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Size and duration of the neuroplastic effects of tDCS depend on stimulation parameters, including stimulation duration and intensity of current. The impact of stimulation parameters on physiological effects is partially non-linear. To improve the utility of this intervention, it is critical to gather information about the impact of stimulation duration and intensity on neuroplasticity, while expanding the parameter space to improve efficacy. Anodal tDCS of 1–3 mA current intensity was applied for 15–30 minutes to study motor cortex plasticity. Sixteen healthy right-handed non-smoking volunteers participated in 10 sessions (intensity-duration pairs) of stimulation in a randomized cross-over design. Transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEP) were recorded as outcome measures of tDCS effects until next evening after tDCS. All active stimulation conditions enhanced motor cortex excitability within the first 2 hours after stimulation. We observed no significant differences between the three stimulation intensities and durations on cortical excitability. A trend for larger cortical excitability enhancements was however observed for higher current intensities (1 vs 3 mA). These results add information about intensified tDCS protocols and suggest that the impact of anodal tDCS on neuroplasticity is relatively robust with respect to gradual alterations of stimulation intensity, and duration.

Recent studies from the field of interoception have highlighted the link between bodily and neural rhythms during action, perception, and cognition. The mechanisms underlying functional body-brain coupling, however, are poorly understood, as are the ways in which they modulate behavior. We acquired respiration and human magnetoencephalography data from a near-threshold spatial detection task to investigate the trivariate relationship between respiration, neural excitability, and performance. Respiration was found to significantly modulate perceptual sensitivity as well as posterior alpha power (8–13 Hz), a well-established proxy of cortical excitability. In turn, alpha suppression prior to detected versus undetected targets underscored the behavioral benefits of heightened excitability. Notably, respiration-locked excitability changes were maximized at a respiration phase lag of around –30° and thus temporally preceded performance changes. In line with interoceptive inference accounts, these results suggest that respiration actively aligns sampling of sensory information with transient cycles of heightened excitability to facilitate performance.

Plateau potentials are a critical feature of neuronal excitability, but their all-or-none behavior is not easily captured in modeling. In this study, we investigated models of plateau potentials in multi-compartment neuron models and found that including glutamate spillover provides robust all-or-none behavior. When glutamate spillover is not included, the all-or-none behavior is very sensitive to the steepness of the Mg block. These results suggest a potentially significant role of glutamate spillover in plateau potential generation, providing a mechanism for robust all-or-none behavior across a wide range of slopes of the Mg block curve. We also illustrate the importance of the all-or-none plateau potential behavior for nonlinear computation with regard to the nonlinear feature binding problem.

This systematic review examines the synergistic effects of Cycloserine and anodal transcranial direct current stimulation (tDCS) on cortical excitability and clinical outcomes. tDCS, a non-invasive neuromodulation technique, modulates cortical excitability, potentially enhancing neuroplasticity. Cycloserine, a partial agonist at NMDA receptors, may potentiate tDCS effects by stabilizing receptor activity. A comprehensive database search identified five eligible studies focusing on healthy participants, with one involving patients with depression. Meta-analysis revealed that Cycloserine prolonged cortical excitability 60 min post-tDCS (SMD: 0.66, 95% CI: 0.05 to 1.27), with the greatest effect observed at a 100 mg dosage (SMD: 0.78, 95% CI: 0.26 to 1.31). Although this suggests a potential enhancement of tDCS efficacy, clinical improvements, such as in depression or motor learning, were not consistently significant across studies. Overall, while Cycloserine appears to extend tDCS-induced cortical excitability, more robust clinical trials are necessary to confirm its therapeutic benefits.

The effects of transcranial direct current stimulation (tDCS) on motor cortical excitability are highly variable between individuals. Inter-individual differences in the electric fields generated in the brain by tDCS might play a role in the variability. Here, we explored whether these fields are related to excitability changes following anodal tDCS of the primary motor cortex (M1). Motor evoked potentials (MEPs) were measured in 28 healthy subjects before and after 20 min sham or 1 mA anodal tDCS of right M1 in a double-blind crossover design. The electric fields were individually modelled based on magnetic resonance images. Statistical analysis indicated that the variability in the MEPs could be partly explained by the electric fields, subjects with the weakest and strongest fields tending to produce opposite changes in excitability. To explain the findings, we hypothesized that the likely locus of action was in the hand area of M1, and the effective electric field component was that in the direction normal to the cortical surface. Our results demonstrate that a large part of inter-individual variability in tDCS may be due to differences in the electric fields. If this is the case, electric field dosimetry could be useful for controlling the neuroplastic effects of tDCS.

   Background Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep. Methods Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy ( n  = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy. Results Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity ( P  < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham. Conclusions Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity.

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.

•Local excitability measures are crucial to understand healthy and pathological brains.•We tested immediate TMS-related responses as non-invasive indexes of M1 excitability.•TMS over M1 elicited immediate TMS-evoked potentials (i-TEPs) in the precentral gyrus.•Immediate TMS-related power (i-TRP) was positively related to motor evoked potentials.•i-TEPs and i-TRP showed distinct spatial and frequency profiles than muscle artifact. The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is typically used to probe cortical excitability at the network level, as local excitability measures were previously not feasible. However, a recent study revealed immediate TMS-evoked potentials (i-TEPs) following primary motor cortex (M1) stimulation, yet their physiological origin remains uncertain. Here, we aimed to test whether this immediate activity is replicable, physiological, and related to motor cortex excitability. Analyses were conducted on data from 28 healthy participants who underwent M1 stimulation using two opposite biphasic current directions. We run a minimal preprocessing and then, upon visual inspection, we divided the sample according to the presence/absence of muscle artifacts (Muscle/NoMuscle groups). First, we successfully replicated i-TEPs for both current directions. Second, source localization revealed that the i-TEPs signal originated in the precentral gyrus of the stimulated hemisphere. Third, we computed the immediate TMS-related power (i-TRP) to disentangle the components contributing to the i-TEP signal. Two oscillatory peaks emerged at 100–200 Hz and 600–800 Hz. Finally, we tested the relationship between i-TRP components and motor evoked potentials (MEPs) amplitude in NoMuscle groups (n = 8 for both current directions, n = 14 for anterior-to-posterior and posterior-to-anterior induced current). The analysis showed a robust positive association between i-TRP in the 600–800 Hz range and MEP amplitude, suggesting that this component reflects M1 excitability. Overall, our findings converge in indicating the physiological nature of immediate TMS-EEG responses, suggesting that they reflect the excitability of the stimulated cortex.

•We developed PRIME, a deep learning framework that predicts binary cortical excitability states from real-time EEG signals with 68 % ROC-AUC (77 % for extreme states).•Our framework combines population-level pretraining with subject-specific calibration and continuous online adaptation to personalize cortical excitability predictions.•PRIME processes and predicts states from EEG data in <10 ms, meeting computational requirements for real-time brain state-dependent stimulation applications.•Predictive information primarily originates from theta and alpha oscillations in fronto-central regions.•PRIME provides a computational foundation for transforming TMS from probabilistic to deterministic therapy by enabling stimulation timing based on predicted brain states. The efficacy of transcranial magnetic stimulation (TMS) is often limited by non-adaptive protocols that disregard instantaneous brain states, potentially constraining therapeutic outcomes. Current EEG-guided approaches are hindered by their reliance on motor-evoked potentials (MEPs), which confound cortical and spinal excitability and restrict applications to the motor cortex, and a dependence on static biomarkers that cannot adapt to changing neurophysiological patterns. We introduce PRIME (Personalized Real-time Inference of Momentary Excitability), a deep learning framework that predicts cortical excitability, quantified by TMS-evoked potential (TEP) amplitude, from raw EEG signals. By targeting cortical excitability directly, PRIME provides a framework that could potentially extend brain state-dependent stimulation beyond the motor cortex, though validation in other cortical regions remains to be established. PRIME incorporates transfer learning and continual adaptation to automatically identify personalized biomarkers, allowing stimulation timing to be adapted across individuals and sessions. PRIME successfully predicts cortical excitability with minimal latency, providing a computational foundation for next-generation, personalized closed-loop TMS interventions.

•Robust extraction of single-trial TMS-evoked potentials from source space.•Pre-stimulus power in alpha, beta, and gamma bands predicts TEP and MEP amplitudes.•Our findings establish EEG biomarkers for brain-state-dependent stimulation. Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) and electromyography (EMG) provides a unique window into instantaneous cortical and corticospinal excitability states. We investigated 50 healthy participants to determine how fluctuations in pre-stimulus brain activity influence single-trial TMS-evoked potentials (TEPs) and motor-evoked potentials (MEPs). We developed a novel automated source-level TEP extraction method using individualized spatiotemporal priors that is robust against poor single-trial signal-to-noise ratios (SNRs) and ongoing oscillations. TEP and MEP amplitudes were predicted with linear mixed-effects models based on pre-stimulation EEG band-powers (theta to gamma), while accounting for temporal drifts (within-session trends), coil control, and inter-subject differences. We found that higher pre-stimulus sensorimotor alpha, beta, and gamma power were each associated with larger TEPs, indicating a more excitable cortical state. Increases in alpha and gamma power immediately before stimulation specifically predicted larger MEPs, reflecting increased corticospinal excitability. These results reveal relationships between ongoing oscillatory brain states and TMS response amplitudes, identifying EEG biomarkers of high- and low-excitability states. In conclusion, our study demonstrates the feasibility of single-trial source-level TMS–EEG analysis and shows that spontaneous alpha-, beta-, and gamma-band oscillations modulate motor cortical and corticospinal responsiveness. These findings can contribute to EEG-informed, brain-state-dependent TMS protocols in optimizing neuromodulatory interventions in clinical and research applications.