The known fluctuations in ovarian hormone concentrations across the eumenorrheic menstrual cycle contribute to modulations in cortical excitability and inhibition. However, how such changes affect spike-timing-dependent plasticity (STDP) has not been systematically studied. This research aimed to determine the effect of the menstrual cycle on corticospinal excitability and STDP. Twelve eumenorrheic female participants (age: 25 ± 5 years), visited the lab in three menstrual cycle phases: early follicular (EF), late follicular (LF), and mid-luteal (ML). Visits comprised of corticospinal excitability (motor evoked potential [MEP]/Mmax), short-intracortical inhibition (SICI), and intracortical facilitation (ICF) measures, recorded in the resting first dorsal interosseous. Followed by a paired associative stimulation (PAS) protocol, utilising ulnar nerve and transcranial magnetic stimulation (25 ms interstimulus interval) to elicit neuroplasticity. To assess the time course of STDP, measurements were repeated at 15 and 30-minutes post PAS. Corticospinal excitability (MEP/Mmax) was greater in the LF phase (p≤0.001) compared to EF and ML, with no phase effects observed for SICI or ICF (p≥0.170). PAS elicited an increase in MEP/Mmax across all phases at 15-minutes (112 ± 5, 116 ± 5, and 114 ± 7% baseline, p≤0.037), whereas at 30-minutes only ML was facilitated (126 ± 5% baseline, p=0.044). The present data demonstrates facilitatory STDP can be induced with PAS across the tested menstrual cycle phases, but responses are prolonged and potentiated in the ML phase. Additionally, increased corticospinal excitability in the LF phase is likely due to intrinsic changes within the descending tract, as no changes in intracortical neurotransmission were observed.

ABSTRACTThe evaluation of cortical inhibition (CI) in dorsolateral prefrontal cortex (DLPFC) using transcranial magnetic stimulation combined with electroencephalography (TMS‐EEG) has focused great attention in recent years. One of the most common procedures to assess such inhibition is the short‐interval cortical inhibition (SICI), a paired‐pulse paradigm defined by the interstimulus interval (ISI). While SICI was initially defined and extensively used in studies targeting the motor cortex, its application to the DLPFC is relatively recent. However, little is known about how ISI values affect the DLFPC, especially in terms of the TMS‐evoked potentials (TEP). This study aims to quantitatively compare the effects of different ISI values in the SICI protocol on CI in the DLPFC by assessing TEPs. Eighteen healthy subjects underwent the SICI protocol using two different ISIs: 2 ms and 4 ms. TMS‐EEG responses for both ISIs were characterized in terms of amplitude, latency, peak‐to‐peak amplitudes, and the area under the rectified curve of the TEPs. The results indicate that TEPs differed depending on the ISI used, finding a significantly greater inhibition with 2 ms ISI, as reflected by a more pronounced reduction in TEP amplitude. These findings are consistent with previous literature on motor cortex stimulation, suggesting that a greater reduction in TEP, and hence greater inhibition, is likely achieved with a 2 ms ISI. Therefore, the study helps in the standardization of SICI protocol in DLFPC.

Increasing the quantity of electrical stimulation pulses reduces cortical response inhibition.

Distinct cortical inhibitory profiles in schizophrenia and bipolar disorder: A TMS-EEG study of GABAb function.

Evidence of widespread brain inhibition following conventional but not individualised non-motor repetitive transcranial magnetic stimulation: A multimodal study.

Hemispheric asymmetry of the ipsilateral silent period following voluntary movement of the opposite hand.

This systematic review investigates the complex relationship between attention deficit hyperactivity disorder (ADHD) and first-episode non-affective psychosis (FEP), focusing on neurodevelopmental, pharmacological and substance use factors that may influence this association. Following PRISMA guidelines, we conducted a comprehensive literature search across PubMed, Scopus, Web of Science and PsycINFO databases for studies published between January 2001 and June 2024. We included experimental and observational studies examining ADHD and FEP in participants aged ≥ 16 years. Quality assessment was performed using standardised tools specific to each study design. From 1243 initially identified records, 13 studies met inclusion criteria. Five studies addressing neurodevelopmental factors revealed shared neurobiological vulnerabilities between ADHD and psychosis, including impaired cortical inhibition, neurophysiological markers and cognitive deficits. Five pharmacological studies demonstrated that whilst stimulant-induced psychosis can occur, the absolute risk appears low, with amphetamines carrying a 1.65-fold higher risk than methylphenidate. Three studies on substance use patterns showed that ADHD patients with FEP had significantly higher rates of substance use disorders, particularly cannabis use, which was associated with earlier psychosis onset and poorer outcomes. Individuals with ADHD, particularly those with persistent symptoms from childhood and neurocognitive deficits, may have an elevated risk of developing FEP. Substance use appears to be an important mediating factor in this relationship. Regarding pharmacological treatment, recent epidemiological evidence provides a more nuanced perspective on stimulant safety, though the evidence remains mixed and requires further investigation. These findings highlight the importance of comprehensive assessment, substance use prevention and individualised risk stratification when managing ADHD patients at risk for psychosis.

BackgroundStroke is a major cause of death and disability worldwide. Approximately 12–25% of stroke survivors develop complex regional pain syndrome type I (CRPS-I) within 3–12 months. CRPS-I is characterized by severe limb pain, abnormal pain, and vasomotor instability, which hinders rehabilitation. Insufficient efficacy and adverse reactions limit the use of current pharmacological treatments, such as non-steroidal anti-inflammatory drugs and gabapentinoids. Post-stroke CRPS-I is characterized by neuroinflammation, maladaptive neural plasticity, and central/peripheral sensitization. Repetitive transcranial magnetic stimulation (rTMS) regulates pain through cortical reorganization and inhibition of neuroinflammation, while acupuncture, particularly the Yuan-Luo Dajiejing (YLDJJ) technique, reduces central sensitization by activating endogenous opioids. However, no randomized controlled trial has compared the efficacy of YLDJJ acupuncture combined with rTMS in the treatment of CRPS-I after stroke.MethodsThis randomized controlled trial will randomly assign eligible participants to three groups in a 1:1:1 ratio: the experimental group (YLDJJ acupuncture + rTMS), the control group 1 (conventional acupuncture + rTMS), and the control group 2 (sham acupuncture + rTMS). The participants will be aged 18–80 years old, with CRPS-I developing after stroke and meeting the specific inclusion criteria. The intervention measures will be administered once daily for 20 days. Pain intensity, assessed using the visual analogue scale (VAS), will be measured at baseline, on days 10 and 20, and at 1 and 3 months after treatment completion. Secondary outcome measures include motor function, muscle tone, shoulder range of motion, activities of daily living, thermal asymmetry, and neuroplasticity-related indicators. The sample size will be 126 participants, accounting for a 20% dropout rate.ConclusionThis trial will evaluate the efficacy and safety of Yuan-Luo Da-Jie-Jing acupuncture combined with rTMS. The results will be compared to two control groups: one receiving conventional acupuncture with rTMS, and the other receiving sham acupuncture with rTMS. The results are expected to provide evidence for formulating clinical treatment strategies for CRPS-I after stroke.Clinical trial registration(ITMCTR, http://itmctr.ccebtcm.org.cn/), No. ITMCTR2025001677.

BackgroundThe periodic (e.g., EEG alpha power density) and aperiodic (offset and slope of EEG power density) components of resting‐state EEG rhythms reflect different aspects of global neural dynamics and have been linked to excitatory/inhibitory balance. This study investigates these components across vigilance stages (wakefulness, flattening, ripples) in patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) compared to healthy elderly (NOLD).MethodSpectral analysis was performed on EEG data recorded from 19 scalp electrodes during a ∼30‐minute session in age‐, sex‐, and education‐matched ADMCI and NOLD participants (n = 17 vs. n = 11) showing transitions from quiet wakefulness (wakefulness stage, characterized by dominant posterior alpha activity at 8–12 Hz) to light sleep (flattening stage, marked by reduced EEG amplitude, and ripples stage, with diffuse theta activity at 4–7 Hz) based on a modified version of Hori's sleep onset classification. Periodic (spectral power in the 8–12 Hz alpha band for posterior electrodes) and aperiodic (offset and slope in the 3–40 Hz range) parameters were analyzed across vigilance stages. ANOVA was performed with Group, Stage, and Region of Interest (Frontal, Central, Temporal, Posterior) as factors.ResultsFor the periodic EEG component, posterior alpha power density showed a significant Group effect, indicating reduced posterior alpha activity from quiet wakefulness to light sleep in ADMCI compared to NOLD (p < 0.01). In contrast, offset and exponent exhibited significant Condition effects, reflecting increased cortical inhibition (higher offset and exponent) across vigilance stages (p < 0.001) with no significant Group differences. Region of Interest effects showed greater inhibition across stages in parietal‐occipital regions compared to anterior regions (p < 0.001).ConclusionIn this study, periodic EEG alpha power was the most sensitive marker of vigilance dysfunctions in ADMCI, while aperiodic EEG parameters primarily captured a general increase in inhibition during transitions from wakefulness to light sleep, independent of disease. Vigilance‐related changes in cortical inhibition do not appear to be a hallmark of prodromal Alzheimer's disease, which is instead characterized by altered oscillatory, frequency‐specific activity. Future research should integrate both periodic and aperiodic EEG features to enhance the understanding of neurophysiological dynamics in Alzheimer's disease.

Reliable and dynamic monitoring changes in cortical excitation and inhibition balance using aperiodic 1/f slope: functions, diseases and drug effects.

Astrocytic GABA controls fidelity of temporal cortical processing in Fragile X Syndrome.

Differential Implications of the mediodorsal thalamic nucleus subdivisions in regulating prefrontal cortex GAD67 and GABAB receptors expression: behavioral and cognitive outcomes.

Cortical Excitability and Heart Rate Variability in Response to Short Duration Transauricular Vagus Nerve Stimulation in Healthy Adults.

Background/Objectives: Deception engages both emotional and cognitive processes, yet individual variability in these responses remains insufficiently understood. This study aimed to investigate how personality traits, perceived stress, and empathic distress shape psychophysiological and neurobiological responses during deception and emotional processing. Methods: Thirty healthy young adults completed a protocol combining a deception task with emotional stimulus exposure, while heart rate (HR), heart rate variability (HRV), and electroencephalographic (EEG) activity were continuously recorded. Participants were characterized using measures of Dark Triad traits, perceived stress (PSS-10), and empathic distress. Results: The results showed increased HR and reduced HRV during deceptive responses, reflecting heightened cognitive effort and autonomic arousal. In contrast, morally or socially evaluative stimuli were associated with right-frontal EEG asymmetry, suggesting engagement of emotional regulation processes. Cluster analysis revealed distinct reactivity profiles: individuals with high stress and empathic distress exhibited amplified autonomic activation and reduced cortical inhibition, whereas those with higher Machiavellianism and psychopathy displayed attenuated HR/HRV modulation and stable EEG patterns, suggestive of emotional detachment and adaptive inhibition. These findings suggest that deception is a dynamic, context-dependent process influenced by individual personality traits and stress-regulation capacities. Conclusions: The study offers valuable insights into the psychophysiological mechanisms underlying deceptive behavior, with meaningful implications for both forensic and affective neuroscience.

Abstract Diffuse gliomas remodel neuronal circuits with prognostic and therapeutic significance for patients. Electrophysiologic measures of cortical excitability hold promise for monitoring disease progression and evaluating therapeutic responses. The power law exponent (aperiodic slope) reflects the balance between excitatory and inhibitory activity within neuronal networks, a critical aspect of normal brain function often disrupted in neurological conditions. Despite its potential, the significance of the aperiodic slope in glioma- infiltrated tissue and its underlying cellular processes has not been fully investigated. We integrated multi-modal electrophysiological analysis with transcriptomic profiling to analyze the aperiodic slope in both normal and glioma-infiltrated cortex in 660 electrodes from 13 patients. We determine that glioma infiltration induces a flattening of the aperiodic slope, indicating a shift toward excitation dominance that varies according to tumor subtype and correlates with impairments in semantic naming. Single-nucleus RNA sequencing of 508,000 cells revealed that cortical regions with flat aperiodic slope exhibit transcriptional programs enriched in glutamatergic signaling, membrane depolarization, and excitatory synaptic transmission in neurons. Additionally, the aperiodic slope was found to respond dynamically to pharmacologically induced changes in cortical inhibition during propofol administration, a GABAA agonist. Our results establish the aperiodic slope as a robust biomarker of glioma-associated excitation-inhibition imbalance, with potential applications in tumor classification and treatment monitoring.

Impaired GABAergic inhibition, so-called neural disinhibition, in the prefrontal cortex and hippocampus has been linked to cognitive deficits. The novel object recognition (NOR) task has been used widely to study cognitive deficits in rodents. However, the contribution of prefrontal cortical and hippocampal GABAergic inhibition to NOR task performance has not been established. Here, we investigated NOR task performance in male Lister hooded rats following regional neural disinhibition or functional inhibition, using intracerebral microinfusion of the GABAA receptor antagonist picrotoxin or agonist muscimol, respectively. Our infusion targets were the medial prefrontal cortex (mPFC), dorsal hippocampus (DH), and ventral hippocampus (VH). Using a within-subject design, we compared NOR task performance (1 min retention delay) following bilateral regional saline, picrotoxin, or muscimol infusions made before the acquisition phase. In mPFC, neither functional inhibition nor neural disinhibition affected object recognition memory. However, in both the DH and VH, neural disinhibition impaired NOR relative to saline control, mainly by reducing novel object exploration time. In addition, functional inhibition of the DH impaired NOR, whereas VH functional inhibition tended to reduce novel object exploration at the highest dose used (alongside substantial nonspecific behavioral effects). Overall, our data suggest that hippocampal, but not prefrontal, GABAergic inhibition contributes to NOR at a 1 min retention delay. Moreover, such NOR performance likely requires balanced neural activity in the DH, with both too little and too much DH activity impairing NOR memory. Our findings support that the NOR task can be used to investigate hippocampal GABAergic dysfunction in rodent models.

Parvalbumin-positive (PV+) interneurons are the most abundant type of interneurons in the cortex. Its characteristic high-frequency non-accommodating firing pattern is critical for cortical inhibition, network activity, and mouse behavior. In the brain, neuromodulation via G protein-coupled receptors (GPCRs) regulates neuronal activities, including the output of neurons. GPCRs are the largest receptor superfamily, and there are GPCRs called “orphan GPCRs” whose endogenous ligands are still not clear. Meanwhile, studies have shown that some of them are constitutively active, but the modulation of these GPCRs on neuronal activity is far from clear. Among orphan GPCRs, Gpr176 is a constitutively active GPCR known for its role in the circadian rhythm in the central nervous system. In the present study, we found that the expression of Gpr176 was mainly expressed in PV + interneurons in the prefrontal cortex, and the knockdown of Gpr176 increased the output of PV + interneurons by increasing the membrane potential change in the repolarizing phase of action potentials in a train. We also found that the synaptic activities of these neurons were not affected. Furthermore, we observed changes in behaviors of mice with the knockdown of Gpr176 in the PV + interneurons of the prefrontal cortex. These data suggest an important role of Gpr176 in the regulation of intrinsic membrane properties of PV + interneurons in the prefrontal cortex.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13041-025-01254-2.

BackgroundAltered excitation/inhibition (E/I) balance is a key mechanism in epilepsy, but its dynamic changes before seizure onset remain unclear. The interictal suppression hypothesis suggests that inhibitory input isolates epileptic regions, yet little is known about E/I dynamics in the pre-ictal phase.MethodsWe analyzed high-density EEG recordings from patients with drug-resistant focal epilepsy, each with at least one recorded seizure. Cortical activity was reconstructed using source modeling, and time-resolved changes in the aperiodic exponent—a non-invasive marker of E/I balance—were computed. Directed functional connectivity was assessed via spectral Granger causality. These metrics were correlated with cortical thickness and neurotransmitter receptor density maps.ResultsThe aperiodic exponent increased progressively in the minutes preceding seizures, reflecting a global shift toward cortical inhibition, with no significant differences between epileptic and non-epileptic regions. Delta and theta power also increased preictally. Epileptic regions showed significantly more outward than inward connectivity, and more outward connectivity than non-epileptic areas. In non-epileptic regions, higher inhibition was associated with greater outward connectivity. Cortical thickness positively correlated with inhibition only in non-epileptic areas. Lower muscarinic receptor density was associated with stronger inhibitory shifts.ConclusionsSeizure onset is preceded by a widespread shift toward inhibition, possibly representing a compensatory mechanism that fails as ictal thresholds are crossed. This shift is linked to altered connectivity and disrupted structure–function coupling in epileptic regions. The dynamic aperiodic exponent emerges as a promising biomarker for seizure prediction and a potential target for neuromodulation strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04447-7.

Associations of screen time and physical activity with TMS-based measures of motor cortical excitability in adolescents.

Investigational transcranial magnetic stimulation measures as predictors of aggression in schizophrenia: A cross-sectional study.