Search

Objective To systematically review how patient characteristics and/or transcranial direct current stimulation (tDCS) parameters influence tDCS effectiveness in respect to upper limb function post-stroke. Methods Three electronic databases were searched for sham-controlled randomised trials using the Fugl-Meyer Assessment for upper extremity as outcome measure. A meta-analysis and nine subgroup-analyses were performed to identify which tDCS parameters yielded the greatest impact on upper limb function recovery in stroke patients. Results Eighteen high-quality studies (507 patients) were included. tDCS applied in a chronic stage yields greater results than tDCS applied in a (sub)acute stage. Additionally, patients with low baseline upper limb impairments seem to benefit more from tDCS than those with high baseline impairments. Regarding tDCS configuration, all stimulation types led to a significant improvement, but only tDCS applied during therapy, and not before therapy, yielded significant results. A positive dose–response relationship was identified for current/charge density and stimulation duration, but not for number of sessions. Conclusion Our results demonstrate that tDCS improves upper limb function post-stroke. However, its effectiveness depends on numerous factors. Especially chronic stroke patients improved, which is promising as they are typically least amenable to recovery. Significance The current work highlights the importance of several patient-related and protocol-related factors regarding tDCS effectiveness.

Objective A recent “bimodal-balance recovery” model suggests that contralesional influence varies based on the amount of ipsilesional reserve: inhibitory when there is a large reserve, but supportive when there is a low reserve. Here, we investigated the relationships between contralesional influence (inter-hemispheric inhibition, IHI) and ipsilesional reserve (corticospinal damage/impairment), and also defined a criterion separating subgroups based on the relationships. Methods Twenty-four patients underwent assessment of IHI using Transcranial Magnetic Stimulation (ipsilateral silent period method), motor impairment using Upper Extremity Fugl-Meyer (UEFM), and corticospinal damage using Diffusion Tensor Imaging and active motor threshold. Assessments of UEFM and IHI were repeated after 5-week rehabilitation (n = 21). Results Relationship between IHI and baseline UEFM was quadratic with criterion at UEFM 43 (95%conference interval: 40–46). Patients less impaired than UEFM = 43 showed stronger IHI with more impairment, whereas patients more impaired than UEFM = 43 showed lower IHI with more impairment. Of those made clinically-meaningful functional gains in rehabilitation (n = 14), more-impaired patients showed further IHI reduction. Conclusions A criterion impairment-level can be derived to stratify patient-subgroups based on the bimodal influence of contralesional cortex. Contralesional influence also evolves differently across subgroups following rehabilitation. Significance The criterion may be used to stratify patients to design targeted, precision treatments.

Objective To understand whether lower limb asymmetry in chronic stroke is related to paretic motor impairment or impaired interlimb coordination. Methods Stroke and control participants performed conventional, unilateral, and bilateral uncoupled pedaling. During uncoupled pedaling, the pedals were mechanically disconnected. Paretic mechanical work was measured during conventional pedaling. Pedaling velocity and muscle activity were compared across conditions and groups. Relative limb phasing was examined during uncoupled pedaling. Results During conventional pedaling, EMG and mechanical work were lower in the paretic than the non-paretic limb (asymmetry). During unilateral pedaling with the paretic limb, muscle activity was larger, but velocity was slower and more variable than during conventional pedaling (evidence of paretic motor impairment). During uncoupled pedaling, muscle activity increased further, but velocity was slower and more variable than in other conditions (evidence of impaired interlimb coordination). Relative limb phasing was impaired in stroke participants. Regression analysis suggested that interlimb coordination may be a stronger predictor of asymmetry than paretic motor impairment. Conclusions Paretic motor impairment and impaired interlimb coordination may contribute to asymmetry during pedaling after stroke. Significance Rehabilitation that addresses paretic motor impairment and impaired interlimb coordination may improve symmetry and maximize improvement.

Objective The now standard cortical stimulation approach of inhibiting contralesional primary motor cortex (cM1) disrupts bimanual coordination while facilitating ipsilesional M1 (iM1) fails to enhance paretic arm function, in severely impaired individuals. We propose an alternative target, enhancing contralesional dorsal premotor cortex (cPMd) to improve bimanual coordination and compare its effects to iM1. Methods Fourteen participants with stroke received 5-Hz repetitive transcranial magnetic stimulation (rTMS) on cPMd or iM1 in a repeated cross-over design. Bimanual force/neuromuscular coordination and cortical excitability were assessed. We also examined the relationship of baseline motor function/interhemispheric inhibition (IHI) to participant’s responses to each stimulation target. Results We identified two patterns of responses. Participants with more severe impairment and weaker IHI improved bimanual force/neuromuscular coordination, ipsilesional activations and reduced IHI after cPMd-rTMS; whereas, those with milder impairment and stronger IHI improved only after iM1-rTMS. Conclusions Cortical stimulation protocols could be tailored to the types of tasks and to individuals’ severity of impairment. Facilitation of cPMd may improve bimanual coordination especially for individuals with limited arm/hand function. Significance Our study is the first to identify cortical stimulation strategies for improving bimanual coordination for individuals with different level of severity of stroke.

The objective of this study was the evaluation of the clinical and neurophysiological effects of intensive robot-assisted hand therapy compared to intensive occupational therapy in the chronic recovery phase after stroke.50 patients with a first-ever stroke occurred at least six months before, were enrolled and randomised into two groups. The experimental group was provided with the Amadeo™ hand training (AHT), whereas the control group underwent occupational therapist-guided conventional hand training (CHT). Both of the groups received 40 hand training sessions (robotic and conventional, respectively) of 45 min each, 5 times a week, for 8 consecutive weeks. All of the participants underwent a clinical and electrophysiological assessment (task-related coherence, TRCoh, and short-latency afferent inhibition, SAI) at baseline and after the completion of the training.The AHT group presented improvements in both of the primary outcomes (Fugl-Meyer Assessment for of Upper Extremity and the Nine-Hole Peg Test) greater than CHT (both p 0.001). These results were paralleled by a larger increase in the frontoparietal TRCoh in the AHT than in the CHT group (p 0.001) and a greater rebalance between the SAI of both the hemispheres (p 0.001).These data suggest a wider remodelling of sensorimotor plasticity and interhemispheric inhibition between sensorimotor cortices in the AHT compared to the CHT group.These results provide neurophysiological support for the therapeutic impact of intensive robot-assisted treatment on hand function recovery in individuals with chronic stroke.

Objective Ipsilateral connectivity from the non-stroke hemisphere to paretic arm muscles appears to play little role in functional recovery, which instead depends on contralateral connectivity from the stroke hemisphere. Yet the incidence of ipsilateral projections in stroke survivors is often reported to be higher than normal. We tested this directly using a sensitive measure of connectivity to proximal arm muscles. Method TMS of the stroke and non-stroke motor cortex evoked responses in pre-activated triceps and deltoid muscles of 17 stroke survivors attending reaching training. Connectivity was defined as a clear MEP or a short-latency silent period in ongoing EMG in ≥ 50% of stimulations. We measured reaching accuracy at baseline, improvement after training and upper limb Fugl-Meyer (F-M) score. Results Incidence of ipsilateral connections to triceps (47%) and deltoid (58%) was high, but unrelated to baseline reaching accuracy and F-M scores. Instead, these were related to contralateral connectivity from the stroke hemisphere. Absolute but not proportional improvement after training was greater in patients with ipsilateral responses. Conclusions Despite enhanced ipsilateral connectivity, arm function and learning was related most strongly to contralateral pathway integrity from the stroke hemisphere. Significance Further work is needed to decipher the role of ipsilateral connections.

Objective Previous studies determined, using between arms position matching assessments, that at least one-half of individuals with stroke have an impaired position sense. We investigated whether individuals with chronic stroke who have impairments mirroring arm positions also have impairments identifying the location of each arm in space. Methods Participants with chronic hemiparetic stroke and age-matched participants without neurological impairments (controls) performed a between forearms position matching task based on a clinical assessment and a single forearm position matching task, using passive and active movements, based on a robotic assessment. Results 12 out of our 14 participants with stroke who had clinically determined between forearms position matching impairments had greater errors than the controls in both their paretic and non-paretic arm when matching positions during passive movements; yet stroke participants performed comparable to the controls during active movements. Conclusions Many individuals with chronic stroke may have impairments matching positions in both their paretic and non-paretic arm if their arm is moved for them, yet not within either arm if these individuals control their own movements. Significance The neural mechanisms governing arm location perception in the stroke population may differ depending on whether arm movements are made passively versus actively.

To examine the relationship of transcallosal pathway microstructure and transcallosal inhibition (TCI) with motor function and impairment in chronic stroke.Diffusion-weighted magnetic resonance imaging and transcranial magnetic stimulation (TMS) data were collected from 24 participants with chronic stroke and 11 healthy older individuals. Post-stroke motor function (Wolf Motor Function Test) and level of motor impairment (Fugl-Meyer score) were evaluated.Fractional anisotropy (FA) of transcallosal tracts between prefrontal cortices and the mean amplitude decrease in muscle activity during the ipsilateral silent period evoked by TMS over the non-lesioned hemisphere (termed NL-iSPmean) were significantly associated with level of motor impairment and motor function after stroke (p0.05). A regression model including age, post-stroke duration, lesion volume, lesioned corticospinal tract FA, transcallosal prefrontal tract FA and NL-iSPmean accounted for 84% of variance in motor impairment (p0.01). Both transcallosal prefrontal tract FA (ΔR(2)=0.12, p=0.04) and NL-iSPmean (ΔR(2)=0.09, p=0.04) accounted for unique variance in motor impairment level.Prefrontal transcallosal tract microstructure and TCI are each uniquely associated with motor impairment in chronic stroke.Utilizing a multi-modal approach to assess transcallosal pathways may improve our capacity to identify important neural substrates of motor impairment in the chronic phase of stroke.

Muscle spasticity is one of the major impairments that limits recovery in hemispheric stroke survivors. One potential contributing mechanism is hyperexcitability of motoneurons. Previously, the response latency of the surface electromyogram (EMG) record evoked by joint rotation has been used to characterize motoneuron excitability. Given the limitations of this method, the objective of the current study was to reexamine the excitability of motoneurons in chronic stroke survivors by estimating reflex latency using single motor unit discharge.We quantified the excitability of spastic motoneurons using the response latency of a single motor unit discharge elicited by a position controlled tap on the biceps brachii tendon. We applied tendon taps of different amplitudes on the biceps tendons of both arms of the stroke survivors. Unitary reflex responses were recorded using intramuscular EMG recordings.Our results showed that the latency of unitary discharge was systematically shorter in the spastic muscle compared with the contralateral muscle, and this effect was consistent across multiple tap amplitudes.This method allowed us to quantify latencies more accurately, potentially enabling a more rigorous analysis of contributing mechanisms.The findings provide evidence supporting a contribution of hyperexcitable motoneurons to muscle spasticity.

Objective Our aim was to investigate any changes in the estimated time-course of the afterhyperpolarisation (AHP) in motoneurones innervating the tibialis anterior following stroke, with a secondary objective to compare the results from two different AHP estimation techniques. Methods Motor units from tibialis anterior on the paretic and non-paretic sides of 15 subjects with chronic stroke were recorded using intramuscular electrodes during voluntary isometric contraction. Participants varied the motor unit firing rate from its lowest rate to approximately 10Hz. The AHP duration was estimated using the interval death rate (IDR) and transition point methods. Results The AHP decay time-constant was significantly different between sides (paretic: 41.7±8.5ms, non-paretic: 36.2±6.4ms). Additionally, the paretic AHP time-constant was significantly longer in participants with low motor recovery (45.9±9.1ms) than with high motor recovery (39.3±10.0ms) as measured by CMSA score. The AHP estimates from the two techniques were correlated ( r =0.78). Conclusions The AHP time-course prolongation on the paretic side of people with chronic stroke is more pronounced in people with low motor recovery. Significance Changes in the motoneurone AHP time course post-stroke were related to muscle function and may play a role in the commonly-observed reduction of motor unit discharge rate during voluntary contractions following stroke.

The efficacy of standard rehabilitation for improving upper limb functionality after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) combined with rehabilitation is a promising approach, but the invasiveness of this technique reduces its clinical application. Recently, a non-invasive technique for stimulating vagus nerve has been developed. Aim of this study is to evaluate safety, feasibility, and efficacy of noninvasive VNS combined with robotic rehabilitation for improving upper limb functionality in chronic stroke. We designed a proof-of-principle, double-blind, semi-randomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 consecutive working days. Efficacy was evaluated by change in upper extremity Fugl-Meyer score. After intervention, there were no adverse events and Fugl-Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in chronic stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach.

Objectives Few studies have assessed short intracortical inhibition (SICI) in the affected hemisphere (AH) in a large number of patients with chronic stroke. In this study, SICI was assessed in chronic stroke patients with severe hemiparesis, and its relationship to clinical parameters was examined. Methods The participants were 72 patients with chronic hemiparetic stroke. SICI of both the AH and the unaffected hemisphere (UH) was assessed. The relationships between SICI and the location of lesion, time from onset, and finger function were studied. Motor function of the paretic finger was assessed with the Stroke Impairment Assessment Set (SIAS) and the Fugl-Meyer test upper extremity motor score. To compare the results with those of healthy subjects, SICI was assessed in seven age-matched control subjects. Results MEPs of the UH were evoked in all 72 subjects, and MEPs of the AH were evoked in 24 subjects. SICI of the AH was inversely correlated with paretic finger motor function and time from stroke onset. SICI of the UH was not correlated with either one. SICI of the UH was higher in the cortical lesion group than in the control group. Conclusions The state of intracortical inhibitory neuron activity depends on the state of motor function and lesion site even in chronic stroke patients with severe hemiparesis. Significance The inhibitory system of the AH is involved in functional recovery of the paretic hand even in the chronic stage of stroke.

Objective The purpose of this study was to compare the torque production in the paretic and non-paretic hands during isokinetic tasks following stroke. Methods We compared torque and power production at the MCP joint of chronic stroke survivors during isometric and isokinetic tasks. We also recorded surface electromyography (EMG) activity in the forearm muscles. Results Isokinetic torque production at all velocities was less than that produced during isometric trials. Both torque and power produced by the paretic hand was substantially impaired. Deficits were substantially greater in extension than flexion trials. EMG data suggests that excessive co-contraction of agonist and antagonist muscles does not greatly affect isokinetic torque production at the MCP joint. Conclusions The fact that movement velocity produces larger deficits in torque and power production may explain why patients who have limited strength impairments still experience functional deficits. Significance This study demonstrates that strength testing of stroke survivors under isometric conditions may underestimate the overall level of impairment.

Objectives Rhythmic Auditory Stimulation (RAS) is a rhythmic sensory cueing to enhance gait patterns. Aim of the study was to research the effectiveness of RAS as an additional treatment for chronic stroke patients. Methods In the randomized controlled study 12 patients were assigned randomly into n = 6 intervention group and n = 6 control group. Both groups completed a 4-week gait training. The intervention group additionally received RAS through music over headphones. Berg Balance Scale, 6-Minute Walk Test, stride length and velocity over a distance of 10 m were used for assessment before and after interventions as well as 12 weeks later (follow up). Results There were no significant differences in relationship to the measured variables between intervention and control group. There were no indications to be drawn that the ability to follow a beat is necessary for effective results. Discussion/Conclusion The effectiveness of RAS with chronic stroke patients in the outpatient setting could not be proven in this study. It still remains in question whether the use of RAS in the treatment of stroke patients in the outpatient setting is effective or not.

Recent studies exploring the combined effect of motor learning and transcranial direct current stimulation (tDCS) have shown conflicting results. The optimization of the employed training paradigms can be one way to maximize treatment effects. Methods A newly developed visuo-motor force tracking task is directed to the improvement of fine force control in the hand. During the task, a target force is presented on a computer screen and controlled by patients by pressing a power grip force manipulandum with the affected hand. In the present pilot study we investigated motor effects of four-week training with the visuo-motor force tracking task combined with tDCS in 11 chronic stroke patients with different levels of paresis. Anodal (0.5 mA; 5 patients) or sham (6 patients) tDCS was applied on the primary motor cortex (M1) of the lesioned side for 20 min twice a day simultaneously with training.Upper Extremity Fugl-Meyer assessment (FMA; the primary outcome measure) was done before, after and on two months follow-up. Parameters of performance – ramp error, hold error, release duration and mean hold force – were calculated. Results Total UE FMA score was significantly increased immediately after the treatment, but had declined at two months follow-up. The most prominent improvement occurred in the shoulderelbow sub-score of the FMA; in this segment (but not in the total UE FMA score) a significantly greater improvement in the Active compared to the Sham group was observed (Fig. 1 Figure options Download full-size image Download high-quality image (338 K) Download as PowerPoint slide ). A clinically significant improvement (FMA > 5) was revealed in four patients out of five in the Active group and in two out of six – in the Sham group. Hold error decreased significantly in all patients; ramp error – in the Active group. Mean Hold Force during the first treatment session predicted the change in total UE FMA score after treatment (Fig. 2 Figure options Download full-size image Download high-quality image (213 K) Download as PowerPoint slide ). Conclusions The results show that this treatment protocol can result in clinically significant improvement of motor function in chronic stroke patients, including patients with severe paresis. Individual clinical characteristics of the patients could explain heterogeneity of results and lack of difference in the total UE FMA score. Performance during the initial session might inform about clinical outcomes and guide tDCS protocol optimization in future combined treatments.

Introduction The inhibition of the contralesional primary motor cortex (CM1) through repetitive transcranial magnetic stimulation (rTMS) has been shown to improve motor recovery in stroke patients. These data have been obtained through the stimulation of the contralesional cortical representation of the hand’s muscles. Nonetheless, and there is no evidence on the effects of contralesional inhibitory rTMS on the proximal muscles of the upper extremity. The aim of this study was to assess the effects of the low frequency-rTMS over the contralesional triceps area on reaching movements of chronic stroke patients. Methods Ten chronic, first ever stroke patients having different motor impairment have been enrolled in this perspective, randomized cross-over study. Patients undergone five daily sessions consisting of 1200 stimuli at 1 Hz, 90% of resting motor threshold, over the contralesional triceps area, and five daily sessions of sham stimulation, in a randomized sequence. The primary outcome measure was the change of kinematic parameters of reaching movement between the five baseline- and the five post-rTMS assessments. Results After rTMS, responding patients showed improved accuracy, smoothness, and velocity of reaching movements. These indices improved by no more than 10% (p Conclusion 1-Hz rTMS of the contralesional triceps area improved the execution of reaching movements of paretic limb in a sample of chronic stroke patients.

Background Different transcranial direct current stimulation (tDCS) paradigms have been implemented to treat post-stroke spasticity, but discordant results have been reported. Objective To determine the efficacy and persistence of dual-tDCS (anode over the affected motor cortex (M1) and cathode over the contralateral) compared to cathodal tDCS (cathode over contralateral M1) on upper limb (UL) functional, behavioral and neurophysiological measures in chronic post-stroke individuals. Methods 10 subjects with UL spasticity (7 men; mean age 62 y; 8 ischaemic stroke; years from event: 2.3 y) were enrolled in a cross-over, double-blinded study. Cathodal tDCS and dual-tDCS, both preceded by one week of sham stimulation 1 month before real, were applied with a 3 months interval. Stimulating paradigm was 20 min for five consecutive days in each block. Evaluations were performed before treatment (T1), after real or sham treatment (T2), and after one (T3), four (T4) and eight weeks (T5). Functional, behavioral and neurophysiological tests were performed at each time. Results Both tDCS paradigms decreased spasticity, increased strength and ameliorated behavioral scales. Cathodal tDCS was indeed superior to dual-tDCS in reducing UL distal spasticity immediately after treatment (T2: cathodal > dual: p = 0.023), and providing a higher and longer lasting reduction at proximal districts (T3: cathodal > dual: 0.042; T4: cathodal > dual: 0.028; T5: cathodal > dual: 0.05). These findings are supported by a slight major effect of cathodal tDCS on H reflex modulation (overall time effect p > 0.002). Conclusions Cathodal tDCS is slightly more effective than dual-tDCS in reducing distal UL spasticity in chronic post-stroke subjects. A modulation of spinal inhibitory mechanisms, as demonstrated by H reflex modifications, supports this finding.

Background Neuromuscular electrical stimulation (NMES) has been applied as one rehabilitative treatment option in stroke patients ( Quandt and Hummel, 2014 ) and a meta-analysis recently showed its positive effects on motor recovery ( Stein et al., 2015 ). One major challenge in stroke patients, especially severely impaired, is the opening of the hand due to extensor weakness accompanied by flexor spasticity. Here, NMES could provide assistance and substitute lost function. Studies in healthy controls have shown, however, that the rapid onset of muscle fatigue is a critical limitation for practical use. Here, we measure muscle fatigue over time during repetitive NMES in stroke patients and evaluate the impact of NMES on spasticity. Methods NMES was applied in a heterogeneous group of 7 chronic stroke patients (FM μ = 34/66, ran 13–51, ARAT μ = 13/57, ran 3–34) with different degrees of spasticity (MAS 0–4) over the extensor digitorum muscles using the MotionStim8, controlled via PC (25 Hz, 25 mA, 200–300 μs). The protocol comprised 6 blocks of stimulation with increasing pulse width (50 μs). Each block consisted of 10 alternating 10 s rest and 10 s stimulation periods. The next block was initiated 3 min later. To measure the impact of stimulation on finger extension, but not on wrist movement, stimulation was combined with an orthosis to stabilize the wrist. Effect of stimulation on finger movement was measured using a force gauge and a bend sensor. The median of the relative stimulation effect (stimulation period – following rest period) was taken and data were normalized between 0 and 1 to allow for comparison across patients. Statistical significance was assessed by modeling a simple linear regression for each patient. The regression coefficients β I were tested in a Students t-test against zero. Results The stimulation induced strength and movement showed a significant reduction over time (force, p = 0.004, sensor deviation, p = 0.017), even though pulse width was increased ( Fig. 1 ). Moreover, a reduction was already detected within a block. Even though a slight recovery occurs after the 3-minute break, break time was not sufficient to recover and reduce muscle fatigue completely. Spasticity of the flexor muscle was reduced after stimulation as measured by the MAS ( μ pr a = 2.6, μ post = 1.6, p = 0.05). Conclusion The effect of NMES on force production and finger extension did significantly decrease over a short period of time. The immediate decline after few hand openings critically underlines the need for measures to reduce muscle fatigue. Increased muscle fatigue during NMES compared to physiological movement could be a result of synchronous fiber stimulation and attempts of spatially distributed stimulation have been made to reduce fatigue in healthy controls ( Sayenko et al., 2014 ).

Objectives Physical therapy exercises that do not enhance motor areas neuroplasticity lead to motor impairment especially at the upper extremity (UE) in the chronic stroke patients. The aim of this study was to assess the effect of using bilateral arm training on motor areas excitability (neuroplasticity) in the chronic stroke patients. Methods Thirty male chronic stroke patients with moderate impairment of UE were assigned into two equal groups. The changes of motor areas excitability (neuroplasticity) were assessed before and after arm training by spectral analysis of mapping electroencephalogram (EEG). Delta, theta, alpha, beta 1 and beta 2 waves were recorded. The equation which was used to detect the neural plasticity and the changing at motor areas excitability was dividing the fast wave/slow waves or detecting the ratio of mean frequency of (beta 2 + beta 1 + alpha/theta + delta). Results Patients in group 1 (G1) received unilateral arm training and patients in group 2 (G2) received bilateral arm training. The Results: Showed significant increase in the excitability (neuroplasticity) at (F4 + F8) and (C4) motor areas in G2 comparing to G1 (p!9 .006) and (p!9 .036 ) respectively. Discussion Bimanual training leads to activation of extensive networks in both hemispheres. Conclusions It was concluded that bilateral arm training is a recommended method to enhance the motor areas excitability (neuroplasticity) in the chronic stroke patients. Significance Post stroke physical therapy can make use of bimanual training for better rehabilitation.

Question After stroke proximal upper limb muscles are innervated not only by contralateral but also by ipsilateral connections. These connections can be probed by transcranial magnetic stimulation (TMS) but whether these connections contribute to the functional recovery of upper limb movements is not clear. Methods We therefore established proximal upper limb muscle active motor evoked potentials (MEPs) when delivering 20 stimulations to both the affected and unaffected hemisphere of 19 chronic stroke survivors (mean age: 59 years, SD 10.2 years, 5 female, average onset since stroke 3 years 8 months,SD 2 year 4 months) at 70% maximal TMS stimulator output (Magstim 200 squared device, figure 8 coil). In addition, we measured each individuals Fugl-Meyer upper limb score, their endpoint accuracy and movement speed when performing a reaching protocol in a robotic manipulandum and proximal muscle power. Spearman and Pearson’s correlations were performed to assess correlations of Fugl-Meyer scores and baseline endpoint accuracy respectively, with MEP measures on a subject-by-subject basis. Results When stimulating the affected hemisphere at 70%, active MEPs were evoked in the affected weak upper limb in an average of 49% of stimulations. Responses were also seen in 19% of the stimulations delivered to the unaffected hemisphere via the ipsilateral pathway. There was a clear correlation of the presence of responses when stimulating the affected hemisphere and Fugl-Meyerscore (rho = .579, p. Conclusion In summary the findings in our stroke population support previous studies showing that intact corticospinal connections from the affected hemisphere are associated with good performance and recovery. We further observe that ipsilateral responses from the unaffected hemisphere are more common after stroke but that they are not correlated to function. Whether the relevance of these connections could be altered by targeted interventions in the acute period after stroke, when neuroplasticity is increased, should be further investigated.

Chronic hemiparesis of an upper limp following stroke has been related to an over-involvement of the ipsilateral hemisphere that inhibits use of the affected limb. Interventions helping to shift back this altered lateralization have been suggested to positively affect upper limp functional recovery. One such intervention is the combination of motor imagery (MI) supported by EEG neurofeedback. However, cortical reorganization requires highly intensive practice. In this feasibility study this was achieved by implementing a mobile EEG neurofeedback system. The training regime consisted of 14 MI sessions over a time course of 4 weeks. Three chronic stroke patients practiced MI neurofeedback using kinaesthetic imagination of a power grip of either the affected or the unaffected hand. Neurofeedback was based on features extracted from the 8-30 Hz frequency range. MI training was conducted at the patients’ home using a fully mobile 24-channel EEG system. Before and after the training, motor functions were assessed using a modified version of the Fugl-Meyer Assessment (FMA) and the modified Motor Assessment Scale (MAS). Moreover, pre- and post-training 96-channel EEG recordings were performed for MI and movement execution (ME) of the power grip task that was used for the MI neurofeedback training. Event-related desynchronization (ERD) in the 8–30 Hz frequency range was extracted offline for a region of interest analysis. Analysis focused on contra- and ipsilateral ERD and on the lateralization of ERD, defined as the difference between contralateral and ipsilateral ERD. All patients remained motivated throughout the training and completed the training regime. During MI and ME with the unaffected hand, patients showed stronger contralateral than ipsilateral activity in both the pre- and the post-training sessions. For the affected hand, MI and ME were however associated with stronger ipsilateral than contralateral activity. Changes were observed over the course of training, that, on a descriptive level, suggest a reduction of the altered lateralization for the affected hand in all three patients during MI. Furthermore, for one patient a significant improvement in the FMA score was observed, which paralleled the changes in MI and ME induced ERD. This study demonstrates that home-based MI neurofeedback training is feasible and allows for highly intensive training regimes. The observations made are in line with the notion of an over-involvement of the ipsilateral hemisphere during activities of the affected limb. The described changes of lateralization with MI neurofeedback training encourage continuing this line of research with larger sample sizes and matched healthy controls, to see if home-based MI neurofeedback training can indeed help to shift MI- and ME-related activation towards the expected lateralization patterns.

Background Affected hand movements are associated with a successive increase of neural activity in both hemispheres in the first weeks after stroke, which then return to levels observed in healthy controls, particularly in patients making full motor recovery. Little is known about the changes of the interplay of brain regions that enable the modulation of motor performance after stroke. In healthy subjects, an important feature of faster hand movements is mediated by a more effective coupling between distinct cortical and subcortical motor areas. But the mechanisms underlying the dynamic modulation of motor behavior in stroke patients related to motor impairment and recovery thereof are still unclear. Methods We, therefore, investigated 10 chronic stroke patients with mild to moderate unilateral hand motor deficits and 10 healthy, age-matched controls by using functional magnetic resonance imaging (fMRI). Motor system activity was assessed by fist closures at different movement frequencies (0.5 Hz, 1.0 Hz, and 2.0 Hz) performed with the affected/right or unaffected/left hand. Results When chronic stroke patients moved their affected, right hand, the fMRI data revealed a stronger frequency-dependent increase of neural activity within both the dorsolateral premotor cortex (PMd) and the superior parietal lobe (SPL), contralateral to the lesioned hemisphere as compared to healthy controls. Conclusion Our findings suggest a critical contribution of contralateral PMd and SPL in the flexible adaption of the brain to varying motor demands in chronic stroke patients controlling temporal and spatial preciseness of recovered complex hand movements in the contralesional hemisphere.

Repetitive facilitative exercise (RFE) is a recently developed approach to the rehabilitation of hemiplegia. RFE can be integrated with neuromuscular electrical stimulation (NMES), direct application of vibratory stimulation (DAVS), and repetitive transcranial magnetic stimulation (rTMS) to achieve further improvement. The aims of the present study were to retrospectively compare the effects of RFE and NMES + DAVS with those of RFE and rTMS and to determine the maximal effect of the combination of RFE with NMES, DAVS, rTMS and pharmacological treatments in chronic stroke patients. Fifty-three stroke patients were enrolled and divided into three groups: 15 who received RFE with rTMS (NMES(−), rTMS(+) group), 19 who received RFE with NMES + DAVS (NMES(+), rTMS(−) group), and 19 who received RFE with NMES + DAVS and rTMS (NMES(+), rTMS(+) group). The increase in the Fugl-Meyer Assessment (FMA) score in the NMES(+), rTMS(−) group was significantly better than that in the NMES(−), rTMS(+) group after 2 weeks. RFE with NMES + DAVS may be more effective than RFE with rTMS for the recovery of upper-limb function. The FMA scores were significantly improved after 4 weeks in the 38 patients of the NMES(+), rTMS(−) and NMES(+) rTMS(+) groups who received RFE with NMES, DAVS, rTMS and pharmacological treatments.

Objective: Brain–computer interface technology has been applied to stroke patients to improve their motor function. Event-related desynchronization during motor imagery, which is used as a brain–computer interface trigger, is sometimes difficult to detect in stroke patients. Anodal transcranial direct current stimulation (tDCS) is known to increase event-related desynchronization. This study investigated the adjunctive effect of anodal tDCS for brain–computer interface training in patients with severe hemiparesis. Subjects: Eighteen patients with chronic stroke. Design: A non-randomized controlled study. Methods: Subjects were divided between a brain–computer interface group and a tDCS-brain–computer interface group and participated in a 10-day brain–computer interface training. Event-related desynchronization was detected in the affected hemisphere during motor imagery of the affected fingers. The tDCS-brain–computer interface group received anodal tDCS before brain–computer interface training. Event-related desynchronization was evaluated before and after the intervention. The Fugl-Meyer Assessment upper extremity motor score (FM-U) was assessed before, immediately after, and 3 months after, the intervention. Results: Event-related desynchronization was significantly increased in the tDCS- brain–computer interface group. The FM-U was significantly increased in both groups. The FM-U improvement was maintained at 3 months in the tDCSbrain–computer interface group. Conclusion: Anodal tDCS can be a conditioning tool for brain–computer interface training in patients with severe hemiparetic stroke.

Transcranial direct current stimulation (TDCS) of primary motor cortex (M1) can transiently improve paretic hand function in chronic stroke. However, responses are variable so there is incentive to try to improve efficacy or to predict response in individual patients. Both excitatory (Anodal) stimulation of ipsilesional M1 and inhibitory (Cathodal) stimulation of contralesional M1 can speed simple reaction time. Here we tested whether combining these two effects simultaneously, by using a bilateral M1–M1 electrode montage, would improve efficacy. We tested the physiological efficacy of Bilateral, Anodal or Cathodal TDCS in changing motor evoked potentials (MEPs) in the healthy brain and their behavioural efficacy in changing reaction times with the paretic hand in chronic stroke. In addition, we aimed to identify clinical or neurochemical predictors of patients’ behavioural response to TDCS. There were three main findings: (1) Unlike Anodal and Cathodal TDCS, Bilateral M1–M1 TDCS (1 mA, 20 min) had no significant effect on MEPs in the healthy brain or on reaction time with the paretic hand in chronic stroke patients; (2) GABA levels in ipsilesional M1 predicted patients’ behavioural gains from Anodal TDCS; (3) Although patients were in the chronic phase, time since stroke (and its combination with Fugl-Meyer score) was a positive predictor of behavioural gain from Cathodal TDCS. These findings indicate the superiority of Anodal or Cathodal over Bilateral TDCS in changing motor corticospinal excitability in the healthy brain and in speeding reaction time in chronic stroke. The identified clinical and neurochemical markers of behavioural response should help to inform the optimization of TDCS delivery and to predict patient outcome variability in future TDCS intervention studies in chronic motor stroke.

Introduction Voluntary movement implies a subjective experience of the intention to move as well as motor execution. Previous patients studies showed that the parietal cortex (PC) plays a key role in awareness of motor intentions. However, the results in lesion studies are conflicting. Objective To clarify the functional relevance of the PC in the awareness of motor intention, we used transient suppression of focal neural processing induced by low-frequency rTMS. Methods Twelve right-handed healthy volunteers participated in the study. The experimental paradigm was based on that of Libet (1983). Subjects were asked to report the position of the clock’s hand at the time they pushed the button (M-judgment) or at the time they first became aware of their intention to move (W-judgment). We applied 0.9 Hz rTMS (1200 total pulses) over individually determined left PC to suppress cortical activity and measured subsequent task performance before, immediately after and 15 min after rTMS. Results rTMS over the left PC significantly prolonged the timing of W-judgment immediately after rTMS. In M-judgment, rTMS over the left PC had no effect on task performance. Conclusion The neural processing in the left PC might be important for the awareness of the intention to move, because the duration from the intention to movement was prolonged after the transient suppression of the left PC. One previous study showed the decrease that duration in patients with PC lesion (Sirigu, 2004). However, there are another study reporting the normal W-judgment time in those patients (Lafargue, 2008). This controversy may be due to the functional compensation in the chronic stage. The functional suppression induced by rTMS may be similar to the acute one, so that the present results cannot be directly comparable to the chronic stroke patients. However, at least, our results suggest the essential role of the left PC in the generation of the intention to move, although the exact role of the left PC is not known yet.

The relation was investigated between functional improvement of hemiparetic arm and change of cortical perfusion (BCP) during voluntary muscle contraction (VOL), EMG-controlled FES (EMG-FES) and simple electrical muscle stimulation (ES) before and after EMG-FES therapy in chronic stroke patients. Sixteen chronic stroke patients with moderate residual hemiparesis underwent 5 months of task-orientated EMG-FES therapy of the paretic arm once or twice a week. Before and after treatment, arm function was clinically evaluated and BCP during VOL, ES and EMG-FES were assessed using multi-channel near-infrared spectroscopy. BCP in the ipsilesional sensory-motor cortex (SMC) was greater during EMG-FES than during VOL or ES; therefore, EMG-FES caused a shift in the dominant BCP from the contralesional to ipsilesional SMC. After EMG-FES therapy, Fugl-Meyer (FM) score and maximal grip strength (GS) were improved significantly even with variability within individual patients. Clinical improvement accompanied an increase in ipsilesional SMC activation during VOL and EMG-FES condition. The EMG-FES may have more influence on ipsilesional BCP than VOL or ES alone. The sensory motor integration during EMG-FES therapy might facilitate BCP of the ipsilesional SMC and influence on brain reorganization, which result in functional improvement of hemiparetic upper extremity.