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.

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.
BACKGROUND: URL: https://cris.nih.go.kr; Registration number: KCT0007601; Date of registration: 11 July 2022.

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.
BACKGROUND: No: ChiCTR2300069315. Registered 13 March, 2023, https://www.chictr.org.cn.

OBJECTIVE: 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.
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].
CONCLUSIONS: 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.

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.

暂无摘要。

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.
CONCLUSIONS: 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.
UNASSIGNED: Australian New Zealand Clinical Trials Registry ACTRN12622000101785.

Sustained attention, as the basis of general cognitive ability, naturally varies across different time scales, spanning from hours, e.g. from wakefulness to drowsiness state, to seconds, e.g. trial-by-trail fluctuation in a task session. Whether there is a unified mechanism underneath such trans-scale variability remains unclear. Here we show that fluctuation of cortical excitation/inhibition (E/I) is a strong modulator to sustained attention in humans across time scales. First, we observed the ability to attend varied across different brain states (wakefulness, postprandial somnolence, sleep deprived), as well as within any single state with larger swings. Second, regardless of the time scale involved, we found highly attentive state was always linked to more balanced cortical E/I characterized by electroencephalography (EEG) features, while deviations from the balanced state led to temporal decline in attention, suggesting the fluctuation of cortical E/I as a common mechanism underneath trans-scale attentional variability. Furthermore, we found the variations of both sustained attention and cortical E/I indices exhibited fractal structure in the temporal domain, exhibiting features of self-similarity. Taken together, these results demonstrate that sustained attention naturally varies across different time scales in a more complex way than previously appreciated, with the cortical E/I as a shared neurophysiological modulator.

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.

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.