Differing effectiveness of transcranial random noise stimulation and transcranial direct current stimulation for enhancing working memory in healthy individuals: a randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (DLPFC) is a promising technique for enhancing working memory (WM) performance in healthy and psychiatric populations. However, limited information is available about the effectiveness of transcranial random noise stimulation (tRNS) applied to the left DLPFC on WM. This study investigated the effectiveness of tRNS on WM compared with that of tDCS, which has established functional evidence. METHODS: This randomized, double-blind, sham-controlled trial enrolled 120 healthy right-handed adults who were randomly allocated to four stimulation groups: tRNS + direct current (DC) offset, tRNS, tDCS, or sham. Each stimulus was placed over the left DLPFC and had a current intensity of 2 mA applied for 20 min during the dual n-back task. The dual n-back task was repeated thrice: pre-stimulation, during stimulation, and post-stimulation. The d-prime scores, and response times were calculated as the main outcome measures. A linear mixed model was created to identify the main effects and interactions between the groups and times, with the group and time as fixed effects, and baseline performance and the subject as a covariate and random effect, respectively. The relationships between the benefit of each stimulus and baseline WM performance were also examined. RESULTS: For the d-prime score during stimulation, the tRNS group significantly performed better than the sham group at online assessment (ß = 0.310, p = 0.001). In the relationships between the benefit of each stimulus and baseline WM performance, the tRNS group had significantly larger negative line slopes than the sham group for the d-prime score (ß = -0.233, p = 0.038). CONCLUSIONS: tRNS applied to the left DLPFC significantly improved WM performance and generated greater benefits for healthy individuals with lower WM performance. These findings highlight the potential utility of tRNS for enhancing WM performance in individuals with lower WM performance and contribute evidence for clinical application to patients with cognitive decline. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registry in Japan (UMIN000047365) on April 1, 2022; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054021 .

Repetitive peripheral magnetic stimulation alone or in combination with repetitive transcranial magnetic stimulation in poststroke rehabilitation: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to comprehensively review the effects of repetitive peripheral magnetic stimulation (rPMS) alone or in combination with repetitive transcranial magnetic stimulation (rTMS) on improving upper limb motor functions and activities of daily living (ADL) in patients with stroke, and to explore possible efficacy-related modulators. METHODS: A literature search from 1st January 2004 to 1st June 2024 was performed to identified studies that investigated the effects of rPMS on upper limb motor functions and ADL in poststroke patients. RESULTS: Seventeen studies were included. Compared with the control, both rPMS alone or rPMS in combination with rTMS significantly improved upper limb motor function (rPMS: Hedge's g = 0.703, p = 0.015; rPMS + rTMS: Hedge's g = 0.892, p < 0.001) and ADL (rPMS: Hedge's g = 0.923, p = 0.013; rPMS + rTMS: Hedge's g = 0.923, p < 0.001). However, rPMS combined with rTMS was not superior to rTMS alone on improving poststroke upper limb motor function and ADL (Hedge's g = 0.273, p = 0.123). Meta-regression revealed that the total pulses (p = 0.003) and the number of pulses per session of rPMS (p < 0.001) correlated with the effect sizes of ADL. CONCLUSIONS: Using rPMS alone or in combination with rTMS appears to effectively improve upper extremity functional recovery and activity independence in patients after stroke. However, a simple combination of these two interventions may not produce additive benefits than the use of rTMS alone. Optimization of rPMS protocols, such as applying appropriate dosage, may lead to a more favourable recovery outcome in poststroke rehabilitation.

Effects of a Wearable-Based Intervention on the Hemiparetic Upper Limb in Persons With Stroke: A Randomized Controlled Trial.

INTRODUCTION: Wearables have emerged as a transformative rehabilitation tool to provide self-directed training in the home. Objective. In this study, we examined the efficacy of a novel wearable device, "Smart Reminder" (SR), to provide home-based telerehabilitation for hemiparetic upper limb (UL) training in persons with stroke. METHODS: Forty stroke survivors from community support groups were randomized (stratified by the period after stroke onset and impairment severity) to either the SR group or the sham device group. Participants received either 20 hours of telerehabilitation using the SR device or training with pictorial handouts and a sham device over 4 weeks. In addition, all participants wore a standard accelerometer for 3 hours each day, 5 times a week, outside the prescribed training. Participants were assessed by a masked assessor at baseline, post-intervention (week 4), and follow-up (week 8). The outcome measures included Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Action Research Arm Test, Motor Activity Log, muscle strength, active range of motion and amount of movement of the UL, and compliance rate of training. RESULTS: The SR group improved substantially in their FMA-UE scores after treatment (mean difference = 2.05, P = .036) compared to the sham group. Also, adherence to the training using the SR device was significantly higher, 97%, than the sham group, 82.3% (P = .038). CONCLUSION: The 4-week telerehabilitation program using a "SR" device demonstrated potential efficacy in improving FMA-UE scores of the hemiparetic upper limb. However, it did not significantly enhance the performance of the affected limb in daily activities. The trial was registered on ClinicalTrial.gov (URL: http://www.clinicaltrials.gov) with the identifier NCT05877183.

Effects of Virtual Reality Motor-Cognitive Training for Older People With Cognitive Frailty: Multicentered Randomized Controlled Trial.

BACKGROUND: Cognitive frailty refers to a clinical syndrome in which physical frailty and mild cognitive impairment coexist. Motor-cognitive training and virtual reality (VR) have been used to launch various therapeutic modalities to promote health in older people. The literature advocates that motor-cognitive training and VR are effective in promoting the cognitive and physical function of older people. However, the effects on older people with cognitive frailty are unclear. OBJECTIVE: This study examined the effects of VR motor-cognitive training (VRMCT) on global cognitive function, physical frailty, walking speed, visual short-term memory, inhibition of cognitive interference, and executive function in older people with cognitive frailty. METHODS: This study used a multicentered, assessor-blinded, 2-parallel-group randomized controlled trial design. Participants were recruited face-to-face in 8 older adult community centers. Eligible participants were aged ≥60 years, were community dwelling, lived with cognitive frailty, had no dementia, and were not mobility restricted. In the intervention group, participants received VRMCT led by interventionists with 16 one-hour training sessions delivered twice per week for 8 weeks. In the control group, participants received the usual care provided by the older adult community centers that the investigators did not interfere with. The primary outcome was global cognitive function. The secondary outcomes included physical frailty, walking speed, verbal short-term memory, inhibition of cognitive interference, and executive function. Data were collected at baseline (T0) and the week after the intervention (T1). Generalized estimating equations were used to examine the group, time, and interaction (time × group) effects on the outcomes. RESULTS: In total, 293 eligible participants enrolled in the study. The mean age of the participants was 74.5 (SD 6.8) years. Most participants were female (229/293, 78.2%), had completed primary education (152/293, 52.1%), were married (167/293, 57.2%), lived with friends (127/293, 43.3%), and had no VR experience (232/293, 79.5%). In the intervention group, 81.6% (119/146) of participants attended >80% (13/16, 81%) of the total number of sessions. A negligible number of participants experienced VR sickness symptoms (1/146, 0.7% to 5/146, 3%). VRMCT was effective in promoting global cognitive function (interaction effect: P=.03), marginally promoting executive function (interaction effect: P=.07), and reducing frailty (interaction effect: P=.03). The effects were not statistically significant on other outcomes. CONCLUSIONS: VRMCT is effective in promoting cognitive functions and reducing physical frailty and is well tolerated and accepted by older people with cognitive frailty, as evidenced by its high attendance rate and negligible VR sickness symptoms. Further studies should examine the efficacy of the intervention components (eg, VR vs non-VR or dual task vs single task) on health outcomes, the effect of using technology on intervention adherence, and the long-term effects of the intervention on older people with cognitive frailty at the level of daily living. TRIAL REGISTRATION: ClinicalTrials.gov NCT04730817; https://clinicaltrials.gov/study/NCT04730817.

Cortical activity during online motor control in children with and without developmental coordination disorder: a cross-sectional functional near-infrared spectroscopy study.

BACKGROUND: Children with developmental coordination disorder (DCD) have impaired online motor control. Researchers posit that this impairment could be due to a deficit in utilizing the internal model control process. However, there is little neurological evidence to support this view because few neuroimaging studies have focused specifically on tasks involving online motor control. Therefore, the aim of this study was to investigate the differences in cortical hemodynamic activity during an online movement adjustment task between children with and without DCD. METHODS: Twenty children with DCD (mean age: 9.88 ± 1.67 years; gender: 14M/6F) and twenty age-and-gender matched children with typical development (TD) (mean age: 9.87 ± 1.59 years; gender: 14M/6F) were recruited via convenience sampling. Participants performed a double-step reaching task under two conditions (with and without online adjustment of reaching). Cortical hemodynamic activity during task in ten regions of interest, including bilateral primary somatosensory cortex, primary motor cortex, premotor cortex, superior parietal cortex, and inferior parietal cortex was recorded using functional near-infrared spectroscopy. In the analyses, change in oxyhemoglobin (ΔHbO) concentration was used to characterize hemodynamic response. Two-way analyses of variance were conducted for each region of interest to compare hemodynamic responses between groups and conditions. Additionally, Pearson's r correlations between hemodynamic response and task performance were performed. RESULTS: Outcome showed that children with DCD required significantly more time to correct their reaching movements compared to the control group (t = 3.948, P < 0.001). Furthermore, children with DCD have a significantly lower ΔHbO change in the left superior parietal cortex during movement correction, compared to children with TD (F = 4.482, P = 0.041). Additionally, a significant negative correlation (r = - 0.598, P < 0.001) was observed between the difference in movement time of reaching and the difference in ΔHbO between conditions in the left superior parietal cortex. CONCLUSIONS: The findings of this study suggest that deficiencies in processing real-time sensory feedback, considering the function of the superior parietal cortex, might be related to the impaired online motor control observed in children with DCD. Interventions could target this issue to enhance their performance in online motor control.

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.

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.

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.

Sex differences in brain excitability revealed by concurrent iTBS/fNIRS.

Sex differences have been claimed an imperative factor in the optimization of psychiatric treatments. Intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation, is a promising non-invasive treatment option. Here, we investigated whether the real-time neural response to iTBS differs between men and women, and which mechanisms may mediate these differences. To this end, we capitalized on a concurrent iTBS/functional near-infrared spectroscopy setup over the left dorsolateral prefrontal cortex, a common clinical target, to test our assumptions. In a series of experiments, we show (1) a biological sex difference in absolute hemoglobin concentrations in the left dorsolateral prefrontal cortex in healthy participants; (2) that this sex difference is amplified by iTBS but not by cognitive tasks; and (3) that the sex difference amplified by iTBS is modulated by stimulation intensity. These results inform future stimulation treatment optimizations towards precision psychiatry.

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.

The Effects of Immersive Virtual Reality-Assisted Experiential Learning on Enhancing Empathy in Undergraduate Health Care Students Toward Older Adults With Cognitive Impairment: Multiple-Methods Study.

BACKGROUND: Immersive virtual reality (IVR)-assisted experiential learning has the potential to foster empathy among undergraduate health care students toward older adults with cognitive impairment by facilitating a sense of embodiment. However, the extent of its effectiveness, including enhancing students' learning experiences and achieving intended learning outcomes, remains underexplored. OBJECTIVE: This study aims to evaluate the impacts of IVR-assisted experiential learning on the empathy of undergraduate health care students toward older people with cognitive impairment as the primary outcome (objective 1) and on their learning experience (objective 2) and their attainment of learning outcomes as the secondary outcomes (objective 3). METHODS: A multiple-methods design was used, which included surveys, focus groups, and a review of the students' group assignments. Survey data were summarized using descriptive statistics, whereas paired 2-tailed t tests were used to evaluate differences in empathy scores before and after the 2-hour IVR tutorial (objective 1). Focus groups were conducted to evaluate the impacts of IVR-assisted experiential learning on the empathy of undergraduate health care students toward older people with cognitive impairment (objective 1). Descriptive statistics obtained from surveys and thematic analyses of focus groups were used to explore the students' learning experiences (objective 2). Thematic analysis of group assignments was conducted to identify learning outcomes (objective 3). RESULTS: A total of 367 undergraduate nursing and occupational therapy students were recruited via convenience sampling. There was a significant increase in the students' empathy scores, measured using the Kiersma-Chen Empathy Scale, from 78.06 (SD 7.72) before to 81.17 (SD 8.93) after (P<.001). Students expressed high satisfaction with the IVR learning innovation, with a high satisfaction mean score of 20.68 (SD 2.55) and a high self-confidence mean score of 32.04 (SD 3.52) on the Student Satisfaction and Self-Confidence scale. Students exhibited a good sense of presence in the IVR learning environment, as reflected in the scores for adaptation (41.30, SD 6.03), interface quality (11.36, SD 3.70), involvement (62.00, SD 9.47), and sensory fidelity (31.47, SD 5.23) on the Presence Questionnaire version 2.0. In total, 3 major themes were identified from the focus groups, which involved 23 nursing students: enhanced sympathy toward older adults with cognitive impairment, improved engagement in IVR learning, and confidence in understanding the key concepts through the learning process. These themes supplement and align with the survey results. The analysis of the written assignments revealed that students attained the learning outcomes of understanding the challenges faced by older adults with cognitive impairment, the importance of providing person-centered care, and the need for an age-friendly society. CONCLUSIONS: IVR-assisted experiential learning enhances students' knowledge and empathy in caring for older adults with cognitive impairment. These findings suggest that IVR can be a valuable tool in professional health care education.

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.

Rapid online correction of reach-to-manipulate movements in children with developmental coordination disorder: A pilot kinematic comparison study.

BACKGROUND: Children with developmental coordination disorder show difficulties in making rapid online corrections, and this has been demonstrated in experiments where reaching/pointing movements were employed. However, typical hand movements in real-life contexts involve subsequent movements, such as grasping and manipulating objects after reaching. This study aimed to reinvestigate online correction of reaching movements that were connected with grasping and object manipulation and to explore its impact on the coordination of subsequent hand movements in children with developmental coordination disorder. METHODS: Five children with developmental coordination disorder and five children with typical development were recruited. Their reach-to-manipulate movements in a double-step task were recorded using motion analysis. The manipulative movements included simple and complex forms of pencil rotation. Movement time, movement velocity, and correlation coefficients between finger joints were derived to quantify their motor performances. FINDINGS: Children with developmental coordination disorder showed longer movement time and deceleration phases during online correction of reaching movement than children without developmental coordination disorder. In subsequent grasping and manipulation movements after online correction, they also exhibited lower correlation coefficients in four to five finger joint couplings that are essential for movement completion, compared to children without developmental coordination disorder. INTERPRETATION: Our findings from the current pilot study suggest that children with developmental coordination disorder have impairments in online correction when reaching for objects and may also have reduced coordination of some finger movements that are important for subsequent grasping and object manipulation. Future studies with larger sample sizes are warranted to confirm these findings.

Measures of quality of life of people with neurogenic overactive bladder: A systematic review of psychometric properties.

OBJECTIVE: To identify psychometrically robust quality-of-life (QOL) outcome measures for evaluating QOL among people with neurogenic overactive bladder (OAB). STUDY DESIGN: Electronic databases (CINAHL, EMBASE, MEDLINE, Scopus and Web of Science) were searched from inception to January 2023. Two independent reviewers participated in study screening, data extraction and quality appraisal. Studies were included if they validated at least one psychometric property of a QOL outcome measure among adults (age ≥ 18 years) with neurogenic OAB. The COnsensus-based Standards for selecting health status Measurement INstruments (COSMIN) checklist and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool were used to evaluate the methodological quality and quality of evidence, respectively, for each included study. RESULTS: Database searches identified 47 studies that tested the psychometric properties of 15 QOL measures in a total of 19,994 participants with stroke, spinal cord injury, Parkinson's disease or multiple sclerosis. The Incontinence Quality of Life Questionnaire (I-QOL), King's Health Questionnaire, Overactive Bladder Questionnaire and Qualiveen were the best validated measures, with strong reliability, validity and responsiveness. I-QOL was the most robust, cross-culturally administered and psychometrically strong measure. The COSMIN checklist indicated sufficient methodological quality for 70% of measures, and the modified GRADE tool indicated quality of evidence ranging from moderate (67%) to high (33%). CONCLUSIONS: This review identified the I-QOL as a culturally diverse measure with robust reliability, validity and responsiveness for assessing QOL among people with neurogenic OAB. These findings are supported by studies with good methodological quality (COSMIN) and high-quality evidence (GRADE).

Validity and Reliability of Upper Limb Kinematic Assessment Using a Markerless Motion Capture (MMC) System: A Pilot Study.

OBJECTIVE: To investigate the validity and test-retest reliability of a customized markerless motion capture (MMC) system that used iPad Pros with a Light Detection And Ranging scanner at two different viewing angles to measure the active range of motion (AROM) and the angular waveform of the upper-limb-joint angles of healthy adults performing functional tasks. DESIGN: Participants were asked to perform shoulder and elbow actions for the investigator to take AROM measurements, followed by four tasks that simulated daily functioning. Each participant attended 2 experimental sessions, which were held at least 2 days and at most 14 days apart. SETTING: A Vicon system and 2 iPad Pros installed with our MMC system were placed at 2 different angles to the participants and recorded their movements concurrently during each task. PARTICIPANTS: Thirty healthy adults (mean age: 28.9, M/F ratio: 40/60). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The AROM and the angular waveform of the upper-limb-joint angles. RESULTS: The iPad Pro MMC system underestimated the shoulder joint and elbow joint angles in all four simulated functional tasks. The MMC demonstrated good to excellent test-retest reliability for the shoulder joint AROM measurements in all 4 tasks. CONCLUSIONS: The maximal AROM measurements calculated by the MMC system had consistently smaller values than those measured by the goniometer. An MMC in iPad Pro system might not be able to replace conventional goniometry for clinical ROM measurements, but it is still suggested for use in home-based and telerehabilitation training for intra-subject measurements because of its good reliability, low cost, and portability. Further development to improve its performance in motion capture and analysis in disease populations is warranted.

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.

Cortical Contributions to Imagined Power Grip Task: An EEG-Triggered TMS Study.

Previous studies have demonstrated that motor imagery leads to desynchronization in the alpha rhythm within the contralateral primary motor cortex. However, the underlying electrophysiological mechanisms responsible for this desynchronization during motor imagery remain unclear. To examine this question, we conducted an investigation using EEG in combination with noninvasive transcranial magnetic stimulation (TMS) during index finger abduction (ABD) and power grip imaginations. The TMS was administered employing diverse coil orientations to selectively stimulate corticospinal axons, aiming to target both early and late synaptic inputs to corticospinal neurons. TMS was triggered based on the alpha power levels, categorized in 20th percentile bins, derived from the individual alpha power distribution during the imagined tasks of ABD and power grip. Our analysis revealed negative correlations between alpha power and motor evoked potential (MEP) amplitude, as well as positive correlations with MEP latency across all coil orientations for each imagined task. Furthermore, we conducted functional network analysis in the alpha band to explore network connectivity during imagined index finger abduction and power grip tasks. Our findings indicate that network connections were denser in the fronto-parietal area during imagined ABD compared to power grip conditions. Moreover, the functional network properties demonstrated potential for effectively classifying between these two imagined tasks. These results provide functional evidence supporting the hypothesis that alpha oscillations may play a role in suppressing MEP amplitude and latency during imagined power grip. We propose that imagined ABD and power grip tasks may activate different populations and densities of axons at the cortical level.

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.