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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.

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.

Objective. To determine the long-term effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional M1 preceding motor task practice on the interhemispheric asymmetry of the cortical excitability and the functional recovery in subacute stroke patients with mild to moderate arm paresis. Methods. Twenty-four subacute stroke patients were randomly allocated to either the experimental or control group. The experimental group underwent rTMS over the contralesional M1 (1 Hz), immediately followed by 30 minutes of motor task practice (10 sessions within 2 weeks). The controls received sham rTMS and the same task practice. Following the 2-week intervention period, the task practice was continued twice weekly for another 10 weeks in both groups. Outcomes were evaluated at baseline (T0), at the end of the 2-week stimulation period (T1), and at 12-week follow-up (T2). Results. The MEP (paretic hand) and interhemispheric asymmetry, Fugl-Meyer motor assessment, Action Research Arm Test, and box and block test scores improved more in the experimental group than controls at T1 (p<0.05). The beneficial effects were largely maintained at T2. Conclusion. LF-rTMS over the contralesional M1 preceding motor task practice was effective in enhancing the ipsilesional cortical excitability and upper limb function with reducing interhemispheric asymmetry in subacute stroke patients with mild to moderate arm paresis. Significance. Adding LF-rTMS prior to motor task practice may reduce interhemispheric asymmetry of cortical excitabilities and promote upper limb function recovery in subacute stroke with mild to moderate arm paresis.

   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.

With the widespread adoption of smartphones, concerns about increased exposure to non-ionizing radiofrequency have emerged. This scoping review examines the effects of mobile phone exposure on neural oscillations and cortical excitability, focusing on both motor and non-motor regions of the cerebral cortex. A scoping review identified seventy-eight studies that involved healthy individuals and employed electroencephalography and only two studies that investigated transcranial magnetic stimulation as primary technical tools. The findings suggest that mobile phone exposure may affect brain oscillations and cortical excitability. However, inconsistencies in experimental methods across studies make it difficult to draw definitive conclusions. Additionally, research on fifth-generation technology, particularly mmWave exposure from next-generation mobile networks, remains limited and needs further exploration. These gaps highlight the need for more in-depth studies on how mobile phone exposure impacts brain function.

Background Transcranial alternating current stimulation (tACS) is a non-invasive technique that modulates neural oscillations, yet its specific effects on cortical excitability are not well-understood. This study investigated the effects of tACS on neuroplasticity in the primary motor cortex (M1) across different frequencies. Methods In this randomized, sham-controlled, crossover study, 18 healthy young adults received β-tACS γ-tACS, and sham stimulation over the M1. Neurophysiological responses were assessed using motor evoked potentials (MEPs), electroencephalograms (EEG), and transcranial evoked potentials (TEPs) to determine the frequency-specific effects of tACS on cortical excitability and neuroplasticity. Results γ-tACS significantly enhanced cortical excitability, as reflected by larger MEP amplitudes compared to both β-tACS and sham stimulation. In addition, γ-tACS resulted in significantly smaller M1-P15 amplitudes in TEP than other stimulation conditions. In contrast, β-tACS did not produce significant changes in either MEPs or TEPs compared to sham stimulation. Conclusion These findings provide evidence that tACS induces frequency-dependent effects on cortical excitability and neuroplasticity within the M1. This selective modulation of cortical excitability with γ-tACS suggests its potential as a therapeutic intervention for optimizing motor function and rehabilitation. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2300074898, date of registration: 2023/08/18).

•We stimulated primary motor cortex (M1) in awake rhesus macaques using sp-TMS.•Recruitment curves (RC) were measured with a motor evoked potential (MEP) readout.•Traditional motor threshold (tradMT, at 100 µV) was near the RC inflection point.•A physiologically relevant motor response threshold was found at 90 % of the tradMT.•Plateau of the RC appears at smaller amplitudes in macaques compared to humans. Cortical excitability (CE) is commonly assessed via motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (sp-TMS). While the motor threshold (MT) remains the most widely used measure of CE, it provides a limited, one-dimensional measure based on a fixed MEP amplitude criterion. In contrast, the recruitment curve (RC) offers a more comprehensive characterization of corticospinal recruitment dynamics. To date, the few available preclinical TMS studies measuring RC in non-human primates have been conducted under anaesthesia with limited translational relevance. Hence, we characterised CE in 20 sessions of 4 awake rhesus macaques by recording RCs at nine stimulation intensity levels and parametrising them using exponentiated sigmoid functions. The traditional 100 µV MEP MT criterion level (SI100µV) aligned most closely with the inflection point of the RC sigmoid fit and was consistent with relative frequency-based traditional MT (tradMT) measured in separate sessions. The onset of the logarithmic recruitment phase of the sigmoid (lower ankle point) was found at 0.9 × SI100µV/tradMT. Well-formed MEPs were measured below the SI100µV/tradMT, but not below the lower ankle point, which is a physiologically relevant response threshold. Thus, in rhesus macaques the 100-µV criterion may be suitable to approximate the RC inflection point, but not the physiological motor threshold. The overall RC shape was consistent with previous human data, however, plateau MEP amplitudes were substantially smaller than those reported in humans. These results lay the groundwork for the adaptation of TMS protocols and CE metrics to non-human primates that is necessary for translationally valid research.