A comparative study of simulated electric fields of transcranial magnetic stimulation targeting different cortical motor regions.

This computational simulation study investigates the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EF) in primary motor cortex (M1) and secondary motor areas. Our results reveal high interindividual variability in the strength of TMS-induced EF responses in secondary motor areas, relative to the stimulation threshold in M1. Notably, the activation of the supplementary motor area requires high-intensity stimulation, which could be attributed to the greater scalp-to-cortex distance observed over this area. These findings emphasize the importance of individualized planning using computational simulation for optimizing neuromodulation strategies targeting the cortical motor system.

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.

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.

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.

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.

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.

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.

Does repetitive transcranial magnetic stimulation have a beneficial effect on improving unilateral spatial neglect caused by stroke? A meta-analysis.

This review aimed to assess the effect of repetitive transcranial magnetic stimulation (rTMS) in improving post-stroke unilateral spatial neglect (USN) using a meta-analysis. Further, we aimed to identify any association between rTMS parameters, patient demographics, and treatment effect sizes using subgroup analyses and meta-regression. A literature search was conducted through four databases from inception to March 6, 2024, to retrieve all relevant controlled trials investigating the effects of rTMS on symptoms of USN in post-stroke patients. Overall, rTMS significantly improved post-stroke USN, as measured by the line bisection test (Hedges' g = - 1.301, p < 0.0001), the cancelation test (Hedge's g = - 1.512, p < 0.0001), and the Catherine Bergego Scale (Hedges'g = - 0.770, p < 0.0001), compared to sham stimulation. Subgroup analysis found that generally larger effect sizes following excitatory rTMS across several outcome measures, indicating that excitatory rTMS on the ipsilesional hemisphere may be more effective than inhibitory rTMS on the contralesional hemisphere in ameliorating neglect symptoms. Meta-regression analysis of the line bisection test showed a significant difference in the chronicity of stroke patients, suggesting that rTMS may be more effective for USN in patients at the acute stage (within 3 months since stroke) than in those at the post-acute stage (p = 0.035). In conclusion, rTMS appears to be effective in promoting recovery from post-stroke USN. Excitatory protocols and early intervention may enhance recovery outcomes for neglect behaviors in post-stroke survivors.

The effect of mindfulness meditation on depressive symptoms during the COVID-19 pandemic: a systematic review and meta-analysis.

Currently, 280 million people worldwide experience depression, ranking it third in the global burden of disease. The incidence of depression has risen due to the COVID-19 pandemic, making it essential to examine evidence-based practices in reducing depressive symptoms during this unprecedented time. This systematic review and meta-analysis aim to analyze randomized controlled trials during the COVID-19 pandemic that evaluated the effect of mindfulness meditation on depressive symptoms in individuals with depression. Four databases (PubMed, Embase, Web of Science, and Scopus) were searched in November 2023 using search terms including meditation, mindfulness, depression, and depressive symptoms. The meta-analysis was conducted using Review Manager 5.4 software (Cochrane Collaboration). A random model and Standard Mean Difference analysis with 95% CIs were used for continuous variables. The systematic review included 26 RCT studies. The meta-analysis showed significant effects of mindfulness meditation interventions (SMD = - 1.14; 95% CI - 1.45 to - 0.83; P < 0.001) in reducing depressive symptoms compared to comparison groups. The findings suggest a positive effect of mindfulness meditation on depressive symptoms in individuals with depression during the COVID-19 pandemic.