Search Results (10,559)

Background: Multiple sclerosis (MS) lacks a single invariant phenotypic core. Patients accumulate heterogeneous combinations of sensory, motor, cognitive, and autonomic impairments over time, reflecting lesions that are disseminated in time and space. Standard scales such as the Expanded Disability Status Scale (EDSS) distribute disability across functional systems, but do not explicitly represent MS phenotype as a mixture of latent symptom modules. Methods: We analyzed 4617 de-identified neurology progress notes from 577 patients with MS at a single academic medical center. A large language model (GPT-5.2) categorized each note with respect to 17 non-mutually-exclusive neurological phenotype features, and note-level features were aggregated to patient-level binary vectors. Non-negative matrix factorization (NMF) was applied to generate three-, four-, and five-module solutions. For each rank, we computed approximate variance captured, relative reconstruction error, and module-level feature loadings. In the preferred four-module solution, we derived patient-level module percentages, identified highly dominant (≥55%) and archetypal (≥70%) module profiles, and quantified admixture using Shannon entropy and the effective number of modules. Results: Three-, four-, and five-module NMF solutions showed similar approximate variance captured (52.7–54.3%) and reconstruction error (0.47–0.53), but the four-module solution provided the clearest clinical interpretation. The four latent modules were sensory-visual-pain, ataxic-spastic-falls, cognitive-psychologic-fatigue, and autonomic-bladder-bowel, aligning closely with established functional systems in MS. Most patients exhibited admixed phenotypes, with module entropies ranging from 0 (single-module dominance) to 1.386 (equal mixture) and effective modules spanning approximately 1 to 4. Using pre-specified thresholds, 154 patients (26.6%) were highly dominant in a single module and 72 (12.5%) were archetypal; these purer phenotypes were most often in the sensory-visual-pain module. Conclusions: MS phenotypic diversity in routine clinical practice can be parsimoniously represented as mixtures of four latent symptom modules rather than as positions along a single severity axis. Most patients show substantial admixture of sensory, motor, cognitive, and autonomic involvement, but a minority exhibit relatively pure or strongly dominant module patterns. This modular representation provides an interpretable framework for quantifying MS phenotype and for generating testable hypotheses about MS subtypes whose biological relevance remains to be established. Full article

Mastication is a fundamental rhythmic motor behavior controlled by a brainstem central pattern generator (CPG) located within the pontine and medullary reticular formations. Coordinated activation of jaw-opening and jaw-closing muscles is generated by this network and continuously refined through sensory feedback from periodontal mechanoreceptors and muscle spindles, together with descending inputs from the cortical masticatory area (CMA), basal ganglia, and cerebellum. Thus, mastication is regulated by distributed neural circuits rather than a single central locus. At the cellular level, the rhythmic activity of the masticatory CPG depends on the coordinated action of voltage-gated and ligand-gated ion channels. Recent electrophysiological and computational studies have identified candidate conductances that are proposed to underlie rhythm generation. Persistent sodium currents are proposed to facilitate burst initiation, whereas T-type calcium channels are thought to promote burst activation through post-inhibitory rebound. HCN channels may contribute to rhythmic timing, while calcium-activated potassium channels are thought to participate in burst termination. This review summarizes the hierarchical neural control of mastication and the biophysical mechanisms by which ion channels shape CPG rhythmogenesis. It also discusses the impact of channelopathies and neurodegenerative disorders on masticatory function, highlighting potential ion-channel-targeted therapeutic approaches for temporomandibular disorders, bruxism, and impaired mastication. Full article

Stereotactic radiosurgery (SRS) delivers high doses of focused ionizing radiation (IR) to a defined target while sparing surrounding tissues. The delivery of focused doses of IR has proven to be an effective modality for the treatment of brain tumors, cerebrovascular lesions, and primary neuropathic pain conditions. More recently, the emerging concept of “radiomodulation” to rewire neural circuitry through the delivery of focused IR to specific neural relay centers has emerged as an alternative way to treat neurological conditions, such as essential tremor, trigeminal neuralgia, and psychiatric illnesses. In this article, we performed a scoping review of the existing data supporting the ability of focused doses of ionizing radiation to achieve modulation of neural circuits for the treatment of neurological conditions. We review the current understanding of the neurophysiological mechanisms of radiomodulation, the gaps in knowledge limiting its widespread use for in-human applications and stress the unmet need for ongoing research to rigorously prove that radiomodulation may be the “final frontier” as a non-invasive, non-pharmacological, versatile, and tunable modality for the treatment of a multitude of neurological conditions. Full article

Background/Objectives: Chemotherapy-induced cognitive impairment, colloquially known as chemobrain, affects a substantial proportion of cancer patients. Preclinical rodent models help clarify underlying drug-specific neurotoxic effects, as well as histological, biochemical, molecular, and behavioral mechanisms. Methods: We conducted a narrative review of animal studies examining cognitive dysfunction following treatment with commonly used chemotherapeutic agents, including doxorubicin, cisplatin, cyclophosphamide, methotrexate, 5-fluorouracil, paclitaxel, and docetaxel. The review focused on behavioral and cognitive outcomes, and experimental parameters such as rodent models and dosing regimens. Results: Across studies, chemotherapeutic exposure has had a consistent negative effect on short-term and working memory, learning and other cognitive domains, with impairments being often mild and detectable even at doses not causing apparent systemic toxicity. Histological analyses revealed reduced neurogenesis, dendritic and myelin alterations, and glial activation, mainly in the hippocampus and prefrontal cortex. Biochemical and molecular changes included oxidative stress, pro-apoptotic signaling, inflammatory cytokine dysregulation, decreased neurotrophic support, and altered neurotransmitter dynamics. Age and sex influenced susceptibility, with juvenile or aged animals and females—particularly older females modeling breast cancer patients—showing greater deficits. Cumulative or repeated dosing exacerbated neurotoxicity, while single administrations produced milder, sometimes transient, impairments. Conclusions: Preclinical models provide compelling evidence that chemotherapeutic agents impair cognitive function via convergent mechanisms involving inflammation, oxidative stress, and synaptic dysregulation. These findings highlight the importance of considering age, sex, and treatment schedule in designing neuroprotective strategies and underscore the translational relevance of rodent models in understanding chemobrain. Full article

Human interaction with the environment depends on the integration of sensory input, cognitive processing, and motor output within dynamic sensorimotor loops. These processes are supported by distributed neural circuits and shaped by learning, memory, and neuroplasticity across the lifespan. This review synthesizes current understanding of the mechanisms underlying sensorimotor integration and highlights how experience-dependent plasticity supports functional recovery and performance optimization in both health and disease. Disruptions such as traumatic brain injury, neurodegenerative disease, and aging may frequently result in combined cognitive and motor impairments. Here, we review non-invasive interventions that leverage neuroplasticity, including physical activity, motor training, and cognitive training, with increasing emphasis on integrated cognitive–motor approaches. Emerging technologies such as virtual reality provide ecologically valid, immersive environments that simultaneously engage perception, cognition, and action, with the potential to enhance training outcomes. However, variability in effectiveness and limited evidence for far transfer remain key challenges. To address these limitations, we highlight the integration of immersive training with objective biological measures. In particular, proton nuclear magnetic resonance (¹H NMR)-based metabolomics offers a promising, non-invasive approach to identify biomarkers of neuroplastic adaptation. The integration of robust biomarker tools may facilitate the development and assessment of effective precision cognitive–motor interventions to optimize rehabilitation approaches and help build resilience in vulnerable individuals. Full article

Background: Anxiety disorders are prevalent and debilitating. Given challenges in maintaining mindfulness at one-month remission, integrative approaches targeting anxiety and psychological resources (especially mindfulness) have gained interest. This study aimed to assess the effectiveness of adding biofeedback to the treatment of anxiety disorders. Methods: Inpatients with anxiety disorder (ICD10 F40/F41) were randomized to three groups: (1) biofeedback for enhancing mindfulness (BFB, n = 76); (2) medication therapy (MT, escitalopram 10 mg/day, n = 46); and (3) combined therapy (BFB + MT, CT, n = 66). Per-protocol analysis: 180 completers; ITT: all 188 randomized patients. The primary outcomes were changes in the Hamilton Anxiety Rating Scale (HAM-A) total score and the Five Facet Mindfulness Questionnaire total score, assessed at baseline, after 10 days of treatment, and at one-month follow-up. The HAM-A assessor was blinded to group allocation. Results: In the per-protocol analysis, the BFB and CT groups showed a significantly greater reduction in the HAM-A score than the MT group did. For example, post-treatment, the mean difference between BFB and MT groups was –6.30 points (95% CI: –9.12 to –3.48, p = 0.00046). The BFB and CT groups did not differ significantly. For mindfulness, the BFB and CT groups showed an increase, whereas the MT group showed a decrease (BFB vs. MT: mean difference 30.28 points, 95% CI: 23.54–37.02, p < 0.000001). Intention-to-treat (ITT) analysis (n = 188) confirmed the robustness of these findings. Conclusions: BFB appears to be a promising approach for reducing anxiety and fostering mindfulness skills; these findings suggest it may be worth exploring further as a potential component of comprehensive therapy for anxiety disorders. Clinical Trial Registration: ClinicalTrials.gov NCT07628153 (retrospectively registered). The trial was retrospectively registered, and the primary analysis was conducted on a per-protocol population. Full article

Background/Objectives: Surgical management of cerebral cavernous malformations (CCMs) within eloquent brain regions presents a high risk of neurological deficits. This study describes the clinical outcomes and technical feasibility of microsurgical resection for symptomatic eloquent CCMs, detailing the integration of advanced intraoperative adjuncts aimed at optimization of seizure control and functional preservation. Methods: We conducted a retrospective multicenter analysis of nine adult patients who underwent microsurgical resection for symptomatic eloquent CCMs between January 2021 and December 2025 across two tertiary centers in Slovenia. Intraoperative modalities included 100% neuronavigation, 55.6% intraoperative ultrasound, 77.8% intraoperative neuromonitoring (IONM) with motor and somatosensory evoked potentials, and 22.2% awake craniotomies. Results: Seizures were the primary clinical presentation in 77.8% of patients (66.7% medically refractory), and the overall hemorrhage rate was 66.7%. Gross total resection of the CCM was achieved in 100% of cases, with complete hemosiderin rim removal in 80% of applicable lesions. Early postoperative complications occurred in four patients, but at the maximum 48-month follow-up, 100% of the cohort achieved complete seizure control, and 44.4% successfully discontinued antiepileptic drugs. Long-term focal neurological deficits persisted in only two patients, while 77.8% were able to work following surgery. Conclusions: Microsurgical resection remains a well-established treatment modality for symptomatic CCMs. In this small, descriptive series of patients with lesions in functionally critical regions, high rates of gross total resection and favorable long-term seizure freedom were observed. These findings suggest that a multimodal approach combining anatomical neuronavigation with functional IONM may help minimize permanent morbidity, though larger cohorts are required to establish definitive efficacy. Full article

Objective: Electroencephalogram (EEG) signals provide a noninvasive and objective method for detecting neural dysfunctions associated with depression. To address the limitations of limited sample sizes and inadequate modeling of spatiotemporal features, the study aims to develop an EEG-based depression recognition framework to capture dynamic patterns of neural activity related to depression. Methods: We propose DR-Net, a novel depression recognition framework integrating generative adversarial network (GAN), transition propagation graph convolution network (TPGCN), and transformer architectures. First, GAN-based data augmentation generates synthetic EEG samples that preserve the statistical properties of real data, improving data diversity and model generalization. Second, brain functional connectivity networks are constructed using the phase lag index, and the TPGCN models the dynamic propagation of information across channels, capturing the spatiotemporal evolution of brain network topologies beyond conventional static graph models. Concurrently, the transformer module employs self-attention to strengthen the modeling of long-range temporal dependencies. The framework also emphasizes the frontal lobe brain region, reducing input dimensionality while improving feature discriminability. Results: The proposed method achieved an accuracy of 98.7%, surpassing baseline and state-of-the-art methods, with no significant class bias. Validation on clinical datasets yielded an accuracy of 96.13%, demonstrating strong robustness and generalizability. Conclusions: By effectively modeling the spatiotemporal dynamics of EEG signals, DR-Net provides a reliable and generalizable approach to the objective diagnosis of depression and advances computational neurodiagnostic by integrating dynamic graph propagation, self-attention mechanisms, and data-efficient augmentation. These findings suggest that DR-Net may support future EEG-based clinical assessment of depression. Full article

Understanding consciousness remains one of the most significant challenges in neuroscience, philosophy, and cognitive science. Despite substantial advances in neuroimaging, electrophysiology, and computational modeling, a comprehensive account of the neural basis of conscious experience has yet to emerge. This review examines several leading contemporary theories of consciousness, including the Global Neuronal Workspace Theory (GNWT), Integrated Information Theory (IIT), Recurrent Processing Theory (RPT), Dendritic Integration Theory (DIT), Predictive Processing (PP), and the Memory Theory of Consciousness (MToC). The philosophical foundations, core theoretical claims, and empirical evidence supporting each framework are critically evaluated. Particular attention is given to how these theories address phenomenal consciousness—the subjective quality of experience—and access consciousness, i.e., the availability of information for cognitive control, report, and behavior. By comparing convergent and divergent predictions across theoretical perspectives, this review highlights key areas of agreement, ongoing debates, and unresolved questions in the field. The analysis suggests that consciousness is likely to involve multiple interacting neural mechanisms operating across different spatial and temporal scales, underscoring the need for continued interdisciplinary research to advance a more comprehensive understanding of conscious experience. Full article

Background: Schizophrenia with comorbid substance use disorder (SUD) is associated with greater clinical severity, poorer adherence, and worse functional outcomes. Third-generation antipsychotics, through partial dopamine agonism, may represent a useful strategy in this complex population. This study compared the long-term efficacy of brexpiprazole and aripiprazole in patients with schizophrenia, with or without comorbid SUD. Methods: Patients (N = 243) with DSM-5/DSM-5-TR schizophrenia orally received 4 mg/day brexpiprazole or 30 mg/day aripiprazole for 12 months in a real-world clinical setting. Psychopathology was assessed at baseline and after 1, 3, 6, and 12 months using the Brief Psychiatric Rating Scale (BPRS) and the Positive And Negative Syndrome Scale (PANSS). Analyses were performed on 217 completers, excluding 26 drop-outs. Outcomes were compared according to drug and presence/absence of comorbid SUD. Results: Both brexpiprazole and aripiprazole were associated with psychotic symptom and global psychopathology improvement over 12 months (p < 0.01). In patients without SUD, the two treatments showed comparable efficacy. Among patients with comorbid SUD, brexpiprazole showed greater improvement in BPRS and PANSS outcomes than aripiprazole (p < 0.01). Treatment response to aripiprazole, but not to brexpiprazole, was diminished by substance use. Brexpiprazole was associated with better tolerability and lower rates of subjective agitation-related discontinuation. Conclusions: Both dopamine partial agonists were effective in treating schizophrenia; however, brexpiprazole was superior in patients with comorbid SUD. Findings suggest that brexpiprazole may represent a promising therapeutic option in dual-disorder patients. Full article

Background/Objectives: Disability in relapsing–remitting multiple sclerosis (RRMS) reflects multiple pathological processes that may not be fully captured by individual MRI markers. Because an EDSS score ≥ 3 represents a clinically meaningful threshold of moderate-to-higher disability, this study evaluated the cross-sectional ability of brain volumetric measures and IVIM-DWI parameters to identify patients with RRMS who had EDSS ≥ 3. Methods: This retrospective cross-sectional study included 189 patients with RRMS who had complete EDSS, lesion count, IVIM-DWI, and brain volumetric MRI data. Patients were stratified into EDSS < 3 and EDSS ≥ 3 groups. Single-marker ROC analyses were performed for lesion count, IVIM-DWI parameters, absolute volumetric measures, and fractional volumetric measures. Combined ROC models were constructed to assess the discriminatory performance of integrating lesion burden, volumetric MRI, and IVIM-DWI metrics. Internal model stability was evaluated using 5-fold cross-validation. Results: Patients with EDSS ≥ 3 had higher lesion count, higher ADC and D values, lower gray matter, white matter, and brain parenchymal volumes, higher CSF volume, higher CSF fraction, and lower brain parenchymal fraction (BPF). In single-marker ROC analysis, BPF and CSF fraction showed the strongest discriminatory performance (AUC = 0.705), followed by lesion count (AUC = 0.696), whereas absolute BV showed minimal discriminatory value (AUC = 0.503). The core lesion count + BPF model achieved an AUC of 0.757 and a cross-validated AUC of 0.737. Adding perfusion fraction (f) produced the numerically highest cross-validated performance, with an AUC of 0.769 and a cross-validated AUC of 0.746, although the incremental improvement over lesion count + BPF was modest and not statistically significant. Conclusions: Fractional volumetric measures showed stronger discriminatory performance than absolute BV for EDSS ≥ 3 stratification in RRMS. The lesion count + BPF + f model achieved the highest cross-validated performance among the evaluated MRI models; however, overall discrimination was moderate, and the incremental improvement associated with f was not statistically significant. These exploratory findings require evaluation in larger longitudinal cohorts with external validation. Full article

Background: A systematic review and meta-analysis of polysomnographic sleep parameters in bipolar disorder was conducted using articles identified through searches of major databases from inception to 5 May 2026. Methods: One hundred and seven studies were identified in the systematic review. Forty-three case-control studies with 670 bipolar patients, 520 healthy controls and 280 patients with unipolar depression were eligible for the meta-analyses. Total sleep time, sleep onset latency, sleep efficiency, wake after sleep onset, REM time and percentage, REM latency, REM density, stage 1, 2, time and percentage, slow wave sleep (DELTA) time and percentage of drug-free patients with bipolar disorder were compared with case-control data of healthy controls and drug-free patients with unipolar depression. The primary outcome was the standard mean difference. Data were fitted with a random effects model. Publication bias assessment was checked by Egger’s regression and funnel plot asymmetry Results: Total sleep time and sleep efficiency were reduced in both manic and depressive drug-free bipolar patients compared with healthy controls. Delta sleep time and percentage were reduced only in the depressive patients, whereas the manic patients showed decreased stage 2 sleep time, reduced REM sleep time, shortened REM latency and increased REM density. Drug-free patients with unipolar depression showed reduced total sleep time and increased REM density compared with drug-free patients with bipolar depression. Drug-treated bipolar patients showed no differences compared with healthy controls, except for reduced % REM, increased REM latency and increased REM density. Conclusions: The results confirm the presence of sleep alterations in bipolar disorder. Although sleep duration is reduced in both manic and depressive patients, reduced delta sleep in depressive patients and increased activity/pressure of REM in manic patients appear to characterize the two phases of the illness. Altered monoaminergic activity during the depressive phase and increased cholinergic activity during the manic phase might possibly be linked to the sleep alterations also contributing to the mood changes and switch mechanisms. Full article

Background/Objectives: The rates of obesity and binge-eating disorder (BED) have increased markedly over the last few decades. The onset of these conditions has been associated in part with the disruption of neural pathways that regulate food reward. Existing literature has implicated the endogenous opioid system as an important mediator of pleasure and reinforcing behaviors associated with food intake. While the relationship between opioids and food intake has been studied extensively, how dysregulated opioid signaling contributes to compulsive eating still remains unclear. Therefore, the aim of this review is to analyze the role of opioid peptides and receptors, and their interactions with dopamine in hedonic feeding. Methods: We conducted a narrative review of preclinical and clinical trials, incorporating studies that were relevant to opioid-mediated feeding and food reward. Results: β-endorphins appear to modulate the hedonic value of food, but their effects appear to be context-dependent. Enkephalins may influence motivational drive toward food, while nociceptin signaling has been linked to the preferential consumption of palatable foods under binge-like conditions. Consistent with these findings, NOP antagonism has been reported to reduce binge-like intake of a high-fat diet (HFD) without affecting homeostatic eating patterns. Lastly, chronic mu-opioid receptor (MOP) activation by palatable foods may induce neuroadaptive changes, including receptor desensitization, dopamine D2 receptor downregulation, and reward hypofunctionality, which overlap with mechanisms associated with substance use disorders. Conclusions: Altered MOP signaling may disrupt the hedonic and behavioral mechanisms that regulate feeding behavior. Pharmacological therapies targeting opioid and opioid-dopamine interactions may show promise for treating obesity and BED. However, additional research is still needed to clarify peptide-specific mechanisms, sex differences, and long-term neurobiological consequences associated with hedonic and compulsive eating. Full article

Background/Objectives: Cisplatin (CP) is a platinum-based chemotherapeutic agent associated with neurotoxicity and cognitive impairment. Due to its high metabolic activity and sensitivity to oxidative stress, the hippocampus represents a particularly vulnerable brain structure. The present study evaluated dose-dependent hippocampal alterations following single-dose cisplatin administration in rats using biochemical, histopathological, and morphometric analyses. Methods: Male Wistar rats were divided into four groups (n = 8): control and cisplatin-treated groups receiving single intraperitoneal doses of 8, 9, or 10 mg/kg. Five days after treatment, hippocampal tissue was analyzed for oxidative stress and inflammatory, apoptotic, and morphological changes. Results: Cisplatin administration significantly increased TBARS and AOPP levels, indicating enhanced lipid and protein oxidation. Elevated hippocampal TNF-α, IL-6, and IL-1β levels demonstrated activation of inflammatory pathways, particularly in animals receiving 9 and 10 mg/kg cisplatin. Higher doses additionally increased Bax/Bcl-2 ratio, caspase-3 content, and DNase I/II activity, consistent with enhanced apoptotic signaling. Histopathological examination revealed neuronal degeneration, pyknotic nuclei, pericellular halo formation, and progressive disruption of hippocampal cytoarchitecture, while morphometric analysis demonstrated significant alterations in neuronal nuclear surface area, predominantly in the 10 mg/kg group. Conclusions: These findings demonstrate that acute cisplatin exposure induces oxidative, inflammatory, apoptotic, and structural progressive hippocampal injury with a threshold-like increase in several endpoints at higher cisplatin doses, with 10 mg/kg producing the most pronounced neurotoxic effects. Full article

Background: Maintaining postural stability requires the integration of multisensory information, including visual, vestibular, and somatosensory inputs. This study aimed to investigate the effects of narrowband noise across different frequency bands on static postural balance and cortical activation in healthy adults. Methods: Twenty healthy adults participated in a repeated-measures experiment in which they maintained a tandem stance with eyes closed under four conditions: no sound, low-frequency narrowband noise (500 Hz), mid-frequency narrowband noise (2000 Hz), and high-frequency narrowband noise (5000 Hz). Static balance was assessed using center of pressure parameters, including sway length, ellipse surface, delta X, and delta Y, recorded via a pressure measurement platform. Cortical activation in the premotor cortex (PMC), frontal eye fields (FEF), superior temporal gyrus (STG), and middle temporal gyrus (MTG) was measured simultaneously using functional near-infrared spectroscopy. Results: Mid-frequency narrowband noise significantly improved postural stability, as evidenced by reductions in sway length, ellipse surface, and delta Y compared to the high-frequency and no-sound conditions (p < 0.05). In contrast, high-frequency narrowband noise consistently produced the greatest postural instability, with significantly larger ellipse surface and delta Y values (p < 0.05). Regarding cortical activation, high-frequency stimulation induced significantly greater bilateral activation in the PMC compared to low-frequency stimulation, while all auditory conditions elicited widespread activation across PMC, STG, and MTG. Conclusions: These findings suggest that the frequency characteristics of auditory stimulation exert differential neurophysiological effects on balance control. Mid-frequency narrowband noise may enhance static balance by facilitating sensorimotor integration, whereas high-frequency narrowband noise may induce PMC hyperactivation, potentially contributing to postural instability. Full article