Search Results (116)

Neuropsychiatric disorders are characterized by complex etiologies, widespread involvement of brain regions, and pronounced clinical heterogeneity, with core pathological mechanisms closely associated with abnormal activity in deep brain structures and their functional networks. Although current pharmacological therapies and conventional neuromodulation techniques have shown therapeutic benefits in certain conditions, they are generally limited by insufficient stimulation depth or the risks associated with invasive procedures. Temporal interference (TI) electrical stimulation has recently emerged as a non-invasive deep neuromodulation technique that generates low-frequency difference-envelope fields through high-frequency carrier signals, thereby enabling relatively precise modulation of deep brain regions while maintaining favorable safety and tolerability. This technique provides a novel technical pathway for precision intervention in neuropsychiatric disorders. In this review, we summarize the principles and technical characteristics of TI stimulation and highlight its recent applications in mood and stress-related disorders, cognitive impairment and neurodegenerative diseases, movement disorders, addiction, and disorders associated with dysregulated neural excitability. We integrate its potential mechanisms across multiple levels, including neural oscillations, deep–cortical network synchronization, reward and motivational circuits, synaptic plasticity and structural remodeling, excitatory-inhibitory balance, and gene and epigenetic regulation. Current evidence suggests that TI stimulation can modulate electrophysiological activity and may engage molecular and network-level processes relevant to functional improvement, although durable clinical benefits remain to be established. Although clinical translation remains challenged by parameter optimization, interindividual variability, and long-term safety evaluation, advances in computational modeling, multimodal neuroimaging, and closed-loop stimulation strategies are expected to facilitate its development. Overall, TI stimulation represents a promising non-invasive deep neuromodulation approach for mechanistic investigation and precision treatment of neuropsychiatric disorders. Full article

The regulation of chloride levels is a crucial part of controlling inhibitory signals, but does not occur uniformly throughout the body. Recent data suggest that chloride is regulated within localized “microdomains” which are defined by the interaction of KCC2 and NKCC1, structural restraints on cells due to their internal structure, the metabolic condition of the cell, and the external environment modified by astrocytes. The gradients of chloride concentrations within these compartment-specific microdomains define the local chloride reversal potential, and thereby determine the directionality (i.e., whether excitatory or inhibitory), magnitude, and timing of GABAergic inhibition. The disruption of this organized chloride gradient within microdomains impairs the stability of inhibitory activity at multiple levels of integration, including dendritic input, spike timing, interneuron synchronization, and network oscillation. Disturbances in inhibitory stability have been found in a variety of diseases, including epilepsy, neonatal seizure, neuropathic pain, and schizophrenia-spectrum disorders. This supports the hypothesis that disturbances in chloride homeostasis lead to a loss of stability in cortical circuits. This review will provide a synthesis of the molecular, spatial, and circuit level principles involved in the regulation of chloride and discuss how failures of these mechanisms produce clinically relevant disturbances in inhibitory signal processing. In addition, we will be discussing new therapeutic strategies for the restoration of chloride homeostasis, including KCC2 repair, selective modulation of NKCC1, targeting astrocytes, and microenvironmental engineering. Overall, the studies reviewed here provide a unified model for understanding the pathophysiology of inhibitory dysfunction, and demonstrate that the regulation of chloride microdomains provides a novel and promising area of research for translational intervention. Full article

Low-field magnetic stimulation (LFMS) has been proposed as a non-invasive approach for modulating cortical oscillations through electromagnetic coupling. Frequency-aligned enhancement of alpha-band activity is of interest due to its association with cortical inhibitory balance and relaxed wakefulness. This study investigates whether a 10 Hz LFMS applied to the occipital area can induce measurable alpha-band modulation. Electromagnetic simulations were performed to determine magnetic flux distributions within a simplified spherical head model with magnetic susceptibility, which was approximating the brain’s parameters. The 10 Hz stimulation waveform—a positive ramp sawtooth—was analyzed in both time and frequency domains. Electroencephalographic (EEG) recordings were obtained before and after stimulation, and spectral analyses of relevant occipital channels were used to quantify the power redistributions. Simulations indicated localized magnetic field gradients in the occipital region. Post-stimulation EEG recordings showed a redistribution of spectral power toward the alpha-band, representing approximately 50% of total occipital spectral power, with relative increases exceeding 140% across the analyzed channels. These combined modeling and electrophysiological findings provide preliminary proof-of-concept evidence that frequency-aligned LFMS is associated with a redistribution of spectral power toward the alpha-band. Full article

Background/Objectives: Advanced childhood cerebral X-linked adrenoleukodystrophy (cALD) is traditionally regarded as an irreversible terminal phase of neurodegeneration driven by inflammatory demyelination and axonal loss. Experimental evidence indicates that endogenous bioelectrical fields regulate central nervous system organisation, raising the possibility that functional network collapse in cALD may be biologically modifiable, even in the presence of persistent structural damage. This study examined whether longitudinal modulation of endogenous bioelectrical network organisation is associated with sustained clinical and neurophysiological stabilisation in advanced cALD. Methods: We performed a longitudinal observational analysis of two paediatric patients with advanced childhood cerebral X-linked adrenoleukodystrophy undergoing repeated neuroregenerative treatment cycles. Standardised scalp electroencephalography was recorded during spontaneous wakefulness and repeated over months under comparable vigilance conditions. Multimodal analysis included conventional EEG, quantitative EEG, independent component analysis, and standardised low-resolution electromagnetic tomography (sLORETA). Clinical function was assessed using validated measures of consciousness, swallowing, and voluntary motor behaviour. Results: Across patients, longitudinal recordings demonstrated sustained stabilisation of consciousness, swallowing, and voluntary motor function, accompanied by reproducible reorganisation of pathological brain rhythms. Delta and theta oscillations showed a consistent topographical redistribution from limbic–frontoinsular networks towards sensorimotor and parietal integrative cortices. These changes were observed across modalities and timepoints and are unlikely to reflect spontaneous fluctuation, delayed effects of haematopoietic stem cell transplantation, or state-dependent EEG variation. Conclusions: Advanced childhood cerebral X-linked adrenoleukodystrophy is associated with disorganisation of endogenous bioelectrical network activity. In this longitudinal analysis, large-scale network reorganisation was temporally associated with sustained clinical stabilisation, supporting a view of late-stage cALD as a dynamic disorder of network-level vulnerability, rather than a fixed terminal state. Full article

Background: Epilepsy is a network disorder, and network-based approaches to its diagnostics and therapies attract growing attention. Identification of prognostic markers of epileptogenesis and long-term risk for developing epilepsy after brain insults is an urgent, unresolved problem. We examined whether intracortical connectivity patterns reflect early epileptogenic changes in the cortex. Methods: We used the audiogenic kindling model, in which cortical epileptogenesis is initiated by repetition of reflex subcortically-driven seizures. Two measures of functional connectivity—mutual information and mean phase coherence—were applied to electrocorticographic recordings obtained from homotopical sites of parietal cortex during interictal and immediate postictal periods in awake rats. Interhemispheric connectivity and synchrony in non-kindled and slightly kindled rats were compared. Cortical spreading depolarization (SD), the first manifestation of growing cortical excitability in several models of epileptogenesis, was used as an electrographic marker of the earliest kindling stage. Results: In kindled animals, baseline levels of hemispheric connectivity and gamma band synchrony were significantly lower compared to seizure-naive rats. Before kindling, subcortical seizures elicited mild postictal depression of cortical gamma oscillations without changes in interhemispheric functional connectivity. Early in kindling, seizures produced wideband postictal depression of cortical activity and a striking drop in hemispheric connectivity. Conclusions: Primary network alterations during epileptogenesis involve hemispheric decoupling and reduced synchronization, both sustained (between seizures) and transient (postictal). Breakdown of long-range intracortical communication may reflect homeostatic plasticity and an active attempt to restrict epileptogenic reorganization of neural networks. We think that resting-state hemispheric hypocoupling could be an early marker of epileptogenesis. Seizure-induced SD contributes to the generation of postictal events. Full article

Slow-oscillation neurofeedback (NF), encompassing slow cortical potential (SCP), infra-low-frequency (ILF), and infra-slow-fluctuation (ISF) protocols, has gained increasing interest as a non-pharmacological intervention in pediatric mental health and neurodevelopmental care. This narrative review synthesizes peer-reviewed literature on the clinical efficacy of slow-oscillation NF in children and adolescents across various conditions, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), epilepsy, tic disorders, and eating-related concerns. SCP NF is the most extensively studied protocol and shows preliminary efficacy in reducing ADHD symptoms, particularly among individuals capable of learning self-regulation. For ASD and other conditions, early evidence from primarily small-scale or uncontrolled studies suggests possible benefits in emotional regulation, impulsivity, and behavioral symptoms, though findings remain mixed and often non-specific. Methodological heterogeneity, including variation in control conditions, training protocols, and outcome measures, limits the comparability of results. ILF and ISF protocols, while promising, are still emerging and require further validation. Overall, slow-oscillation NF appears to offer potential as a personalized therapeutic option for pediatric populations, but robust, well-controlled trials are needed to clarify its clinical utility and optimize its integration into multimodal care. Full article

Background: Deep brain stimulation (DBS) is increasingly understood as a precision-oriented neuromodulation therapy capable of influencing distributed basal ganglia–thalamo–cortical and cerebellothalamic networks. Although its symptomatic benefits in Parkinson’s disease, essential tremor, and dystonia are well established, the extent to which DBS supports motor learning, adaptive plasticity, and participation in rehabilitation remains insufficiently defined. Traditional interpretations of DBS as a focal or lesion-like intervention are being challenged by electrophysiological and imaging evidence demonstrating multiscale modulation of circuit dynamics. Objectives and methods: DBS may enhance rehabilitation outcomes by stabilizing pathological oscillations and reducing moment-to-moment variability in motor performance, thereby enabling more consistent task execution and more effective physiotherapy, occupational therapy, and speech–language interventions. However, direct comparative evidence demonstrating additive or synergistic effects of DBS combined with rehabilitation remains limited. As a result, this potential is not fully realized in clinical practice due to interindividual variability, limited insight into how individual circuit architecture shapes therapeutic response, and the limited specificity of current connectomic biomarkers for predicting functional gains. Results: Technological advances such as tractography-guided targeting, directional leads, sensing-enabled devices, and adaptive stimulation are expanding opportunities to align neuromodulation with individualized circuit dysfunction. Despite these developments, major conceptual and empirical gaps persist. Few controlled studies directly compare outcomes with versus without structured rehabilitation following DBS. Heterogeneity in therapeutic response and rehabilitation access further complicates the interpretation of outcomes. Clarifying these relationships is essential for developing precision-informed frameworks that integrate DBS with rehabilitative strategies, recognizing that current connectomic and physiological biomarkers remain incompletely validated for predicting functional outcomes. Conclusions: This review synthesizes mechanistic, imaging, and technological evidence to outline a network-informed perspective of DBS as a potential facilitator of rehabilitation-driven functional improvement and identifies priorities for future research aimed at optimizing durable functional restoration. Full article

Functional constipation (FC) is a common functional gastrointestinal disorder thought to arise from the brain–gut axis dysfunction, yet direct human neurophysiological evidence is lacking. We recorded high-density electroencephalography (EEG) data in 21 FC patients and 37 healthy controls across resting, cognitive, and defecation-related tasks. We observed that FC patients displayed a consistent, task-dependent signature compared with healthy controls. At the regional level, FC patients exhibited increased alpha during both resting and defecation-related tasks, reduced temporal gamma during defecation-related tasks, as well as elevated temporal theta during the cognitive task. At the global level, we found altered network properties, such as global efficiency in the delta and beta band networks during resting and defecation-related tasks. These findings establish a direct neurophysiological link between specific, condition-dependent perturbations in cortical rhythm activity and FC pathophysiology. Our work implicates the brain–gut axis in symptom generation and opens a path toward EEG-based biomarkers and targeted neuromodulatory therapies. Full article

Assessing preferences for heating, ventilation, and air conditioning (HVAC) sounds is important for improving comfort in living spaces. Recently, preference assessments using neurophysiological measurements have gained attention. However, associations between HVAC sound preferences and cortical activity remain insufficiently understood to establish neurophysiological indices. In this study, we developed machine learning models that estimate preference scores from magnetoencephalographic (MEG) signals recorded during HVAC sound presentation. We also developed spatial filters based on the common spatial pattern to extract MEG signals associated with the preferences. Both were trained for each participant using MEG signal pairs and participant’s paired-comparison judgments of HVAC sounds based on either coolness or preference. The preference scores estimated from the training data were strongly correlated with the average preference scores obtained through a psychological paired-comparison method (r > 0.98). Analysis of trained linear models revealed that the spatial filters primarily contributing to score estimation extracted theta (4–8 Hz) and alpha (8–13 Hz) oscillations. These suggest that the signals extracted by the spatial filters may reflect cortical activity associated with the coolness and preference of HVAC sounds, and that the preference estimation models may capture the relationship between cortical activity and psychological scales of HVAC sound preferences. Full article

Background: Neural efficiency theory proposes that expert athletes optimize brain resource allocation and functioning. Beta band oscillations are associated with attention, motor preparation, and emotional control, reflecting adaptive patterns of reduced cortical energy expenditure (absolute power) and greater temporal precision (peak frequency). Slow cortical potential (SCP) neurofeedback has emerged as a method to train voluntary cortical regulation, yet its application in sports—particularly in precision-demanding disciplines such as golf—remains underexplored. The aim of this study was to evaluate the effects of SCP neurofeedback on beta band activity in competitive golfers. Methods: Forty-two golfers were randomly assigned to either an intervention group (n = 21), which completed 16 SCP neurofeedback sessions (2560 trials), or a control group (n = 21). SCP activity was measured during activation and deactivation trials, while EEG beta oscillations were analyzed in terms of peak frequency and absolute power at C3, O2, F8, and T5. These sites were chosen for their relevance to golf: C3 (motor execution), O2 (visual processing), F8 (inhibitory and emotional control), and T5 (visuospatial integration). Results: The intervention group showed significant increases in positive SCP trials, reflecting improved voluntary cortical inhibition. Peak frequency increased in Beta 1 (C3) and Beta 2 (O2), while absolute power decreased at F8 and T5, which seems to indicate a reduced cortical overload and enhanced visuospatial integration. Conclusions: SCP neurofeedback modulated beta activity in golfers, enhancing neural efficiency and supporting its potential as an innovative tool to optimize performance in precision sports. Full article

Background: Exercise duration at maximum oxygen uptake ($\dot{\mathrm{V}}$O₂max) appears to be influenced not only by metabolic factors but also by the interplay between brain dynamics and ventilatory regulation. This study examined how cortical activity, assessed via electroencephalography (EEG), relates to performance and acute fatigue regulation during a constant-load cycling test. We hypothesized that oscillatory activity in the theta, alpha, and beta bands would be associated with ventilatory coordination and endurance capacity. Methods: Thirty trained participants performed a cycling test to exhaustion at 90% maximal aerobic power. EEG and gas exchange were continuously recorded; ratings of perceived exertion were assessed immediately after exhaustion. Results: Beta power was negatively correlated with time spent at $\dot{\mathrm{V}}$O₂max (r = −0.542, p = 0.002). Theta and Alpha power alone showed no direct associations with endurance, but EEG–metabolic ratios revealed significant correlations. Specifically, the time to reach $\dot{\mathrm{V}}$O₂max correlated with Alpha/$\dot{\mathrm{V}}$O₂ (p < 0.001), Alpha/$\dot{\mathrm{V}}$CO₂ (p < 0.001), and Beta/$\dot{\mathrm{V}}$CO₂ (p = 0.002). The time spent at $\dot{\mathrm{V}}$O₂max correlated with Theta/$\dot{\mathrm{V}}$O₂ (p = 0.002) and Theta/$\dot{\mathrm{V}}$CO₂ (p < 0.001). The time-to-exhaustion was correlated with Theta/$\dot{\mathrm{V}}$CO₂ (p < 0.001) and Alpha/$\dot{\mathrm{V}}$CO₂ (p < 0.001). Conclusions: These findings indicate that cortical oscillations were associated with different aspects of acute fatigue regulation. Beta activity was associated with fatigue-related neural strain, whereas Theta and Alpha bands, when normalized to metabolic load, were consistent with a role in ventilatory coordination and motor control. EEG–metabolic ratios may provide exploratory indicators of brain–metabolism interplay during high-intensity exercise and could help guide future brain-body interactions in endurance performance. Full article

The balance between cortical excitation and inhibition (E/I balance) in the cerebral cortex is critical for cognitive processing and neuroplasticity. Modulation of this balance has been linked to a wide range of neuropsychiatric and neurodegenerative disorders. The human visual system has well-differentiated magnocellular (M) and parvocellular (P) pathways, which provide a useful model to study cortical excitability using non-invasive visual flicker stimulation. We present an Arduino-driven non-image forming system to deliver controlled flickering light stimuli at different frequencies and wavelengths. By triggering the critical flicker fusion (CFF) frequency, we attempt to modulate the M-pathway activity and attenuate P-pathway responses, in parallel with induced optical scattering. EEG recordings were used to monitor cortical excitability and oscillatory dynamics during visual stimulation. Visual stimulation in the CFF, combined with induced optical scattering, selectively enhanced magnocellular activity and suppressed parvocellular input. EEG analysis showed a modulation of cortical oscillations, especially in the high frequency beta and gamma range. Our results support the hypothesis that visual flicker in the CFF, in addition to spatial degradation, initiates detectable neuroplasticity and regulates cortical excitation and inhibition. These findings suggest new avenues for therapeutic manipulation through visual pathways in diseases such as Alzheimer’s disease, epilepsy, severe depression, and schizophrenia. Full article

(1) Background: Biofeedback and neurofeedback are gaining attention as non-invasive rehabilitation strategies in Parkinson’s disease (PD) treatment, aiming to modulate motor and non-motor symptoms through the self-regulation of physiological signals. (2) Objective: This review explores the application of biofeedback techniques, electromyographic (EMG) biofeedback, heart rate variability (HRV) biofeedback, and electroencephalographic (EEG) neurofeedback in PD rehabilitation, analyzing their impacts on motor control, autonomic function, and cognitive performance. (3) Methods: This review critically examined 15 studies investigating the efficacy of electromyographic (EMG), heart rate variability (HRV), and electroencephalographic (EEG) feedback interventions in PD. Studies were selected through a systematic search of peer-reviewed literature and analyzed in terms of design, sample characteristics, feedback modality, outcomes, and clinical feasibility. (4) Results: EMG biofeedback demonstrated improvements in muscle activation, gait, postural stability, and dysphagia management. HRV biofeedback showed positive effects on autonomic regulation, emotional control, and cardiovascular stability. EEG neurofeedback targeted abnormal cortical oscillations, such as beta-band overactivity and reduced frontal theta, and was associated with improvements in motor initiation, executive functioning, and cognitive flexibility. However, the reviewed studies were heterogeneous in design and outcome measures, limiting generalizability. Subgroup trends suggested modality-specific benefits across motor, autonomic, and cognitive domains. (5) Conclusions: While EMG and HRV systems are more accessible for clinical or home-based use, EEG neurofeedback remains technically demanding. Standardization of protocols and further randomized controlled trials are needed. Future directions include AI-driven personalization, wearable technologies, and multimodal integration to enhance accessibility and long-term adherence. Biofeedback presents a promising adjunct to conventional PD therapies, supporting personalized, patient-centered rehabilitation models. Full article

Background: Sensorimotor beta oscillations are critical for motor control and become synchronized with muscle activity during sustained contractions, forming corticomuscular coherence (CMC). Although beta activity manifests in transient bursts, suggesting nonlinear behavior, most studies rely on linear analyses, leaving the underlying dynamic structure of brain–muscle interactions underexplored. Objectives: To investigate the nonlinear dynamics underlying beta oscillations during isometric contraction. Methods: MEG and EMG were recorded from 17 right-handed healthy adults performing a 10 min isometric pinch task. Lyapunov exponent (LE), fractal dimension (FD), and correlation dimension (CD) were computed in 10 s windows to assess temporal stability. Signal similarity was assessed using Pearson correlation of amplitude envelopes and the nonlinear features. Burstiness was estimated using the coefficient of variation (CV) of the beta envelope to examine how transient fluctuations in signal amplitude relate to underlying nonlinear dynamics. Phase-randomized surrogate signals were used to validate the nonlinearity of the original data. Results: In contrast to FD, LE and CD revealed consistent, structured dynamics over time and significantly differed from surrogate signals, indicating sensitivity to non-random patterns. Both MEG and EMG signals demonstrated temporal stability in nonlinear features. However, MEG–EMG similarity was captured only by linear envelope correlation, not by nonlinear features. CD was strongly associated with beta burstiness in MEG, suggesting it reflects information similar to that captured by the amplitude envelope. In contrast, LE showed a weaker, inverse relationship, and FD was not significantly associated with burstiness. Conclusions: Nonlinear features capture intrinsic, stable dynamics in cortical and muscular beta activity, but do not reflect cross-modal similarity, highlighting a distinction from conventional linear analyses. Full article

Empathy has been linked to enhanced processing of social information, yet the neurophysiological correlates of such individual differences remain underexplored. Objectives: The aim of this study was to investigate how individual differences in trait empathy are reflected in oscillatory brain activity during the perception of non-verbal social cues. Methods: In this EEG study involving 30 participants, we examined spectral and time–frequency dynamics associated with trait empathy during a visual task requiring the interpretation of others’ body gestures. Results: FFT Power spectral analyses (applied to alpha/mu, beta, high beta, and gamma bands) revealed that individuals with high empathy quotients (High-EQ) exhibited a tendency for increased beta-band activity over frontal regions and markedly decreased alpha-band activity over occipito-parietal areas compared to their low-empathy counterparts (Low-EQ), suggesting heightened attentional engagement and reduced cortical inhibition during social information processing. Similarly, time–frequency analysis using Morlet wavelets showed higher alpha power in Low-EQ than High-EQ people over occipital sites, with no group differences in mu suppression or desynchronization (ERD) over central sites, challenging prior claims linking mu ERD to mirror neuron activity in empathic processing. These findings align with recent literature associating frontal beta oscillations with top-down attentional control and emotional regulation, and posterior alpha with vigilance and sensory disengagement. Conclusions: Our results indicate that empathic traits are differentially reflected in anterior and posterior oscillatory dynamics, supporting the notion that individuals high in empathy deploy greater cognitive and attentional resources when decoding non-verbal social cues. These neural patterns may underlie their superior ability to interpret body language and mental states from visual input. Full article