Search Results (89)

Background: Optically pumped magnetometers (OPMs) have emerged as a promising technology for neuromagnetic recording in humans. Current state-of-the-art OPM systems are housed in large magnetically shielded rooms to reduce external electromagnetic noise and typically comprise sensor arrays covering the entire head. Such systems are extremely costly to purchase and install, and take up large amounts of physical space, which limits the accessibility of this technology to research groups with limited funding. Here we sought to evaluate the utility of a more accessible “starter” OPM system comprising a small cylindrical mu-metal shield and partial sensor coverage. Methods: Twelve participants underwent right-sided median nerve stimulation (MNS) intended to elicit ubiquitous sensorimotor responses: somatosensory-evoked fields (SEFs, comprising N20m, P35m and P60m components) and event-related (de)synchronization (ERD/ERS) of oscillatory neuronal rhythms in the mu and beta frequency ranges. Results: Following MNS, we observed robust N20m and P60m peaks, as well as the expected mu ERD and beta ERS effects. Moreover, these responses could be localized to expected cortical generators. However, we observed markedly lower SNR than that seen in state-of-the-art systems. We make recommendations for further improvements to this system and others like it. Full article

Human performance in critical environments is frequently degraded by mistimed communication delivered during periods of visual–cognitive saturation. In such settings, failures arise not only from individual limitations but also from poor coordination between operators under rapidly changing workload conditions. We present a dual-loop neuro-adaptive simulation framework based on real-time spectral–topographic EEG representations, in which multichannel cortical activity is transformed into dynamic spatial maps and decoded to regulate both operator assistance and team communication. The system integrates 14-channel wireless EEG (Emotiv EPOC X, 256 Hz), gaze tracking, telemetry, and communication events through an LSL-based multimodal synchronization pipeline. A hybrid CNN–LSTM model processes sequences of spectral-topographic EEG maps to classify three operationally actionable neurocognitive states—Channelized Attention, Diverted Attention, and Surprise/Startle—while also estimating a continuous Cognitive Load Index (CLI). These representation-derived features are then used by a multi-agent proximal policy optimization (MAPPO) controller to generate two coordinated outputs: (i) adaptive haptic guidance for the pilot, designed to reduce reliance on overloaded visual and auditory channels, and (ii) a traffic-light communication gate for the telemetry engineer, regulating whether radio intervention should proceed, be delayed, or be withheld. In a high-fidelity dual-station simulation with 25 pilot–engineer pairs, the proposed framework was associated with a reduction of more than 30% in communication breakdown errors relative to open-loop telemetry, with the strongest effects observed during peak-load windows, while preserving realistic task progression. It also improved pilot reaction time to time-critical warnings and reduced engineer decision load under the tested conditions. These findings support the use of spectral-topographic EEG representations as a practical basis for combining multimodal neurophysiological sensing, spatiotemporal pattern decoding, and adaptive coordination in high-pressure human–machine teams. At the same time, the study should be interpreted as evidence of controlled feasibility in a simulated setting rather than as definitive proof of field-level generalization. We further discuss deployment constraints and propose privacy-by-design safeguards to ensure that neurocognitive signals are used exclusively for operational adaptation rather than employability assessment or performance scoring. Full article

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

Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) provides a powerful framework to probe and modulate human cortical and corticospinal excitability. In recent years, brain state-dependent EEG–TMS paradigms have gained increasing interest by synchronizing stimulation to ongoing neural activity. However, traditional approaches relying on single oscillatory features or fixed thresholds have yielded heterogeneous and often inconsistent results, motivating the adoption of machine learning (ML) and artificial intelligence (AI) methods to model brain state in a multivariate, data-driven manner. This review synthesizes current ML and deep learning (DL) approaches aimed at predicting cortical and corticospinal excitability from pre-stimulus EEG. We contextualize these methods within brain state-dependent EEG–TMS frameworks based on oscillatory phase, power, and network-level features, and within evolving definitions of brain state that move beyond local biomarkers toward distributed, large-scale, and dynamically evolving neural representations. The reviewed studies span feature-engineered models, data-driven decoding approaches, and emerging adaptive closed-loop frameworks. Finally, we discuss key methodological challenges, translational barriers, and future directions toward personalized, interpretable, and fully closed-loop neuromodulation systems. Full article

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. 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

Background: Navigated repetitive TMS (nrTMS) is widely used for non-invasive mapping of cortical functions. Methodological improvement might be achieved by optimizing coil positioning based on electric-field modeling and augmented reality (AR)-guided neuronavigation to enhance spatial targeting accuracy and stimulation-induced language errors. Therefore, we compared electric-field-optimized, AR-guided nrTMS with conventional nrTMS using manually planned coil positioning. Methods: Twenty-eight healthy subjects underwent two MRI-guided left hemispheric nrTMS language mapping sessions. Each session used 10 Hz stimulation at a 100% resting motor threshold applied for 1.5 s per region of interest (ROI) during a synchronized object naming task. ROIs were defined according to the Corina cortical parcellation system. Manually defined and electric-field-optimized coil placements obtained using SimNIBS (v4.1.0) were applied; the optimized session was assisted by AR goggles. The primary outcome was the quantitative and categorical differences in cortical regions mapped as language-eloquent. Resting-state fMRI was acquired to provide a reference for comparing nrTMS-derived language maps. Outcomes: Electric-field-optimized nrTMS did not result in an increase in positively mapped ROIs. A different distribution of language errors was observed between sessions. Manual mapping roughly followed the extracted resting-state language and motor networks, whereas electric-field-optimized mapping might correspond less. Optimized coil positions were not always practically feasible. AR guidance improved target location accuracy. Conclusions: While AR was a useful addition to the TMS experiment, electric-field optimization did not translate into significant behavioral differences. However, altered distribution of language errors can give insight into underlying neurophysiological processes of rTMS. 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

Voluntary movement arises from a sequence of neural processes that involve planning, preparation, and execution within distributed cortical networks. The readiness potential, a slow negative brain signal preceding self-initiated actions, represents a sensitive indicator of motor preparation. However, it remains unclear how this signal reflects concurrent variations in mechanical and temporal demands. In this study, twenty-eight healthy participants performed self-paced elbow flexions under nine combinations of mechanical load and movement duration while brain electrical activity, muscle activity, and movement kinematics were simultaneously recorded. Linear mixed-effects analyses revealed that the amplitude of the readiness potential increased progressively with greater mechanical load, indicating that cortical readiness scales with the intensity of preparatory effort. In contrast, longer movement durations produced smaller amplitudes, suggesting that extended temporal windows reduce the efficiency of preparatory synchronization. No significant interaction between load and duration was observed, supporting the idea of partially independent neural mechanisms for effort and timing. These findings identify the readiness potential as a neural marker integrating the energetic and temporal dimensions of voluntary movement and provide a basis for understanding how cortical readiness dynamically optimizes human motor performance. Full article

Background: Rhythmic sensory stimulation, including structured musical interventions, has gained renewed interest as a non-pharmacological strategy that may modulate cortical excitability and network stability in focal epilepsy. Although several small studies have reported changes in seizure frequency or epileptiform activity during rhythmic or music exposure, the underlying mechanisms and translational relevance remain insufficiently synthesized. Objective: This narrative review summarizes clinical evidence on music-based and rhythmic sensory interventions in focal epilepsy, outlines plausible neurophysiological mechanisms related to neural entrainment and large-scale network regulation, and discusses emerging opportunities for digital delivery of rhythmic protocols in everyday self-management. Methods: A structured search of recent clinical, neurophysiological, and rehabilitation literature was performed with emphasis on rhythmic auditory, tactile, and multimodal stimulation in epilepsy or related conditions. Additional theoretical and translational sources addressing oscillatory dynamics, entrainment, timing networks, and patient-centered digital tools were reviewed to establish a mechanistic framework. Results: Existing studies—although limited by small cohorts and heterogeneous methodology—suggest that certain rhythmic structures, including specific musical compositions, may transiently modulate cortical synchronization, reduce epileptiform discharges, or alleviate seizure-related symptoms in selected patients. Evidence from neurologic music therapy and rhythmic stimulation in other neurological disorders further supports the concept that externally delivered rhythms can influence timing networks, attentional control, and interhemispheric coordination. Advances in mobile health platforms enable structured rhythmic exercises to be delivered and monitored in real-world settings. Conclusions: Music-based and rhythmic sensory interventions represent a promising but underexplored adjunctive approach for focal epilepsy. Their effectiveness likely depends on individual network characteristics and on the structure of the applied rhythm. Digital integration may enhance personalization and adherence. Rigorous clinical trials and mechanistic studies are required to define optimal parameters, identify responders, and clarify the role of rhythmic stimulation within modern epilepsy care. Full article

Background/Objectives: Tinnitus causes significant cognitive and emotional distress; however, its clinical assessment mostly relies on subjective measures without evaluation of objective indices. In this narrative review, we examined the potential of electroencephalography (EEG)-based neurophysiological markers as objective biomarkers in tinnitus assessment. Methods: The Web of Science, PubMed, EMBASE, and MEDLINE databases were searched to identify research articles on EEG-based analysis of individuals with tinnitus. Studies in which treatment and control groups were compared across four analytical domains (spectral power analysis, functional connectivity, microstate analysis, and entropy measures) were included. Qualitative synthesis was conducted to elucidate neurophysiological mechanisms, methodological characteristics, and clinical implications. Results: Analysis of 18 studies (n = 1188 participants) revealed that tinnitus is characterized by distributed neural dysfunction that extends beyond the auditory system. Spectral power analyses revealed sex-dependent, frequency-specific abnormalities across distributed brain regions. Connectivity analyses demonstrated elevated long-range coupling in high-frequency bands concurrent with diminished low-frequency synchronization. Microstate analyses revealed alterations in spatial configuration and transition probabilities. Entropy quantification indicated elevated complexity, particularly in the frontal and auditory cortices. Conclusions: EEG-derived neurophysiological markers demonstrate associations with tinnitus in group analyses and show potential for elucidating pathophysiological mechanisms. However, significant limitations, including low spatial resolution, small sample sizes, methodological heterogeneity, and lack of validation for individual-level diagnosis or treatment prediction, highlight the need for cautious interpretation. Standardized analytical protocols, larger validation studies, multimodal neuroimaging integration, and demonstration of clinical utility in prospective trials are required before EEG markers can be established as biomarkers for tinnitus diagnosis and management. Full article

Background/Objectives: Subcortical local field potentials (LFPs) provide a valuable in vivo window into the neurophysiology of the dystonia network. These signals can be recorded through Deep Brain Stimulation (DBS) devices and combined with whole-head techniques such as magnetoencephalography (MEG) to study cortical–subcortical interactions. However, simultaneous LFP-MEG acquisition poses challenges, including interference from the DBS device and synchronization issues. We present preliminary data on the feasibility and signal quality of concurrent LFP and MEG recordings in dystonia patients. Methods: We assessed simultaneous MEG-LFP recordings in 11 patients with inherited or idiopathic dystonia who underwent bilateral DBS lead implantation in the Globus Pallidus Internus (GPi). Two synchronization strategies were tested: (1) the Tapping method, using an accelerometer placed on the DBS device, and (2) the Stimulation method, which generated detectable artifacts during sham stimulation. Results: Both methods successfully aligned MEG and LFP signals with a mean temporal delay of 91 ± 22 ms for the Tapping method and 288 ± 166 ms for the Stimulation method. Post-implantation signal-to-noise ratio analysis revealed slight degradation but no significant impact on MEG quality (gradiometers: −0.12 ± 1.85 dB; magnetometers: −0.47 ± 2.03 dB). Conclusions: Simultaneous MEG-LFP recordings in dystonic patients are feasible, yielding high-quality signals, and reliable synchronization. Temporal alignment improved with practice, suggesting a short learning curve. This method opens new opportunities to study cortical-subcortical dynamics and strengthens the potential of combining MEG-LFP approaches for investigating dystonia. Full article

The electrical stimulation of the primary occipital cortex can evoke luminous perceptions known as phosphenes, forming the basis for cortical visual prostheses for blind individuals. In this study, cortical dynamics during phosphene perception were investigated in a blind subject implanted with a 10 × 10 Utah microelectrode array in the visual cortex. EEG analyses revealed significant event-related synchronization/desynchronization (ERS/ERD) differences in the 4–7.5 Hz range, primarily in frontal regions, 250–750 ms post-stimulus. Connectivity analysis using the directed transfer function (DTF) showed directional connections from temporal to frontal areas during perception. These findings provide preliminary insights into the cortical dynamics associated with phosphene perception and highlight the potential of EEG for characterizing neural activity in such contexts. Full article

Drug-resistant epilepsy remains a therapeutic challenge, requiring new molecular targets beyond conventional antiepileptic drugs. Small-conductance calcium-activated potassium (SK) channels and Na/K-ATPase (NKA) contribute to afterhyperpolarization via distinct mechanisms, offering complementary ways to suppress hyperexcitability. We examined SK activation and NKA modulation in synchronized epileptiform activity in a primary culture of cortical neurons obtained from rat embryos. Epileptiform discharges were induced by magnesium-free solution and assessed by patch-clamp and calcium imaging. The SK2/3 activator CyPPA (10 µM) reduced epileptiform current (EC) amplitude and integral and decreased synchronized calcium transient (CT) frequency but gradually elevated basal calcium. In contrast, ouabain (1 nM), a selective modulator of high-affinity NKA isoforms, attenuated EC amplitude, strongly suppressed CTs, and showed persistent effects after washout, accompanied by asynchronous glial calcium activity. Co-application of CyPPA with ouabain abolished CyPPA-induced calcium elevation while maintaining suppression of neuronal synchrony. The broader SK/IK activator NS309 (10 µM) reduced CT frequency and basal calcium without affecting glia. Thus, SK activation and NKA signaling suppress epileptiform synchronization through distinct yet convergent pathways: SK channels via afterhyperpolarization and NKA via afterhyperpolarization and calcium-dependent signaling. Their combination enhances efficacy and prevents adverse calcium buildup, supporting SK–NKA co-targeting as a strategy against drug-resistant epilepsy. Full article

The mechanisms of ictal discharge initiation remain incompletely understood, particularly the paradoxical role of inhibitory fast-spiking interneurons in seizure generation. Using simultaneous whole-cell recordings of interneurons and pyramidal neurons combined with extracellular [K⁺]_o monitoring in mouse entorhinal cortex-hippocampal slices (4-aminopyridine model of epileptiform activity), we identified a critical transition sequence: interneurons displayed high-frequency firing during the preictal phase before entering depolarization block (DB). DB onset coincided with the peak of rate of extracellular [K⁺] accumulation. Pyramidal cells remained largely silent during interneuronal hyperactivity but started firing within 1.1 ± 0.3 s after DB onset, marking the transition to ictal discharges. This consistent sequence (interneuron DB → [K⁺]_o rate peak → pyramidal cell firing) was observed in 100% of entorhinal cortex recordings. Importantly, while neurons across all entorhinal cortical layers synchronously fired during the first ictal discharge, hippocampal CA1 neurons showed fundamentally different activity: they generated high-frequency interictal bursts but did not participate in ictal events, indicating region-specific seizure initiation mechanisms. Our results demonstrate that interneuron depolarization block acts as a precise temporal switch for ictogenesis and suggest that the combined effect of disinhibition and K⁺-mediated depolarization triggers synchronous pyramidal neuron recruitment. These findings provide a mechanistic framework for seizure initiation in focal epilepsy, highlighting fast-spiking interneurons dysfunction as a potential therapeutic target. Full article