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Muscle vibration modifies corticomotor excitability in healthy subjects and reduces muscle tonus in stroke patients.
This study examined whether repeated muscle vibration (rMV) applied over the flexor carpi radialis (FCR) and biceps brachii (BB) can induce long-lasting changes, using transcranial magnetic stimulation (TMS), in patients with chronic...
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Citations
... These vibrations have a stimulating effect on the processes of brain plasticity and long-term motor recovery. To date, research in this area has focused on chronic stroke, which has been positively evaluated and proven [43]. Referring to the functional and structural changes in neuronal networks that occur in the first hours after stroke onset, Toscano et al., (2019) conducted a study using rMV in patients in the acute phase. ...
Intracerebral hemorrhage (ICH) is a serious neurological disease with a 30-day mortality rate of 34–50%. Rehabilitation can reduce disability and improve recovery from a stroke; however, it is uncertain whether early rehabilitation is safe. There are many studies and reviews on rehabilitation for chronic conditions, but there is not enough information on the details of rehabilitation in the acute and subacute phases of ICH. We analyzed clinical trials from the electronic databases PubMed, PubMedCentral, Medline, Cochrane Library, Embase, Scopus and PEDro. Based on the data, we determined that early rehabilitation of patients with ICH has beneficial effects on improving ADL scores, motor function, functional independence, quality of life, improved gait, improved trunk control and reduced mortality. Varying the duration and intensity of rehabilitation in patients with ICH may improve health status, functional outcomes and reduce the length of stay in the hospital. The earliest protocol for initiating rehabilitation after ICH included up to 24 h after stroke onset. The medical literature indicates the need for more randomized controlled group trials of early rehabilitation in patients with acute and subacute ICH with a precise timing of rehabilitation initiation. This narrative review aims to summarize the existing evidence and provide insights into the current state of knowledge regarding the safety of early rehabilitation. There is a need for a clear definition of “early rehabilitation” when determining the most appropriate time to begin rehabilitation therapy.
... Vibratory stimulation suppresses muscle tone by directly stimulating the muscles affected by spasticity, or by stimulating the antagonist muscles corresponding to the affected muscles 5,6) . However, the effect of vibratory stimulation on suppressing muscle tone persists only during the period of stimulation, and is impaired immediately when the stimulation is terminated 7) . ...
Purpose] This study aimed to examine the effects of unilateral vibratory stimulation on contralateral homonymous muscle. [Participants and Methods] The study included 14 participants without a history of any disease. Participants were tested under three separate conditions: vibratory stimulation, pressure stimulation, and rest. F-waves were measured at two time points for 15 seconds in the rest position under each of the testing conditions. [Results] The F/M amplitude ratio analysis showed interactions between the vibratory stimulation‒pressure stimulation and vibratory stimulation‒rest conditions. The F-wave persistence analysis demonstrated interactions between the vibratory and pressure stimulation conditions. Vibratory stimulation significantly decreased the F/M amplitude ratio and F-wave persistence at two time points, before and during the stimulation. [Conclusion] The vibratory stimulation used in this study could suppress the contralateral homonymous muscle tone.
... Each patient underwent fMV in association with conventional physiotherapy three times a week, for 5 three weeks, for a total of 9 sessions, similar to our previous study. 15 The vibration was applied using a pneumatic vibration device (EVM Endomedica, Italy) at a frequency of 100 Hz and an amplitude of 0.2 mm. Each session consisted of three stimulation blocks of 10 minutes each, interspersed with 1 minute of rest. ...
Musculoskeletal pain is a common symptom of Parkinson's disease (PD) that is not adequately treated with current dopaminergic drugs. This pilot study sought to investigate the effect of focal muscle vibration (fMV) on a group of Parkinson's disease patients suffering from chronic cervical pain. In addition to conventional physiotherapy, twenty-two patients with idiopathic Parkinson's disease (Hoehn and Yahr stages II-III) received three weeks of bilateral focal musclevibration to the trapezius muscles. The Visual Analogue Scale (VAS), the Short-form McGill, and the Present PainIntensity scales were used to assess pain at baseline (T0), after three weeks of treatment (T1), one week after the last treatment session (T2), and three weeks after T2 (T3). Pain intensity decreased significantly from baseline to T1 across all pain scales (p < 0.0001). Furthermore, the beneficial effect of fMV on cervical pain lasted up to one month after treatment. Our findings show that fMV, in combination with conventional physiotherapy, is effective at reducing pain intensity in PD patients, with results visible even after a month of follow-up.
... The meta-analysis of Zeng et al 3 showed a spasticity prevalence of 40% in a hemiparetic subacute stroke population following a first stroke. In a chronic stroke population, Marconi et al 25 found a reduction of spasticity parallel to an increase in the arm function (+11 points, Motricity Index) after 3 days of vibrations. Moreover, in a study of an acute stroke population, Toscano et al 27 found an increased arm function (+18.5 points, Motricity Index) after 3 days of vibrations. ...
... therefore, -1.68 points on the modified Ashworth scale (MAS), in comparison with -1 point. 25 Thus, we hypothesised that 15% of our patients in the intervention group would develop spasticity, in comparison with 40% in the control group. Moreover, this effect could be strengthened as our protocol lasts 6 weeks, much longer than the protocols used in the previously cited studies. ...
... Several studies have already demonstrated the clear temporary benefit of one LMV session on spasticity, both on contracted and relaxed muscles. 25 37 38 This can be partly explained by the post-vibration H-reflex reduction of the vibrated muscle, 18 as post-stroke spasticity is associated with an increased H-reflex. 23 39 40 Functional benefits, measured by clinical scales (ie, Fugl-Meyer, Wolf motor function test), often accompanied this spasticity reduction in these previous studies. ...
Introduction
Spasticity is a frequent disabling consequence following a stroke. Local muscle vibrations (LMVs) have been proposed as a treatment to address this problem. However, little is known about their clinical and neurophysiological impacts when used repeatedly during the subacute phase post-stroke. This project aims to evaluate the effects of a 6-week LMV protocol on the paretic limb on spasticity development in a post-stroke subacute population.
Methods and analysis
This is an interventional, controlled, randomised, single-blind (patient) trial. 100 participants over 18 years old will be recruited, within 6 weeks following a first stroke with hemiparesis or hemiplegia. All participants will receive a conventional rehabilitation programme, plus 18 sessions of LMV (ie, continuously for 30 min) on relaxed wrist and elbow flexors: either (1) at 80 Hz for the interventional group or (2) at 40 Hz plus a foam band between the skin and the device for the control group.
Participants will be evaluated at baseline, at 3 weeks and 6 weeks, and at 6 months after the end of the intervention. Spasticity will be measured by the modified Ashworth scale and with an isokinetic dynamometer. Sensorimotor function will be assessed with the Fugl-Meyer assessment of the upper extremity. Corticospinal and spinal excitabilities will be measured each time.
Ethics and dissemination
This study was recorded in a clinical trial and obtained approval from the institutional review board (Comité de protection des personnes Ile de France IV, 2021-A03219-32). All participants will be required to provide informed consent. The results of this trial will be published in peer-reviewed journals to disseminate information to clinicians and impact their practice for an improved patient’s care.
Trial registration number
Clinical Trial: NCT05315726
Dataset
EUDRAct
... Following the screening process, studies with irrelevant titles and abstracts were excluded. Ultimately, 21 articles Ayvat et al. 2021;Calabrò et al. 2017;Caliandro et al. 2012;Camerota et al. 2016;Casale et al. 2014;Celletti et al. 2017;Choi 2017;Cordo et al. 2022;Costantino et al. 2017;Lee et al. 2013;Marconi et al. 2011;Noma et al. 2012;Önal et al. 2022;Paoloni et al. 2010;Peppe et al. 2019;Seo et al. 2020;Seo et al. 2019;Spina et al. 2016;Spolaor et al. 2020;Tavernese et al. 2013) were included in the systematic review as illustrated in Figure 1. Among these, 16 were focused on stroke Calabrò et al. 2017;Caliandro et al. 2012;Casale et al. 2014;Celletti et al. 2017;Choi 2017;Cordo et al. 2022;Costantino et al. 2017;Lee et al. 2013;Marconi et al. 2011;Noma et al. 2012;Önal et al. 2022;Paoloni et al. 2010;Seo et al. 2020;Seo et al. 2019;Tavernese et al. 2013), two pertained to multiple sclerosis (Ayvat et al. 2021;Spina et al. 2016) and three were relevant to Parkinson's disease (Camerota et al. 2016;Peppe et al. 2019;Spolaor et al. 2020). ...
... Ultimately, 21 articles Ayvat et al. 2021;Calabrò et al. 2017;Caliandro et al. 2012;Camerota et al. 2016;Casale et al. 2014;Celletti et al. 2017;Choi 2017;Cordo et al. 2022;Costantino et al. 2017;Lee et al. 2013;Marconi et al. 2011;Noma et al. 2012;Önal et al. 2022;Paoloni et al. 2010;Peppe et al. 2019;Seo et al. 2020;Seo et al. 2019;Spina et al. 2016;Spolaor et al. 2020;Tavernese et al. 2013) were included in the systematic review as illustrated in Figure 1. Among these, 16 were focused on stroke Calabrò et al. 2017;Caliandro et al. 2012;Casale et al. 2014;Celletti et al. 2017;Choi 2017;Cordo et al. 2022;Costantino et al. 2017;Lee et al. 2013;Marconi et al. 2011;Noma et al. 2012;Önal et al. 2022;Paoloni et al. 2010;Seo et al. 2020;Seo et al. 2019;Tavernese et al. 2013), two pertained to multiple sclerosis (Ayvat et al. 2021;Spina et al. 2016) and three were relevant to Parkinson's disease (Camerota et al. 2016;Peppe et al. 2019;Spolaor et al. 2020). Figure 2 illustrated the risk of bias evaluation. ...
... Figure 2 illustrated the risk of bias evaluation. Out of the total, 11 studies were categorised as high risk Ayvat et al. 2021;Caliandro et al. 2012;Celletti et al. 2017;Choi 2017;Marconi et al. 2011;Noma et al. 2012;Önal et al. 2022;Paoloni et al. 2010;Seo et al. 2020;Tavernese et al. 2013). Additionally, five studies were determined as unclear risk (Camerota et al. 2016;Cordo et al. 2022;Costantino et al. 2017;Lee et al. 2013;Spina et al. 2016) while another five studies were assessed as low risk (Calabrò et al. 2017;Casale et al. 2014;Peppe et al. 2019;Seo et al. 2019;Spolaor et al. 2020). ...
ABSTRAK Kajian sistematik ini bertujuan untuk menyiasat kesan getaran fokus (FV) terhadap tonus otot, parameter kinematik dan fungsi motor pada individu yang menghidapi penyakit strok, Parkinson dan sklerosis berbilang. Kajian ini juga bertujuan untuk menentukan pengaruh parameter getaran seperti frekuensi dan amplitud, tempoh sesi stimuli, dan jumlah keseluruhan sesi intervensi pada hasil ukuran. Carian artikel yang relevan dengan kajian ini telah dilakukan melalui pangkalan data PubMed, Scopus, Cochrane, Web of Science dan EBSCO. Sebanyak 21 artikel telah memenuhi kriteria kemasukan yang ditetapkan. Dalam tempoh seminggu selepas rawatan, FV telah terbukti berkesan untuk mengurangkan spastisiti pada bahagian siku (P = 0.04), meningkatkan parameter kinematik anggota atas (SMD =-0.75, 95% CI:-1.50 hingga-0.01), dan meningkatkan kefungsian anggota atas (P = 0.05) dalam kalangan pesakit strok. Rawatan FV juga secara signifikan meningkatkan parameter kinematik anggota bawah pesakit Parkinson apabila dibandingkan dengan kumpulan kawalan (P = 0.03). Namun, kesan FV didapati tidak signifikan dalam mengurangkan spastisiti anggota atas pesakit strok (P = 0.25) serta dalam meningkatkan parameter kinematik anggota bawah pesakit Parkinson (SMD = 0.38, 95% CI:-0.58 hingga 1.35) apabila penilaian dilakukan selepas lebih dari seminggu dari sesi rawatan. Jumlah keseluruhan sesi terapi didapati berkait secara signifikan dengan saiz kesan (p = 0.042) terhadap hasil ukuran kefungsian 41 ABSTRACT This systematic review aimed to investigate the effect of focal vibration (FV) on muscle tone, kinematic parameters and motor functions in individuals with stroke, Parkinson' disease and multiple sclerosis. It also determined the influence of vibration parameters such as frequency and amplitude, stimulation session duration, and the total number of intervention sessions on the outcome measures. PubMed, Scopus, Cochrane, Web of Science, and EBSCO were searched, yielding 21 qualifying articles. Within a week post-treatment, FV effectively reduced elbow spasticity (P = 0.04), improved upper limb kinematic parameters (SMD =-0.75, 95% CI:-1.50 to-0.01), and enhanced upper limb motor function (P = 0.05) in stroke patients. FV significantly improved lower limb kinematic parameters of Parkinson's disease patients (P = 0.03). Over a week post-treatment, the effect of FV was not significant in reducing spasticity for upper limb in stroke (P = 0.25) and improving kinematic parameters for lower limb in Parkinson's disease (SMD = 0.38, 95% CI:-0.58 to 1.35). The total therapy sessions significantly associated with the effect size (p = 0.042) for upper limb motor function outcome measure. Conclusion, integrating FV into rehabilitation may benefit patients with neurological disorders such as stroke, Parkinson's disease, and multiple sclerosis.
... FMV is gaining increasing interest in neurological disease management [5,36]. It is being explored as an innovative primary and adjunctive therapy in various medical fields, including spinal cord injury rehabilitation to facilitate functional recovery and improve the overall quality of life for individuals with neurological impairments [5,27,41,42,43]. FMV offers a distinct advantage in SCI management by providing a safe and targeted approach to neuromodulation. ...
Introduction: The pathophysiology of spinal cord injury (SCI) is still not completely understood. Current SCI rehabilitation strategies remain ineffective. Focal muscle vibrations (FMVs), through afferent nerve stimulation, modulate peripheral and central pathways and have potential as a complementary and easy to administer rehabilitation tool in treating SCI populations, however the exact effectiveness of FMVs remains unknown.
Methods: This study is a systematic review on the use of FMVs in SCIs. Sensorimotor function, and mobility and strength were the main outcomes considered. Science Direct, PubMed, Cochrane library, PEDro, Google Scholar and Springer databases were searched for original studies until June 2023. The PEDro scale was used to assess the methodological quality of the studies.
Results: Twenty-three studies were included. Nine studies using FMV in the upper limb and fourteen in the lower limb. The analysis includes 422 SCI patients and 132 non-disabled participants, with a focus on male, chronic SCI cases, and a prevalence in North American studies.
Conclusion: Our findings suggest potential benefits of FMV on sensory perception, motor function, mobility, and strength in both upper and lower limbs of SCI patients. However, there is acute need for further research to optimize the application of FMV through its vibration parameters, location, duration and understanding its long-term effects. Due to the lack larger sample sizes and longitudinal studies, any conclusions derived here and within these studies should be interpreted with caution.
... An EEG-based study found that focal vibration applied to limb muscles modulated neurophysiological oscillations and increased contralateral S1-M1 excitability in healthy volunteers (Lopez et al., 2017). A randomized controlled study was conducted by Marconi et al. (2011) involving 30 hemiplegia patients who had suffered from a stroke. The experimental group, which received focal vibration stimulation in addition to physiotherapy, exhibited a Bold indicates statistical significance (*P < 0.05; **P < 0.01; ***P < 0.001). ...
Objective
The purpose of this study was to utilize functional near-infrared spectroscopy (fNIRS) to identify changes in cortical activity caused by focal muscle vibration (FMV), which was directly administered to the affected forearm flexor muscles of hemiplegic stroke patients. Additionally, the study aimed to investigate the correlation between these changes and the clinical characteristics of the patients, thereby expanding the understanding of potential neurophysiological mechanisms linked to these effects.
Methods
Twenty-two stroke patients with right hemiplegia who were admitted to our ward for rehabilitation were selected for this study. The fNIRS data were collected from subjects using a block-design paradigm. Subsequently, the collected data were analyzed using the NirSpark software to determine the mean Oxyhemoglobin (Hbo) concentrations for each cortical region of interest (ROI) in the task and rest states for every subject. The stimulation task was FMV (frequency 60 Hz, amplitude 6 mm) directly applied to belly of the flexor carpi radialis muscle (FCR) on the affected side. Hbo was measured in six regions of interest (ROIs) in the cerebral cortex, which included the bilateral prefrontal cortex (PFC), sensorimotor cortex (SMC), and occipital cortex (OC). The clinical characteristics of the patients were assessed concurrently, including Lovett’s 6-level muscle strength assessment, clinical muscle tone assessment, the upper extremity function items of the Fugl-Meyer Assessment (FMA-UE), Bruunstrom staging scale (BRS), and Modified Barthel index (MBI). Statistical analyses were conducted to determine the activation in the ROIs and to comprehend its correlation with the clinical characteristics of the patients.
Results
Statistical analysis revealed that, except for right OC, there were statistically significant differences between the mean Hbo in the task state and rest state for bilateral SMC, PFC, and left OC. A positive correlation was observed between the muscle strength of the affected wrist flexor group and the change values of Hbo (Hbo-CV), as well as the beta values in the left SMC, PFC, and OC. However, no statistical correlation was found between muscle strength and Hbo-CV or beta values in the right SMC, PFC, and OC. The BRS of the affected upper limb exhibited a positive correlation with the Hbo-CV or beta values in the left SMC and PFC. In contrast, no statistical correlation was observed in the right SMC, PFC, and bilateral OC. No significant correlation was found between the muscle tone of the affected wrist flexor group, FMA-UE, MBI, and Hbo-CV or beta values of cortical ROIs.
Conclusion
FMV-evoked sensory stimulation applied directly to the FCR belly on the paralyzed side activated additional brain cortices, including bilateral PFC and ipsilesional OC, along with bilateral SMC in stroke patients. However, the clinical characteristics of the patients were only correlated with the intensity of ipsilesional SMC and PFC activation. The results of this study provide neurophysiological theoretical support for the expanded clinical application of FMV.
... stroke [18,20,22,23], while one study did not report the side of lesion [22]. The time since stroke was not described in 2 studies [18,24]. ...
... The time since stroke was not described in 2 studies [18,24]. The subtypes of VT were categorized as WBV [24][25][26][27][28][29] and LMV [18][19][20][21][22][23]. Regarding the vibration frequency, 4 trials were ≤ 20 Hz and 9 trials were > 20 Hz. ...
... First, vibration can increase the excitability of the motor cortex and produce intracortical inhibition, thereby reducing muscle tension. Marconi et al. [23] found that the activation area of M1 was increased, and the maximum motor evoked potential and short-interval intracortical inhibition were significantly improved after vibration. Lapole et al. [30] also found that the amplitude of motor-evoked potential increased significantly after vibration stimulation of the Achilles tendon. ...
Background
The efficacy of vibration therapy (VT) in people with post-stroke spasticity (PSS) remains uncertain. This study aims to conduct a comprehensive meta-analysis to assess the effectiveness of VT in PSS.
Methods
PubMed, Embase, Cochrane Library, Physiotherapy Evidence Database, and Web of Science were searched from inception to October 2022 for randomized controlled trials (RCTs) of VT in people with PSS. The primary outcome was spasticity, and secondary outcomes included pain, motor function, gait performance, and adverse events. A meta‑analysis was performed by pooling the standardized mean difference (SMD) with 95% confidence intervals (CI).
Results
A total of 12 studies met the inclusion criteria. Overall, VT had significant effects on reducing spasticity (SMD = − 0.77, 95% CI − 1.17 to − 0.36, P < 0.01) and pain (SMD = − 1.09, 95% CI − 1.74 to − 0.45, P < 0.01), and improving motor function (SMD = 0.42, 95% CI 0.21 to 0.64, P < 0.01) in people with PSS. However, VT had no significant effect on gait performance (SMD = − 0.23, 95% CI − 0.56–0.10). In addition, subgroup differences in short-term anti-spasticity effects between different vibration subtypes, vibration frequencies, vibration durations, frequency of sessions, control therapy, spasticity distribution, and population classification were not significant.
Conclusion
We found that VT significantly alleviated spasticity and pain in people with PSS and improved motor function, but its effect on gait performance was unclear. However, further studies are needed to validate these findings.
... Although evidence about the impact of VIB on neural networks remains scarce, it does underscore that vibrationinduced afferents interact with motor cortex and corticospinal networks. However, most previous studies tested the after-effects of a repeated VIB application on corticomotor excitability (15,17,18). Therefore, the time course of corticospinal excitability tested during the perception of a kinesthetic illusion has not been extensively studied and could provide important knowledge on time-specific mechanisms of sensorimotor processing occurring during the illusion. ...
... However, there are conflicting results in the literature regarding the effects of VIB on TMS measurements. There are studies having reported an increased, unchanged, or lower corticospinal excitability for vibrated (2,22) and nonvibrated muscles (17,21,23). Such contrasting findings between studies could be related to different timings of TMS delivered during VIB that were so far arbitrarily applied [e.g., 1 s after VIB start for (12), 3 s for (23) and 4 s for (2)]. ...
... Whether this modulation of excitability actually depends on the time-specific emergence of a clearly perceptible illusion remains to be validated in the future. Results from previous studies have demonstrated promising effects of VIB on motor function and neural plasticity in corticospinal networks (17,36,45); however, the underlying explanatory mechanisms remain poorly understood. A better understanding of these mechanisms is needed before considering this modality in the clinical management of proprioceptive disorders. ...
... Some studies have demonstrated that FV can have an effect on improving motor function in some patients with stroke, spinal cord injury, Parkinson, and multiple sclerosis by the reorganization of the sensorimotor cortex [29]. For example, FV can improve arm stability [30], improve gait performance [28], and alleviate upper limb spasticity [31,32]. The rehabilitation effect on the mitigation of spasticity and the improvement in motor function was associated with the reshaping of corticospinal plasticity and the reorganization of the motor cortex [31,32]. ...
... For example, FV can improve arm stability [30], improve gait performance [28], and alleviate upper limb spasticity [31,32]. The rehabilitation effect on the mitigation of spasticity and the improvement in motor function was associated with the reshaping of corticospinal plasticity and the reorganization of the motor cortex [31,32]. Besides, FV integrated with motor training can have a greater effect on the improvement of motor function and the reorganization of sensorimotor cortical compared with motor training alone [32]. ...
... The application of FV at low amplitude (100 μm-2 mm) and high frequency (50-120 Hz) over specific muscles can offer strong proprioceptive inputs by stretching muscle fiber to induce the firing of primary spindle endings [29,32]. The strong proprioceptive inputs can activate proprioceptive pathways from the muscle spindle, which decussates in the caudal medulla through the posterior column-medial lemniscus pathway, up to S1-M1 [31,32]. In our study, the frequency of FV (75 Hz) is within this frequency range that can activate the firing of primary spindle endings. ...
Background
Sensory stimulation can play a fundamental role in the activation of the primary sensorimotor cortex (S1-M1), which can promote motor learning and M1 plasticity in stroke patients. However, studies have focused mainly on investigating the influence of brain lesion profiles on the activation patterns of S1-M1 during motor tasks instead of sensory tasks. Therefore, the objective of this study is to explore the lesion-specific activation patterns due to different brain lesion profiles and types during focal vibration (FV).
Methods
In total 52 subacute stroke patients were recruited in this clinical experiment, including patients with basal ganglia hemorrhage/ischemia, brainstem ischemia, other subcortical ischemia, cortical ischemia, and mixed cortical–subcortical ischemia. Electroencephalograms (EEG) were recorded following a resting state lasting for 4 min and three sessions of FV. FV was applied over the muscle belly of the affected limb’s biceps for 3 min each session. Beta motor-related EEG power desynchronization overlying S1-M1 was used to indicate the activation of S1-M1, while the laterality coefficient (LC) of the activation of S1-M1 was used to assess the interhemispheric asymmetry of brain activation.
Results
(1) Regarding brain lesion profiles, FV could lead to the significant activation of bilateral S1-M1 in patients with basal ganglia ischemia and other subcortical ischemia. The activation of ipsilesional S1-M1 in patients with brainstem ischemia was higher than that in patients with cortical ischemia. No activation of S1-M1 was observed in patients with lesions involving cortical regions. (2) Regarding brain lesion types, FV could induce the activation of bilateral S1-M1 in patients with basal ganglia hemorrhage, which was significantly higher than that in patients with basal ganglia ischemia. Additionally, LC showed no significant correlation with the modified Barthel index (MBI) in all patients, but a positive correlation with MBI in patients with basal ganglia lesions.
Conclusions
These results reveal that sensory stimulation can induce lesion-specific activation patterns of S1-M1. This indicates FV could be applied in a personalized manner based on the lesion-specific activation of S1-M1 in stroke patients with different lesion profiles and types. Our study may contribute to a better understanding of the underlying mechanisms of cortical reorganization.
