Virtual stimulation of the interictal EEG network localizes the EZ as a measure of cortical excitability.

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain. Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1 year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome. Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%. Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG.

Motor-evoked potentials as biomarkers for sexual arousal?

BACKGROUND: Motor cortex excitability may represent the neuronal endpoint of motivational processes and was shown to be modulated by both sexual arousal and deceptive behavior. AIM: This is the first study to investigate the influence of lying and sex in heterosexual women and men based on motor-evoked potentials (MEPs) measured while viewing sexually arousing pictures. METHODS: Sixteen heterosexual couples were shown 360 trials consisting of pictures displaying both almost naked females and males and neutral control images. In a subsequent forced-choice question about wanting to see the respective pictures fully naked, they were instructed to either answer in agreement with or opposite to their sexual preference. Participants went through 2 blocks of answering truthfully and 2 blocks of lying, with these 4 blocks being shown in a randomized alternating order. OUTCOMES: To measure cortical excitability, MEPs were used, evoked by single transcranial magnetic stimulation pulses between image presentation and response. RESULTS: In normalized MEPs, women and men showed higher amplitudes for preferred over non-preferred sexual stimuli, but only on a descriptive level. Planned contrasts showed higher non-normalized MEPs for lying in all picture categories. Direct comparisons to a preliminary study showed overall lower effect sizes. CLINICAL IMPLICATIONS: Both sexes tend to show higher MEPs in response to their sexually preferred stimuli. MEPs are not stable markers for willful volitionally controlled deception although lying does increase cortical excitability. The present experimental design does not seem valid enough to serve as a diagnostic marker for sexual preference or paraphilia and malingering. STRENGTHS AND LIMITATIONS: This is the first study investigating whether sexual motivational stimuli modulate MEPs in women, while also examining the influence of lying for both sexes. The sample was too small for some found effects to be significant. Also, the experimental setup may have been less suited for female participants in comparison to male ones. CONCLUSION: The operationalization of sexual motivation via MEPs seems to highly depend on different experimental factors including the sex of the participants, induced motivation, and lying.

Repetitive transcranial magnetic stimulation in new daily persistent headache patients: a single arm open label study.

BACKGROUND: New daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients. METHODS: This was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks. RESULTS: Fifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point's reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively. CONCLUSION: rTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms. TRIAL REGISTRATION: CTRI/2023/05/053247.

Altered Corticospinal and Intracortical Excitability After Stroke: A Systematic Review With Meta-Analysis.

BACKGROUND: Intracortical inhibitory/faciliatory measures are affected after stroke; however, the evidence is conflicting. OBJECTIVE: This meta-analysis aimed to investigate the changes in motor threshold (MT), motor evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), and identify sources of study variability using a machine learning approach. METHODS: We identified studies that objectively evaluated corticospinal excitability and intracortical inhibition/facilitation after stroke using transcranial magnetic stimulation. Pooled within- (ie, affected hemisphere [AH] vs unaffected hemisphere [UH]) and between-subjects (ie, AH and UH vs Control) standardized mean differences were computed. Decision trees determined which factors accurately predicted studies that showed alterations in corticospinal excitability and intracortical inhibition/facilitation. RESULTS: A total of 35 studies (625 stroke patients and 328 healthy controls) were included. MT was significantly increased and MEP was significantly decreased (ie, reduced excitability) in the AH when compared with the UH and Control (P < .01). SICI was increased (ie, reduced inhibition) for the AH when compared with the UH, and for the AH and UH when compared with Control (P < .001). ICF was significantly increased (ie, increased facilitation) in the AH when compared with UH (P = .016) and decreased in UH when compared with Control (P < 0.001). Decision trees indicated that demographic and methodological factors accurately predicted (73%-86%) studies that showed alterations in corticospinal and intracortical excitability measures. CONCLUSIONS: The findings indicate that stroke alters corticospinal and intracortical excitability measures. Alterations in SICI and ICF may reflect disinhibition of the motor cortex after stroke, which is contrary to the notion that stroke increases inhibition of the affected side.

Exploring the use of bimodal transcranial direct current stimulation to enhance movement in individuals with patellofemoral pain-A sham-controlled double blinded pilot study.

Introduction: In individuals with patellofemoral pain (PFP), addressing increased knee valgus during weight-bearing activities typically involves strengthening weak hip muscles. However, recent literature highlights the role of altered descending central control in abnormal movements associated with PFP. While transcranial direct current stimulation (tDCS) has demonstrated the capacity to enhance neuroplasticity, its application targeting the corticomotor function of gluteal muscles in PFP remains unexplored. This study aimed to investigate the effects of combining bimodal tDCS with exercise on frontal plane kinematics in individuals with PFP. The hypothesis was that bimodal tDCS, specifically targeting the corticomotor function of the gluteal muscles, would augment the effectiveness of exercise interventions in improving frontal plane kinematics compared to sham stimulation. Methods: Ten participants with PFP participated in two sessions involving either bimodal tDCS or sham stimulation, concurrently with hip strengthening exercises. Weight-bearing tasks, including single leg squat, single leg landing, single leg hopping, forward step-down, and lateral step-down, were performed and recorded before and after each session. Pain visual analog scale (VAS) scores were also documented. A one-way ANOVA with repeated measures was employed to compare kinematics, while a Friedman test was used to compare VAS across the three conditions (pre-test, post-tDCS, and post-Sham). Results: We observed no significant differences in trunk lean angle, hip and knee frontal plane projection angles, or dynamic valgus index among the three conditions during the five weight-bearing tasks. VAS scores did not differ across the three conditions. Discussion and conclusion: A single session of tDCS did not demonstrate immediate efficacy in enhancing frontal plane kinematics or relieving pain in individuals with PFP. Considering observed positive outcomes in other neurological and orthopedic populations with multi-session tDCS applications, suggesting potential cumulative effects, further research is essential to explore the effects of multi-session tDCS on weight-bearing movement and underlying neurophysiology in individuals with PFP.

'Remote inhibition' of motor cortex in Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS): A TMS based cortical excitability study.

OBJECTIVES: The study compared real-time motor cortex excitability using transcranial magnetic stimulation (TMS)-derived parameters between children with epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and age-matched neurotypical controls. The EE-SWAS group received steroids as standard of care and were longitudinally followed for three months. MATERIALS & METHODS: Children aged 5-12 years with immunotherapy-naive EE-SWAS (spike-wave-index≥50 %) and neurotypical controls were enrolled. Cognitive and behavioral assessments were performed using valid psychometric tools. Real-time motor cortex excitability was assessed by measuring resting motor threshold (RMT), short intra-cortical inhibition (SICI) and long intra-cortical inhibition (LICI) in both groups. In EE-SWAS group, a follow up evaluation with TMS at 4- and 12-week intervals, EEG, and neurobehavioral assessments at 12-weeks were performed to assess the effect of steroids on cortical excitability and to determine electroclinical outcome. RESULTS: Forty-eight children with suspected EE-SWAS and 26 neurotypical controls were screened; 20 were enrolled in each group. Children with EE-SWAS (mean age: 8.05 ± 1.76 years) had cognitive and behavioral problems (20/20), and ongoing seizures (12/20). At baseline, the dominant motor cortex was significantly inhibited in the EE-SWAS group compared to neurotypical children{RMT(%)[86.3 ± 6.96 vs 58.05 ± 4.71(p < 0.0001)]; LICI(%)[55.05 ± 4.39 vs 73.9 ± 3.75(p < 0.0001)]; SICI(%)[39.2 ± 4.36 vs 55.45 ± 4.78(p < 0.0001)]}. Reversal of motor cortex inhibition was sequentially observed in EE-SWAS group at 4- and 12-week follow-ups{(RMT[4, 12 weeks]: 71.45 ± 9.83, 63.45 ± 8.48); (LICI[4, 12 weeks]: 66.00 ± 6.26, 74.50 ± 5.36); (SICI[4, 12 weeks]: 49.35 ± 6.24, 56.05 ± 5.57)}[repeated-measures ANOVA: p < 0.0001]. CONCLUSION: Motor cortex is remotely inhibited in EE-SWAS, which may contribute to neurobehavioral impairment. Steroids can disinhibit/reverse the epilepsy-induced motor cortex inhibition leading to improvement in neurobehavior.

Spatial sensorimotor mismatch between the motor command and somatosensory feedback decreases motor cortical excitability. A transcranial magnetic stimulation-virtual reality study.

Effective control of movement predominantly depends on the exchange and integration between sensory feedback received by our body and motor command. However, the precise mechanisms governing the adaptation of the motor system's response to altered somatosensory signals (i.e., discrepancies between an action performed and feedback received) following movement execution remain largely unclear. In order to address these questions, we developed a unique paradigm using virtual reality (VR) technology. This paradigm can induce spatial incongruence between the motor commands executed by a body district (i.e., moving the right hand) and the resulting somatosensory feedback received (i.e., feeling touch on the left ankle). We measured functional sensorimotor plasticity in 17 participants by assessing the effector's motor cortical excitability (right hand) before and after a 10-min VR task. The results revealed a decrease in motor cortical excitability of the movement effector following exposure to a 10-min conflict between the motor output and the somatosensory input, in comparison to the control condition where spatial congruence between the moved body part and the area of the body that received the feedback was maintained. This finding provides valuable insights into the functional plasticity resulting from spatial sensorimotor conflict arising from the discrepancy between the anticipated and received somatosensory feedback following movement execution. The cortical reorganization observed can be attributed to functional plasticity mechanisms within the sensorimotor cortex that are related to establishing a new connection between somatosensory input and motor output, guided by temporal binding and the Hebbian plasticity rule.

Effects of DLPFC tDCS Followed by Treadmill Training on Dual-Task Gait and Cortical Excitability in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Gait disturbances are exacerbated in people with Parkinson's disease (PD) during dual-task walking (DTW). Transcranial direct current stimulation (tDCS) has been shown to exert beneficial effects on gait performance and cortical excitability in PD; however, its combined effects with treadmill training (TT) remain undetermined. OBJECTIVE: To investigate the effects of tDCS followed by TT on DTW performance and cortical excitability in individuals with PD. METHODS: Thirty-four PD participants were randomized to dorsal lateral prefrontal cortex (DLPFC) tDCS and TT group (DLPFC tDCS + TT group) or sham tDCS and TT group (sham tDCS + TT group) for 50 minutes per session (20 minutes tDCS followed by 30 minutes TT), 12 sessions within 5 weeks (2-3 sessions each week). Outcome measures included cognitive dual-task walking (CDTW), motor dual-task walking (MDTW), usual walking performance, cortical excitability, functional mobility, cognitive function, and quality of life. RESULTS: The DLPFC tDCS + TT group exerted significantly greater improvement in CDTW velocity (P = .046), cadence (P = .043), and stride time (P = .041) compared to sham tDCS + TT group. In addition, DLPFC tDCS + TT group demonstrated a significant increase in resting motor threshold of stimulated hemisphere compared with sham tDCS + TT group (P = .026). However, no significant differences between groups were found in MDTW performance and other outcomes. CONCLUSION: Twelve-session DLPFC tDCS followed by TT significantly improved CDTW performance and decreased cortical excitability more than TT alone in individuals with PD. Applying DLPFC tDCS prior to TT could be suggested for gait rehabilitation in individuals with PD. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12622000101785.

Acute aerobic exercise modulates cognition and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD) and healthy controls.

Evidence suggests aerobic exercise has beneficial effects on cognitive performance in adults with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms might depend on mechanisms of exercise-mediated brain physiology. The study aims to investigate the effects of acute aerobic exercise on cortical excitability and cognitive performance, and the correlation between these phenomena in adults with ADHD. Twenty-six drug-naïve ADHD adults, and twenty-six age-, and gender-matched healthy controls were assessed with respect to cortical excitability and cognitive performance before and after acute aerobic exercise (a single session for 30 min) or a control intervention. The results show significantly enhanced intracortical facilitation (ICF) and decreased short intracortical inhibition (SICI) after aerobic exercise in healthy subjects. In contrast, SICI was significantly enhanced following acute aerobic exercise in ADHD. In ADHD, furthermore inhibitory control and motor learning were significantly improved after the acute aerobic exercise intervention. Alterations of SICI induced by aerobic exercise, and inhibitory control and motor learning improvement were significantly positively correlated in the ADHD group. Aerobic exercise had partially antagonistic effects in healthy controls, and ADHD patients. Furthermore, aerobic exercise-induced cognition-enhancing effects in ADHD depend on specific alterations of brain physiology, which differ from healthy humans.

Immediate Effects of Preconditioning Intermittent Theta Burst Stimulation on Lower Extremity Motor Cortex Excitability in Healthy Participants.

BACKGROUND: Previous studies have found that inhibitory priming with continuous theta burst stimulation (cTBS) can enhance the effect of subsequent excitatory conditioning stimuli with intermittent theta burst stimulation (iTBS) in the upper limbs. However, whether this combined stimulation approach elicits a comparable compensatory response in the lower extremities remains unclear. This study aimed to investigate how cTBS preconditioning modulated the effect of iTBS on motor cortex excitability related to the lower limb in healthy individuals. METHODS: Using a randomised cross-over design, a total of 25 healthy participants (19 females, mean age = 24.80 yr) were recruited to undergo three different TBS protocols (cTBS + iTBS, sham cTBS + iTBS, sham cTBS + sham iTBS) in a random order. Each TBS intervention was administered with one-week intervals. cTBS and iTBS were administered at an intensity of 80% active motor threshold (AMT) delivering a total of 600 pulses. Before intervention (T0), immediately following intervention (T1), and 20 min after intervention (T2), the corticomotor excitability was measured for the tibialis anterior muscle of participants' non-dominant leg using a Magneuro100 stimulator and matched double-cone coil. The average amplitude of the motor-evoked potential (MEP) induced by applying 20 consecutive monopulse stimuli at an intensity of 130% resting motor threshold (RMT) was collected and analysed. RESULTS: Compare with T0 time, the MEP amplitude (raw and normalised) at T1 and T2 showed a statistically significant increase following the cTBS + iTBS protocol (p < 0.01), but no significant differences were observed in amplitude changes following other protocols (sham cTBS + iTBS and sham cTBS + sham iTBS) (p > 0.05). Furthermore, no statistically significant difference was found among the three protocols at any given time point (p > 0.05). CONCLUSIONS: Preconditioning the lower extremity motor cortex with cTBS prior to iTBS intervention can promptly enhance its excitability in healthy participants. This effect persists for a minimum duration of 20 min. CLINICAL TRIAL REGISTRATION: No: ChiCTR2300069315. Registered 13 March, 2023, https://www.chictr.org.cn.

Feasibility of Simultaneous Anodal Transcranial Direct Current Stimulation During Gait Training in Chronic Stroke Patients: A Randomized Double-Blind Pilot Clinical Trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a therapeutic tool for improving post-stroke gait disturbances, with ongoing research focusing on specific protocols for its application. We evaluated the feasibility of a rehabilitation protocol that combines tDCS with conventional gait training. METHODS: This was a randomized, double-blind, single-center pilot clinical trial. Patients with unilateral hemiplegia due to ischemic stroke were randomly assigned to either the tDCS with gait training group or the sham stimulation group. The anodal tDCS electrode was placed on the tibialis anterior area of the precentral gyrus while gait training proceeded. Interventions were administered 3 times weekly for 4 weeks. Outcome assessments, using the 10-meter walk test, Timed Up and Go test, Berg Balance Scale, Functional Ambulatory Scale, Modified Barthel Index, and European Quality of Life 5 Dimensions 3 Level Version, were conducted before and after the intervention and again at the 8-week mark following its completion. Repeated-measures analysis of variance (ANOVA) was used for comparisons between and within groups. RESULTS: Twenty-six patients were assessed for eligibility, and 20 were enrolled and randomized. No significant differences were observed between the tDCS with gait training group and the sham stimulation group in gait speed after the intervention. However, the tDCS with gait training group showed significant improvement in balance performance in both within-group and between-group comparisons. In the subgroup analysis of patients with elicited motor-evoked potentials, comfortable pace gait speed improved in the tDCS with gait training group. No serious adverse events occurred throughout the study. CONCLUSIONS: Simultaneous anodal tDCS during gait training is a feasible rehabilitation protocol for chronic stroke patients with gait disturbances. CLINICAL TRIAL REGISTRATION: URL: https://cris.nih.go.kr; Registration number: KCT0007601; Date of registration: 11 July 2022.

Effects of Anti-CGRP Monoclonal Antibodies on Neurophysiological and Clinical Outcomes: A Combined Transcranial Magnetic Stimulation and Algometer Study.

BACKGROUND: the aim of this study was to investigate the neurophysiological effect of anti-CGRP monoclonal antibodies on central and peripheral levels in migraine patients. METHODS: An observational cohort study in patients with migraine was performed. All subjects underwent Single-Pulse and Paired-Pulse Transcranial Magnetic Stimulation, as well as a Pressure Pain Threshold assessment. The same protocol was repeated three and four months after the first injection of anti-CGRP monoclonal antibodies. RESULTS: A total of 11 patients with a diagnosis of migraine and 11 healthy controls were enrolled. The main findings of this study are the significant effects of anti-CGRP mAb treatment on the TMS parameters of intracortical inhibition and the rise in the resting motor threshold in our group of patients affected by resistant migraine. The clinical effect of therapy on migraine is associated with the increase in short-interval intracortical inhibition (SICI), resting motor threshold (RMT), and Pressure Pain Threshold (PPT). In all patients, all clinical headache parameters improved significantly 3 months after the first injection of mAbs and the improvement was maintained at the 1-month follow-up. At baseline, migraineurs and HCs had significant differences in all TMS parameters and in PPT, while at follow-up assessment, no differences were observed on RMT, SICI, and PPT between the two groups. After anti-CGRP monoclonal antibody injection, a significant increase in the intracortical inhibition, in the motor threshold, and in the Pressure Pain Threshold in critical head areas was observed in patients with migraine, which was related to significant clinical benefits. CONCLUSIONS: Anti-CGRP monoclonal antibodies improved clinical and neurophysiological outcomes, reflecting a normalization of cortical excitability and peripheral and central sensitization. By directly acting on the thalamus or hypothalamus and indirectly on the trigeminocervical complex, treatment with anti-CGRP monoclonal antibodies may modulate central sensorimotor excitability and peripheral sensitization pain.

Non-Dominant Hemisphere Excitability Is Unaffected during and after Transcranial Direct Current Stimulation of the Dominant Hemisphere.

Transcranial direct current stimulation (tDCS) increases primary motor cortex (M1) excitability and improves motor performance when applied unilaterally to the dominant hemisphere. However, the influence of tDCS on contralateral M1 excitability both during and after application has not been quantified. The purpose was to determine the influence of tDCS applied to the dominant M1 on the excitability of the contralateral non-dominant M1. This study employed a double-blind, randomized, SHAM-controlled, within-subject crossover experimental design. Eighteen young adults performed two experimental sessions (tDCS, SHAM) in counterbalanced order separated by a one-week washout. Transcranial magnetic stimulation (TMS) was used to quantify the excitability of the contralateral M1 to which anodal tDCS was applied for 20 min with a current strength of 1 mA. Motor evoked potential (MEP) amplitudes were assessed in 5 TMS test blocks (Pre, D5, D10, D15, and Post). The Pre and Post TMS test blocks were performed immediately before and after tDCS application, whereas the TMS test blocks performed during tDCS were completed at the 5, 10, and 15 min stimulation timepoints. MEPs were analyzed with a 2 condition (tDCS, SHAM) × 5 test (Pre, D5, D10, D15, Post) within-subject ANOVA. The main effect for condition (p = 0.213), the main effect for test (p = 0.502), and the condition × test interaction (p = 0.860) were all not statistically significant. These results indicate that tDCS does not modulate contralateral M1 excitability during or immediately after application, at least under the current set of common tDCS parameters of stimulation.

Correlation of bilateral M1 hand area excitability and overall functional recovery after spinal cord injury: protocol for a prospective cohort study.

BACKGROUND: After spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown. OBJECTIVE: To clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation. METHODS: This study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment. DISCUSSION: The present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI. TRIAL REGISTRATION NUMBER: ChiCTR2300068831.

Impact of repetitive transcranial magnetic stimulation on cortical activity: a systematic review and meta-analysis utilizing functional near-infrared spectroscopy evaluation.

BACKGROUND: Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex. OBJECTIVE: This systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS. METHODS: Original articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data. RESULTS: Among 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions. CONCLUSION: Diverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity.

Exercise effects on cortical excitability in pain populations: A systematic review and meta-analysis.

BACKGROUND: Transcranial Magnetic Stimulation (TMS) studies examining exercise-induced neuroplasticity in pain populations have produced contradictory findings. We conducted a systematic review to explore how exercise impacts cortical excitability in pain populations using TMS metrics. This review aims to summarize the effect sizes and to understand their sources of heterogeneity. METHODS: We searched multiple databases from inception to December 2022. We included randomized controlled trials (RCTs) with any type of pain population, including acute and chronic pain; exercise interventions were compared to sham exercise or other active interventions. The primary outcomes were TMS metrics, and pain intensity was the secondary outcome. Risk of bias assessment was conducted using the Cochrane tool. RESULTS: This review included five RCTs (n = 155). The main diagnoses were fibromyalgia and cervical dystonia. The interventions included submaximal contractions, aerobic exercise, physical therapy, and exercise combined with transcranial direct current stimulation. Three studies are considered to have a high risk of bias. All five studies showed significant pain improvement with exercise. The neurophysiological data revealed improvements in cortical excitability measured by motor-evoked potentials; standardized mean difference = 2.06, 95% confidence interval 1.35-2.78, I2 = 19%) but no significant differences in resting motor threshold. The data on intracortical inhibition/facilitation (ICI/ICF) was not systematically analyzed, but one study (n = 45) reported higher ICI and lower ICF after exercise. CONCLUSIONS: These findings suggest that exercise interventions positively affect pain relief by modifying corticospinal excitability, but their effects on ICI/ICF are still unclear. While the results are inconclusive, they provide a basis for further exploration in this area of research; future studies should focus on establishing standardized TMS measurements and exercise protocols to ensure consistent and reliable findings. A large-scale RCT that examines various exercise interventions and their effects on cortical excitability could offer valuable insights to optimize its application in promoting neuroplasticity in pain populations.

Conditioning of Motor Evoked Responses After Anterior Cruciate Ligament Reconstruction: Effects of Stimulus Intensity.

BACKGROUND: Operant conditioning of motor evoked torque (MEPTORQUE) can directly target the corticospinal pathway in patients with anterior cruciate ligament (ACL) reconstruction. However, it remains unclear whether operant conditioning can elicit short-term improvements in corticospinal excitability and whether these improvements are influenced by stimulus intensity. HYPOTHESIS: Quadriceps MEPTORQUE responses can be upconditioned in a single session and will elicit short-term adaptations in corticospinal excitability, with higher stimulus intensities eliciting greater effects. STUDY DESIGN: Randomized controlled laboratory study. LEVEL OF EVIDENCE: Level 2. METHODS: Thirty-six participants were assessed during a single session of an operant conditioning protocol. Participants were randomized into 1 of 3 groups for stimulus intensity used during operant conditioning based on the participant's active motor threshold (AMT: 100%, 120%, and 140%). Quadriceps MEPTORQUE amplitude was evaluated during a block of control transcranial magnetic stimulation trials (CTRL) to establish baseline corticospinal excitability, and 3 blocks of conditioning trials (COND) during which participants trained to upcondition their MEPTORQUE. MEPTORQUE recruitment curves were collected to evaluate the effect of operant conditioning on acute corticospinal adaptations. RESULTS: Participants with ACL reconstruction could upcondition their MEPTORQUE in a single session (P < 0.01; CTRL, 17.27 ± 1.28; COND, 21.35 ± 1.28 [mean ± standard error [SE] in N·m]), but this ability was not influenced by the stimulus intensity used during training (P = 0.84). Furthermore, significant improvements in corticospinal excitability were observed (P = 0.05; PRE, 687.91 ± 50.15; POST, 761.08 ± 50.15 [mean ± SE in N·m %AMT]), but stimulus intensity did not influence corticospinal adaptations (P = 0.67). CONCLUSION: Operant conditioning can elicit short-term neural adaptations in ACL-reconstructed patients. Future operant conditioning paradigms may effectively use any of the 3 stimulus intensities studied herein. CLINICAL RELEVANCE: Operant conditioning may be a feasible approach to improve corticospinal excitability after ACL reconstruction.

Phosphene and motor transcranial magnetic stimulation thresholds are correlated: A meta-analytic investigation.

Transcranial magnetic stimulation (TMS) is commonly delivered at an intensity defined by the resting motor threshold (rMT), which is thought to represent cortical excitability, even if the TMS target area falls outside of the motor cortex. This approach rests on the assumption that cortical excitability, as measured through the motor cortex, represents a 'global' measure of excitability. Another common approach to measure cortical excitability relies on the phosphene threshold (PT), measured through the visual cortex of the brain. However, it remains unclear whether either estimate can serve as a singular measure to infer cortical excitability across different brain regions. If PT and rMT can indeed be used to infer cortical excitability across brain regions, they should be correlated. To test this, we systematically identified previous studies that measured PT and rMT to calculate an overall correlation between the two estimates. Our results, based on 16 effect sizes from eight studies, indicated that PT and rMT are correlated (ρ = 0.4), and thus one measure could potentially serve as a measure to infer cortical excitability across brain regions. Three exploratory meta-analyses revealed that the strength of the correlation is affected by different methodologies, and that PT intensities are higher than rMT. Evidence for a PT-rMT correlation remained robust across all analyses. Further research is necessary for an in-depth understanding of how cortical excitability is reflected through TMS.

EEG Changes in Migraine-Can EEG Help to Monitor Attack Susceptibility?

Migraine is a highly prevalent brain condition with paroxysmal changes in brain excitability believed to contribute to the initiation of an attack. The attacks and their unpredictability have a major impact on the lives of patients. Clinical management is hampered by a lack of reliable predictors for upcoming attacks, which may help in understanding pathophysiological mechanisms to identify new treatment targets that may be positioned between the acute and preventive possibilities that are currently available. So far, a large range of studies using conventional hospital-based EEG recordings have provided contradictory results, with indications of both cortical hyper- as well as hypo-excitability. These heterogeneous findings may largely be because most studies were cross-sectional in design, providing only a snapshot in time of a patient's brain state without capturing day-to-day fluctuations. The scope of this narrative review is to (i) reflect on current knowledge on EEG changes in the context of migraine, the attack cycle, and underlying pathophysiology; (ii) consider the effects of migraine treatment on EEG features; (iii) outline challenges and opportunities in using EEG for monitoring attack susceptibility; and (iv) discuss future applications of EEG in home-based settings.

An investigation of the acute effects of aerobic exercise on executive function and cortical excitability in adolescents with attention deficit hyperactivity disorder (ADHD).

Previous studies have shown that aerobic exercise has beneficial effects on executive function in adolescents with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms could be partially due to aerobic exercise-induced cortical excitability modulation. The aim of this study was to explore the effects of acute aerobic exercise on executive functions and cortical excitability and the association between these phenomena in adolescents with ADHD. The study was conducted using a complete crossover design. Executive functions (inhibitory control, working memory, and planning) and cortical excitability were assessed in twenty-four drug-naïve adolescents with ADHD before and after acute aerobic exercise or a control intervention. Inhibitory control, working memory, and planning improved after acute aerobic exercise in adolescents with ADHD. Moreover, cortical excitability monitored by transcranial magnetic stimulation (TMS) decreased after intervention in this population. Additionally, improvements in inhibitory control and working memory performance were associated with enhanced cortical inhibition. The findings provide indirect preliminary evidence for the assumption that changes in cortical excitability induced by aerobic exercise partially contribute to improvements in executive function in adolescents with ADHD.