141.

Chung

Hoy

Fitzgerald

PB.

Theta-burst stimulation: a new form of TMS treatment for depression?

Depress Anxiety 2015; 32: 182–192.

Tiksnadi

Murakami

Wiratman

, et al. Direct comparison of efficacy of the motor cortical plasticity induction and the interindividual variability between TBS and QPS. Brain Stimul 2020; 13: 1824–1833.

10.

Wang

Tsai

Yang

, et al. Differential effect of conditioning sequences in coupling inhibitory/facilitatory repetitive transcranial magnetic stimulation for poststroke motor recovery. CNS Neurosci Ther 2014; 20: 355–363.

11.

Lefaucheur

Aleman

Baeken

, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018). Clin Neurophysiol 2020; 131: 474–528.

12.

Fisicaro

Lanza

Grasso

, et al. Repetitive transcranial magnetic stimulation in stroke rehabilitation: review of the current evidence and pitfalls. Ther Adv Neurol Disord 2019; 12: 1756286419878317.

13.

Hordacre

McCambridge

Ridding

, et al. Can transcranial direct current stimulation enhance poststroke motor recovery? Development of a theoretical patient-tailored model. Neurology 2021; 97: 170–180.

14.

Rocha

Silva

Foerster

, et al. The impact of transcranial direct current stimulation (tDCS) combined with modified constraint-induced movement therapy (mCIMT) on upper limb function in chronic stroke: a double-blind randomized controlled trial. Disabil Rehabil 2016; 38: 653–660.

15.

Cho

Lee

Kim

, et al. Dual-mode noninvasive brain stimulation over the bilateral primary motor cortices in stroke patients. Restor Neurol Neurosci 2017; 35: 105–114.

16.

Marangolo

The potential effects of transcranial direct current stimulation (tDCS) on language functioning: combining neuromodulation and behavioral intervention in aphasia. Neurosci Lett 2020; 719: 133329.

17.

Thair

Holloway

Newport

, et al. Transcranial direct current stimulation (tDCS): a beginner’s guide for design and implementation. Front Neurosci 2017; 11: 641.

18.

Charvet

Kasschau

Datta

, et al. Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols. Front Syst Neurosci 2015; 9: 26.

19.

Charvet

Shaw

Dobbs

, et al. Remotely supervised transcranial direct current stimulation increases the benefit of at-home cognitive training in multiple sclerosis. Neuromodulation 2018; 21: 383–389.

20.

Sivan

O'Connor

Makower

, et al. Systematic review of outcome measures used in the evaluation of robot-assisted upper limb exercise in stroke. J Rehabil Med 2011; 43: 181–189.

21.

Chang

Kim

YH.

Robot-assisted therapy in stroke rehabilitation. J Stroke 2013; 15: 174–181.

22.

Xie

SQ.

Exoskeleton robots for upper-limb rehabilitation: state of the art and future prospects. Med Eng Phys 2012; 34: 261–268.

23.

Singh

Saini

Kumar

, et al. Evidence of neuroplasticity with robotic hand exoskeleton for post-stroke rehabilitation: a randomized controlled trial. J Neuroeng Rehabil 2021; 18: 76.

24.

Westlake

Patten

Pilot study of Lokomat versus manual-assisted treadmill training for locomotor recovery post-stroke. J Neuroeng Rehabil 2009; 6: 18.

25.

Tomida

Sonoda

Hirano

, et al. Randomized controlled trial of gait training using Gait Exercise Assist Robot (GEAR) in stroke patients with hemiplegia. J Stroke Cerebrovasc Dis 2019; 28: 2421–2428.

26.

Ranzani

Lambercy

Metzger

, et al. Neurocognitive robot-assisted rehabilitation of hand function: a randomized control trial on motor recovery in subacute stroke. J Neuroeng Rehabil 2020; 17: 115.

27.

Chien

Chong

Tse

, et al. Robot-assisted therapy for upper-limb rehabilitation in subacute stroke patients: a systematic review and meta-analysis. Brain Behav 2020; 10: e01742.

28.

Akbari

Haghverd

Behbahani

Robotic home-based rehabilitation systems design: from a literature review to a conceptual framework for community-based remote therapy during COVID-19 pandemic. Front Robot Ai 2021; 8: 612331.

29.

Manjunatha

Pareek

Jujjavarapu

, et al. Upper limb home-based robotic rehabilitation during COVID-19 outbreak. Front Robot Ai 2021; 8: 612834.

30.

Weber

Barr

Gough

, et al. How commercially available virtual reality-based interventions are delivered and reported in gait, posture, and balance rehabilitation: a systematic review. Phys Ther 2020; 100: 1805–1815.

31.

Proffitt

Lange

Considerations in the efficacy and effectiveness of virtual reality interventions for stroke rehabilitation: moving the field forward. Phys Ther 2015; 95: 441–448.

32.

Saposnik

Mamdani

Bayley

; EVREST Study Group for the Stroke Outcome Research Canada Working Groupet al. Effectiveness of Virtual Reality Exercises in STroke Rehabilitation (EVREST): rationale, design, and protocol of a pilot randomized clinical trial assessing the Wii gaming system. Int J StrokeSociety 2010; 5: 47–51.

33.

Adamovich

August

Merians

, et al. A virtual reality-based system integrated with fMRI to study neural mechanisms of action observation-execution: a proof of concept study. Restor Neurol Neurosci 2009; 27: 209–223.

34.

Doumas

Everard

Dehem

, et al. Serious games for upper limb rehabilitation after stroke: a meta-analysis. J Neuroeng Rehabil 2021; 18: 100.

35.

Laver

Lange

George

, et al. Virtual reality for stroke rehabilitation. Cochrane Database Syst Rev 2017; 11: Cd008349.

36.

Park

Lee

BH.

Clinical usefulness of the virtual reality-based postural control training on the gait ability in patients with stroke. J Exerc Rehabil 2013; 9: 489–494.

37.

Chen

Chou

Jheng

, et al. Development of a computerized device for evaluating vestibular function in locomotion: a new evaluation tool of vestibular hypofunction. Front Neurol 2020; 11: 485.

38.

Kayabinar

Alemdaroğlu-Gürbüz

Yilmaz

Ö.

The effects of virtual reality augmented robot-assisted gait training on dual-task performance and functional measures in chronic stroke: a randomized controlled single-blind trial. Eur J Phys Rehabil Med 2021; 57: 227–237.

39.

Ammirati

Augmented reality in brain tumor surgery using the microscope focal point as the virtual pointer. Acta Neurochir (Wien) 2022; 164: 1.

40.

Chang

Boudier-Revéret

Usefulness of telerehabilitation for stroke patients during the COVID-19 pandemic. Am J Phys Med Rehabil 2020; 99: 582.

41.

Laver

Adey-Wakeling

Crotty

, et al. Telerehabilitation services for stroke. Cochrane Database Syst Rev 2020; 1: Cd010255.

42.

Chen

Sun

Zhang

, et al. Effects of home-based telerehabilitation in patients with stroke: a randomized controlled trial. Neurology 2020; 95: e2318–e2330.

43.

Jagos

David

Haller

, et al. A framework for (tele-) monitoring of the rehabilitation progress in stroke patients: eHealth 2015 Special Issue. Appl Clin Inform 2015; 6: 757–768.

44.

Yang

Waterson

Eng

JJ.

Implementation and evaluation of the virtual Graded Repetitive Arm Supplementary Program (GRASP) for individuals with stroke during the COVID-19 pandemic and beyond. Physical Therapy 2021; 101: pzab083.

45.

Chun

Chang

Lee

SJ.

The effects of forest therapy on depression and anxiety in patients with chronic stroke. Int J Neurosci 2017; 127: 199–203.

46.

Montemurro

Telemedicine: could it represent a new problem for spine surgeons to solve?

Global Spine J 2022; 12: 1306–1307.

47.

Wang

, et al. Effects of non-invasive brain stimulation on post-stroke spasticity: a systematic review and meta-analysis of randomized controlled trials. Brain Sci 2022; 12: 12.

48.

Antal

Alekseichuk

Bikson

, et al. Low intensity transcranial electric stimulation: safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol 2017; 128: 1774–1809.

49.

Bessler

Prange-Lasonder

Schaake

, et al. Safety assessment of rehabilitation robots: a review identifying safety skills and current knowledge gaps. Front Robot Ai 2021; 8: 602878.

50.

Park

Lee

Full-immersion virtual reality: adverse effects related to static balance. Neurosci Lett 2020; 733: 134974.

51.

Al-Shorjabji

Brown

, et al. Applying the resilient health system framework for universal health coverage. Stud Health Technol Inform 2016; 231: 54–62.