Theta burst stimulation for enhancing upper extremity motor functions after stroke: a systematic review of clinical and mechanistic evidence.

This systematic review aimed to evaluate the effects of different theta burst stimulation (TBS) protocols on improving upper extremity motor functions in patients with stroke, their associated modulators of efficacy, and the underlying neural mechanisms. We conducted a meta-analytic review of 29 controlled trials published from January 1, 2000, to August 29, 2023, which investigated the effects of TBS on upper extremity motor, neurophysiological, and neuroimaging outcomes in poststroke patients. TBS significantly improved upper extremity motor impairment (Hedge's g = 0.646, p = 0.003) and functional activity (Hedge's g = 0.500, p < 0.001) compared to controls. Meta-regression revealed a significant relationship between the percentage of patients with subcortical stroke and the effect sizes of motor impairment (p = 0.015) and functional activity (p = 0.018). Subgroup analysis revealed a significant difference in the improvement of upper extremity motor impairment between studies using 600-pulse and 1200-pulse TBS (p = 0.002). Neurophysiological studies have consistently found that intermittent TBS increases ipsilesional corticomotor excitability. However, evidence to support the regional effects of continuous TBS, as well as the remote and network effects of TBS, is still mixed and relatively insufficient. In conclusion, TBS is effective in enhancing poststroke upper extremity motor function. Patients with preserved cortices may respond better to TBS. Novel TBS protocols with a higher dose may lead to superior efficacy compared with the conventional 600-pulse protocol. The mechanisms of poststroke recovery facilitated by TBS can be primarily attributed to the modulation of corticomotor excitability and is possibly caused by the recruitment of corticomotor networks connected to the ipsilesional motor cortex.

Priming transcranial direct current stimulation for improving hemiparetic upper limb in patients with subacute stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates brain states by applying a weak electrical current to the brain cortex. Several studies have shown that anodal stimulation of the ipsilesional primary motor cortex (M1) may promote motor recovery of the affected upper limb in patients with stroke; however, a high-level clinical recommendation cannot be drawn in view of inconsistent findings. A priming brain stimulation protocol has been proposed to induce stable modulatory effects, in which an inhibitory stimulation is applied prior to excitatory stimulation to a brain area. Our recent work showed that priming theta burst magnetic stimulation demonstrated superior effects in improving upper limb motor function and neurophysiological outcomes. However, it remains unknown whether pairing a session of cathodal tDCS with a session of anodal tDCS will also capitalise on its therapeutic effects. METHODS AND ANALYSIS: This will be a two-arm double-blind randomised controlled trial involving 134 patients 1-6 months after stroke onset. Eligible participants will be randomly allocated to receive 10 sessions of priming tDCS+robotic training, or 10 sessions of non-priming tDCS+robotic training for 2 weeks. The primary outcome is the Fugl-Meyer Assessment-upper extremity, and the secondary outcomes are the Wolf Motor Function Test and Modified Barthel Index. The motor-evoked potentials, regional oxyhaemoglobin level and resting-state functional connectivity between the bilateral M1 will be acquired and analysed to investigate the effects of priming tDCS on neuroplasticity. ETHICS AND DISSEMINATION: The study has been approved by the Research Ethics Committee of the Shanghai Yangzhi Rehabilitation Center (reference number: Yangzhi2023-022) and will be conducted in accordance with the Declaration of Helsinki of 1964, as revised in 2013. TRIAL REGISTRATION NUMBER: ChiCTR2300074681.

Resting-state cortical electroencephalogram rhythms and network in patients after chronic stroke.

OBJECTIVE: To investigate the resting-state cortical electroencephalogram (EEG) rhythms and networks in patients with chronic stroke and examine their correlation with motor functions of the hemiplegic upper limb. METHODS: Resting-state EEG data from 22 chronic stroke patients were compared to EEG data from 19 age-matched and 16 younger-age healthy controls. The EEG rhythmic powers and network metrics were analyzed. Upper limb motor functions were evaluated using the Fugl-Meyer assessment-upper extremity scores and action research arm test. RESULTS: Compared with healthy controls, patients with chronic stroke showed hemispheric asymmetry, with increased low-frequency activity and decreased high-frequency activity. The ipsilesional hemisphere of stroke patients exhibited reduced alpha and low beta band node strength and clustering coefficient compared to the contralesional side. Low beta power and node strength in the delta band correlated with motor functions of the hemiplegic arm. CONCLUSION: The stroke-affected hemisphere showed low-frequency oscillations and decreased influence and functional segregation in the brain network. Low beta activity and redistribution of delta band network between hemispheres were correlated with motor functions of hemiplegic upper limb, suggesting a compensatory mechanism involving both hemispheres post-stroke.

Computational simulation of transcranial magnetic stimulation-induced electric fields in the dorsolateral prefrontal cortex of heavy cannabis using individuals.

We aimed to investigate the influence of demographic and clinical modulators on the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EFs) in the left dorsolateral prefrontal cortex (lDLPFC) in heavy cannabis using individuals. Structural T1-weighted magnetic resonance imaging scans of 20 heavy cannabis using individuals and 22 non-cannabis users (the controls) in the age range of 18-25 were retrieved. Computational simulations of TMS-induced EFs in the lDLPFC were performed. No significant difference in the strength of TMS-induced EFs was observed between heavy cannabis using individuals and the controls. A negative correlation between the scalp-to-cortex distance demonstrated and the strength of the induced EFs. The severity of cannabis use related problems did not correlate with the induced EFs in the lDLPFC of heavy cannabis using individuals. However, the severity of alcohol use related problems was negatively correlated with the induced EF in the lDLPFC localized by the 5-cm method in the whole sample. Early adulthood seems related to an increase in the induced EFs in the lDLPFC. In conclusion, the dominant factor influencing TMS-induced EFs was the scalp-to-cortex distance. In early adulthood, the interaction between age and comorbid substance use may influence with the magnitude of TMS-induced EFs, thereby complicating the treatment effect of TMS in young people with substance use disorders.

Determining the Optimal Stimulation Sessions for TMS-Induced Recovery of Upper Extremity Motor Function Post Stroke: A Randomized Controlled Trial.

To find out the optimal treatment sessions of repetitive transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) for upper extremity dysfunction after stroke during the 6-week treatment and to explore its mechanism using motor-evoked potentials (MEPs) and resting-state functional magnetic resonance imaging (rs-fMRI), 72 participants with upper extremity motor dysfunction after ischemic stroke were randomly divided into the control group, 10-session, 20-session, and 30-session rTMS groups. Low-frequency (1 Hz) rTMS over the contralesional M1 was applied in all rTMS groups. The motor function of the upper extremity was assessed before and after treatment. In addition, MEPs and rs-fMRI data were analyzed to detect its effect on brain reorganization. After 6 weeks of treatment, there were significant differences in the Fugl-Meyer Assessment of the upper extremity and the Wolf Motor Function Test scores between the 10-session group and the 30-session group and between the 20- and 30-session groups and the control group, while there was no significant difference between the 20-session group and the 30-session group. Meanwhile, no significant difference was found between the 10-session group and the control group. The 20-session group of rTMS decreased the excitability of the contralesional corticospinal tract represented by the amplitudes of MEPs and enhanced the functional connectivity of the ipsilesional M1 or premotor cortex with the the precentral gyrus, postcentral gyrus, and cingulate gyrus, etc. In conclusion, the 20-session of rTMS protocol is the optimal treatment sessions of TMS for upper extremity dysfunction after stroke during the 6-week treatment. The potential mechanism is related to its influence on the excitability of the corticospinal tract and the remodeling of corticomotor functional networks.

Considerable effects of lateralization and aging in intracortical excitation and inhibition.

Introduction: Findings based on the use of transcranial magnetic stimulation and electromyography (TMS-EMG) to determine the effects of motor lateralization and aging on intracortical excitation and inhibition in the primary motor cortex (M1) are inconsistent in the literature. TMS and electroencephalography (TMS-EEG) measures the excitability of excitatory and inhibitory circuits in the brain cortex without contamination from the spine and muscles. This study aimed to investigate the effects of motor lateralization (dominant and non-dominant hemispheres) and aging (young and older) and their interaction effects on intracortical excitation and inhibition within the M1 in healthy adults, measured using TMS-EMG and TMS-EEG. Methods: This study included 21 young (mean age = 28.1 ± 3.2 years) and 21 older healthy adults (mean age = 62.8 ± 4.2 years). A battery of TMS-EMG measurements and single-pulse TMS-EEG were recorded for the bilateral M1. Results: Two-way repeated-measures analysis of variance was used to investigate lateralization and aging and the lateralization-by-aging interaction effect on neurophysiological outcomes. The non-dominant M1 presented a longer cortical silent period and larger amplitudes of P60, N100, and P180. Corticospinal excitability in older participants was significantly reduced, as supported by a larger resting motor threshold and lower motor-evoked potential amplitudes. N100 amplitudes were significantly reduced in older participants, and the N100 and P180 latencies were significantly later than those in young participants. There was no significant lateralization-by-aging interaction effect in any outcome. Conclusion: Lateralization and aging have independent and significant effects on intracortical excitation and inhibition in healthy adults. The functional decline of excitatory and inhibitory circuits in the M1 is associated with aging.

Intracortical and intercortical networks in patients after stroke: a concurrent TMS-EEG study.

BACKGROUND: Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) recording provides information on both intracortical reorganization and networking, and that information could yield new insights into post-stroke neuroplasticity. However, a comprehensive investigation using both concurrent TMS-EEG and motor-evoked potential-based outcomes has not been carried out in patients with chronic stroke. Therefore, this study sought to investigate the intracortical and network neurophysiological features of patients with chronic stroke, using concurrent TMS-EEG and motor-evoked potential-based outcomes. METHODS: A battery of motor-evoked potential-based measures and concurrent TMS-EEG recording were performed in 23 patients with chronic stroke and 21 age-matched healthy controls. RESULTS: The ipsilesional primary motor cortex (M1) of the patients with stroke showed significantly higher resting motor threshold (P = 0.002), reduced active motor-evoked potential amplitudes (P = 0.001) and a prolonged cortical silent period (P = 0.007), compared with their contralesional M1. The ipsilesional stimulation also produced a reduction in N100 amplitude of TMS-evoked potentials around the stimulated M1 (P = 0.007), which was significantly correlated with the ipsilesional resting motor threshold (P = 0.011) and motor-evoked potential amplitudes (P = 0.020). In addition, TMS-related oscillatory power was significantly reduced over the ipsilesional midline-prefrontal and parietal regions. Both intra/interhemispheric connectivity and network measures in the theta band were significantly reduced in the ipsilesional hemisphere compared with those in the contralesional hemisphere. CONCLUSIONS: The ipsilesional M1 demonstrated impaired GABA-B receptor-mediated intracortical inhibition characterized by reduced duration, but reduced magnitude. The N100 of TMS-evoked potentials appears to be a useful biomarker of post-stroke recovery.

Immediate Effects of Intermittent Theta Burst Stimulation on Primary Motor Cortex in Stroke Patients: A Concurrent TMS-EEG Study.

The neurophysiological effect of intermittent theta burst stimulation (iTBS) has been examined with TMS-electromyography (EMG)-based outcomes in healthy people; however, its effects in intracortical excitability and inhibition are largely unknown in patients with stroke. Concurrent transcranial magnetic stimulation and electroencephalogram (TMS-EEG) recording can be used to investigate both intracortical excitatory and inhibitory circuits of the primary motor cortex (M1) instantly and the property of brain networks at once. This study was to investigate the immediate effects of iTBS on intracortical excitatory and inhibitory circuits, neural connectivity, and network properties in patients with chronic stroke, using TMS-EEG and TMS-EMG approaches. In this randomized, sham-controlled, crossover study, 20 patients with chronic stroke received two separate stimulation conditions: a single-session iTBS or sham stimulation applied to the ipsilesional M1, in two separate visits, with a washout period of five to seven days between the two visits. A battery of TMS-EMG and TMS-EEG measurements were taken before and immediately after stimulation during the visit. Compared with sham stimulation, iTBS was effective in enhancing the amplitude of ipsilesional MEPs (p = 0.015) and P30 of TMS-evoked potentials located at the ipsilesional M1 (p = 0.037). However, iTBS did not show superior effects on ipsilesional intracortical facilitation, cortical silent period, or short-interval intracortical inhibition. Regarding the effects on TMS-related oscillations, and neural connectivity, comparisons of iTBS and sham did not yield any significant differences. iTBS facilitates intracortical excitability in patients with chronic stroke, but it does not show modulatory effects in intracortical inhibition.

Does intermittent theta burst stimulation improve working memory capacity? A randomized controlled cross-over experiment.

OBJECTIVE: It has been hypothesized that intermittent theta burst stimulation (iTBS) can produce a memory-enhancing effect by inducing long-term potentiation (LTP)-like plasticity in the dorsolateral prefrontal cortex (DLPFC). However, the hemispheric difference by which iTBS modulates working memory in healthy adults has not been well investigated. The objective of the present study is to investigate the effects of iTBS on the left dorsolateral prefrontal cortex (LDLPFC) and right dorsolateral prefrontal cortex (RDLPFC) on working memory performance in healthy adults. METHODS: In this randomized cross-over experiment, 31 right-hand dominant healthy adults received a single-session of iTBS to their LDLPFC, RDLPFC and sham stimulation, in three different visits separated by a seven-day waiting period. Working memory capacity was assessed before and immediately after stimulation, by using 2-and 3-back tasks. RESULTS: After stimulation, significant time effects were found in overall accuracy when performing both 2- (p = 0.013) and 3-back tasks (p = 0.027), as well as the total reaction time during 3-back tasks (p = 0.021). Analysis of secondary outcomes showed an increase in the number of correction rejections in 2-back tasks (p = 0.009). However, all of the time-by-group interaction effects were not significant. CONCLUSION: This experiment did not find any additional memory-enhancing effects with a single-session of iTBS to either the RDLPFC or the LDLPFC in healthy adults beyond the practice effects.

Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial.

BACKGROUND: Intermittent theta burst stimulation (iTBS) creates a state with increased excitability that permits treatment modalities to induce neuroplasticity and motor learning. Continuous theta burst stimulation before iTBS may induce metaplasticity and boost the facilitatory effect of iTBS. This study investigated the effects of priming iTBS (ie, applying continuous theta burst stimulation before iTBS) on poststroke hemiparetic upper limb recovery. METHODS: In this randomized controlled trial, 42 patients with chronic stroke were recruited and randomly allocated to 10 sessions of either priming iTBS, nonpriming iTBS, or sham stimulation to the ipsilesional motor cortex, immediately before robot-assisted training. Outcomes included Fugl-Meyer Assessment-Upper Extremity, Action Research Arm Test and mean movement velocity during each robot-assisted training session. Twenty-one patients were enrolled for measuring the sensorimotor beta event-related desynchronization induced by either mirror visual feedback or movement. RESULTS: The Fugl-Meyer Assessment-Upper Extremity scores revealed a significant time-by-group interaction (P=0.011). Priming and nonpriming iTBS were both superior to sham stimulation in post hoc comparisons; however, the superiority was diminished at follow-up. Among patients with a higher functioning upper limb, priming iTBS yielded a significantly greater improvement in Fugl-Meyer Assessment-Upper Extremity scores than nonpriming iTBS (P=0.025) and sham stimulation (P=0.029) did. No significant interaction was found when analyzing the Action Research Arm Test and mean movement velocity. Priming iTBS enhanced the patients' mirror visual feedback-induced high beta sensorimotor event-related desynchronization over their ipsilesional hemisphere. CONCLUSIONS: Priming and nonpriming iTBS are both superior to sham stimulation in enhancing treatment gains from robot-assisted training, and patients with a higher functioning upper limb may experience more benefits from priming iTBS. Priming iTBS may facilitate poststroke motor learning by enhancing the permissiveness of the ipsilesional sensorimotor area to therapeutic sensory modalities, such as the mirror visual feedback. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04034069.

Biomarkers for prognostic functional recovery poststroke: A narrative review.

Background and objective: Prediction of poststroke recovery can be expressed by prognostic biomarkers that are related to the pathophysiology of stroke at the cellular and molecular level as well as to the brain structural and functional reserve after stroke at the systems neuroscience level. This study aimed to review potential biomarkers that can predict poststroke functional recovery. Methods: A narrative review was conducted to qualitatively summarize the current evidence on biomarkers used to predict poststroke functional recovery. Results: Neurophysiological measurements and neuroimaging of the brain and a wide diversity of molecules had been used as prognostic biomarkers to predict stroke recovery. Neurophysiological studies using resting-state electroencephalography (EEG) revealed an interhemispheric asymmetry, driven by an increase in low-frequency oscillation and a decrease in high-frequency oscillation in the ipsilesional hemisphere relative to the contralesional side, which was indicative of individual recovery potential. The magnitude of somatosensory evoked potentials and event-related desynchronization elicited by movement in task-related EEG was positively associated with the quantity of recovery. Besides, transcranial magnetic stimulation (TMS) studies revealed the potential values of using motor-evoked potentials (MEP) and TMS-evoked EEG potentials from the ipsilesional motor cortex as prognostic biomarkers. Brain structures measured using magnetic resonance imaging (MRI) have been implicated in stroke outcome prediction. Specifically, the damage to the corticospinal tract (CST) and anatomical motor connections disrupted by stroke lesion predicted motor recovery. In addition, a wide variety of molecular, genetic, and epigenetic biomarkers, including hemostasis, inflammation, tissue remodeling, apoptosis, oxidative stress, infection, metabolism, brain-derived, neuroendocrine, and cardiac biomarkers, etc., were associated with poor functional outcomes after stroke. However, challenges such as mixed evidence and analytical concerns such as specificity and sensitivity have to be addressed before including molecular biomarkers in routine clinical practice. Conclusion: Potential biomarkers with prognostic values for the prediction of functional recovery after stroke have been identified; however, a multimodal approach of biomarkers for prognostic prediction has rarely been studied in the literature. Future studies may incorporate a combination of multiple biomarkers from big data and develop algorithms using data mining methods to predict the recovery potential of patients after stroke in a more precise way.

The Modulatory Effects of Intermittent Theta Burst Stimulation in Combination With Mirror Hand Motor Training on Functional Connectivity: A Proof-of-Concept Study.

Mirror training (MT) is an observation-based motor learning strategy. Intermittent theta burst stimulation (iTBS) is an accelerated form of excitatory repetitive transcranial magnetic stimulation (rTMS) that has been used to enhance the cortical excitability of the motor cortices. This study aims to investigate the combined effects of iTBS with MT on the resting state functional connectivity at alpha frequency band in healthy adults. Eighteen healthy adults were randomized into one of three groups-Group 1: iTBS plus MT, Group 2: iTBS plus sham MT, and Group 3: sham iTBS plus MT. Participants in Groups 1 and 3 observed the mirror illusion of the moving (right) hand in a plain mirror for four consecutive sessions, one session/day, while participants in Group 2 received the same training with a covered mirror. Real or sham iTBS was applied daily over right motor cortex prior to the training. Resting state electroencephalography (EEG) at baseline and post-training was recorded when participants closed their eyes. The mixed-effects model demonstrated a significant interaction effect in the coherence between FC4 and C4 channels, favoring participants in Group 1 over Group 3 (Δß = -0.84, p = 0.048). A similar effect was also found in the coherence between FC3 and FC4 channels favoring Group 1 over Group 3 (Δß = -0.43, p = 0.049). In contrast to sham iTBS combined with MT, iTBS combined with MT may strengthen the functional connectivity between bilateral premotor cortices and ipsilaterally within the motor cortex of the stimulated hemisphere. In contrast to sham MT, real MT, when combined with iTBS, might diminish the connectivity among the contralateral parietal-frontal areas.

The Effects of Priming Intermittent Theta Burst Stimulation on Movement-Related and Mirror Visual Feedback-Induced Sensorimotor Desynchronization.

The potential benefits of priming intermittent theta burst stimulation (iTBS) with continuous theta burst stimulation (cTBS) have not been examined in regard to sensorimotor oscillatory activities recorded in electroencephalography (EEG). The objective of this study was to investigate the modulatory effect of priming iTBS (cTBS followed by iTBS) delivered to the motor cortex on movement-related and mirror visual feedback (MVF)-induced sensorimotor event-related desynchronization (ERD), compared with iTBS alone, on healthy adults. Twenty participants were randomly allocated into Group 1: priming iTBS-cTBS followed by iTBS, and Group 2: non-priming iTBS-sham cTBS followed by iTBS. The stimulation was delivered to the right primary motor cortex daily for 4 consecutive days. EEG was measured before and after 4 sessions of stimulation. Movement-related ERD was evaluated during left-index finger tapping and MVF-induced sensorimotor ERD was evaluated by comparing the difference between right-index finger tapping with and without MVF. After stimulation, both protocols increased movement-related ERD and MVF-induced sensorimotor ERD in high mu and low beta bands, indicated by significant time effects. A significant interaction effect favoring Group 1 in enhancing movement-related ERD was observed in the high mu band [F (1,18) = 4.47, p = 0.049], compared with Group 2. Our experiment suggests that among healthy adults priming iTBS with cTBS delivered to the motor cortex yields similar effects with iTBS alone on enhancing ERD induced by MVF-based observation, while movement-related ERD was more enhanced in the priming iTBS condition, specifically in the high mu band.

Immediate and long-term effects of BCI-based rehabilitation of the upper extremity after stroke: a systematic review and meta-analysis.

BACKGROUND: A substantial number of clinical studies have demonstrated the functional recovery induced by the use of brain-computer interface (BCI) technology in patients after stroke. The objective of this review is to evaluate the effect sizes of clinical studies investigating the use of BCIs in restoring upper extremity function after stroke and the potentiating effect of transcranial direct current stimulation (tDCS) on BCI training for motor recovery. METHODS: The databases (PubMed, Medline, EMBASE, CINAHL, CENTRAL, PsycINFO, and PEDro) were systematically searched for eligible single-group or clinical controlled studies regarding the effects of BCIs in hemiparetic upper extremity recovery after stroke. Single-group studies were qualitatively described, but only controlled-trial studies were included in the meta-analysis. The PEDro scale was used to assess the methodological quality of the controlled studies. A meta-analysis of upper extremity function was performed by pooling the standardized mean difference (SMD). Subgroup meta-analyses regarding the use of external devices in combination with the application of BCIs were also carried out. We summarized the neural mechanism of the use of BCIs on stroke. RESULTS: A total of 1015 records were screened. Eighteen single-group studies and 15 controlled studies were included. The studies showed that BCIs seem to be safe for patients with stroke. The single-group studies consistently showed a trend that suggested BCIs were effective in improving upper extremity function. The meta-analysis (of 12 studies) showed a medium effect size favoring BCIs for improving upper extremity function after intervention (SMD = 0.42; 95% CI = 0.18-0.66; I2 = 48%; P < 0.001; fixed-effects model), while the long-term effect (five studies) was not significant (SMD = 0.12; 95% CI = - 0.28 - 0.52; I2 = 0%; P = 0.540; fixed-effects model). A subgroup meta-analysis indicated that using functional electrical stimulation as the external device in BCI training was more effective than using other devices (P = 0.010). Using movement attempts as the trigger task in BCI training appears to be more effective than using motor imagery (P = 0.070). The use of tDCS (two studies) could not further facilitate the effects of BCI training to restore upper extremity motor function (SMD = - 0.30; 95% CI = - 0.96 - 0.36; I2 = 0%; P = 0.370; fixed-effects model). CONCLUSION: The use of BCIs has significant immediate effects on the improvement of hemiparetic upper extremity function in patients after stroke, but the limited number of studies does not support its long-term effects. BCIs combined with functional electrical stimulation may be a better combination for functional recovery than other kinds of neural feedback. The mechanism for functional recovery may be attributed to the activation of the ipsilesional premotor and sensorimotor cortical network.

Effects of priming intermittent theta burst stimulation on upper limb motor recovery after stroke: study protocol for a proof-of-concept randomised controlled trial.

INTRODUCTION: Intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), delivered to the ipsilesional primary motor cortex (M1), appears to enhance the brain's response to rehabilitative training in patients with stroke. However, its clinical utility is highly subject to variability in different protocols. New evidence has reported that preceding iTBS, with continuous theta burst stimulation (cTBS) may stabilise and even boost the facilitatory effect of iTBS on the stimulated M1, via metaplasticity. The aim of this study is to investigate the effects of iTBS primed with cTBS (ie, priming iTBS), in addition to robot-assisted training (RAT), on the improvement of the hemiparetic upper limb functions of stroke patients and to explore potential sensorimotor neuroplasticity using electroencephalography (EEG). METHODS AND ANALYSIS: A three-arm, subjects and assessors-blinded, randomised controlled trial will be performed with patients with chronic stroke. An estimated sample of 36 patients will be needed based on the prior sample size calculation. All participants will be randomly allocated to receive 10 sessions of rTMS with different TBS protocols (cTBS+iTBS, sham cTBS+iTBS and sham cTBS+sham iTBS), three to five sessions per week, for 2-3 weeks. All participants will receive 60 min of RAT after each stimulation session. Primary outcomes will be assessed using Fugl-Meyer Assessment-Upper Extremity scores and Action Research Arm Test. Secondary outcomes will be assessed using kinematic outcomes generated during RAT and EEG. ETHICS AND DISSEMINATION: Ethical approval has been obtained from The Human Subjects Ethics Sub-committee, University Research Committee of The Hong Kong Polytechnic University (reference number: HSEARS20190718003). The results yielded from this study will be presented at international conferences and sent to a peer-review journal to be considered for publication. TRIAL REGISTRATION NUMBER: NCT04034069.

Enhancing mirror visual feedback with intermittent theta burst stimulation in healthy adults.

BACKGROUND: Excitatory brain stimulation, in the form of intermittent theta burst stimulation (iTBS), combined with mirror visual feedback (MVF), is hypothesized to promote neuroplasticity and motor performance. OBJECTIVE: This study aimed to investigate the combined effects of iTBS with mirror training (MT) on the MVF-induced sensorimotor event-related desynchronization (ERD) and the non-dominant hand motor performance in healthy adults. METHODS: Eighteen healthy right-handed subjects were randomly assigned to one of three groups (Group 1: iTBS plus MT, Group 2: iTBS plus sham MT, or Group 3: sham iTBS plus MT). For participants in Groups 1 and 3, motor training was performed for 15 minutes for the right hand over four consecutive days, with MVF superimposing on their inactive left hand behind a mirror. Participants in Group 2 received the same right-hand motor training, but the mirror was covered without MVF. iTBS or sham iTBS was applied daily over the right primary motor cortex prior to the training. Electroencephalography at pre/post-training was recorded while participants performed right-hand movement under mirror and direct view. Motor performance was assessed at baseline and post-training. RESULTS: Baseline comparisons demonstrated that a shift in sensorimotor ERD towards the right hemisphere was induced by MVF, in mu-1 (8-10 Hz) (p = 0.002), mu-2 (10-12 Hz) (p = 0.004) and beta-1 (12-16 Hz) (p = 0.049) bands. After the training, participants in Group 1 showed a stronger MVF-induced sensorimotor ERD in mu-1 (p = 0.017) and mu-2 (p = 0.009) bands than those in Group 3. No significant between-group difference in motor outcomes was observed. CONCLUSIONS: iTBS appears to prime subjects' brain to be more receptive to MVF.