Neurorehabilitation for stroke is important for upper limb motor recovery. Conventional rehabilitation such as occupational therapy has been used, but novel technologies are expected to open new opportunities for better recovery. Virtual reality (VR) is a technology with a set of informatics that provides interactive environments to patients. VR can enhance neuroplasticity and recovery after a stroke by providing more intensive, repetitive, and engaging training due to several advantages, including: (1) tasks with various difficulty levels for rehabilitation, (2) augmented real-time feedback, (3) more immersive and engaging experiences, (4) more standardized rehabilitation, and (5) safe simulation of real-world activities of daily living. In this comprehensive narrative review of the application of VR in motor rehabilitation after stroke, mainly for the upper limbs, we cover: (1) the technologies used in VR rehabilitation, including sensors; (2) the clinical application of and evidence for VR in stroke rehabilitation; and (3) considerations for VR application in stroke rehabilitation. Meta-analyses for upper limb VR rehabilitation after stroke were identified by an online search of Ovid-MEDLINE, Ovid-EMBASE, the Cochrane Library, and KoreaMed. We expect that this review will provide insights into successful clinical applications or trials of VR for motor rehabilitation after stroke.
Stroke is one of the leading causes of disability and socioeconomic burden worldwide . Although the age-standardized stroke incidence has decreased in most regions, the growth of aging populations, who are at risk of stroke, may lead to an increase in the crude incidence of stroke . According to a policy statement by an American Heart Association working group, approximately 4% of US adults will have a stroke by 2030 . Stroke-related mortality has shown a remarkable decline due to better management in the acute phase, which means there are more people living with disabilities after stroke [1,3].Upper limb hemiparesis is one of the most common impairments after stroke  and is associated with activity limitation and a worse quality of life [5,6,7]. Therefore, adequate recovery of upper limb weakness is necessary. Spontaneous motor recovery occurring up to one year after stroke can be accelerated with active rehabilitation strategies [8,9]. However, the effects of conventional rehabilitation modalities are limited and novel therapeutic approaches are required .Virtual rehabilitation using virtual reality (VR) technology is a novel promising modality for motor rehabilitation after stroke  that can add beneficial components to current rehabilitation strategies. Considering motor learning theory, task-oriented, intensive (that is, more doses and movements), and repetitive training is essential for promoting neuroplasticity and thereby, motor recovery (Figure 1) . Several advantages of virtual rehabilitation can be suggested in terms of rehabilitation intensity and motivation. VR can motivate patients’ participation by increasing enjoyment and gamification—“the process of adding game-design elements and game principles to something (e.g., task) so as to encourage participation”—thereby increasing task repetition (intensity) [13,14,15]. Flexible and individualized rehabilitation design is possible according to the patient’s motor impairment, which makes the step-by-step approach possible. A low-cost virtual rehabilitation system can be used as an adjunctive therapy to conventional rehabilitation, with less direct supervision by a therapist , and it can also be considered for use as a tele- or home-based rehabilitation tool . Functional assessment and digital tracking of patients’ progress is possible using motion sensors combined with VR systems for rehabilitation .
Figure 1. Approaches to promote neural plasticity.In this comprehensive narrative review of the application of VR in motor rehabilitation after stroke, we will cover (1) the technologies used in VR rehabilitation including sensors, haptic devices, and VR displays; (2) the clinical application and evidence for VR in motor rehabilitation in stroke; and (3) considerations for VR application in stroke rehabilitation. We expect that this review will provide insights into successful clinical applications or trials of VR for motor rehabilitation after stroke.[…]
Background. Patients with an upper limb motor impairment are likely to develop wrist hyper-resistance during the first months post stroke. The time course of wrist hyper-resistance in terms of neural and biomechanical components, and their interaction with motor recovery, is poorly understood. Objective. To investigate the time course of neural and biomechanical components of wrist hyper-resistance in relation to upper limb motor recovery in the first 6 months post stroke.
Methods. Neural (NC), biomechanical elastic (EC), and viscous (VC) components of wrist hyper-resistance (NeuroFlexor device), and upper limb motor recovery (Fugl-Meyer upper extremity scale [FM-UE]), were assessed in 17 patients within 3 weeks and at 5, 12, and 26 weeks post stroke. Patients were stratified according to the presence of voluntary finger extension (VFE) at baseline. Time course of wrist hyper-resistance components and assumed interaction effects were analyzed using linear mixed models.
Results. On average, patients without VFE at baseline (n = 8) showed a significant increase in NC, EC, and VC, and an increase in FM-UE from 13 to 26 points within the first 6 months post stroke. A significant increase in NC within 5 weeks preceded a significant increase in EC between weeks 12 and 26. Patients with VFE at baseline (n = 9) showed, on average, no significant increase in components from baseline to 6 months whereas FM-UE scores improved from 38 to 60 points.
Conclusion. Our findings suggest that the development of neural and biomechanical wrist hyper-resistance components in patients with severe baseline motor deficits is determined by lack of spontaneous neurobiological recovery early post stroke.
Recovery of post-stroke upper limb motor impairment is heterogeneous. Recent studies suggest that most patients follow a predictable pattern of spontaneous neurobiological recovery within the first 3 months after stroke, while 20% to 30% of the patients fail to show any motor recovery.1–3 Previous observational studies have shown that early control of voluntary finger extension (VFE) is an important determinant of upper limb motor recovery at 6 months post stroke.4,5 In addition, several studies suggested that patients with poor motor recovery are likely to show increased resistance to passive muscle stretch,6–8 that is, hyper-resistance. This hyper-resistance is hypothesized to be caused by a poorly understood and complex interaction between pathological neuromuscular activation due to damage to descending pathways as well as non-neural biomechanical changes in the muscles and soft tissues spanning the joint post stroke.9–11 The neural components of hyper-resistance may be divided into velocity-dependent stretch hyperreflexia (altered set point and/or gain of the stretch reflex, ie, spasticity following the definition of Lance)9,12 and non-velocity-dependent involuntary activation (ie, increased background levels of contraction).11,13 Biomechanical components of joint hyper-resistance include altered tissue properties, for example, elasticity, viscosity and muscle shortening.11,14
In particular, there is a lack of knowledge about the time course of wrist hyper-resistance in terms of its neural and biomechanical components, and its interaction with motor recovery early post stroke,15 yet this is important for understanding observed improvements in motor control of the upper paretic limb in terms of behavioral restitution and compensation strategies.16,17 Development of the velocity and non-velocity-dependent neural components, among which spasticity, as a reflection of reorganization of spared descending pathways, might reflect neural repair processes during upper limb recovery, further influencing behavioral restitution.16,18 Moreover, information about the time course of different components of wrist hyper-resistance may help to optimize individualized treatment decisions, for example, when and to whom to apply botulinum toxin treatment19–21 during the early post-stroke phase. Considering the target mechanism of botulinum toxin, blocking neural signal transmission to the muscle, it is expected that patients with an increased neural component of wrist hyper-resistance will benefit most from this treatment. Recently, a new measurement technique, called NeuroFlexor (Aggero MedTech, AB), has been developed for the quantification of neural and biomechanical elastic and viscous components of wrist hyper-resistance, which has proved to be valid22,23 and reliable23,24 in patients with chronic stroke.
The first aim of the present study was to investigate the time course of wrist hyper-resistance in the first 6 months post stroke, separated into its neural and biomechanical elastic and viscous components. This was done in patients with and without VFE within 3 weeks post stroke, in relation to the critical time-window of spontaneous neurobiological recovery as reflected by improvements observed using the Fugl-Meyer upper extremity scale (FM-UE). Findings were compared with healthy reference data. The second aim was to investigate the association between neural and biomechanical elastic and viscous components of wrist hyper-resistance in the first 6 months post stroke.
We hypothesized that in patients without VFE within 3 weeks post stroke, in the absence of spontaneous neurobiological recovery, both the neural and biomechanical components of wrist hyper-resistance would gradually increase over time.15 In addition, we hypothesized that the neural component would increase within the time-window of spontaneous neurobiological recovery, while an increase of the biomechanical components would not be restricted to this specific time-window. In a similar vein, we hypothesized that an increase in the neural component would be accompanied by an increase in biomechanical components, in reaction to a pathological neuromuscular activation. In patients with VFE within 3 weeks post stroke, that is, those showing spontaneous neurobiological recovery, components of wrist hyper-resistance were hypothesized to normalize to values seen in age- and gender-matched healthy subjects.
All patients with stroke who were admitted to Revant Rehabilitation Center Breda, The Netherlands, for inpatient rehabilitation were screened for eligibility between July 2015 and July 2016. The inclusion criteria for this study were (1) a first-ever ischemic stroke within the past 3 weeks, with an initial upper limb deficit as defined by the National Institutes of Health Stroke Scale item 5 a/b score >0 (ie, not able to hold the affected arm at a 90° angle for at least 10 seconds), (2) ≥18 years of age, (3) able to sit in a chair for at least 1 hour, and (4) sufficient cognitive ability to follow test instructions as indicated by a score higher than 17 on the Mini Mental State Examination.25 Exclusion criteria were (1) a history of other neurological impairments and (2) limitations of arm-hand function of the affected side prior to the stroke. A group of healthy, right-handed, age- and gender-matched adults without wrist function restrictions served as a reference group. Ethical approval was obtained from the Medical Ethics Reviewing Committee of the VU University medical center, Amsterdam, The Netherlands (protocol number 2014.140). In accordance with the Declaration of Helsinki (2013), all participants gave written informed consent.
Study Design and Procedures
In this prospective cohort study, repeated measurements were performed at fixed times post stroke, that is within 3 weeks, and at 5, 12, and 26 weeks. The first measurement was performed as soon as possible after stroke onset, with more intensive repeated measurements within the window of nonlinear spontaneous neurobiological recovery within the first 12 weeks post stroke3 and a follow-up measurement at the start of the chronic phase after stroke.26 Demographics and stroke characteristics were collected at baseline. All measurements were performed by a trained assessor. In the healthy controls, neural and biomechanical components of wrist hyper-resistance were determined for the dominant arm. All patients received usual care. The use of botulinum toxin injections was recorded throughout the study period.
At baseline, patients were stratified into 2 groups, based on the presence or absence of VFE within 3 weeks post stroke4,5: (1) a group of patients showing any VFE, according to the FM-UE item of finger extension >0, within 3 weeks and (2) a group of patients showing no VFE (FM-UE item finger extension = 0) within 3 weeks.
Neural and biomechanical elastic and viscous components of resistance to passive wrist extension were assessed with a validated and commercially available measurement technique, the NeuroFlexor, feasible for use in clinical practice (Figure 1).22 This motor-driven device imposes isokinetic wrist displacements with extended fingers from 20° palmar flexion to 30° dorsal flexion at 2 controlled velocities (5 and 236 deg/s), for which a minimal passive wrist extension of 40° is needed. A force sensor, placed underneath the moveable hand platform, measures the resistance trace during the passive wrist movement. The participant was seated comfortably parallel to the device with the shoulder in 45° of abduction, 0° of flexion, the elbow in 90° of flexion, with the forearm fastened to the device in pronation, and the hand with extended fingers fastened to the hand platform. Participants were instructed to relax their arm and to look ahead of them during the measurements. The experimental session consisted of 5 slow movements (5 deg/s) followed by 10 fast movements (236 deg/s). The first movement at both velocities was excluded from analysis to avoid bias from startle reflexes and mechanical hysteresis. The resting torque of the hand before onset of stretch was subtracted from the resistance traces prior to further calculations. Using the biomechanical model described by Lindberg et al,22 the different components of wrist hyper-resistance, that is, the velocity-dependent part of the neural component (NC), the biomechanical elastic component (EC), and viscous component (VC), were derived from the resistance traces (using the NeuroFlexor Scientific v0.06 software program, Supplemental File 1 and Supplemental Figure 1). The NC was determined as a derivative of the velocity-dependent resistance to passive wrist extension, which is to reflect the neural, velocity-dependent part of wrist hyper-resistance, that is, assumed proxy of spasticity as defined by Lance,12 not including the non-velocity-dependent part of neural activity, that is, involuntary background activation. The length-dependent EC was determined as the resistance at the end of the slow movement. It was assumed that the velocity-dependent VC was highest during the initial acceleration and continued at a lower level, that is, 20%, during further extension movement. The developers of the NeuroFlexor have previously underpinned the validity of the NC based on 3 arguments: (1) the NC as measured by the device was reduced after an ischemic nerve block, (2) the NC correlated with the integrated electromyography (EMG) across subjects and in the same subject during the ischemic nerve block, and (3) the NC was found to be velocity dependent.22 In a recent study,23 the NeuroFlexor method was suggested to be construct-valid against clinical assessments using the modified Ashworth and Tardieu scales. In addition, good to excellent reliability was shown for the quantification of the different components.23,24 As a result of the positioning of the fingers, the measured resistance was a combination of resistance caused by wrist and finger flexor muscle groups. Measurements were performed twice at the same occasion, and mean values were used for further analysis.
There is a need to translate promising basic research about environmental enrichment to clinical stroke settings. The aim of this study was to assess the effectiveness of enriched, task-specific therapy in individuals with chronic stroke.
This is an exploratory study with a within-subject, repeated-measures design. The intervention was preceded by a baseline period to determine the stability of the outcome measures. Forty-one participants were enrolled at a mean of 36 months poststroke. The 3-week intervention combined physical therapy with social and cognitive stimulation inherent to environmental enrichment. The primary outcome was motor recovery measured by Modified Motor Assessment Scale (M-MAS). Secondary outcomes included balance, walking, distance walked in 6 minutes, grip strength, dexterity, and multiple dimensions of health. Assessments were made at baseline, immediately before and after the intervention, and at 3 and 6 months.
The baseline measures were stable. The 39 participants (95%) who completed the intervention had increases of 2.3 points in the M-MAS UAS and 5 points on the Berg Balance Scale (both P < 0.001; SRM >0.90), an improvement of comfortable and fast gait speed of 0.13 and 0.23 m/s, respectively. (P < 0.001; SRM = 0.88), an increased distance walked over 6 minutes (24.2 m; P < 0.001; SRM = 0.64), and significant improvements in multiple dimensions of health. The improvements were sustained at 6 months.
Discussion and Conclusions:
Enriched, task-specific therapy may provide durable benefits across a wide spectrum of motor deficits and impairments after stroke. Although the results must be interpreted cautiously, the findings have implications for enriching strategies in strokerehabilitation.
Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A304).
The overall burden of stroke has increased across the globe and is the second commonest cause of death and a leading cause of adult disability worldwide.1 Many individuals with stroke face long-term consequences, which are usually complex and heterogeneous and can result in problems across multiple domains of functioning.2 The most common deficit after stroke is hemiparesis, which predisposes individuals to sedentary behaviors, seriously hampers postural control, and increases the risk of falls.3 Restoring impaired movement and associated functions is therefore a key goal in strokerehabilitation.
Over the years, various approaches to physical rehabilitation for recovery of function and mobility after stroke have been developed.4 Many rehabilitation strategies used task-oriented and goal-directed training and include feedback, repetition, intensity, and specificity to regain lost functions.2,4 Such task- and context-specific training should target goals that are relevant for the needs of individuals with stroke.2 Many treatment methods are available to minimize functional disability, such as constraint-induced movement therapy, weight-supported treadmill training, cardiovascular training, and goal-directed physical exercise.2 High-intensity, high-dose, task-specific treatment strategies for strokerehabilitation have also been developed.5 Nevertheless, individuals with stroke are increasingly left with persistent impairment,2 and many lack adequate stimulation, exercise, and socialization.6 The strokerehabilitation field consequently faces a dual challenge: implementing new strategies to improve long-term outcome and tailoring treatment regimens to meet the needs of individuals with stroke.7
A growing amount of research suggests that the key to maximizing functional recovery after stroke is to combine a selection of components from different approaches.4,8,9 Combinational therapies have considerable potential to provide optimal gains in functional recovery after stroke by tapping into the multiple, complementary mechanisms that underlie neuroplasticity and repair.10 To further aid recovery from stroke, task-specific therapy could be combined with environmental enrichment (EE).10 Environmental enrichment that enhances motor, cognitive, sensory, and social stimulation is shown to increase neuroplasticity in rodents, as compared with standard housing (Figure 1A and B).8,10
Figure 1: (A). A typical enriched environment condition composed of increased space and equipped with various objects that stimulate motor function by providing exercise, balancing or climbing activities (running wheel, igloos, tunnels, tube mazes, and ladders), and cognition (a variety of toys and objects to interact with and navigate in). The location and types of objects are changed regularly to maintain the concept of novelty and complexity in the environment, thereby offering multisensory stimulation (visual, acoustic, smell, touch, push, and sensory-motor challenges). Multiple animals are introduced to the stimulating environment simultaneously to facilitate social interaction (allogrooming, sniffing, and play-soliciting activities). (B). A standard housing condition that generally entails a cage with bedding and access to water and food.
A combination of different therapies is expected to have additive or even synergistic effects on neuroplasticity processes harnessed to aid rehabilitation after stroke.6,8,10,11 These findings support the idea that combinational therapies can aid recovery from stroke-related deficits.12 Despite the evidence that supports the potential of EE to enhance brain plasticity, it has largely remained a laboratory phenomenon, with little translation to clinical settings.13
Based on the fundamental principle of EE—that interventions should engage participants in concurrent physical, sensory, cognitive, and social activities or experiences—we designed an exploratory study of the EE paradigm in a clinical setting. Specifically, we investigated whether an intervention that combines high-dose and task-specific therapy with the sensory-motor, social, and cognitive stimulation inherent to EE could aid the recovery from stroke. The aim of the study was to assess the effectiveness of an enriched, task-specific therapy (ETT) program in enhancing functional motor performance as well as balance, gait, hand strength, and dexterity in individuals with residual hemiplegia in the chronic phase after stroke. We also investigated whether ETT improves confidence in task performance and health-related quality of life and reduces fatigue and depression.[…]
The recovery of walking capacity is one of the main aims in stroke rehabilitation. Being able to predict if and when a patient is going to walk after stroke is of major interest in terms of management of the patients and their family’s expectations and in terms of discharge destination and timing previsions. This article reviews the recent literature regarding the predictive factors for gait recovery and the best recommendations in terms of gait rehabilitation in stroke patients. Trunk control and lower limb motor control (e.g. hip extensor muscle force) seem to be the best predictors of gait recovery as shown by the TWIST algorithm, which is a simple tool that can be applied in clinical practice at 1 week post-stroke. In terms of walking performance, the 6-min walking test is the best predictor of community ambulation. Various techniques are available for gait rehabilitation, including treadmill training with or without body weight support, robotic-assisted therapy, virtual reality, circuit class training and self-rehabilitation programmes. These techniques should be applied at specific timing during post-stroke rehabilitation, according to patient’s functional status.
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Background and purpose: There is a need to translate promising basic research about environmental enrichment to clinical stroke settings. The aim of this study was to assess the effectiveness of enriched, task-specific therapy in individuals with chronic stroke.
Methods: This is an exploratory study with a within-subject, repeated-measures design. The intervention was preceded by a baseline period to determine the stability of the outcome measures. Forty-one participants were enrolled at a mean of 36 months poststroke. The 3-week intervention combined physical therapy with social and cognitive stimulation inherent to environmental enrichment. The primary outcome was motor recovery measured by Modified Motor Assessment Scale (M-MAS). Secondary outcomes included balance, walking, distance walked in 6 minutes, grip strength, dexterity, and multiple dimensions of health. Assessments were made at baseline, immediately before and after the intervention, and at 3 and 6 months.
Results: The baseline measures were stable. The 39 participants (95%) who completed the intervention had increases of 2.3 points in the M-MAS UAS and 5 points on the Berg Balance Scale (both P < 0.001; SRM >0.90), an improvement of comfortable and fast gait speed of 0.13 and 0.23 m/s, respectively. (P < 0.001; SRM = 0.88), an increased distance walked over 6 minutes (24.2 m; P < 0.001; SRM = 0.64), and significant improvements in multiple dimensions of health. The improvements were sustained at 6 months.
Discussion and conclusions: Enriched, task-specific therapy may provide durable benefits across a wide spectrum of motor deficits and impairments after stroke. Although the results must be interpreted cautiously, the findings have implications for enriching strategies in stroke rehabilitation.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A304
Transcranial direct current stimulation (tDCS) is a treatment used in the rehabilitation of stroke patients aiming to improve functionality of the plegic upper extremity. Currently, tDCS is not routinely used in post stroke rehabilitation. The aim of this study was to establish the effects of bihemspheric tDCS combined with physical therapy (PT) and occupational therapy (OT) on upper extremity motor function.
Thirty-two stroke inpatients were randomised into 2 groups. All patients received 15 sessions of conventional upper extremity PT and OT over 3 weeks. The tDCS group (n = 16) also received 30 minutes of bihemispheric tDCS and the sham group (n = 16) 30 minutes of sham bihemispheric tDCS simultaneously to OT. Patients were evaluated before and after treatment using the Fugl Meyer upper extremity (FMUE), functional independence measure (FIM), and Brunnstrom stages of stroke recovery (BSSR) by a physiatrist blind to the treatment group
The improvement in FIM was higher in the tDCS group compared to the sham group (P = .001). There was a significant within group improvement in FMUE, FIM and BSSR in those receiving tDCS (P = .001). There was a significant improvement in FIM in the chronic (> 6months) stroke sufferers who received tDCS when compared to those who received sham tDCS and when compared to subacute stroke (3-6 months) sufferers who received tDCS/sham.
Upper extremity motor function in hemiplegic stroke patients improves when bihemispheric tDCS is used alongside conventional PT and OT. The improvement in functionality is greater in chronic stroke patients.
To investigate the effects of various rehabilitative interventions aimed at enhancing poststroke motor recovery by assessing their effectiveness when compared with no treatment or placebo and their superiority when compared with conventional training program (CTP).
A literature search was based on 19 Cochrane reviews and 26 other reviews. We also updated the searches in PubMed up to September 30, 2017.
Randomized controlled trials associated with 18 experimented training programs (ETP) were included if they evaluated the effects of the programs on either upper extremity (UE) or lower extremity (LE) motor recovery among adults within 6 months poststroke; included ≥10 participants in each arm; and had an intervention duration of ≥10 consecutive weekdays.
Four reviewers evaluated the eligibility and quality of literature. Methodological quality was assessed using the PEDro scale.
Among the 178 included studies, 129 including 7450 participants were analyzed in this meta-analysis. Six ETPs were significantly effective in enhancing UE motor recovery, with the standard mean differences (SMDs) and 95% confidence intervals outlined as follow: constraint-induced movement therapy (0.82, 0.45-1.19), electrostimulation (ES)-motor (0.42, 0.22-0.63), mirror therapy (0.71, 0.22-1.20), mixed approach (0.21, 0.01-0.41), robot-assisted training (0.51, 0.22-0.80), and task-oriented training (0.57, 0.16-0.99). Six ETPs were significantly effective in enhancing LE motor recovery: body-weight-supported treadmill training (0.27, 0.01-0.52), caregiver-mediated training (0.64, 0.20-1.08), ES-motor (0.55, 0.27-0.83), mixed approach (0.35, 0.15-0.54), mirror therapy (0.56, 0.13-1.00), and virtual reality (0.60, 0.15-1.05). However, compared with CTPs, almost none of the ETPs exhibited significant SMDs for superiority.
Certain experimented interventions were effective in enhancing poststroke motor recovery, but little evidence supported the superiority of experimented interventions over conventional rehabilitation.
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After traumatic brain injury (TBI), motor impairment is less common than neurocognitive or behavioral problems. However, about 30% of TBI survivors have reported motor deficits limiting the activities of daily living or participation. After acute primary and secondary injuries, there are subsequent changes including increased GABA-mediated inhibition during the subacute stage and neuroplastic alterations that are adaptive or maladaptive during the chronic stage. Therefore, timely and appropriate neuromodulation by transcranial direct current stimulation (tDCS) may be beneficial to patients with TBI for neuroprotection or restoration of maladaptive changes.
Technologically, combination of imaging-based modelling or simultaneous brain signal monitoring with tDCS could result in greater individualized optimal targeting allowing a more favorable neuroplasticity after TBI. Moreover, a combination of task-oriented training using virtual reality with tDCS can be considered as a potent tele-rehabilitation tool in the home setting, increasing the dose of rehabilitation and neuromodulation, resulting in better motor recovery.
This review summarizes the pathophysiology and possible neuroplastic changes in TBI, as well as provides the general concepts and current evidence with respect to the applicability of tDCS in motor recovery. Through its endeavors, it aims to provide insights on further successful development and clinical application of tDCS in motor rehabilitation after TBI.
Traumatic brain injury (TBI) is defined as “an alteration in brain function (loss of consciousness, post-traumatic amnesia, and neurologic deficits) or other evidence of brain pathology (visual, neuroradiologic, or laboratory confirmation of damage to the brain) caused by external force” . The incidence and prevalence of TBI are substantial and increasing in both developing and developed countries. TBI in older age groups due to falling has been on the rise in recent years, becoming the prevalent condition in all age groups [2, 3]. TBI causes broad spectrum of impairments, including cognitive, psychological, sensory or motor impairments [4, 5], which may increase the socioeconomic burdens and reduce the quality of life [6, 7]. Although motor impairment, such as limb weakness, gait disturbance, balance problem, dystonia or spasticity, is less common than neurocognitive or behavioral problems after TBI, about 30% of TBI survivors have reported motor deficits that severely limited activities of daily living or participation .
Motor impairment after TBI is caused by both focal and diffuse damages, making it difficult to determine the precise anatomo-clinical correlations [9, 10]. According to previous clinical studies, recovery after TBI also seems worse than that after stroke, although the neuroplasticity after TBI may also play an important role for recovery . Therefore, a single unimodal approach for motor recovery, including conventional rehabilitation, may be limiting, and hence, requiring a novel therapeutic modality to improve the outcome after TBI.
Transcranial direct current stimulation (tDCS) – one of the noninvasive brain stimulation (NIBS) methods – can increase or decrease the cortical excitability according to polarity (anodal vs. cathodal) and be used to modulate the synaptic plasticity to promote long-term functional recovery via long-term depression or potentiation [12, 13]. Recent clinical trials evaluating patients with stroke have reported the potential benefits of tDCS for motor recovery . Neuroplastic changes after TBI and results from animal studies also suggest that tDCS could improve the motor deficit in TBI, although clinical trials using tDCS for motor recovery in TBI are currently lacking .
In this review, we will cover (1) the pathophysiology and possible neuroplastic changes in TBI; (2) physiology of tDCS; (3) current clinical evidence of tDCS in TBI for motor recovery; (4) general current concept of tDCS application for motor recovery; and (5) the future developments and perspectives of tDCS for motor recovery after TBI. Although the scope of motor recovery is wide, this review will focus primarily on the recovery of limb function, especially that of the upper limb. We expect that this review can provide insights on further successful development and clinical application of tDCS in motor rehabilitation after TBI.[…]
Fig. 3Schematic classification of personalized tDCS for motor recovery. Depending on electrode size, shape, and arrangement, tDCS can be broadly classified into a Conventional tDCS, b Customized Electrode tDCS, and c Distributed Array or High-Definition tDCS. Red color represents anodes and blue color represents cathodes
Fig. 5Merged system with tDCS and virtual reality. Patient with TBI can use this system in the hospital setting with the supervision of clinican (a) and can continue to use it at their home with tele-monitored system (b)
Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types.
We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. PROSPERO ID: CRD42016042055.
We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events.
Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.
An emerging approach for enhancing neural plasticity and hence rehabilitation outcomes after stroke is non-invasive brain stimulation (NIBS). Several stimulation procedures are available, such as repetitive transcranial magnetic stimulation (rTMS) , transcranial direct current stimulation (tDCS) [2, 3, 4], transcranial alternating current stimulation (tACS) , and transcranial pulsed ultrasound (TPU) . In recent years a considerable evidence base for NIBS has emerged, especially for rTMS and tDCS.
tDCS is relatively inexpensive, easy to administer and portable, hence constituting an ideal adjuvant therapy during stroke rehabilitation. It works by applying a weak and constant direct current to the brain and has the ability to either enhance or suppress cortical excitability, with effect lasting up to several hours after the stimulation [7, 8, 9]. Hypothetically, this technique makes tDCS a potentially useful tool to modulate neuronal inhibitory and excitatory networks of the affected and the non-affected hemisphere post stroke to enhance, for example, upper limb motor recovery [10, 11]. Three different stimulation types can be distinguished.
In anodal stimulation, the anodal electrode (+) usually is placed over the lesioned brain area and the reference electrode over the contralateral orbit . This leads to subthreshold depolarization, hence promoting neural excitation .
In cathodal stimulation, the cathode (−) usually is placed over the non-lesioned brain area and the reference electrode over the contralateral orbit , leading to subthreshold polarization and hence inhibiting neural activity .
Dual tDCS means the simultaneous application of anodal and cathodal stimulation .
However, the literature does not provide clear guidelines, not only regarding the tDCS type, but also regarding the electrode configuration , the amount of current applied and the duration of tDCS, or the question if tDCS should be applied as a standalone therapy or in combination with other treatments, like robot-assisted therapy .
There is so far conflicting evidence from systematic reviews of randomised controlled trials on the effectiveness of different tDCS approaches after stroke. For example, over the past two decades more than 30 randomised clinical trials have investigated the effects of different tDCS stimulation techniques for stroke, and there are 55 ongoing trials . However, the resulting network of evidence from randomised controlled trials (RCTs) investigating different types of tDCS (i.e., anodal, cathodal or dual) as well as their comparators like sham tDCS, physical rehabilitation or pharmacological agents has not yet been analyzed in a systematic review so far.
A network meta-analysis (NMA), also known as multiple treatment comparison meta-analysis or mixed treatment comparison analysis, allows for a quantitative synthesis of the evidence network. This is made possible by combining direct evidence from head-to-head comparisons of three or more interventions within randomised trials with indirect evidence across randomised trials on the basis of a common comparator [17, 18, 19, 20]. Network meta-analysis has many advantages over traditional pairwise meta-analysis, such as visualizing and facilitating the interpretation of the wider picture of the evidence and improving understanding of the relative merits of these different types of neuromodulation when compared to sham tDCS and/or another comparator such as exercise therapy and/or pharmacological agents [21, 22]. By borrowing strength from indirect evidence to gain certainty about all treatment comparisons, network meta-analysis allows comparative effects that have not been investigated directly in randomised clinical trials to be estimated and ranked [22, 23].
The aim of our systematic review with NMA was to give an overview of the evidence network of randomised controlled trials of tDCS (anodal, cathodal, or dual) for improving capacity in activities of daily living (ADL) and upper limb function after stroke, as well as its safety, and to estimate and rank the relative effectiveness of the different stimulation types, while taking into account potentially important treatment effect modifiers.
Background: Most stroke survivors continue to experience motor impairments even after hospital discharge. Virtual reality-based techniques have shown potential for rehabilitative training of these motor impairments. Here we assess the impact of at-home VR-based motor training on functional motor recovery, corticospinal excitability and cortical reorganization.
Objective: The aim of this study was to identify the effects of home-based VR-based motor rehabilitation on (1) cortical reorganization, (2) corticospinal tract, and (3) functional recovery after stroke in comparison to home-based occupational therapy.
Methods: We conducted a parallel-group, controlled trial to compare the effectiveness of domiciliary VR-based therapy with occupational therapy in inducing motor recovery of the upper extremities. A total of 35 participants with chronic stroke underwent 3 weeks of home-based treatment. A group of subjects was trained using a VR-based system for motor rehabilitation, while the control group followed a conventional therapy. Motor function was evaluated at baseline, after the intervention, and at 12-weeks follow-up. In a subgroup of subjects, we used Navigated Brain Stimulation (NBS) procedures to measure the effect of the interventions on corticospinal excitability and cortical reorganization.
Results: Results from the system’s recordings and clinical evaluation showed significantly greater functional recovery for the experimental group when compared with the control group (1.53, SD 2.4 in Chedoke Arm and Hand Activity Inventory). However, functional improvements did not reach clinical significance. After the therapy, physiological measures obtained from a subgroup of subjects revealed an increased corticospinal excitability for distal muscles driven by the pathological hemisphere, that is, abductor pollicis brevis. We also observed a displacement of the centroid of the cortical map for each tested muscle in the damaged hemisphere, which strongly correlated with improvements in clinical scales.
Conclusions: These findings suggest that, in chronic stages, remote delivery of customized VR-based motor training promotes functional gains that are accompanied by neuroplastic changes.
After initial hospitalization, many stroke patients return home relatively soon despite still suffering from impairments that require continuous rehabilitation . Therefore, ¼ to ¾ of patients display persistent functional limitations for a period of 3 to 6 months after stroke . Although clinicians may prescribe a home exercise regimen, reports indicate that only one-third of patients actually accomplish it . Consequently, substantial gains in health-related quality of life during inpatient stroke rehabilitation may be followed by equally substantial declines in the 6 months after discharge . Multiple studies have shown, however, that supported discharge combined with at home rehabilitation services does not compromise clinical inpatient outcomes [5–7] and may enhance recovery in subacute stroke patients . Hence, it is essential that new approaches are deployed that help to manage chronic conditions associated with stroke, including domiciliary interventions  and the augmentation of current rehabilitation approaches in order to enhance their efficiency. There should be increased provision of home-based rehabilitation services for community-based adults following stroke, taking cost-effectiveness, and a quick family and social reintegration into account .
One of the latest approaches in rehabilitation science is based on the use of robotics and virtual reality (VR), which allow remote delivery of customized treatment by combining dedicated interface devices with automatized training scenarios [10–12]. Several studies have tested the acceptability of VR-based setups as an intervention and evaluation tool for rehabilitation [13–15]. One example of this technology is the, so called, Rehabilitation Gaming System (RGS) , which has been shown to be effective in the rehabilitation of the upper extremities in the acute and the chronic phases of stroke . However, so far little work exists on the quantitative assessment of the clinical impact of VR based approaches and their effects on neural reorganization that can directly inform the design of these systems and their application in the domiciliary context. The main objective of this paper is to further explore the potential and limitations of VR technologies in domiciliary settings. Specifically, we examine the efficacy of a VR-based therapy when used at home for (1) assessing functional improvement, (2) facilitating functional recovery of the upper-limbs, and (3) inducing cortical reorganization. This is the first study testing the effects of VR-based therapy on cortical reorganization and corticospinal integrity using NBS.
We conducted a parallel-group, controlled trial in order to compare the effectiveness of domiciliary VR-based therapy versus domiciliary occupational therapy (OT) in inducing functional recovery and cortical reorganization in chronic stroke patients.
Participants were first approached by an occupational therapist from the rehabilitation units of Hospital Esperanza and Hospital Vall d’Hebron from Barcelona to determine their interest in participating in a research project. Recruited participants met the following inclusion criteria: (1) mild-to-moderate upper-limbs hemiparesis (Proximal MRC>2) secondary to a first-ever stroke (>12 months post-stroke), (2) age between 45 and 85 years old, (3) absence of any major cognitive impairment (Mini-Mental State Evaluation, MMSE>22), and (4) previous experience with RGS in the clinic. The ethics committee of clinical research of the Parc de Salut Mar and Vall d’Hebron Research Institute approved the experimental guidelines. Thirty-nine participants at the chronic stage post-stroke were recruited for the study by two occupational therapists, between October 2011 and January 2012, and were assigned to a RGS (n=20) or a control group (n=19) using stratified permuted block randomization methods for balancing the participants’ demographics and clinical scores at baseline (Table 1). One participant in the RGS group refused to participate. Prior to the experiment, participants signed informed consent forms. This trial was not registered at or before the onset of participants’ enrollment because it is a pilot study that evaluates the feasibility of a prototype device. However, this study was registered retrospectively in ClinicalTrials.gov and has the identifier NCT02699398.
Description of the Rehabilitation Gaming System
The RGS integrates a paradigm of goal-directed action execution and motor imagery , allowing the user to control a virtual body (avatar) through an image capture device (Figure 1). For this study, we developed training and evaluation scenarios within the RGS framework. In the Spheroids training scenario (Figure 1), the user has to perform bilateral reaching movements to intercept and grasp a maximum number of spheres moving towards him . RGS captures only joint flexion and extension and filters out the participant’s trunk movements, therefore preventing the execution of compensatory body movements . This task was defined by three difficulty parameters, each of them associated with a specific performance descriptor: (1) different trajectories of the spheres require different ranges of joint motion for elbow and shoulder, (2) the size of the spheres require different hand and grasp precision and perceptual abilities, and (3) the velocity of the spheres require different movement speeds and timing. All these parameters, also including the range of finger flexion and extension required to grasp and release spheroids, were dynamically modulated by the RGS Adaptive Difficulty Controller  to maintain the performance ratio (ie, successful trials over the total trials) above 0.6 and below 0.8, optimizing effort and reinforcement during training . […]