NeuroSci doi: 10.3390/neurosci7040091

Authors: Sarah-Marie Gallert Julia Taube Anna-Laura Potthoff Thomas Zeyen Valeri Borger Motaz Hamed Rainer Surges Hartmut Vatter Christoph Helmstaedter Matthias Schneider

Background: Neurocognitive testing in neuro-oncological patients often relies on time-intensive batteries with limited feasibility in this patient cohort. We evaluated the feasibility of the Bonn Leistungs Tracking Test (BLTT), a time-efficient screening tool assessing episodic memory, semantic memory, and executive functions in patients with high-grade temporal lobe gliomas. Methods: Twenty patients undergoing resection of temporal high-grade glioma between 2019 and 2022 underwent preoperative cognitive assessment using either the BLTT or a comprehensive neuropsychological battery routinely applied in temporal lobe epilepsy surgery. Results: Twelve patients (60%) underwent the BLTT, and eight (40%) underwent the standard neuropsychological test battery. The BLTT was feasible in all 12 individuals (0% drop-out), whereas only four of eight patients (50% drop-out) were able to complete the standard battery. The mean BLTT total score was 69.3 (SD 4.5), indicating impaired neurocognitive performance relative to normative data. The BLTT provided evaluable domain-specific measures across episodic memory, semantic memory, and executive functioning despite the high discontinuation rate observed with standard testing. Conclusions: The BLTT showed high feasibility for preoperative neurocognitive testing in patients with temporal high-grade gliomas. Its brief administration time and consistent applicability across relevant cognitive domains support its utility for routine neurocognitive assessment.

NeuroSci doi: 10.3390/neurosci7040090

Authors: April Mae Flynn Ahmed Hankir Mahera Abdulrahman Nouf Al-Rumaihi Frederick Robert Carrick

Menopause represents a major neuroendocrine transition characterized by substantial hormonal, metabolic, vascular, and inflammatory changes that may increase vulnerability to cognitive decline and neurodegenerative disease. Declining estrogen levels during the menopausal transition influence multiple neural processes, including synaptic plasticity, cerebral glucose metabolism, mitochondrial function, neuroinflammatory signaling, and cerebrovascular regulation. Women account for nearly two-thirds of individuals diagnosed with Alzheimer’s disease, and mounting evidence suggests that menopause may represent a period of heightened neurological vulnerability. Physical exercise has emerged as one of the most promising non-pharmacological strategies for preserving cognitive health and reducing neurodegeneration risk in aging women. Current evidence demonstrates that exercise interventions after menopause are associated with improvements in executive function, memory performance, attention, and global cognition. These benefits appear to result from converging biological mechanisms that include enhanced neurotrophic signaling, increased brain-derived neurotrophic factor (BDNF) expression, improved cerebrovascular function, reduced systemic inflammation, improved insulin sensitivity, enhanced metabolic regulation, and preservation of structural brain integrity. Neuroimaging studies further demonstrate exercise-associated increases in hippocampal volume, cortical thickness, functional connectivity, and cerebral blood flow. Different exercise modalities appear to produce distinct but complementary neurological benefits. Aerobic exercise is strongly associated with improved cerebrovascular function and hippocampal integrity, resistance training demonstrates favorable effects on executive function and white matter preservation, and multimodal interventions combining aerobic, resistance, balance, and cognitively engaging activities appear to produce the broadest cognitive benefits. Emerging evidence further suggests that the timing of exercise initiation relative to menopause may influence outcomes, with earlier interventions potentially conferring greater neuroprotection. This review synthesizes current evidence regarding the effects of exercise on cognitive function in postmenopausal women, with emphasis on biological mechanisms, neuroimaging findings, exercise modality, timing considerations, and implications for neurodegeneration prevention. Understanding these relationships provides a scientific rationale for positioning exercise as a foundational strategy for preserving cognitive health and reducing neurodegenerative disease burden in postmenopausal women.

NeuroSci doi: 10.3390/neurosci7040089

Authors: Andrew T. McKenzie Aschwin de Wolf Alexander Grotemeyer Emil Kendziorra Alexander German

Perfusion impairment is one of the major barriers to using machine perfusion to prepare brain tissue for research and clinical applications. As ischemia progresses, multiple mechanisms, including intravascular obstructions, perivascular cellular edema, mural cell contraction, and vessel wall breakdown, progressively limit the uniform delivery of preservative solutions. This problem is particularly important for connectomics, wherein successful preservation requires both widespread distribution of preservative chemicals and the maintenance of the cellular ultrastructure needed for circuit reconstruction. We conducted a narrative review of interventions used to ameliorate perfusion impairment across multiple fields, including organ transplantation, resuscitation medicine, forensic pathology, embalming, and neuroscience. We evaluated the evidence for these approaches in their original contexts and considered their potential application for brain banking aimed at preserving tissue for connectome reconstruction. We classify interventions into several categories, including anticoagulants, fibrinolytics, vasodilators, washout solutions, surfactants, osmotic agents, colloids, hypothermia, and perfusion pressure optimization. Many of these interventions have the potential to improve perfusion, but each also carries tradeoffs that may adversely affect tissue preservation. As connectomics advances toward profiling larger volumes of human brain tissue, overcoming perfusion impairment is likely to become an increasingly important challenge. This review provides a mechanistic framework for evaluating existing interventions and guiding the development of future perfusion protocols.

NeuroSci doi: 10.3390/neurosci7040088

Authors: David Osvaldo Salinas-Sánchez Manasés González-Cortazar Franceli Itzel Batalla-Martinez Alejandro Zamilpa Maura Téllez-Téllez María Guadalupe Valladares-Cisneros César Sotelo-Leyva Rodolfo Figueroa-Brito Ma Dolores Pérez-García Dante Avilés-Montes

Malpighia mexicana has been traditionally used in Mexican ethnomedicine for the treatment of central nervous systems disorders. Previous studies have demonstrated neuropharmacological activity of crude extracts, but the contribution of enriched phytochemical fractions remains unclear. A phenolic-enriched fraction (G4) obtained from the aerial parts of M. mexicana was evaluated for antidepressant-like and anticonvulsant activities in mice. Antidepressant-like effects were assessed using the forced swimming test (FST) and tail suspension test (TST), while locomotor activity was evaluated in the open field test. Anticonvulsant activity was determined using the pentylentetrazole (PTZ)-induced seizure model. The phytochemical profile of G4 was characterized by HPLC-DAD analysis. G4 (50 and 200 mg/kg, p.o.) significantly reduced immobility time in both FST and TST compared to the vehicle group (p < 0.05) without affecting locomotor activity in the OFT, suggesting a specific antidepressant-like effect. In the PTZ model, G4 significantly increased latency to clonic and tonic seizures and reduced seizure severity. HPLC-DAD analysis revealed the presence of phenolic compounds, with kaempferol and p-coumaric acid as major constituents. The phenolic-enriched G4 fraction from M. mexicana exhibits antidepressant-like and anticonvulsant effects in murine models, supporting its traditional use. These findings suggest that phenolic constituents, particularly kaempferol and p-coumaric acid, may contribute to the observed neuropharmacological activity. However, since only the G4 fraction was pharmacologically evaluated and not the isolated compounds, the specific role of each constituent remains to be established. Further studies are required to elucidate the underlying mechanisms of action and the contribution of individual compounds and potential synergistic interactions.

NeuroSci doi: 10.3390/neurosci7040087

Authors: Ugo Nocentini

Multiple sclerosis (MS) is the second-leading cause of disability in young adults [...]

NeuroSci doi: 10.3390/neurosci7040086

Authors: Simonida Delic Svetlana Miletic Drakulic Snezana Lazarevic Milos Stepovic Nikoleta Janicijevic Maja Vulovic Aleksandra Mitrovic Zivanovic Danica Igrutinovic Melanija Tepavcevic Milica Dimitrijevic Katarina Manojlovic Bojana Markovic Nebojsa Igrutinovic Vladimir Markovic Ana Azanjac Arsic

Background: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system. Our study aimed to examine the relationship between serum iron levels and the following clinical parameters: depression, anxiety, fatigue, neuropathic pain, and disease activity on magnetic resonance imaging in patients with relapsing-remitting multiple sclerosis (RRMS). Material and methods: This study was designed as a clinical observational, cross-sectional study. This study was conducted at the Clinic of Neurology of the University Clinical Center Kragujevac, from 2022 to 2024, according to the ethical code of the Declaration of Helsinki. Demographic and clinical data on patients were obtained from the medical history. All MS patients were diagnosed according to the McDonald criteria (2017). This study included 65 patients in the experimental group and 11 healthy individuals in the control group, with an average age of 39.68 years. Serum iron levels were biochemically analyzed from venous blood. The following standardized tests were used to collect data on depression, anxiety, fatigue, and neuropathic pain: Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), Modified Fatigue Impact Scale (MFIS), PainDETECT Questionnaire (PD-Q), and Visual Analogue Scale (VAS). Results: Serum iron level significantly correlates with disease activity on magnetic resonance imaging in patients with multiple sclerosis. Serum iron showed a moderate positive correlation with hemoglobin, hematocrit, total and direct bilirubin, and a weak positive correlation with uric acid, while a moderate negative correlation was observed with erythrocyte sedimentation rate. No statistically significant difference was found between serum iron levels and depression, anxiety, fatigue, and severity of neuropathic pain. The ROC curves show the diagnostic potential of the combined parameters in differentiating RRMS from controls, as well as the potential of iron in differentiating active from inactive MS. The presence of disease, hemoglobin and total bilirubin were recorded as significant independent predictors. Conclusion: This study is a descriptive attempt to present the potential role of iron in the radiological activity of the disease. High serum iron level may be associated with radiological disease activity in patients with multiple sclerosis.

NeuroSci doi: 10.3390/neurosci7040085

Authors: Giulia D’Alvano Salvatore Del Giudice Francesca D’Anna Vincenzo Todisco Alessandro Tessitore Alvino Bisecco

Background: Current treatments for myasthenia gravis (MG), while improving outcomes, are often associated with adverse effects, and a proportion of patients remain refractory to standard therapies. Eculizumab, a humanized monoclonal antibody targeting complement protein C5, is approved for refractory anti-acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG). Aim of the present study is to explore the rapidity of onset of eculizumab efficacy in a single-center cohort of MG patients. Methods: This retrospective, observational, single-center study evaluated the real-world effectiveness and rapidity of response to eculizumab in patients with AChR-Ab+ gMG. Patients received eculizumab according to the approved regimen and were assessed at baseline (T0), 5 weeks (T1), and 3 months (T2) using the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, Quantitative Myasthenia Gravis (QMG) score, and Myasthenia Gravis Foundation of America (MGFA) classification. Results: Eight patients were eligible for the study with a mean age of 73.1 years. A rapid clinical improvement was observed after treatment initiation. Mean MG-ADL scores decreased from 8.38 at T0 to 2.13 at T1 (p < 0.001; Cohen’s d = 2.075), while QMG scores declined from 13.75 to 5.63 (p = 0.001; Cohen’s d = 1.824). Improvements were maintained at T2. Mean percentage reductions from T0 to T1 were 73.5% for MG-ADL and 60.6% for QMG. Eculizumab was well tolerated. Conclusions: These real-world findings confirm a rapid and clinically meaningful response to eculizumab in elderly patients with refractory gMG. These findings highlight its potential role in achieving early symptom control and reducing disease burden in this clinically vulnerable population.

NeuroSci doi: 10.3390/neurosci7040084

Authors: Denis Shevchuk Yulia Kuzmenko Mariya Zakharova Vadim Karpov Elizaveta Starodubova Anastasia Latanova

Background: Cell and mouse models studies demonstrate NLRP3 inflammasome involvement in amyotrophic lateral sclerosis (ALS) neuroinflammation. Peripheral blood mononuclear cells (PBMCs) are a promising, yet understudied, source of in vivo inflammasome activation biomarkers. Our study reviewed the literature on PBMC-based inflammasome studies of ALS and other neurodegenerative diseases and tested different conditions for PBMC handling to evaluate inflammasome and inflammation-related protein expression in these cells. Methods: Expression of NLRP3 inflammasome components and inflammation-related proteins was analyzed by Real-time qPCR and Western blot in non-cultivated/cultivated PBMCs of 23 ALS patients and 20 Healthy controls. IL-1β and IL-18 levels were measured in plasma and cultivated PBMC supernatants by ELISA. Results: Cultivation of PBMCs decreased expression of inflammasome components and inflammation-related cytokines on the mRNA but not protein level. NLRP3 mRNA expression was significantly higher in ALS-cultivated PBMCs. In both ALS and Healthy controls, IL-18 was detected in plasma, and IL-1β in supernatants of cultivated PBMCs. Conclusions: Our findings suggest that PBMC handling conditions, i.e., cell cultivation, may determine particular parameters associated with NLRP3 inflammasome expression and activation pathway, so they should be carefully selected for PBMC-based studies of inflammasome in neurodegenerative and non-neurological disorders and taken into account when interpreting the study results.

NeuroSci doi: 10.3390/neurosci7040083

Authors: Nibras M. Alkhamis Hussain A. Almohammed Tanveer N. Khan Jory H. Alzahrani Lama A. Alsalboud Randah T. Alzahrani Hamad A. Alseni Amara M. Mufti Lujeen H. Alghourab Thekra F. Abuhaimed Manar M. Alshabaan Maha E. Alsubaie Manar A. Jamlalail Saud A. Alnaaim

Background: Atrial fibrillation (AF) is a common but frequently undiagnosed cause of ischemic stroke, particularly among patients with cryptogenic stroke and embolic stroke of undetermined source (ESUS). Implantable cardiac monitors (ICMs) enable prolonged continuous rhythm monitoring and may improve AF detection following ischemic stroke or transient ischemic attack (TIA). This systematic review and meta-analysis aimed to evaluate the diagnostic yield, clinical impact, and safety of prolonged ICM monitoring in patients with ischemic stroke or TIA. Methods: This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines and registered with PROSPERO (CRD42024573913). PubMed, Google Scholar, and the Cochrane Library were systematically searched. Randomized controlled trials and observational studies evaluating the use of ICMs after ischemic stroke or TIA were included. Randomized evidence was synthesized narratively, whereas single-arm random-effects meta-analyses of observational studies were performed to estimate pooled proportions for AF detection, oral anticoagulation initiation, recurrent ischemic stroke or TIA, and device-related adverse events. Results: Twelve completed studies involving 4563 participants met the inclusion criteria, including two randomized controlled trials and ten observational studies. One additional ongoing randomized controlled trial (Find-AF 2) involving a planned enrollment of 5200 participants was identified and is described narratively. Across the observational studies, the pooled AF detection rate during prolonged ICM monitoring was 25.9% (95% CI, 18.9–33.5%), although substantial heterogeneity was observed (I2 = 95%). Oral anticoagulation was initiated in 94.2% (95% CI, 79.4–100.0%) of patients diagnosed with AF. Device-related complications were uncommon, with a pooled incidence of 3.7% (95% CI, 2.0–6.0%; I2 = 0%), while the pooled rate of recurrent ischemic stroke or TIA during follow-up was 6.2% (95% CI, 3.9–9.2%). Narrative synthesis of the randomized evidence demonstrated that ICMs significantly increased AF detection compared with conventional monitoring but did not demonstrate a significant reduction in recurrent stroke during the available follow-up period. Conclusions: Prolonged implantable cardiac monitoring identifies AF in approximately one-quarter of patients following ischemic stroke or TIA and frequently leads to the initiation of oral anticoagulation, with a favorable safety profile. Although ICMs substantially improve AF detection, current evidence remains insufficient to confirm that increased detection translates into a reduction in recurrent stroke. Large, adequately powered randomized controlled trials are needed to determine the long-term clinical benefits of ICM-guided management and to define the optimal monitoring strategy for patients following ischemic stroke.

NeuroSci doi: 10.3390/neurosci7040082

Authors: Jiwon Yang Hyeon-Mi Park Yeong-Bae Lee

Mitofusin-2 (MFN2) variants are a well-established cause of Charcot–Marie–Tooth disease type 2A, although central nervous system involvement has increasingly been recognized in a subset of affected patients. We report a 51-year-old woman carrying a likely pathogenic MFN2 variant (c.2119C>T, p.Arg707Trp) who developed rapidly progressive spastic paraplegia and became wheelchair-dependent within several months. Neurological examination demonstrated severe pyramidal tract signs with preserved sensory function. Nerve conduction studies were suggestive of distal motor axonal involvement, while transcranial magnetic stimulation and somatosensory evoked potentials indicated corticospinal and central sensory pathway dysfunction in the lower extremities. Brain magnetic resonance imaging revealed extensive bilateral confluent periventricular and deep white matter hyperintensities. Comprehensive investigations excluded inflammatory, vascular, metabolic, infectious, neoplastic, and common genetic causes of hereditary spastic paraplegia. Targeted next-generation sequencing identified a heterozygous likely pathogenic MFN2 p.Arg707Trp variant. Although central nervous system manifestations have previously been described in MFN2-related disease, this phenotype is unusual because of the combination of late-onset rapidly progressive spastic paraplegia, and extensive cerebral white matter abnormalities associated with the p.Arg707Trp variant. This case further expands the recognized phenotypic spectrum of MFN2-related disease and highlights that MFN2 variants should be considered in the differential diagnosis of selected patients with late-onset progressive spastic paraplegia accompanied by cerebral white matter abnormalities and distal motor axonal neuropathy.

NeuroSci doi: 10.3390/neurosci7040081

Authors: Yue Tu Qinghui Fu Canghao Sun Jing Deng Haoning Qin Xianlin Zeng Yuchuan Wang Shulan Qiu Weixiong Zhang

Rodent models, especially chronic stress paradigms, are essential in depression research, yet existing behavioral assessments often struggle to capture pathophysiological heterogeneity. We developed the Multimodal Behavior Scoring (MBS) algorithm, which integrates results from standard behavioral tests (sucrose preference, open field, and forced swim tests) into a single severity metric. Validated in two distinct chronic stress models (CUMS and CSDS), MBS reliably distinguished stressed from control mice and demonstrated high cross-cohort reproducibility. Furthermore, MBS successfully stratified stress-resilient subpopulations and revealed model-specific phenotypic patterns. By providing an integrative, biologically grounded framework, MBS enhances the resolution of chronic stress-induced behavioral phenotyping and may support future biomarker discovery and pharmacological validation studies.

NeuroSci doi: 10.3390/neurosci7040080

Authors: Sang Seok Yeo Dong Hyun Byun Fang He

(1) Background: The effects of posterior parietal cortex (PPC)-targeted transcranial direct current stimulation (tDCS) on postural stability and cortical activity remain unclear. Therefore, this study aimed to investigate and compare changes in cortical activity and postural stability before and following tDCS conditions. (2) Methods: Eight right-handed adults completed a baseline assessment followed by three stimulation sessions: left-anodal/right-cathodal (L-A/R-C), left-cathodal/right-anodal (L-C/R-A), and sham on the PPC. The sessions were administered in a randomized Latin square design with a minimum 4-day washout period between each. At baseline and following each tDCS session, cortical activity was measured using functional near-infrared spectroscopy, and postural stability during a tandem stance was assessed utilizing the Balance Error Scoring System (BESS) and a force platform. (3) Results: Compared with the baseline measurements, significant deactivation in the right middle temporal gyrus (MTG) was observed following L-C/R-A stimulation. Furthermore, postural stability measures revealed significantly higher BESS error scores and greater sway length following L-C/R-A stimulation compared to both the baseline and L-A/R-C conditions. (4) Conclusions: Bilateral tDCS over the PPC differentially influences cortical activity and postural control depending on the stimulation polarity. Specifically, L-C/R-A stimulation was associated with impaired visual–vestibular integration and postural stability. These preliminary findings highlight the critical role of interhemispheric parietal balance in posture regulation and suggest that polarity-specific tDCS protocols may be important considerations for the future.

NeuroSci doi: 10.3390/neurosci7040079

Authors: Olivia C. Brandon Kylie A. Corry Zheyu Ruby Jin Kate F. DiNucci Matthew J. Magoon Nels Schimek Daniel H. Moralejo Sandra E. Juul Patrick M. Boyle Elizabeth A. Nance Thomas R. Wood Sarah E. Kolnik

Brain injury after hypoxia–ischemia (HI) is the leading cause of morbidity and mortality in term and near-term neonates worldwide. The ferret is a promising translational model to study HI due to its gyrified brain and white-to-gray matter ratio that more closely resembles humans compared to rodents. Caffeine, an adenosine A2A receptor (A2AR) antagonist, shows neuroprotective potential after HI, but its effects have not been fully characterized. We sought to evaluate caffeine’s effect on neuronal cell death, cytotoxicity, and inflammatory and oxidative stress markers in a term-equivalent ferret organotypic brain slice model of HI. Slices were cultured for 72 h, exposed to two hours of oxygen–glucose deprivation (OGD), and randomized to OGD alone, OGD with caffeine (20 or 50 mg/L), or OGD with caffeine and an A2AR agonist. Healthy slices served as controls. Outcomes included global cell death, regional cell death, microglial morphology, and expression of inflammatory and oxidative stress genes (46–48 slices/group for cell death assays and 18 slices/group for imaging, balanced by sex). Caffeine 50 mg/L significantly reduced global cell death compared to OGD (p = 0.02), and this effect persisted despite co-administration of an A2AR agonist (p = 0.01), suggesting that protection was not primarily mediated through A2AR signaling. Caffeine also did not change regional pyknotic nuclei counts (p > 0.05). Caffeine altered microglial morphology, increasing the proportion of microglia with features characteristic of control conditions. OGD significantly increased expression of inflammatory and oxidative stress-related genes (p < 0.05) compared with control slices, whereas caffeine did not significantly alter gene expression. In summary, caffeine partially reversed global cell death after OGD and altered microglial morphology. Larger, higher-powered studies are needed to further investigate caffeine’s effects on neonatal HI.

NeuroSci doi: 10.3390/neurosci7040078

Authors: Giuseppina Bevacqua Eleonora Becattini Valentina Grespi Carlo Conti

Traumatic intracranial aneurysms (TICAs) are rare lesions accounting for <1% of intracranial aneurysms and are associated with high morbidity and mortality. They frequently arise after blunt trauma and may develop days to months following the initial injury, often evading early vascular imaging. Pseudoaneurysms predominate and carry a high risk of rupture. We report the case of a patient who sustained a severe head injury with a comminuted open depressed temporoparietal skull fracture, epidural hematoma, subarachnoid hemorrhage, and mandibular fracture after a road traffic accident. Initial vascular imaging revealed no aneurysm. At six-month follow-up, CT angiography demonstrated a 7 × 5 mm pseudoaneurysm arising from the rolandic branch of the right M3 middle cerebral artery, within an area of post-traumatic encephalomalacia. The aneurysm was confirmed by MRI/MRA and treated successfully with microsurgical clipping. This case underscores the importance of delayed vascular imaging in trauma patients with skull fractures or parenchymal injury, even when early angiography is normal. TICAs may develop over several months, and timely identification permits definitive management before rupture.

NeuroSci doi: 10.3390/neurosci7040077

Authors: Chiara Zilli Giada Giuliani Giulio Tancredi Mariangela Fratino Benedetta Pitzalis Marta Altieri

Background: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway represent an effective preventive treatment for chronic migraine, including in patients with multiple prior therapeutic failures. However, a substantial proportion of patients exhibit a suboptimal or delayed response. The role of personality traits in modulating treatment response remains poorly understood. Methods: In this prospective observational study, adults with chronic migraine received anti-CGRP monoclonal antibodies and were followed for 12 months. Monthly headache days (MHDs), monthly acute medication use (MAM), and disability scores (MIDAS and HIT-6) were recorded at baseline and at 3, 6, and 12 months. Responders were defined as patients achieving a ≥50% reduction in monthly headache days (MHDs) compared with baseline. Changes in disability measures were evaluated as secondary clinical outcomes. Personality traits were assessed using the Millon Clinical Multiaxial Inventory-III. Results: Thirty-eight patients were included, of whom 71% had medication overuse headaches. Responder rates increased over time (31.6% at 3 months and 39.5% at 12 months). Histrionic traits (37.5% vs. 6.7%, p = 0.048) and dysthymic features (21.4% vs. 0%, p = 0.046) were significantly more prevalent among non-responders. Conclusions: Histrionic and dysthymic personality features were associated with a lower likelihood of response to anti-CGRP therapy in patients with chronic migraine. Given the exploratory design, limited sample size, and absence of correction for multiple comparisons, these findings should be considered preliminary and hypothesis-generating. Further studies in larger cohorts are needed to confirm these observations.

NeuroSci doi: 10.3390/neurosci7040076

Authors: Clara R. LaCorte Mya C. Delesdernier Cay Anderson-Hanley

This study investigated whether neuro-exergaming with an interactive physical and cognitive exercise system (iPACES), might alleviate symptoms in college students with symptoms of Attention Deficit Hyperactivity Disorder (sxADHD). It was hypothesized that challenges with attention and executive function, often experienced by those with sxADHD, would improve after an acute bout of pedal-n-play exercise. College students (n = 33; 18 with sxADHD) participated in a 20 min single bout of exercise, pedaling along a virtual pathway (tour), while steering the tablet. Mental exercise included a working memory (focus) task to steer toward assigned locations along the path. An exploratory experimental condition was also embedded in the basic pre/post design, wherein half of the students were randomly assigned collectibles (coins) in the pathway. Cognition was assessed (e.g., paper and digital Stroop, Trails, Digit Span) before and after the acute bout of exercise. Paired t-tests revealed significant improvements in executive function on both paper and electronic Stroop tasks for those with sxADHD, while significant change was also seen on Trails and Digit Span for normative students. Surprisingly, those with sxADHD, assigned to the experimental “multi-tasking” collectible (coin) challenge, performed significantly better on tests of executive functioning than normative peers, who improved more without coins. It is hypothesized that the collectible challenge provided additional mental stimulation or reward needed to increase attentional focus for those with sxADHD, leading to improved performance, post-exercise. While the findings of this study are preliminary, additional research can further explore possible designs for combined, interactive mental and physical exercise challenges, as well as further possible synergistic or differential neural activation, in order to maximize outcomes from the same amount of time exercising. Additionally, future research could examine longer-term use of neuro-exergaming, through a clinical trial, as an alternative to, or in conjunction with, medication for sxADHD treatment and symptom relief.

NeuroSci doi: 10.3390/neurosci7040075

Authors: Hanna Valeria Venegas-Mora Octavio Ispanixtlahuatl-Meraz Diana Emilia Martínez-Fernández Irene Guadalupe Aguilar-García David Fernández-Quezada

Noise exposure has become an increasingly prevalent public health concern, with effects extending beyond the auditory system. Accumulating evidence indicates that chronic noise exposure induces both structural and functional alterations in the central nervous system, ultimately affecting cognitive and emotional processes. This review summarizes the impact of noise on key brain regions, including the hippocampus, prefrontal cortex, and auditory cortex. Structurally, noise exposure is associated with reduced neurogenesis, dendritic remodeling, synaptic loss, alterations in white matter and changes in glial activity. Functionally, it disrupts synaptic plasticity mechanisms—such as long-term potentiation and long-term depression—as well as neuronal connectivity, leading to impairments in higher-order cognitive and behavioral functions. These effects are mediated by interconnected mechanisms, including activation of the hypothalamic–pituitary–adrenal axis, neuroinflammation, oxidative stress, and alterations in neurotrophic signaling.

NeuroSci doi: 10.3390/neurosci7030074

Authors: Christopher F. Sharpley Vicki Bitsika Christopher B. Watson

Melancholia remains a severe and complex form of depression. One possible avenue to a better understanding of melancholia and potentially improved methods of treating it, is via examination of the profiles of brain electrical activity of patients suffering from melancholia. However, apart from work using fMRI, relatively little is known about the electrophysiological basis of melancholia despite the potential for this to inform targeted effective treatments such as Transcranial Magnetic Stimulation. To better understand the state of research regarding EEG variables and melancholia, a systematic review was undertaken. Results indicated that there was a large degree of complexity in the association between melancholia and various EEG parameters, and that many specific aspects of brain electrical activity remain under-studied. Suggestions are made for future research.

NeuroSci doi: 10.3390/neurosci7030073

Authors: Alexsa J. Zurowski Eugene Y. H. Yeung

Background: Creating antibiograms solely for adults may overestimate resistance of antimicrobials for certain pathogens in children. The Canadian Paediatric Society comments that areas with no cephalosporin-resistant Streptococcus pneumoniae cases should consider ceftriaxone or cefotaxime monotherapy for meningitis, despite most experts recommending adding vancomycin. The present study created age-specific antibiograms using LifeLabs data to report incidences of resistant bacterial meningitis pathogens at the regional level to determine the need for duo-coverage. Methods: Data of common bacterial meningitis pathogen susceptibility was collected from 1 January 2023 to 31 December 2024, in the LifeLabs community laboratory on Vancouver Island. Results: Most Streptococcus pneumoniae isolates (78/83) were susceptible to ceftriaxone using the meningitis breakpoint; the remaining five isolates showed intermediate susceptibility to ceftriaxone. There was a significant difference when comparing S. pneumoniae susceptibility using penicillin-meningitis and penicillin-non-meningitis breakpoints (82% vs. 99%, respectively; p < 0.05). There was a significant difference between the three age groups (<18 years, 18–50 years, >50 years) when analyzing ciprofloxacin susceptibility of isolates [82% (n = 462), 77% (n = 2452), 75% (n = 8352), respectively, p < 0.05]. Conclusions: Ceftriaxone should remain the drug of choice for community-acquired bacterial meningitis and might be sufficient as a monotherapy for pneumococcal meningitis on Vancouver Island. The age-specific differences in E. coli susceptibilities to ciprofloxacin showed the importance of age-specific antibiograms.

NeuroSci doi: 10.3390/neurosci7030072

Authors: Oscar Arias-Carrión Emmanuel Ortega-Robles

The human spinal cord is increasingly recognized as an active and adaptable component of sensorimotor function, contributing to motor control, pain modulation, and recovery after neurological injury. Within this framework, the Hoffmann reflex (H-reflex) has evolved from a classical electrophysiological phenomenon into a useful probe of spinal circuit function. Rather than reflecting motoneuron excitability alone, H-reflex amplitude and modulation arise from the interaction of Ia afferent transmission, presynaptic inhibition, homosynaptic depression, and interneuronal networks that regulate sensorimotor gain in a state-dependent manner. This review synthesizes classical and contemporary evidence to position the H-reflex as an indirect measure of spinal inhibitory function in humans. We integrate physiological mechanisms with findings from studies in chronic pain syndromes, spasticity, Parkinson’s disease, and recovery after central nervous system injury, where alterations in spinal inhibitory processes have been described. We further discuss methodological and conceptual challenges that limit clinical translation, including state dependence, protocol heterogeneity, and the lack of normative reference frameworks. Finally, we outline directions for integrating H-reflex paradigms with complementary approaches to improve the interpretation of spinal circuit function and its relation to clinical phenomena. Framed in this context, the H-reflex can be considered a valuable experimental and translational tool, whose utility depends on careful methodological implementation and physiologically informed interpretation.

NeuroSci doi: 10.3390/neurosci7030071

Authors: Federico Tosto Concetta Lobianco Giuseppe Magro Angelo Pascarella

Background: Acute focal neurological deficits require rapid differentiation between ischemic stroke and stroke mimics to avoid treatment delays and inappropriate therapy. Seizures, including ictal deficits, status epilepticus, and post-ictal/Todd’s phenomena, are among the most challenging mimics. This review summarizes the role of multimodal neuroimaging in distinguishing acute ischemic stroke from seizure-related deficits. Methods: We performed a focused narrative review of neuroimaging findings in acute stroke mimics, emphasizing non-contrast computed tomography (CT), CT angiography, CT perfusion, magnetic resonance imaging (MRI), including diffusion weighted imaging (DWI), apparent diffusion coefficient (ADC), fluid attenuated inversion recovery (FLAIR), and arterial spin labeling (ASL) sequences. Imaging patterns, diagnostic pitfalls, and practical clues for hyperacute stroke pathways were synthesized. Results: Acute ischemic stroke is typically suggested by vascular-territorial abnormalities, including arterial occlusion or stenosis, territorial hypoperfusion, and congruent DWI/ADC restriction. Seizure-related deficits more often show non-territorial cortical perfusion changes, ictal or status-related hyperperfusion, reversible MRI abnormalities, and absence of arterial occlusion. However, post-ictal hypoperfusion, peri-ictal diffusion restriction, and reperfusion-related hyperperfusion may overlap with ischemic patterns. Conclusions: A multimodal approach integrating vascular imaging, perfusion distribution, DWI/ADC, ASL, clinical timing, and EEG findings can improve diagnostic accuracy in the stroke–seizure differential without delaying treatment in true acute ischemic stroke.

NeuroSci doi: 10.3390/neurosci7030070

Authors: Sheharyar S. Baig Mudasar Aziz Sara Sara Sarah Ingram Arshad Majid Elizabeth Abbey Lucy A. Eaves Noor Sharrack Ali Ali Jessica N. Redgrave

Background: The nationally advertised mass media campaign Act-FAST UK, delivered in multiple waves since its launch in 2009, has increased public awareness of stroke symptoms. However, many stroke patients still delay in calling for help and reach the hospital too late to receive emergency treatments. The reasons for this cognitive dissonance between recognition of symptoms and urgent seeking of emergency medical services (EMS) are unclear. Aims: This study aimed to quantify cognitive, psychological, and knowledge-based barriers to help-seeking in patients with acute stroke or transient ischaemic attack (TIA), as well as in intervening witnesses, and to examine their association with the use of EMS as the initial point of contact. Methods: We interviewed patients admitted to a hyperacute stroke unit with a stroke or transient ischaemic attack (TIA) from 2013 to 2016. People who contacted emergency services on the patient’s behalf (intervening witnesses (IWs)) were also interviewed when available. Reasons given for delays in calling for help were related to correct symptom recognition, and whether/at what time, emergency services were contacted after symptoms onset. Results: A total of 602 patients (429 with stroke, 173 with TIA) along with 128 witnesses who intervened in calling for help in those cases (IWs) were interviewed. In the subset of patients with both measures available, there was a strong positive correlation between NIHSS score and number of FAST symptoms (Spearman’s rho = 0.645, p < 0.001), providing supportive evidence for the use of FAST symptom count as a proxy measure of stroke severity. A total of 469 (77.9%) of the patients were aware of a media education campaign about stroke, but only 145 (24.1%) had attributed their own symptoms to stroke at onset. However, correct self-diagnosis of stroke was not associated with direct calls to the EMS (OR 1.43, 95% CI 0.84–2.45). Cognitive, psychological or emotional barriers to help-seeking, as reported by prior published studies, were reported by 463 (81.2%) of the patients we interviewed but in only 63 (53.3%) of the IWs (p < 0.001). Amongst the patient cohort, “not thinking symptoms were serious” (275, 45.7%) and “waiting to see if symptoms would go away” (285, 47.3%) were most strongly negatively associated with EMS use (OR 0.52, 95% CI 0.32–0.84 and OR 0.34, 95% CI 0.21–0.55, respectively). Only 55 (9.1%) of the patients interviewed had been aware of any time-critical stroke treatment prior to their stroke. Eighteen stroke patients (4.2%) reached hospital in time to receive thrombolysis, but an additional 170 (39%) could have been considered for this treatment (i.e., had no apparent other contraindications from a notes review) had they arrived within 4 h of symptom onset. Conclusions: Future public education campaigns may be more effective if they specifically address factors associated with delays in calling for help after stroke symptoms and emphasise the existence of emergency treatments, which are also time-critical. More effective public education may have the potential to increase the proportion of patients arriving in time to benefit from such treatments.

NeuroSci doi: 10.3390/neurosci7030069

Authors: Liam C. Tapsell Molly E. Coventry Colin Sylvester Casey Whife Myles C. Murphy

Objective: Evaluate the test–retest reliability of quadriceps corticospinal excitability and intracortical excitability using transcranial magnetic stimulation (TMS). Design: A test–retest observational cohort study. Methods: Twelve healthy adults attended two laboratory sessions, seated with their knee at 90 degrees and fitted with electrodes on the rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM). TMS was used to assess the active motor threshold (AMT), motor evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Individual results were calculated as the mean and median of the 10 trials of each measure for MEP, SICI and ICF. Intraclass correlation coefficients were calculated. Results: All muscles showed good or excellent reliability for the mean and median measures of the MEP amplitude (ICC ≥ 0.820) as well as the AMT of the RF (ICC = 0.991). SICI showed good reliability in the mean and median measures of the RF and the mean measure of the VL (ICC ≥ 0.809), moderate reliability in both measures of the VM (ICC ≥ 0.655) and was not significant for the median measure of the VL (ICC = 0.513). ICF showed excellent reliability in the mean measure of each muscle and median measure of the RF (ICC ≥ 0.906), with good reliability in the median measure of the VL (ICC = 0.888) and moderate reliability in the median measure of the VM (ICC = 0.719). Conclusion: The mean of an individual’s quadriceps corticospinal excitability and intracortical excitability have good or excellent reliability for every TMS measure, in every muscle (except SICI of the VM). With the previous reliability of TMS measures mostly investigating the upper limbs, these results offer important context for neurophysiological research in the quadriceps.

NeuroSci doi: 10.3390/neurosci7030068

Authors: Melissa Huynh Mabry Irina Podkorytova Ebenezer Chinedu-Eneh Sasha Alick-Lindstrom Kan Ding Ryan Hays Ghazala Perven

Drug-resistant epilepsy (DRE) secondary to viral brain infections (VBI) may have multiple seizure foci, making it not amenable to surgical resection but could respond to responsive neurostimulation (RNS). We aimed to evaluate characteristics of DRE patients with a VBI history who did or did not respond to RNS therapy; 9 patients met criteria. Four out of 9 patients were responders to RNS therapy with ≥50% of seizure-frequency reduction at an average 39-month follow-up. Five patients were non-responders, an average 47-month follow-up. Two responders had a prior destructive surgery. Four non-responders had a prior neurosurgery including 1 focal resection, 2 vagus nerve stimulation, and 1 prior RNS. Patients in the responder group had shorter DRE duration prior to RNS placement than in the non-responder group (average 11.0 years versus 14.4 years). Three responders and four non-responders had a history of focal to bilateral tonic–clonic seizures (FBTC) pre-RNS. Post-RNS, all responders and 2 non-responders stopped experiencing FBTC. Our study demonstrates that RNS therapy could be effective in patients with DRE secondary to VBI, even if the patients failed previous surgical intervention(s). Patients in both responder and non-responder groups had reduction of convulsive seizures. These findings should be considered preliminary observations due to a small sample-size.

NeuroSci doi: 10.3390/neurosci7030067

Authors: Jaime R. Gutiérrez Cristofer Zarate-Calderon Fiorella Fadanelli-Sánchez Abdiel A. Demuner-Mendoza René Zempoalteca-Ramírez Luis Beltrán Parrazal Donaji Chi-Castañeda Luis I. García

Objective: We aimed to determine whether sexual experience modulates the soleus H-reflex in male rats and to assess the specific contribution of vermis lobules 6a and 7 to cerebellar-dependent spinal plasticity. Methods: Thirty-six male Wistar rats were divided into sexually inexperienced (SI) and sexually experienced (SE) groups and assigned to one of three cerebellar conditions: intact control, lobule 6a lesion, or lobule 7 lesion. SE rats underwent repeated mating sessions until they achieved efficient copulatory performance. Subsequently, targeted electrolytic lesions were made, and electromyographic recordings of the soleus H-reflex were obtained under urethane anesthesia to quantify H-wave amplitude and temporal parameters. Results: The global linear mixed model yielded no significant main effects of sexual experience, cerebellar condition, or their interaction on H-wave amplitude. Planned contrasts revealed a near-significant trend toward higher H-wave amplitude in sexually experienced intact animals compared with inexperienced controls (p = 0.061, Cohen’s d = 0.592, 95% CI [−1.44, 0.04] V), and significant amplitude reductions following lobule 6a (p = 0.029, d = 1.450, 95% CI [0.13, 2.33] V) and lobule 7 (p = 0.002, d = 2.256, 95% CI [0.74, 3.08] V) lesions specifically in sexually experienced animals. Neither sexual experience nor lesions significantly affected H-wave latency or duration, suggesting that modulation primarily targets synaptic excitability rather than axonal conduction. M-wave latency showed a significant effect of sexual experience (p = 0.026, d = 1.405, 95% CI [0.03, 0.45] ms). Conclusions: Sexual experience appears to be associated with cerebellar-dependent modulation of soleus H-reflex excitability; lobules 6a and 7 of the cerebellar vermis contribute to this effect specifically in experienced animals. Shorter M-wave latency in experienced animals suggests parallel peripheral motor reorganization. Adequately powered confirmatory studies are needed to characterize the mechanisms underlying this association.

NeuroSci doi: 10.3390/neurosci7030066

Authors: Hassaan Abid Sohana Memon Vishan Das Kaneez Fatima Muhammad Mukhlis Muhammad Vazaym

Background: Parkinson’s disease and dementia are major neurodegenerative disorders that substantially contribute to disability, dependency, and mortality worldwide. Although prior CDC WONDER studies have separately evaluated Parkinson’s disease and dementia mortality trends, fewer analyses have examined national mortality patterns in which both conditions are recorded on death certificates simultaneously over extended time periods. Methods: We analyzed U.S. death certificates from 1999 through 2025 using the CDC WONDER Multiple Cause of Death database, identifying deaths among adults aged ≥45 years in which both Parkinson’s disease (ICD-10 G20) and dementia-related codes (F01, F03, G30, G31) were recorded anywhere on the certificate. This operational definition captures co-recorded diagnoses and does not identify clinically confirmed Parkinson’s disease dementia. Age-adjusted mortality rates (AAMRs) per 100,000 were standardized to the 2000 U.S. standard population, a method that controls for shifts in population age structure over time and allows valid temporal comparisons independent of absolute population growth. Joinpoint regression was used to quantify trends. Sensitivity analyses excluded 2025 provisional data and the COVID-19 period (1999–2019). Results: A total of 337,721 deaths were identified. Overall AAMR increased from 5.75 (95% CI: 5.60–5.90) in 1999 to 11.15 (95% CI: 10.98–11.32) in 2025 (AAPC: 2.07; p = 0.002). A sharp transient increase occurred in 2020, attributable to pandemic-related factors including disproportionate COVID-19 mortality among older adults with neurodegenerative conditions, care disruptions, and changes in death-certificate coding practices. Following this pandemic-era peak, AAMRs declined significantly through 2025 and should be interpreted cautiously given provisional data. Males (AAPC: 2.14), non-Hispanic White individuals (AAPC: 2.29), the Midwest region (AAPC: 2.65), and non-metropolitan areas carried the highest mortality burden. Mortality was greatest among adults aged ≥85 years. Conclusion: Population-level death rates involving co-recorded Parkinson’s disease and dementia demonstrated significant temporal changes over the study period, with marked demographic and geographic disparities. These findings reflect death-certificate surveillance data and cannot establish clinical co-occurrence, causal relationships, or individual disease risk.

NeuroSci doi: 10.3390/neurosci7030065

Authors: Petar Vuleković Mario Ganau Lukas Rasulić Đula Đilvesi Jagoš Golubović

Introduction: Neurosurgery has evolved from an anatomy-driven analog discipline into a digitally augmented field supported by multimodal imaging, neuronavigation, intraoperative imaging, neurophysiological monitoring, robotics, augmented reality, and artificial intelligence. Objective: To examine how this transition has altered professional responsibility, informed consent, training, and medico-legal accountability in neurosurgical practice. Methods: We performed a structured narrative review of the literature on digital neurosurgery and its ethical and professional implications, focusing on publications from 1990 onward and supplemented by landmark historical papers. Sources were selected for relevance to cranial, spinal, skull base, stereotactic, and neuro-oncological neurosurgery, and then synthesized into thematic domains including brain shift, eloquent cortex preservation, stereotactic accuracy, intraoperative neurophysiology, workflow integration, equity, and liability. Results: Digital systems improve lesion localization, function-preserving surgery, stereotactic precision, documentation, and training, but they also introduce new vulnerabilities related to registration error, brain shift, platform dependence, data overload, cost, cybersecurity, deskilling, and diffuse accountability. Conclusions: Digital augmentation expands rather than diminishes the neurosurgeon’s responsibility. The neurosurgeon remains accountable for surgical indication, interpretation of technology-generated information, intraoperative override, and communication of technology-specific risks. The central ethical challenge is to integrate digital tools without weakening patient-centered judgment.

NeuroSci doi: 10.3390/neurosci7030064

Authors: Timothy Jern Yu Tan Zhuo Zhang Kai Keng Ang Jennifer Ang

Fatigue monitoring and detection are crucial for improving efficiency and safety due to their influence on reducing cognitive and physical performance that may result in safety-related incidents. This paper proposes a filter bank-based approach that decomposes electroencephalography (EEG) signals into delta, theta, alpha, beta, and gamma sub-bands for feature extraction to enhance fatigue detection using a wearable EEG-based brain–computer interface (BCI). The study utilized a publicly available EEG dataset from 40 participants collected with a dry-EEG headband while performing two cognitive tasks: a Cognitive Vigilance Task (CVT) and a Multi-Modal Integration Task (MMIT). The data was previously investigated for stress detection on the MMIT. In this study, we investigate fatigue detection on the CVT. Subjects who were not fatigued post-CVT were iteratively removed. Two models were trained with five models to classify the fatigued state from the non-fatigued state, one using features extracted from a broadband filter approach and the other from the proposed filter bank approach. Leave-one-subject-out cross-validation yielded accuracies of 75.8% ± 10.4% (95% confidence interval) from the broadband filter approach, and 86.4% ± 8.3% (95% confidence interval) from the proposed filter bank approach, yielding an overall increase of 10.6%. These results demonstrate the potential of filter bank-based feature extraction for fatigue detection in wearable EEG-based BCI systems.

NeuroSci doi: 10.3390/neurosci7030063

Authors: Luca Andreoli Davide Caputo Fabio M. Doniselli Giuliana Messina Elisa Granocchio Barbara Castellotti Elena Freri

Periventricular nodular heterotopia (PVNH) is a genetically heterogeneous malformation of cortical development with variable neurological outcomes. Among recessive forms, ARFGEF2-related disorder is uniquely characterised by the association of diffuse PVNH and progressive microcephaly. We describe a two-year-old boy born to consanguineous parents who presented with severe developmental delay, hypotonia, progressive microcephaly, and infantile-onset epileptic spasms with developmental regression. Brain MRI showed extensive bilateral PVNH associated with callosal hypoplasia and ventriculomegaly. EEG revealed dysmature background activity with multifocal epileptiform discharges and runs of asynchronous fast activity during sleep. Genetic testing identified a novel homozygous nonsense variant in ARFGEF2. The clinical course was characterised by drug-resistant epilepsy and multisystemic involvement, including feeding difficulties and recurrent respiratory infections. To contextualise this case, we performed a comprehensive review of previously reported patients, further delineating the clinical, neuroradiological, and electroclinical spectrum of ARFGEF2-related disorder. This case highlights progressive microcephaly as a key distinguishing feature of ARFGEF2-related PVNH and underscores the importance of early genetic diagnosis to guide targeted surveillance for extra-CNS complications and multidisciplinary care.

NeuroSci doi: 10.3390/neurosci7030062

Authors: Lennart W. Sannwald Andrej Pala Dag Moskopp Mats L. Moskopp

Since 1999, sellar xanthogranulomas (XGs) have been recognized as a distinct pathological entity characterized by cholesterol clefts, macrophages, chronic inflammatory infiltrates with multinucleated giant cells, necrotic debris, and hemosiderin, suggesting a chronic inflammatory process with repetitive intralesional bleeding. This study aims to characterize the clinical phenomenology of the rare XG entity and to explore its correlation with other lesions. A retrospective screening was conducted of 628 sellar surgeries performed during the 2007–2024 period at a major communal hospital in Berlin and 529 surgeries between 2015 and 2024 at Ulm University. Eight XGs were analyzed. Eight XGs (0.6% of 1157 surgeries) showed mixed intra- and suprasellar localization. Visual deficits and endocrinological insufficiencies were the most common symptoms (four out of eight each). Visual recovery was favorable (three out of four complete, one out of four marked improvement), whereas endocrinological recovery was limited (one out of four). One patient experienced recurrence. Intraoperatively, seven out of eight lesions contained characteristic fluid described as ‘golden water of Gdansk.’ Postoperatively, transient arginine vasopressin deficiency occurred in four out of eight patients. The illustrative case demonstrated transformation of a Rathke’s cleft cyst, while two cases were associated with pituitary adenomas. Sellar XGs are benign, chronic inflammatory and hemorrhagic lesions with low recurrence risk. Their frequent association with other sellar pathologies supports a secondary reactive origin.

NeuroSci doi: 10.3390/neurosci7030061

Authors: Sharon Nguyen Bilal Khoncarly Timothy N. Holbrook Simran Demla Xuan Wang Leslie Rodriguez Lavanya Srinivasan Alexander Bastidas Jennifer A. Walker

Introduction: Delirium is associated with worse outcomes in critically ill patients. Factors that could reduce delirium are patients’ environment and maintaining circadian cycles, but whether certain room characteristics improve the incidence of delirium is unclear. Our objective was to investigate whether the presence of windows or doors in patients’ rooms is associated with lower rates of delirium. Methods: In this retrospective, cohort study, adult, medical patients admitted to the Intensive Care Unit (ICU) between 1 January 2024 and 1 July 2024 were identified. Clinical and room characteristics were collected. The primary outcome was the development of Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) positive status. Secondary outcomes included ICU and hospital length of stay (LOS) and mortality. Results: Four hundred fifty-eight (458) patients met inclusion criteria (mean age 61.7 +/− 16.4 years; 51.3% male). In the adjusted multivariate analysis, neither the presence of windows (aOR 2.2; 95% CI 0.7–6.2; p = 0.155) nor closed-format rooms (aOR 0.1; 95% CI 0.0–1.2; p = 0.077) were significantly associated with CAM-ICU positivity. Although an initial association was observed between the presence of windows and increased hospital LOS (aMR 1.4; 95% CI 1.1–1.8; p = 0.008), this did not maintain statistical significance after False Discovery Rate (FDR) correction (q > 0.05). No significant associations were found for other secondary outcomes, including ICU mortality or ICU LOS. Conclusion: Room characteristics were not significantly associated with delirium or secondary outcomes after FDR correction. However, given the study’s limited power to detect moderate differences, these findings do not definitively rule out an architectural influence on delirium and warrant further investigation in larger cohorts. Studies with more discrete measurement of room characteristics are needed to investigate these associations further.

NeuroSci doi: 10.3390/neurosci7030060

Authors: Mariya Ivanova Liliya Panayotova-Ovcharova Detelina Nedyalkova-Petkova Petar Petkov Georgi Boshev Evgeniya Vladeva

Background: Peripheral neuropathy is a common and clinically heterogeneous neurological condition caused by metabolic, inflammatory, toxic, or traumatic factors and is associated with sensory deficits, neuropathic pain, motor impairment, and reduced functional capacity. Management remains challenging and often requires multimodal therapeutic approaches, as pharmacological monotherapy frequently provides incomplete symptom control. Objective: This narrative review explores the conceptual rationale for combining galantamine with iontophoresis and Black Sea brine-based therapy as a potential multimodal strategy for peripheral neuropathy management. Main Findings: Galantamine, a reversible acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, has demonstrated neuroprotective, neuromodulatory, and anti-inflammatory properties in experimental settings. Iontophoresis may provide a non-invasive method for targeted local drug delivery while reducing systemic exposure. Black Sea brine, widely used in Bulgarian balneological and rehabilitation practice, has been associated with improved circulation, pain reduction, and neuromuscular support. The reviewed evidence suggests biologically plausible complementary mechanisms; however, no direct clinical studies evaluating the combined intervention were identified. Limitations: Current evidence is indirect and derived from separate investigations of galantamine, iontophoresis, and brine-based therapy, as well as heterogeneous historical and regional sources. Therefore, the proposed combination should be considered hypothesis-generating rather than evidence-established. Conclusions: The combination of galantamine, iontophoresis, and Black Sea brine represents a potentially interesting multimodal concept for peripheral neuropathy rehabilitation. Well-designed preclinical and clinical studies are required to determine safety, feasibility, optimal treatment parameters, and therapeutic efficacy.

NeuroSci doi: 10.3390/neurosci7030059

Authors: Narayanaswamy Venketasubramanian

Peripheral artery disease (PAD) is found in 10.9% of patients with ischaemic stroke (IS). This cross-sectional study was performed to investigate the prevalence of PAD and its risk factors among acute IS patients in Singapore. Patients admitted for IS were recruited. Data was collected on sex, age, body mass index (BMI), history of hypertension, diabetes mellitus (DM), hypercholesterolaemia, cigarette smoking, prior stroke (PS) and ischaemic heart disease (IHD). IS was classified as a lacunar infarct (LI) or non-lacunar infarct (NLI) based on neuroimaging. Carotid intima–medial thickening (IMT) and carotid plaques (CP) were determined by ultrasonography. The ankle–brachial Index (ABI) was calculated in both lower limbs; PAD was diagnosed if the ABI was ≤0.9 in any limb. The estimated sample size was 150 subjects. In total, 150 subjects were recruited; the mean age was 62.7 ± 10.2 years, 44.7% were female, and the mean BMI was 24.1 ± 4.1. A total of 63.3% reported hypertension, 42.7% DM, 30.0% hypercholesterolaemia, 38.0% smoking, 18.7% PS, and 6.0% IHD. A total of 30.7% had IMT, 77.3% had CP, and 8.0% had carotid stenosis ≥50%. LI occurred in 64.7%. PAD was diagnosed in 22.0% (95% CI 16.1–29.3). On univariate analysis, based on vascular risk factors alone, PAD was associated with age (p = 0.03), hypercholesterolaemia (p = 0.03), and IHD (p = 0.004). On logistic regression, PAD was only associated with IHD (aOR 6.42, 95% CI 1.25–32.84; p = 0.03). When IMT and CP were added to the model, the association with IHD remained (aOR 5.45, 95% CI 1.03–28.71; p = 0.045). When the results of neuroimaging were added, the association was only with NLI (aOR 2.78, 95% CI 1.09–7.14; p = 0.03). This study found a high prevalence of PAD among Asian patients with IS. It was associated with a non-lacunar infarction.

NeuroSci doi: 10.3390/neurosci7030058

Authors: Yikang An Hongying Lan Jialong Xiong Ruoyan Jing Dongjin Gu Haoyang Zhang Xinping Liu Qi Zhao Feng Wang

Neurofilaments (NFs) are the predominant type IV intermediate filaments in differentiated neurons, functioning not just as static scaffolds, but as active drivers of radial axonal growth and nerve conduction velocity. While their physical properties are well characterized, a critical gap remains in synthesizing how their dynamic assembly and developmental subunit switching directly dictate neurodegenerative outcomes. This review breaks down the molecular architecture and stepwise kinetic assembly of NFs, detailing their role in polarized transport and the formation of a protective viscoelastic gel network within axons. We specifically highlight the physiological expression switching of early subunits, such as alpha-internexin and peripherin, during neuronal maturation, a process often overlooked in traditional structural reviews. By examining how specific gene mutations and aberrant hyperphosphorylation trigger axonal transport jams and protein aggregation, we map the direct pathways leading to amyotrophic lateral sclerosis (ALS) and Charcot–Marie–Tooth (CMT) disease. Finally, we emphasize that a precise mechanistic decoding of NF structural dynamics and their pathological disruption is essential for understanding the fundamental etiology of these neurodegenerative conditions.

NeuroSci doi: 10.3390/neurosci7030057

Authors: Giuseppe Forte Maria Casagrande

Recent advances in neurodegenerative disease research increasingly support the existence of multiple trajectory signatures underlying the heterogeneity of cognitive decline syndromes. Originally proposed in Parkinson’s disease, the brain-first and body-first models have emerged as conceptual frameworks to explain variability in disease onset, prodromal features, and progression across dementia-related disorders. Brain-first phenotypes are defined by the early emergence of central nervous system pathology and cognitive symptoms, whereas body-first phenotypes are characterized by prominent peripheral or autonomic dysfunctions that precede central involvement. Within this perspective, neurodegeneration is not viewed as a uniform, brain-restricted process, but a dynamic interaction between central, peripheral, and network-level mechanisms. Integrating central and peripheral biomarkers, autonomic physiology, and alterations in functional connectivity provides a coherent framework for interpreting phenotypic heterogeneity and prodromal dysregulation across dementia syndromes. Current evidence supporting brain-first and body-first trajectories is largely associative, and their clinical translation requires rigorous validation. Accordingly, this narrative perspective review aims to provide a critical and integrative conceptual framework that synthesizes existing evidence, identifies unresolved questions, and outlines research priorities for trajectory-based stratification, rather than offering a definitive diagnostic classification or pharmacological evaluation. The present work adopts a conceptual and mechanistic perspective rather than a clinically prescriptive or trial-oriented one. Its aim is to articulate a generative framework capable of producing testable hypotheses about disease trajectories and biomarker constellations across neurodegenerative syndromes.

NeuroSci doi: 10.3390/neurosci7030056

Authors: Andrei Buciuta Horia George Coman Bogdan Nemeș Mihaela Elvira Cimpianu Radu Oroian Mihaela Laura Vică Matei Horea-Vladi Matei

Background: Only a subset of cannabis users develop persistent psychosis, implying that genetic vulnerability modulates risk. HLA-DR/DQ variation is a strong non-dopaminergic risk locus for schizophrenia, but its role in cannabis-related psychosis is unclear. Methods: We studied 296 cannabis users from Romanian psychiatric services, grouped as non-psychosis (0), non-schizophrenia psychosis (1) and schizophrenia (2). High-resolution HLA-DRB1, DRB3/4/5 and inferred DRB1-DQB1 haplotypes were tested using Fisher’s exact tests with FDR correction in a universal contrast (0 vs. 1+2) and 0-1-2 pairwise comparisons, with Firth logistic regression and resampling as supportive analyses. Results: In the universal analysis, DRB1*16, DRB5 and the DRB1*16-DQB1*05 haplotype were associated with roughly two- to threefold higher odds of psychosis, whereas DRB1*07 and DRB4/DRB3 paralogs showed protective effects or trends. In the 0-1-2 contrasts, DRB1*16 was enriched in non-schizophrenia psychosis. DRB4/DRB3 paralogs were under-represented in schizophrenia relative to both cannabis users without psychosis and those with non-schizophrenia psychosis, suggesting a schizophrenia-specific protective association. Firth models supported effect directions but were underpowered. Conclusions: HLA class II immunogenetic background may modify psychosis risk among cannabis users: DRB5/DRB1*16-containing backgrounds were associated with increased vulnerability, whereas DRB4/DRB3 paralogs were associated with reduced schizophrenia risk in this cohort. These findings are hypothesis-generating, do not establish causality, and warrant replication in larger cohorts.

NeuroSci doi: 10.3390/neurosci7030055

Authors: Sydney F. Pell Katherine J. Blandin Taylor R. Bradish Chloe V. Lau Danielle Santana-Coelho Madison Wallis Colton W. Kelley Josh J. Thayil Ashley Smelley Gautham Cheliah David A. Narvaiz Kendall N. Lally Leighton Douglas Joaquin N. Lugo

Early-life seizures lead to long-term behavioral deficits, stimulate cytokine release, and disrupt the intracellular PI3K/AKT/mTOR signaling pathway. This study examined whether inhibiting the mTOR pathway, neuroinflammatory signaling, or both reduces behavioral comorbidities in adulthood. Female C57BL/6J mice received kainic acid on postnatal day 10 to induce status epilepticus. Three hours later, the mice were treated with saline, minocycline, rapamycin, or both. Three months later, behavioral assessments were conducted that measured activity, anxiety, social behavior, repetitive behavior, and learning. Early-life seizures resulted in social behavior deficits in the social chamber test, altered anxiety in the elevated plus maze, and an increase in repetitive behavior in the nose poke assay. Rapamycin and minocycline/rapamycin groups showed reduced distance traveled in the saline groups. We did not find any changes in cytokines IL6, IL-1β, and TNFα in the hippocampus or cortex using RT-qPCR. Through Western blotting, we found that rapamycin reduced the phosphorylated S6 levels. Minocycline decreased phosphorylated S6 in controls, but restored phosphorylated S6 levels in the seizure group. Early-life seizures had long-term impacts on behavioral comorbidities. Rapamycin and minocycline, alone or combined, did not restore the behavioral or molecular changes after early-life seizures. These findings clarify the behavioral outcomes after early-life seizures and therapeutic modulation.

NeuroSci doi: 10.3390/neurosci7030054

Authors: Wan-Chun Su Tony George Marc H. Bornstein Thien Nguyen Amir Gandjbakhche

Background: Posture–inhibitory control dual-tasking is critical for safe daily functioning. Although functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging tool, is increasingly used to examine neural mechanisms of dual-tasking, its reliability across posture transitions remains unclear. This study examined the reliability of behavioral and neural measures during sit-to-stand transitions and explored the neural mechanisms underlying posture–inhibitory control dual-tasking. Methods: Eighteen healthy adults (M age 42.8, SE = 3.3) completed tasks with varying posture challenges (sitting, standing, and tandem stance) and inhibitory demands (no task, congruent, and incongruent). Cortical activation was measured using fNIRS and reassessed after a 1 min sit-to-stand task. Results: Under lower task demands, activation in prefrontal and pre/postcentral regions increased with greater postural and inhibitory load, whereas this pattern reversed under higher demands. Behavioral performance demonstrated poor-to-excellent reliability (ICC range: 0.24 to 0.95; |r| = 0.33–0.97), whereas fNIRS measures showed poor-to-good reliability following sit-to-stand transitions (ICC range: <0 to 0.72; |r| = 0.02–0.79). Exploratory analyses suggested a shift from under- to over-additive cortical activation after posture transitions. Conclusions: Findings support the Capacity Sharing Theory, suggesting that postural and cognitive tasks compete for shared resources. Additionally, our findings reveal variable reliability of behavioral and neural measures across posture transitions. Future studies should account for postural changes when interpreting behavioral and neural findings.

NeuroSci doi: 10.3390/neurosci7030053

Authors: Ross Terada Jennifer Dailey Sherry Yan Michael Punsoni Eric T. Wong

Background: Severe neurocognitive decline is often seen in elderly glioblastoma patients after treatment with radiation and chemotherapy. But the mechanism behind their deterioration is unclear. We describe one such patient with concomitant primary age-related tauopathy (PART) in bilateral hippocampi. Case presentation: An 88-year-old woman experienced unsteadiness, memory loss, and slurred speech that was caused by an epithelioid glioblastoma with wild-type isocitrate dehydrogenase-1 and methylated promoter of O6-methylguanine-DNA methyltransferase. She was treated with gross total resection, followed by intensity-modulated radiotherapy and daily temozolomide. Shortly after starting treatment, she developed fatigue, anorexia, and neurocognitive impairment, which were refractory to corticosteroids. After two cycles of adjuvant temozolomide, she experienced impulsivity, disorientation, hallucinations, somnolence, and incontinence despite stable neuroimaging findings. Treatment was subsequently discontinued, and she died 20 months from the time of her glioblastoma diagnosis. Autopsy revealed tau-positive neurofibrillary tangles, but rare Aβ plaques, in the trans-entorhinal and entorhinal cortices of both hippocampi. These findings are consistent with a diagnosis of PART. Conclusions: Undiagnosed tauopathy could be a negative modifier of glioblastoma treatment. The identification of PART and other tauopathies as risk factors in the elderly population may be important to guide treatment decision.

NeuroSci doi: 10.3390/neurosci7030052

Authors: Ruth Narramore Mudasar Aziz Sheharyar Baig Joyce S. Balami Arshad Majid Ali N. Ali

Vagus nerve stimulation (VNS) may improve cognition and promote underlying brain health through various mechanisms including the noradrenaline and cholinergic pathways. Whilst early human studies used invasive devices (iVNS), recent decades have seen the emergence of non-invasive devices that stimulate the vagus nerve transcutaneously (tVNS) via either the cervical branches in the neck (tcVNS) or the auricular branch in the ear (taVNS). With this increase in more accessible devices, tVNS is gaining interest as a novel therapy in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). This targeted review aims to understand the current evidence in human trials in this specific population. PubMed, Cochrane, EMBASE, MEDLINE, and Google Scholar were searched. Six human interventional studies were found (one iVNS; five taVNS). VNS is well tolerated and study designs demonstrate feasibility within this population for future blinded and appropriately powered long-term studies with participants applying tVNS at home. However, protocols and tVNS settings remain variable. Working memory domains such as verbal fluency and 3D processing show the most promise but global cognitive scores were also sensitive in some cases. The role of biomarkers of tVNS activity and its effect on AD markers and neuroinflammation should be considered in the design of future studies.

NeuroSci doi: 10.3390/neurosci7030051

Authors: Ayman El-Menyar Naushad Ahmad Khan Hassan Al-Thani

Background: Conducting research in emergency departments and critical care units is crucial for improving patient management through evidence-based practices. Healthcare professionals and researchers in the field of traumatic brain injury (TBI) have a moral and legal obligation to inform patients before conducting any diagnostic test or therapy as part of a clinical study. However, challenges and barriers to conducting research in these high-pressure environments must be acknowledged. Shall the pathway to obtain informed consent in TBI-related research be revisited? We sought to map literature, identify gaps, and clarify the bioethics that should be followed in TBI-related research. Methods: A Scoping review was conducted to identify the obstacles and challenges investigators encounter in clinical and translational TBI research, with a specific emphasis on informed consent and regulatory impediments that often serve as bottlenecks or rate-limiting steps for participant enrollment and overall study success. This review used google scholar and Midline from inception to 2025. Results: Patients with TBI or their surrogates may be unable to provide informed consent within limited therapeutic windows. Despite international regulations and national laws, restrictions on obtaining consent are often criticized as ambiguous in certain situations. Furthermore, the fast-paced, emotionally charged atmosphere in emergency settings poses a risk of delaying crucial research interventions. There are accepted alternatives to informed consent, such as proxy consent, deferred consent, exceptions from consent, and waivers of consent, which are ethically and socially acceptable and compliant with regulations. However, these alternatives are underutilized or may be abused in some cases. Conclusions: This review calls for clarifying and modifying arbitrary regulatory restrictions on research and streamlining the Common Rule. Scientists should also share their innovative solutions to strike a balance between ethical considerations and the minimization of research barriers.

NeuroSci doi: 10.3390/neurosci7030050

Authors: Sílvio A. Carvalho Pedro Bezerra José E. Teixeira Pedro Forte Rui M. Silva José M. Cancela-Carral

This systematic review synthesized the existing evidence on neurofeedback interventions applied to football players, aiming to clarify their effects on cognitive, technical–tactical, physical and psychological performance. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, four databases (PubMed, Web of Science, SCOPUS and SportsDiscus) were searched up to November 2025. Seven studies met the inclusion criteria, involving 133 players across youth, amateur, national and elite levels. Neurofeedback protocols primarily targeted alpha or sensorimotor rhythm (SMR) activity, and some were combined with heart rate variability (HRV) biofeedback. Across studies, neurofeedback may be associated with improvements in several cognitive outcomes, including improvements in working memory, visuospatial memory, task switching, mental rotation and decision-making. Limited evidence suggests potential improvements in technical skills (particularly shooting accuracy) and tactical decision-making. Some studies reported changes in physiological markers and stress-recovery capacity, although their interpretation remains uncertain. However, the evidence base remains constrained by small samples, heterogeneous protocols and limited use of randomized controlled designs. Overall, neurofeedback appears to be a potentially promising but still experimental tool to support cognitive and psychophysiological readiness in football, warranting more rigorous and standardized research to establish efficacy and optimal training parameters.

NeuroSci doi: 10.3390/neurosci7030049

Authors: Avital Schurr

In 1988, two seminal studies were published almost simultaneously in the same scientific journal. Both spurred the field of brain energy metabolism research in new directions, culminating in a long-lasting debate that appeared to split its practitioners into two factions that seem unwilling to agree on what metabolic processes are fueling the active brain with adenosine triphosphate (ATP). The first study used rat hippocampal slices to demonstrate the ability of lactate to support neuronal function as the sole oxidative mitochondrial substrate. The second study demonstrated that upon brain stimulation, glucose consumption is not accompanied by respective oxygen consumption, but a non-oxidative glucose utilization or what has become known as “aerobic glycolysis”. Consequently, for almost four decades, researchers in this field have been divided between those who profess that brain activity is supported by oxidative lactate metabolism and those who insist that non-oxidative glucose metabolism supports it. Hypotheses for both concepts were offered, “The Astrocyte Neuron Lactate Shuttle Hypothesis” and “The Efficiency Tradeoff Hypothesis,” respectively. To bridge the gap between the two groups, a recent editorial, authored by over twenty leading investigators, was published. The editorial received two separate responses from investigators who supported the non-oxidative glucose consumption as the main process supporting neural activity, signaling that the gap between the two groups remained. The present perspective highlights the principal disagreements that divide this utmost important field of research. It argues that the main reason for these disagreements is rooted in the assumption that pyruvate is the end-product of aerobic glycolysis, even when many among those who adhere to this assumption accept that in the active brain glycolysis is the main provider of the necessary ATP and the end-product is lactate under aerobic conditions. The consideration of a paradigm shift, according to which lactate is the real end-product of glycolysis, independent of the presence or absence of oxygen, could bridge the great divide between those who separate glycolysis into two outcomes and those who profess that there is only one, prefix-less glycolytic pathway that always ends with the production of lactate.

NeuroSci doi: 10.3390/neurosci7020048

Authors: Massimo Mastrangelo Salvatore Mazzeo Eleonora Ferrante Giulia Bruschi Gianni Cutillo Elisa Bortolin Alessandro Bombaci Irene Borzillo Giuseppe Isgrò Massimo Chessa Alessandro Giamberti Marco Ranucci Massimo Filippi Maria Salsone

Neonates undergoing surgery for congenital heart disease (CHD) are at high risk for brain function impairment. Reliable early predictors of postoperative neurological complications are lacking. We examined a retrospective cohort of 55 surgically treated CHD neonates systematically monitored by concomitant conventional electroencephalography (cEEG) and amplitude-integrated EEG (aEEG). Neonates underwent cEEG/aEEG at three time points: T0 (preoperative, duration: 90–120 min); T1 (24–48 h after cardiac surgery, duration: ≥11 h); and T2 (7–10 days post-surgery, duration: 90–120 min). For each patient, aEEG background activity was evaluated and scored, and clinical and surgical data were retrieved to establish short-term post-surgical outcomes. Patients with normal T0 monitoring had significantly higher aEEG bandwidths in T1. A lower Aristotle basic score was associated with an improvement in aEEG at T1. Inversely, a narrower aEEG bandwidth in T1 was associated with post-surgical neurological deterioration. The aEEG bandwidth accurately predicted short-term neurological outcome; in particular, a minimal aEEG amplitude above 17.5 µV excluded poor neurological outcome with a negative predictive value of 81.48%. Our results demonstrated that aEEG bandwidth and trend dynamics may be associated with surgical complexity and neurological outcomes. aEEG background trend monitoring may provide relevant prognostic information on neurological outcomes in surgically treated CHD neonates.

NeuroSci doi: 10.3390/neurosci7020047

Authors: Paul Glogau Junqiao Mi Patrick Meybohm Malgorzata Burek

Brain metastases remain a major problem for cancer patients, impacting their treatment and survival. The pathogenesis of brain metastases is largely unknown. Recent reports indicate that the adhesion molecule protocadherin γ C3 (PCDHGC3) is differentially expressed in various cancer cells and endothelial cells of the blood–brain barrier (BBB), suggesting its involvement in the development of brain metastases. Therefore, we generated a PCDHGC3 knockout (KO) in the triple-negative breast cancer cell line HCC1806 and the malignant melanoma cell line A2058. Control and KO cells were compared using cell proliferation, adhesion and invasion assays, gene expression analyses and matrix metalloproteinase (MMP) activity assays. While the PCDHGC3 KO mutation led to increased proliferation in HCC1806 cells, with no difference observed in A2058, it significantly increased adhesion to in vitro BBB models as well as invasion in both HCC1806 and A2058 KO cell lines. Although changes in mRNA expression of genes involved in metastasis, angiogenesis and cell adhesion were found in PCDHGC3 KO breast cancer and melanoma cells, the number of genes with significantly increased mRNA expression was higher in A2058 KO cells than in HCC1806 KO cells. While the mRNA expression of MMP1 and 2 was increased in A2058 KO cells, no significant changes were found in HCC1806 KO cells. However, increased MMP activity in the cell culture medium was detected in HCC1806 KO cells, while A2058 KO cells showed lower MMP-activity compared to control. These findings provide insights into the role of PCDHGC3 in cancer cell extravasation during metastatic process and identify potential therapeutic targets for further investigation.

NeuroSci doi: 10.3390/neurosci7020046

Authors: Karel Kostev Henning Sievert Marcel Konrad Christian Tanislav Jens Bohlken

Background: The IQVIA Disease Analyzer (DA) database is a major outpatient electronic health record dataset in Germany. Over recent years, it has been increasingly used to study neurological diseases, comorbidities, treatment patterns, and long-term sequelae. We narratively summarized neurology-related studies using the German IQVIA Disease Analyzer (DA) database published since 2020 and to highlight methodological considerations relevant for interpreting DA-based neurological research. Methods: We conducted a narrative review of DA-based studies published between January 2020 and December 2025. PubMed was searched using DA-related keywords and major neurological disease terms. Eligible articles included peer-reviewed cohort, case–control, or descriptive studies using DA outpatient data. Results: The review identified studies covering epilepsy, cerebrovascular outcomes, Parkinson’s disease, dementia, multiple sclerosis, migraine, and sensory disorders. Most used retrospective cohort or nested case–control designs with regression or propensity score methods. Follow-up durations ranged from 3 to 10 years. Results consistently reflected routine care outpatient diagnostic and prescribing patterns. Discussion: Strengths of DA studies include large patient populations, long follow-up, and detailed prescription information. Limitations include reliance on outpatient ICD-10 coding, lack of detailed neurological phenotyping, and potential residual confounding and bias. Conclusions: DA-based analyses generate clinically relevant routine care evidence on neurological conditions in the German outpatient setting. Proper methodological safeguards and complementary data sources are required to contextualize findings for clinical and epidemiological use.

NeuroSci doi: 10.3390/neurosci7020045

Authors: Kawsar Ullah Chowdhury Subhrajit Bhattacharya Md Reaz Uddin Miranda N. Reed Soon Goo Lee Vishnu Suppiramaniam

Polysialic acid (PSA), a highly negatively charged glycan attached mainly to the neural cell adhesion molecule (NCAM), is emerging as a critical but underrecognized extracellular regulator of glutamatergic neurotransmission. While previous literature has focused on PSA’s developmental roles, increasing evidence indicates that PSA–NCAM also contributes to synaptic plasticity mechanisms in the mature brain. This review integrates evidence from structural biophysics, single-channel electrophysiology, and disease models to explain how PSA modulates glutamate receptor gating to control learning and memory. We synthesize findings from biochemical reconstitution, electrophysiological recordings, and in vivo studies to show that PSA can modulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor open probability, burst duration, and cooperative gating without affecting conductance, thereby promoting long-term potentiation. Conversely, PSA selectively suppresses GluN2B-containing extrasynaptic N-methyl D-Aspartate (NMDA) receptor activity by lowering open probability and calcium influx, maintaining an optimal balance between potentiation and depression while providing neuroprotection. Disruption of PSA–NCAM signaling in developmental and disease models, including prenatal cannabinoid exposure and neurodegeneration, produces cognitive deficits reversible by PSA restoration. Notably, much of the current evidence derives from in vitro systems, with relatively few studies conducted in vivo, and studies employing PSA mimetics mostly, which should be considered when interpreting physiological relevance. Collectively, the available evidence suggests that PSA functions as an extracellular modulator linking synaptic glycans to glutamate receptor regulation and plasticity related signaling pathways, highlighting the potential importance of extracellular glycan mechanisms in the control of synaptic function.

NeuroSci doi: 10.3390/neurosci7020044

Authors: Maria-Delia Mihailov Mirela Simona Manea Ioana-Cristina Olariu Gabriela Simona Doros

Background: Subacute sclerosing panencephalitis (SSPE) is a chronic, progressive disease of the central nervous system (CNS) caused by persistent infection at this level with the wild measles virus. Its incidence is negatively correlated with measles vaccination coverage. The pathogenesis isn’t fully understood, but infection before the age of 2 is an important risk factor. Methods: This is a retrospective observational study conducted at the Louis Turcanu Emergency Children’s Hospital in Timisoara, Romania, based on the analysis of the medical records of patients diagnosed with SSPE between January 2021 and December 2025. We analyzed demographic and epidemiological factors, clinical and paraclinical findings, management, and outcomes. Results: Seven children were diagnosed during the study period, with a mean age of 8.4 years (range 7–11 years). Six of them had contracted measles during their first year of life, and one at the age of four. The mean latency period was 7.1 years (range 4–9 years). On admission, all patients presented symptoms consistent with clinical stage II, with periodic slow wave discharges on electroencephalogram (EEG). The initial brain Magnetic Resonance Imaging (MRI) was normal in two cases, while revealing varied abnormalities in all others. Despite complex treatment with isoprinosine and anticonvulsants, progressive cognitive and neurological deterioration continued in all patients. Conclusions: SSPE is a rare but serious, debilitating disease despite its complex, multidisciplinary care. Following a 10-year SSPE-free period, the reappearance of these pediatric cases constitutes a public health alert, unequivocally demonstrating the importance of measles vaccination.

NeuroSci doi: 10.3390/neurosci7020043

Authors: Riad Abdulmoniem Mia Rivers Gabriel Carter Syed J. Khundmiri Jahn N. O’Neil

Apolipoprotein epsilon (APOE) is a small molecular protein that regulates lipid and lipoprotein homeostasis. Several reports demonstrated that apolipoprotein epsilon-4 allele (APOE4) expression significantly increases the genetic risk of Alzheimer’s disease (AD) and chronic kidney disease. However, there is inconsistent evidence of the association of AD with dietary habits, especially salt intake. Therefore, we hypothesized that high dietary salt intake would exacerbate cognitive decline in mice expressing the human APOE4 allele. We used human APOE (APOE4 and APOE3) knock-in mice to test this hypothesis. Young adult male and female mice aged 5–7 months old (n = 18 in each group) were fed a 4% NaCl (high-salt) or a 0.1% NaCl (low-salt) diet for 4 weeks. Metabolic cage studies were used to assess 24 h measurements of food and water intake, and urine output. Spatial memory and learning were determined using the Barnes maze test. Both the APOE3 and APOE4 mice on a low-salt diet had significantly decreased urinary volume, and female mice had lower body weight. The APOE4 mice on the low-salt diet (0.1%) performed significantly better on the 72 h probe test as compared to the APOE4 mice on 4% salt diet. The results demonstrate an association among dietary salt, memory, and APOE4 genotype.

NeuroSci doi: 10.3390/neurosci7020042

Authors: Madela Hasani Ilektra Sidiropoulou Anna Christakou Antonia Marazioti Spyridon Konitsiotis Epameinondas Lyros

Background and purpose: Balance and gait problems pose a significant burden in Parkinson’s disease (PD), and they are often poorly treated with levodopa. We intended to summarize evidence of mid- and long-term impact of various physiotherapeutic interventions (≥3 months post-intervention) on dynamic balance, gait, and general motor function in patients with PD. Method: A systematic search was conducted across the PubMed, Cochrane Library, and Scopus databases to identify controlled clinical trials on sustained effects of various exercise interventions in PD on the outcomes of interest (lasting ≥ 3 months after completion of the exercise program). We conducted meta-analyses on commonly used clinical measures of dynamic balance and gait ability, as well as on UPDRS-III scores using the Comprehensive Meta-Analysis Software (CMA). Results: A total of 26 studies were included in meta-analyses, with a total of 1261 participants in the experimental and 989 participants in the control groups. Positive cumulative effects at the post-exercise follow-up (3 to 23 months) were shown in favor of the intervention group regarding balance (SMD = 0.512, 95% CI [0.240, 0.785], p < 0.001, I2 = 87%), gait (SMD = 0.614, 95% CI [0.301, 0.926], p < 0.001, I2 = 75%), and general motor function (SMD = 0.922, 95% CI [0.559, 1.285], p < 0.001, I2 = 87%). Heterogeneity among studies was high for all three outcomes, apparently reflecting diversity with regard to patient characteristics, type, and duration of intervention, as well as the method of outcome assessment. The certainty of evidence was consequently judged as ‘’low’’ to ‘’moderate,’’ according to the GRADE system. Subgroup analyses revealed that balance can sustainably improve mostly through multimodal rather than targeted balance-oriented exercise but also through dual-task exercise, tai chi, and Pilates. Gait showed improvement at follow-up mainly through multimodal exercise, aerobic exercise, dual-task exercise, and Pilates, with benefits confined to early- and mid-stage disease. Sustained UPDRS-III improvement could be achieved through multimodal exercise, which showed a large overall effect but also through aerobic, resistance, and dual-task training, tai chi and qigong. Conclusions: Exercise interventions can improve balance and gait, as well as preserve the overall motor function in patients with PD, also in the mid- and long-term post-intervention periods.

NeuroSci doi: 10.3390/neurosci7020041

Authors: Maria Eugenia Martelli Simone Colella Roberta Meloni Federica Gigliotti Antonello Rosato Massimo Panella Carla Sogos

The increasing prevalence of Autism Spectrum Disorder (ASD) has intensified research efforts aimed at clarifying its neurobiological underpinnings. Electroencephalography (EEG) has enabled the identification of functional alterations in neuronal networks, contributing to the characterization of ASD-related brain dynamics and supporting the investigation of links between neural processes and behavioral impairments. In recent years, Artificial Intelligence (AI) methods have been increasingly applied to EEG analysis, allowing the extraction of complex, high-dimensional features. However, the limited interpretability of many AI-based models represents a major barrier to their clinical translation. To address this issue, Explainable Artificial Intelligence (XAI) approaches have emerged as promising tools to enhance model transparency and neurobiological interpretability. This systematic review examined studies explicitly applying XAI techniques to EEG or event-related potential data from individuals with ASD. A comprehensive literature search was conducted across multiple electronic databases up to November 2025. Studies were included if they involved ASD populations, electrophysiological data, and AI-based analytical approaches with explicit explainability components. Due to substantial methodological heterogeneity, a qualitative narrative synthesis was performed. Eleven studies met the inclusion criteria. Overall, included articles highlighted partially overlapping electrophysiological patterns involving spectral alterations, functional connectivity, and network organization; however, some studies also revealed marked heterogeneity in study design and limited clinical characterization. Consequently, they should be interpreted with caution, as the field remains at a preliminary stage. This review outlines current trends, methodological limitations, and key gaps in XAI-driven EEG research in ASD, and discusses future directions toward clinically meaningful and interpretable neurophysiological biomarkers. The review protocol was registered in PROSPERO (CRD420251231630).

NeuroSci doi: 10.3390/neurosci7020040

Authors: Marharyta Kamarova Ali Alhashimi Mudasar Aziz Joyce Balami Alison Buck Madeline McGinnis Arshad Majid Ali Ali Sheharyar Baig

Introduction: Remote ischaemic conditioning (RIC) is a promising treatment for neurological disorders. It involves cycles of temporary ischaemic stimulus, usually applied to a limb, and has shown significant improvement in neurological function in many trials. This review focuses on identifying and summarising the biomarkers of RIC that can enhance clinical practice and understanding of its mechanisms. Methods: A search was conducted in MEDLINE and EMBASE up to August 2025 using terms related to ischaemic conditioning. Studies were included if they were RCTs involving cerebrovascular disease, used RIC as treatment, and measured mechanistic biomarkers. We extracted and summarised data on study design, participant characteristics, RIC intervention protocols (including timing, frequency, duration, and pressure), biomarker types and measurement methods, timing of biomarker assessment, and main findings relating biomarker changes to clinical outcomes. Results: The review identified twenty-one RCTs examining biomarkers, including serum biomarkers, imaging markers, and other physiological indicators. Key biomarkers identified include systemic inflammatory cytokines and various imaging markers such as cerebral blood flow (CBF), white matter hyperintensities (WMH), and brachial artery flow-mediated dilation (BA-FMD). Conclusions: The evidence suggests that RIC modulates various biomarkers linked to neuroprotection and recovery. Reliable biomarkers of RIC would enhance the understanding of its mechanisms and improve targeted therapies. The clinical utility of these biomarkers requires further validation through large-scale trials. Standardised protocols and longitudinal studies are essential for optimising RIC therapy and improving patient outcomes in stroke and cerebral small vessel disease. Future research should focus on expanding our understanding of these biomarkers and their interactions with RIC, leading to more personalised and effective treatments.

NeuroSci doi: 10.3390/neurosci7020039

Authors: Mengyu Duan Zhuorui Liu Li Sui

Numerosity can be represented in symbolic formats and non-symbolic dot arrays. How numerosity load unfolds across WM encoding/maintenance and test-stage comparison within a single paradigm remains unclear, especially within the tested 4–6 range. We used a delayed match-to-sample task manipulating numerosity (4–6) and match status, with two test blocks (dot–digit and dot–dot). Behaviorally, a higher numerosity reduced accuracy and increased RTs in both blocks, with larger costs in dot–dot; the mismatch reliably slowed RTs. At sample onset, occipital P1 and N1 amplitudes decreased with increasing numerosity, consistent with greater perceptual/processing demands at higher load, with the strongest differences at the high end of the range. During the delay, numerosity modulation was temporally specific, emerging in the 450–650 ms posterior window and remaining significant after FDR correction across the four consecutive delay windows. At the test, the mismatch elicited a more negative N2 in both blocks (larger in dot–dot), while numerosity also modulated N2 only in dot–dot, showing a monotonic increase in negativity with load. Controlling for condition-mean logRT did not eliminate these N2 effects. P3 showed no reliable modulation, whereas a later positive component was enhanced by mismatch selectively in dot–dot. Together, these results indicate stage-differentiated effects: numerosity load impacts early encoding and a circumscribed maintenance interval, whereas mismatch effects arise primarily during the test-stage comparison, with additional late evaluative activity when formats are aligned.

NeuroSci doi: 10.3390/neurosci7020038

Authors: Marina Papadogiani Theodoros Fasilis Akyllina Despoti Vasiliki Kamtsadeli Maria Hantzopoulou Niki Tsinia Evdoxia Lykou Lina Chatziantoniou Dimitrios Chousos Kostas Siarkos John D. Papatriantafyllou

The Benson Complex Figure Test (BCFT) is a neuropsychological tool designed to assess visuospatial construction and visual memory with lower complexity than traditional tests. This study evaluated its ability to differentiate between major dementia subtypes. In a retrospective cross-sectional analysis of 1428 participants from a Greek third-age day center (healthy participants [Controls]; patients diagnosed with Alzheimer’s disease dementia [ADD], Lewy body dementia [LBD], Frontotemporal dementia [FTD: behavioral variant (BV), non-fluent variant (NFV), semantic variant (SV)], Corticobasal dementia [CBD], Parkinson’s disease dementia [PDD], and mixed Cardiovascular dementia with Alzheimer’s disease [CVD/AD]), all participants completed the BCFT and the Mini-Mental State Examination (MMSE). Multinomial logistic regression, adjusted for age, sex, and education, revealed distinct BCFT profiles across dementia subtypes. Patients with CBD showed significantly lower copy scores than those with ADD (p = 0.006). The FTD-NFV group exhibited superior memory scores compared to all other dementia subtypes (p < 0.001). Poorer BCFT recognition performance was strongly associated with diagnoses of ADD (OR = 0.39, p = 0.012), FTD-BV (OR = 0.22, p = 0.025), and PDD (OR = 0.26, p < 0.001). Classification accuracy was highest for controls and ADD (sensitivity > 89%) but low for rarer subtypes (<25%), partly reflecting sample size limitations. In conclusion, the BCFT captures distinct visuospatial and memory profiles across dementia syndromes, supporting its potential utility in differential diagnosis, particularly for common subtypes such as ADD. Its simpler design may facilitate assessment in older adults, although validation in larger and more balanced cohorts is required for rarer dementias.

NeuroSci doi: 10.3390/neurosci7020037

Authors: Lamees A. Alhajri Renad S. Manez Husna Irfan Thalib Abdulelah F. Alshehri Amjad M. Alramadan Lama M. Alsulami Mustafa A. Al Shankiti Mahmoud Alhajji Abdullah Almaqhawi

Introduction: Vestibular migraine (VM) is a frequent but underdiagnosed cause of episodic vertigo, characterized by vestibular symptoms often accompanied by migrainous features. Despite its relatively high prevalence, diagnosis remains clinically challenging and may differ depending on the diagnostic criteria used. This systematic review evaluates VM prevalence and clinical features across age groups to improve recognition and guide age-appropriate management. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO. This research was conducted using PubMed, Google Scholar, Cochrane, Web of Science, Wiley Online Library, and Embase. Two independent reviewers screened studies by title and abstract, and a separate pair screened full texts. Eligible studies were observational and reported prevalence or clinical features of VM. Results: A total of 874 publications were identified, leading to the review of 21 studies. Prevalence of VM varied widely, ranging from 6% to 35% in children and 2.7% to 40.9% in adults. Pooled prevalence across studies was 19% overall, 25% in children, and 14% in adults. Among patients with vertigo, the pooled prevalence was higher at 26%, with 33% in children and 18% in adults. Vertigo was the most consistent symptom in both age groups, and female predominance was observed in all age groups. Prevalence variability likely reflects diversity in applied diagnostic criteria and study design across included studies. Conclusion: VM is a common cause of vertigo, particularly in pediatric populations. Age-specific clinical features highlight the need for tailored diagnostic and management strategies. Future research should focus on large-scale prospective studies.

NeuroSci doi: 10.3390/neurosci7020036

Authors: Ángela Acosta-Amaya Salvador Sánchez-Badajos David J. Dávila-Ortiz de Montellano Alberto Ortega-Vázquez Ramiro Ruiz-Garcia Nancy Monroy-Jaramillo Yaneth Rodríguez-Agudelo

Mild behavioral impairment (MBI) constitutes a late-life transition state that is associated with an increased risk of cognitive impairment and dementia. Herein, we cross-sectionally describe the MBI construct and its relationship with cognitive status in Mexican-Mestizos (MM) older adults. Participants were classified according to their cognitive and behavioral statuses using tests administered to older adults and their informants. APOE_rs429358/rs7412 variants were genotyped by real-time PCR. Multivariate correlation and Principal Components Analysis (PCA) were used in statistical analysis. A total of 246 participants were included, 56.1% were classified as individuals with NC, 13.0% had subjective cognitive decline, and 30.9% had mild cognitive impairment. A total of 37% (91/246) of participants from all over the cognitive spectrum met the MBI criteria; among this group, APOEε4 homozygosity was associated with two subdomains of the MBI. Subjective cognitive complaint, symptoms of depression, and cognitive decline reported by the informant were associated with an increased risk for MBI (ORs in the range of 4.7–15.89). The first three components of PCA explained 68.0% of the variance of the dataset, including the MBI-checklist total score as a main contributor. Well-known risk factors for dementia also correlated with this PCA. MBI could be a potential marker for cognitive decline in non-demented MM elderly people; however, observed associations should be confirmed in future longitudinal studies.

NeuroSci doi: 10.3390/neurosci7020035

Authors: Klaudia Rojewska Natalia Dynowska Iwona Rotter Małgorzata Niekrasz

Creutzfeldt–Jakob disease (CJD) is a rare, fatal prion disease of the central nervous system that develops due to the conversion of the normal cellular protein PrPc to the abnormal PrPSc molecule. The first clinical cases were described in the 1920s. The aim of this paper is to present the clinical progress of the disease and the diagnostic process, including some of the most common diagnostic traps. The paper highlights a range of symptoms that should serve as a potential warning signal for clinicians—not just neurologists—indicating the need to evaluate the patient more thoroughly.

NeuroSci doi: 10.3390/neurosci7020034

Authors: Mohammad Yazdan Panah Mehra Fekri Zahra Zahedi Hossein Bagheri Saeed Vaheb Farhad Mahmoudi Vahid Shaygannejad Omid Mirmosayyeb

Background: Slowly expanding lesions (SELs) have been introduced as a radiological marker of chronic active demyelination and smoldering inflammation. These lesions are recognized as indicators of disability worsening and brain atrophy in people with multiple sclerosis (PwMS). We aimed to provide an overview of the available evidence on the prevalence and clinical relevance of SELs in PwMS. Methods: PubMed, Embase, Scopus, and Web of Science were systematically searched up to 25 May 2025, to identify studies evaluating SELs in PwMS. Risk of bias was assessed using the Newcastle–Ottawa Scale. We conducted a thorough review to evaluate the clinical relevance of SELs in MS. Additionally, a meta-analysis was performed using R software to estimate the pooled prevalence of SELs in MS. Results: Twenty studies on 4970 PwMS met the inclusion criteria. Meta-analysis indicated that the pooled prevalence of SELs in PwMS was 57.1% (95% CI: 44.9% to 69.3%). Moreover, the systematic review showed that SELs were associated with chronic neuroinflammation, ongoing demyelination, disability, microstructural damage, and axonal degeneration. Intervention studies also indicated that the number and volume of SELs were decreased following the administration of disease-modifying therapies. Conclusions: SELs are revealed to affect around half of PwMS and are associated with disability and disease progression in MS. These results highlight the potential role of SELs as a critical radiomarker in MS. However, future studies are warranted to validate these preliminary findings.

NeuroSci doi: 10.3390/neurosci7020033

Authors: Yasin Said Almakadma Jouhara Jouhar Abdulaziz Farooq Tahani Albatarni

Background: Lower limb (LL) and low back Radicular Syndromes (RSs) may result from discopathy of the lumbo-sacral spine. Consistent benefits are reported from Epidural Adhesiolysis (EA). Aim: To evaluate clinical and European Quality of Life items (EQ-5D) of Peri-Neural Release interventions (PNR, a modified approach and terminology for EA) among patients diagnosed with lumbo-sacral discopathy associated radicular syndromes. Methods: A retrospective study was conducted by retrieving records of patients e treated by PNR for low back and lower limbs pain between January 2018 and December 2024. Eligible patients were adults who were diagnosed with lumbo-sacral discopathy, stenosis, or Post Lumbar Surgery Syndrome (PLSS). Data on Patient-Reported Outcome Measures (PROMs) adopting the European Quality of Life five items (Euro-QoL 5D) that includes self-ratings of mobility, active daily living, self-care, pain and discomfort, anxiety and depression) was collected before the procedure and on subsequent follow-up visits. Other clinical outcomes included numerical pain rating scales (NRSs), sleep quality, time to pain during activity, and self-reported health scores. Results: A total of 221 patients were included in this analysis. Of these, 56.6% were female, with a mean age of 45.1 ± 14.7 years. In total, 50.2% of patients underwent PNR alone, followed by 28.1% who underwent PNR balloon decompression neuroplasty. Of the remaining patients, 7.2% underwent epiduroscopic PNR, 6.3% PNR combined with annuloplasty (biacuplasty) and 8.1% underwent PNR combined with nucleoplasty. Significant improvements were observed across all EQ-5D and NRS (p < 0.001) at follow-up assessments without major complications. The interventions were associated with a decrease in NRS from 7.9 to 3.1, and an increase in the duration of pain-free activity (walking, standing, sitting) (p < 0.001). Self-reported overall health scores improved from 53.9 ± 18.4 to 81.1 ± 15.1. In terms of complications, two patients reported post-operative headache. The remaining side effects included coccydynia at the site of intervention, resolving with application of non-steroid anti-inflammatory topicals and self-resolving lower limb numbness in five cases. Conclusions: The presented data suggest that PNR—whether performed alone or in combination with adjunctive intradiscal procedures—is a safe intervention, and is associated, in the majority of patients, with substantial pain relief and improvement in EQ-5D both in the short- and long-term follow-up.

NeuroSci doi: 10.3390/neurosci7020032

Authors: Giorgos Sideris George Korres Ilias Lazarou Eleni Vasileiou Amanda Male Diego Kaski

While typical benign paroxysmal positional vertigo (BPPV) presents with reproducible patterns of nystagmus and vertigo during positional testing, atypical variants often deviate from typical patterns, making diagnosis more complex. Recognizing atypical BPPV is crucial to avoid misdiagnosis and inappropriate management. This study aims to describe the clinical spectrum of atypical BPPV, differentiate it from central positional vertigo, and provide practical diagnostic guidance for clinicians. A narrative review was conducted to explore the clinical spectrum of atypical BPPV. Findings indicate that it may present with vertigo without nystagmus, conflicting torsional components in bilateral cases, or persistent symptoms despite repositioning maneuvers. Canal switch and pseudo-spontaneous nystagmus have also been described. Although these variants may mimic central etiologies, the absence of consistent neurological signs supports a peripheral mechanism. Diagnosis relies on detailed assessment of nystagmus characteristics—such as latency, /duration, and direction—as well as the exclusion of red flags, like direction-changing nystagmus without head movement, vomiting, or non-positional ocular motor abnormalities. Atypical BPPV remains a diagnostic challenge and requires careful bedside assessment and clinical testing. Understanding these variants is essential for timely and appropriate treatment. When doubt persists and resolution with treatment does not occur, neuroimaging should be considered to exclude central pathology.

NeuroSci doi: 10.3390/neurosci7020031

Authors: Eric Altieri Luca Battaglini

Charles Bonnet syndrome (CBS) is characterized by complex visual hallucinations in visually impaired individuals who maintain intact cognitive function. Despite significant progress in understanding this condition, the precise neural mechanisms underlying CBS remain incompletely understood. This review synthesizes current evidence regarding the pathophysiology of CBS, with particular emphasis on emerging neurobiological models that extend beyond simple cortical hyperexcitability. Recent neuroimaging, neurophysiological, and computational modeling studies suggest that CBS hallucinations may arise from complex interactions among deafferentation-induced neural plasticity, neurotransmitter imbalances, and altered functional connectivity within visual processing hierarchies. The evidence increasingly points toward a model involving desynchronization between bottom-up and top-down visual processing pathways, rather than mere hyperexcitability of deafferented visual cortex. This integrated perspective has important implications for both the theoretical understanding of visual perception and the development of targeted therapeutic interventions.

NeuroSci doi: 10.3390/neurosci7020030

Authors: Jagoš Golubović Bojan Jelača Dušan Rodić Slobodan Torbica Srđan Stošić Đula Đilvesi

Lumbar intervertebral disc herniation is a common cause of low back and radicular leg pain, traditionally managed with a combination of conservative therapies and, when indicated, surgical discectomy. An intriguing phenomenon observed in many patients is the spontaneous resorption of herniated disc material over time, often correlating with significant symptom improvement. This article is presented as a narrative review synthesizing experimental, imaging, and clinical literature relevant to spontaneous disc resorption and its implications for clinical decision-making. This paper provides a comprehensive overview of spontaneous disc herniation resorption, exploring the underlying pathophysiological mechanisms and the factors that predict which herniations are likely to regress without surgery. Key mechanisms include inflammatory-mediated degradation of disc fragments, neovascularization with macrophage infiltration and phagocytosis of extruded nucleus pulposus tissue, and biological processes such as enzymatic matrix breakdown and cellular apoptosis that collectively lead to shrinkage of the herniated mass. Patient and disc characteristics that favour spontaneous resorption are identified, such as younger age, extruded or sequestered fragment type, larger initial herniation size, and robust inflammatory response on imaging, whereas certain chronic degenerative changes may reduce this likelihood. We also review current clinical guidelines and expert recommendations on when surgical intervention is warranted versus when conservative management and observation are appropriate. Understanding the probability of natural disc fragment resolution is critical in guiding treatment decisions. In the absence of severe neurological deficits or intractable pain, a period of non-operative management can often be pursued safely, given that the majority of patients experience substantial relief within a few months as discs regress. Conversely, timely surgery is advised for those with neurological compromise or refractory symptoms. By synthesizing the latest evidence on spontaneous disc herniation resorption and its predictors, this review aims to assist neurosurgeons and spine specialists in optimizing patient selection for conservative care and identifying the proper timing for surgical intervention to achieve the best clinical outcomes. Given the narrative design, conclusions are based on synthesis of heterogeneous evidence rather than formal comparative analysis.

NeuroSci doi: 10.3390/neurosci7020029

Authors: Mona Buhusi Catalin V. Buhusi

The neuronal cell adhesion molecule NrCAM is widely expressed in the nervous system across the lifespan and has important physiological functions in the development of neuronal circuits through axonal growth and guidance and formation and maintenance of synapses in the cortex. NrCAM gene polymorphisms are associated with vulnerability to neuropsychiatric disorders such as schizophrenia, as well as vulnerability to substance use disorders. We investigated the effects of acute and chronic stress and the effects of systemic administration of AMPAR antagonist CNQX and NMDAR antagonist MK-801 on delay discounting in male NrCAM knockout (KO) mice and their wild-type littermate controls (WT). Under the no-stress condition, no discounting differences were found. Acute stress increased discounting and impulsivity in WTs but not in NrCAM KO mice. Chronic stress increased discounting and impulsivity in both genotypes. CNQX increased impulsive choice in WT controls but not in NrCAM KOs; impulsive choice decreased in both genotypes after MK-801 administration. Relative to WTs, NrCAM KOs had more neuronal activation in the prelimbic and orbitofrontal cortices. In NrCAM KO mice, a low dose of MK-801 decreased neuronal activation in the ventral orbitofrontal cortex and increased activation in the accumbens shell and core. These results indicate differential effects of genotype, stress, and response to glutamatergic drugs and support a role for NrCAM in stress-induced behavioral alterations relevant to addiction and psychiatric disorders.

NeuroSci doi: 10.3390/neurosci7020028

Authors: Christina Flourou Nikolaos Dietis Sotirios Tsiordas Georgios Hadjigeorgiou George D. Vavougios

Background and aim: Alterations in immune signaling have emerged as a key factor contributing to Parkinson’s disease pathophysiology. Increasing evidence also suggests that MASLD and Parkinson’s disease may share common immunological mechanisms. Among these, TLR4 has been linked to immune surveillance processes and inflammatory responses in both the central nervous system and the liver. The aim of our study was to delineate TLR4-mediated immune networks underpinning the molecular overlap between MASLD and Parkinson’s disease. Methods: Disease–disease and gene–disease associations were systematically retrieved from the DisGeNet database to map TLR4-related molecular networks across both conditions. Functional enrichment analyses were subsequently applied to identify biological pathways significantly associated with TLR4, including potential gene–drug interactions. Guided by these results, a scoping review of the literature was undertaken to summarize existing evidence addressing TLR4-dependent mechanisms in MASLD and Parkinson’s disease. Results: DisGeNet analysis indicated 978 shared genes and 39 SNPs shared between both diseases. TLRs, including TLR4-associated coreceptors such as CD14, are among these shared genes. Among these, TLR4 and its missense SNP rs4986791 emerged as key shared immunometabolic nodes linking both diseases. Among the shared SNPs identified in both diseases, we focused on TLR4, where the common variant was rs4986791. Gene set enrichment analysis revealed multiple biological processes associated with cytokine signaling, inflammation, and fibrogenesis. Gene–drug enrichment analysis identified statins and fibrates among the compounds enriched in TLR4-containing networks. Conclusions: These findings support a role for TLR4-associated pathways in linking immunometabolic processes across MASLD and Parkinson’s disease. Disruption of these pathways is associated with aberrant inflammatory regulation, with tissue-specific effects further contributing to the distinct molecular pathology observed in each condition. Consequently, modulation of TLR4 signaling represents a plausible strategy for the development or repositioning of disease-modifying interventions applicable to both conditions.

NeuroSci doi: 10.3390/neurosci7010027

Authors: Rosalinda Calandrelli Carlo Augusto Mallio Caterina Bernetti Luca Massimi Fabio Pilato

Purpose: The aim of this narrative review is to update current knowledge on Moyamoya vasculopathy (MMV) by addressing key diagnostic debates—including laterality; genetic subtypes; regional epidemiology; and features distinguishing Moyamoya Disease (MMD), Moyamoya Syndrome (MMS) and their mimics. Methods: Key and representative studies were identified through PubMed/MEDLINE and Scopus, focusing on publications from 2014–2025 while also considering earlier seminal works. Results: MMD typically presents with bilateral steno-occlusion of the terminal internal carotid arteries (ICAs) and proximal middle and anterior cerebral arteries (MCAs/ACAs) due to concentric vascular thickening, accompanied by characteristic ‘puff-of-smoke’ collaterals, whereas MMS shows a similar but more often unilateral pattern with fewer collaterals, influenced by the underlying condition. However, this distinction often fails to reflect the full clinical and radiological variability of the Moyamoya spectrum. Atypical moyamoya-like patterns, often confined to M1 or A1 segments, further complicate diagnosis. Clinical manifestations ranged from asymptomatic cases to ischemic or hemorrhagic strokes, and occasionally seizures. Diagnosis relied on multimodal imaging (DSA, MRA, CTA), but genetic mutations, contributing to radiological variability, often complicate differentiation between MMD, MMS, and mimics. Management is pattern-specific: MMS and atypical forms are generally managed conservatively, whereas MMD frequently requires surgical revascularization, particularly in children and symptomatic adults. Nevertheless, variability within diagnostic categories limits the applicability of rigid treatment protocols. Conclusions: Current diagnostic algorithms remain limited. Integrating advanced imaging findings with clinical, genetic, and epidemiological data is essential to define the full disease spectrum, improve diagnostic accuracy, and inform patient management and outcome assessment.

NeuroSci doi: 10.3390/neurosci7010026

Authors: Jeremy Ramsden Marika Chikviladze Nino Mamulashvili Lali Shanshiashvili David Mikeladze

Multiple sclerosis (MS) pathogenesis involves not only immune-mediated myelin injury but also glial responses. We examined how three charge isomers of myelin basic protein (MBP)—native (C1), phosphorylated (C4), and citrullinated (C8)—modulate rat astrocytes. Cytokines were quantified and grouped (pro/anti-inflammatory, chemotactic, neurotrophic, angiogenic, tissue remodeling), and regulatory markers assessed. C1 strongly upregulated the lipid-sensing receptor LXR, and reduced global DNA methylation; C4 moderately enhanced LXR; C8 failed to activate LXR or alter methylation. Functionally, C1 attenuated IL-1β, IL-6 and GM-CSF while increasing IL-10 and certain chemokines. C4 elicited an intermediate pattern, inducing CX3CL1 (fractalkine), CCL20, VEGF-A and TIMP-1 with minor effects on classical cytokines. In contrast, C8 triggered a robust pro-inflammatory phenotype, increasing IL-1α/β, TNF-α and GM-CSF, with higher IL-10, fractalkine, CCL20, VEGF-A and TIMP-1. All isomers suppressed IFN-γ, IL-4 and CNTF. These data indicate that MBP post-translational modifications drive distinct astrocyte phenotypes through integrated cytokine, metabolic and epigenetic pathways: C1 favors immune regulation and repair, C4 blends inflammatory and reparative cues, and C8 amplifies neuroinflammation. Understanding how modified MBP shapes astrocyte behavior provides mechanistic insight into lesion evolution in MS and suggests astrocyte-directed strategies to modulate neuroinflammation and promote remyelination.

NeuroSci doi: 10.3390/neurosci7010025

Authors: Brittany Nackley Bruce H. Friedman

Traditional interoception research investigates cardioception, respiroception, or gastroception as a proxy for the sense of the body as a whole. These single-organ tasks sacrifice construct and ecological validity for a content validity that has been elusive. We propose that interoception is better captured by one’s sense of their own autonomic nervous system, or ANSception. The ANS integrates multimodal signals via lesser-myelinated neurons, making it an integral part of the interoceptive nervous system. Thirty-four participants moved a slider to reflect their perceived sympathetic activation (ANSception) while their physiology was monitored. Most participants reported integrating information from two or more organ systems during ANSception. The relationship between ANSception and physiology showed unique but often robust responses by condition and physiological measure. For example, one participant had a negative-to-positive-to-negative pattern for ANSception-EDA correlations from baseline to stimulus to recovery (r = −0.677; 0.657; −0.507, p < 0.001). Another participant had a strong positive correlation between their ANSception and blood pressure (r = 0.601, p < 0.001) during a five-minute reportedly meditative state. We propose that the role of interoception is to scan, integrate and manage information across organ systems, and we conclude that ANSception better captures this role than traditional single-organ tasks.

NeuroSci doi: 10.3390/neurosci7010024

Authors: Huanwen Chen Rachel K. Laursen Matthew K. McIntyre Monika Jain Hamza A. Salim Dhairya A. Lakhani Ajay Malhotra Dheeraj Gandhi Marco Colasurdo

Background: Intravenous thrombolysis (IVT) is relatively contraindicated in acute ischemic stroke (AIS) patients with intracranial vascular malformations per current guidelines. Thus, the presence of cerebral cavernous malformations (CCMs) may complicate treatment decision-making. Methods: We performed a literature review of the PubMed, Embase, Scopus, and Web of Science databases through July 2025, identifying reported cases of IVT administration in AIS patients with CCMs. Additionally, we conducted a retrospective cohort study using the Nationwide Readmissions Database (2016–2022) of AIS patients with CCM, and assessed outcomes with IVT versus no IVT treatment. The primary outcome was functional independence at discharge; secondary outcomes included mortality and intracranial hemorrhage (ICH). Results: Only 34 CCM patients across 7 studies were identified in the literature, with symptomatic ICH occurring in 2 cases (5.9%). In the nationwide cohort, 846 AIS patients with CCMs were included, of whom 240 (28.4%) received IVT. Compared to no IVT treatment, IVT was associated with significantly higher rates of functional independence (46.4% vs. 24.6%, adjusted OR [aOR] 3.04 [95% CI 1.98–4.68], p < 0.001), without significant differences in mortality (8.5% vs. 8.3%, aOR 1.40 [95% CI 0.52–3.76], p = 0.50) or ICH (20.3% vs. 16.1%, adjusted OR 1.01 [95% CI 0.53–1.93], p = 0.97). Conclusions: The current literature on the safety and efficacy of IVT in AIS patients with CCMs is limited. Our nationwide study suggests that IVT was associated with higher rates of early functional independence without increased risks of hemorrhage or death among patients with CCM.

NeuroSci doi: 10.3390/neurosci7010023

Authors: Adrian Jorda Kenia Alvarez-Gamez Ignacio Campo-Palacio Juan Campos-Campos Carlos Colmena Sandeep Kumar Singh Maria Jose Chiva Miralles Constanza Aldasoro Martin Aldasoro Soraya L. Valles

Alzheimer’s disease (AD) is marked by amyloid plaques, hyperphosphorylated TAU proteins, and neuroinflammation. The APP/PS1 mouse model is widely used to study AD pathogenesis. In this study, we investigated the expression of chemokines and their receptors, which may play a role in AD’s pathological mechanisms, using brain cortex tissue from female APP/PS1 mice aged 20–21 months. We analyzed several chemokine receptors (CCR1, CCR2, CCR3, CCR4, CCR6, CCR7, CCR9, and CCR10) by Western blot and focused on CCR6, CCR7, and CCR10 using RT-PCR. Additionally, we quantified the levels of chemokines (CCL6, CCL8, CCL19, CCL20, CCL24, and CCL27) by RT-PCR. Our results showed a significant decrease in CCL8 and CCL19, along with their respective receptors, in the APP/PS1 mice compared to controls. On the other hand, we observed a notable increase in CCL6, CCL24, CCL20, CCL27, and their receptors. Chemokines like CCL8 and CCL20, involved in inflammatory responses, may reveal how neuroinflammation contributes to AD. CCL19 and CCL27 are linked to immune cell trafficking, which may help explain immune cell interactions with amyloid plaques and TAU tangles in the CNS. Overall, the altered expression of chemokines such as CCL24 could serve as biomarkers for early AD detection and monitoring disease progression. These findings suggest potential therapeutic targets to modulate immune responses and reduce neuroinflammation in AD.

NeuroSci doi: 10.3390/neurosci7010022

Authors: Ali Al-Salahat Rohan Sharma

Background: Prior SMA mortality studies have shown excess mortality in people with SMA, but the literature lacks data on disparities in SMA-related mortality. This study examined disparities in SMA-related mortality in the United States in the post-treatment era (2018–2023). Methods: This was a population-based study using the CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. The International Classification of Disease (ICD), 10th Revision, Clinical Modification codes, G12.0, G12.1, G12.8, and G12.9, were used to identify SMA. The data were stratified by biological sex, race/ethnicity (Non-Hispanic/NH White, NH Black, Hispanic, Asian) and Census regions (West, Northeast, Midwest, South). The analysis was conducted by calculating rate ratios (RR) of age-adjusted mortality rate (AAMR). Results: There were 821 (45.8% female) SMA-related deaths across the study period. Males were associated with higher AAMR than females (RR = 1.189, 95% CI: 1.035 to 1.366). The SMA-AAMR for NH White individuals was the highest compared to Hispanic individuals (RR = 1.808, 95% CI: 1.420 to 2.300), followed by NH Black and Asian individuals. The West carried the highest AAMR compared to the Northeast (RR = 1.581, 95% CI: 1.263 to 1.978), followed by the Midwest and the South. The age at death distribution showed a bimodal pattern, as follows: 5–14 years and 65–74 years. The infant age group (<1 year) was associated with the highest AAMR compared to all other age groups. Conclusion: Our findings showed that SMA-related mortality was highest in infants, NH White individuals, the West, and males. These data may assist future efforts to reduce the burden of SMA.

NeuroSci doi: 10.3390/neurosci7010021

Authors: Tihomir Taskov Juliana Dushanova

Developmental dyslexia (DD) often involves difficulties in phonological processing of speech. Objectives: While underlying neural changes have been identified in terms of stimulus- and task-related responses within specific brain regions and their neural connectivity, there is still limited understanding of how these changes affect the overall organization of brain networks. Methods: This study used EEG and functional network analysis, focusing on small-world propensity across various frequency bands (from δ to γ), to explore the global brain organization during the auditory discrimination of words and pseudowords in children with DD. Results: The main finding revealed a systemic inefficiency in the functional network of individuals with DD, which did not achieve the optimal small-world propensity. This inefficiency arises from a fundamental trade-off between localized specialization and global communication. During word listening, the δ-/γ1-networks (related to impaired syllabic and phonemic processing of words) and the θ-/β-networks (related to pseudoword listening) in the DD group showed lower local clustering and connectivity compared to the control group, resulting in reduced functional segregation. In particular, the θ-/β-networks for words in the DD group exhibited a less optimal balance between specialized local processing and effective global communication. Centralized midline hubs, such as the postcentral gyrus (PstCG) and inferior frontal gyrus (IFG), which are crucial for global coordination, attention, and executive control, were either absent or inconsistent in individuals with DD. Consequently, the DD network adopted a constrained, motor-compensatory, and left-lateralized strategy. This led to the redirection of information flow and processing effort toward the left PstCG/IFG loop, interpreted as a compensatory effort to counteract automatic processing failures. Additionally, the γ1-network, which is involved in phonetic feature binding, lacked engagement from posterior sensory hubs, forcing this critical process into a slow and effortful motor loop. The γ2-network exhibited unusual activation of right-hemisphere posterior areas during word processing, while it employed a simpler, less mature routing strategy for pseudoword listening, which further diminished global communication. Conclusions: This functionality highlights the core phonological and temporal processing deficits characteristic of dyslexia.

NeuroSci doi: 10.3390/neurosci7010020

Authors: Carmen Rodriguez-Cerdeira

5a-reductase (5a-R) isozymes are essential for androgen metabolism and neurosteroid biosynthesis, linking endocrinology and neuropsychiatry. This systematic review, conducted in accordance with PRISMA 2020 guidelines, aimed to synthesize current evidence on the tissue distribution of SRD5A1, SRD5A2, and SRD5A3 and their implications in mental health. A systematic search of the PubMed, Scopus, and Web of Science databases up to February 2025 identified 257 articles, of which 83 met the inclusion criteria. SRD5A1 is broadly expressed in the liver, skin, and central nervous system, contributing to allopregnanolone synthesis; SRD5A2 is mainly restricted to androgen-dependent tissues, playing a key role in prostate development and alopecia; and SRD5A3 is associated with glycosylation processes and oncogenesis. Converging evidence suggests that impaired neurosteroidogenesis due to 5α-R inhibition may underlie vulnerability to anxiety, depression, and suicidality. While earlier epidemiological findings were heterogeneous, recent pharmacovigilance data have strengthened the evidence supporting this association. Pharmacovigilance and clinical reports show that a subset of patients treated with finasteride or dutasteride may experience persistent psychiatric and sexual adverse effects, known as post-finasteride syndrome. The current findings underscore the need for careful patient counseling, systematic monitoring, and further translational studies integrating genetics, neuroendocrine markers, and standardized psychiatric outcomes to identify individuals at risk and advance personalized medicine in this field.

NeuroSci doi: 10.3390/neurosci7010019

Authors: Matthew K. McIntyre Huanwen Chen Dheeraj Gandhi Ajay Malhotra Ryan Priest Marco Colasurdo

Objective: The safety of intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) patients with pituitary neoplasms is unclear. This study aims to assess IVT’s safety and efficacy in this patient population. Methods: We reviewed PubMed, Scopus, EMBASE, and Web of Science through July 2025 for reports of IVT administration in AIS patients with pituitary neoplasia. We also performed a retrospective analysis of the Nationwide Readmissions Database (NRD) from 2016 to 2022 to compare outcomes of IVT versus no IVT for AIS patients with pituitary neoplasia, and outcomes of IVT-treated AIS patients with versus without pituitary neoplasia. Outcomes of interest include post-stroke functional status, intracranial hemorrhage (ICH), mortality, and pituitary apoplexy. Multivariate regression analyses were performed to adjust for confounders. Results: The literature review identified 5 AIS patients with pituitary neoplasia, of whom 3/5 (60%) experienced intracranial hemorrhage and none developed apoplexy. In the nationwide analysis of 1,246,750 AIS patients, 1661 (0.13%) had concomitant pituitary neoplasm. Among these patients, IVT was associated with higher odds of functional independence at discharge (adjusted OR 2.46 [95%CI 1.56–3.87]), without increased risk of ICH or in-hospital death (p > 0.05). No cases of pituitary apoplexy were observed. Outcomes among all IVT-treated AIS patients did not differ between those with and without pituitary neoplasms (all p > 0.05). Interpretation: Only five cases of IVT for AIS patients with pituitary neoplasia were identified, highlighting a striking lack of clinical data. In a large U.S. cohort of AIS patients, IVT was associated with improved hospitalization outcomes without increased risk of ICH or pituitary apoplexy.

NeuroSci doi: 10.3390/neurosci7010018

Authors: Elias Manjarrez Ignacio Méndez-Balbuena Saul M. Dominguez-Nicolas Oscar Arias-Carrión

Monosynaptic reflexes (MSRs) elicited by constant-intensity group I afferent stimulation exhibit marked amplitude variability, commonly attributed to stochastic presynaptic modulation and dynamic postsynaptic excitability. Here, we tested whether this variability could be attenuated using the Ott–Grebogi–Yorke (OGY) chaos–control algorithm, which stabilizes unstable periodic orbits in low-dimensional nonlinear systems. In spinalized, anesthetized cats, real-time implementation of the OGY method failed to reduce MSR amplitude variability, as quantified by the coefficient of variation, and the return map structure showed no evidence of orbit stabilization. These negative results contrast with successful applications of OGY control in physical systems, cardiac tissue, hippocampal slices, and stochastic neuronal models. We interpret this failure in the context of the intense, ongoing synaptic bombardment characteristic of dorsal horn circuitry, which likely obscures or destroys the low-dimensional geometric structure required for OGY-based control. Our findings delineate a fundamental limit to classical chaos–control algorithms in intact neural circuits and highlight the need for control strategies explicitly robust to high dimensionality and physiological noise.

NeuroSci doi: 10.3390/neurosci7010017

Authors: Aleeza Safdar Ali Osman Rouzbeh Motiei-Langroudi

The management of spinal cord cavernous malformations (SCCMs) involves critical decisions between surgical and conservative treatments, informed by the patient’s preoperative neurological status, lesion characteristics, and timing of intervention (early or delayed surgery). Surgery remains an option for symptomatic patients, especially those with significant or progressive neurological deficits and large lesions, aiming for gross total excision to prevent (re)hemorrhage and improve outcomes. Conversely, conservative management is appropriate for small, asymptomatic lesions, with regular monitoring to detect changes necessitating surgery. Studies highlight the benefits and risks of both approaches. Surgical resection typically leads to neurological recovery, although worse preoperative status and larger lesions predict poorer outcomes. Other factors influencing surgical success include lesion location and timing of surgery, with early surgery (within 3 months) generally yielding better long-term outcomes. Future research should focus on the optimal timing of surgery, particularly the benefits of urgent intervention.

NeuroSci doi: 10.3390/neurosci7010016

Authors: Oscar Alexis Becerra-Casillas Karen Alejandra Diaz-Lozano Mario Treviño Paulina Osuna-Carrasco Braniff de la Torre-Valdovinos

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.

NeuroSci doi: 10.3390/neurosci7010015

Authors: Leigh Martin Riby Dimana Kardzhieva Sam Fenwick Sophia Fowler Mark Moss

Rosemary (Salvia rosmarinus) has been linked to improvements in psychological wellbeing through cholinergic mechanisms. However, this study investigated whether individual differences in eye blink rate (EBR) and blink variability (EBV), which are proxies of dopaminergic activity and attentional control, influence the cognitive and mood-enhancing properties of a rosemary-containing drink. Forty-eight healthy adults completed a three-stimulus odd-ball cognitive task under rosemary or control conditions, while vertical electrooculograms were recorded. Event-related brain potentials (ERPs) were also measured using the P3a component at the Cz scalp electrode as an additional index of dopaminergic activity. Subjective mood and arousal (alert, contented, calm) were collected pre- and post-task using Bond–Lader visual analogue scales. Reaction times during the task were modelled with ex-Gaussian parameters (μ, σ, τ). Rosemary ingestion led to increased alertness and contentedness following the task. Cognitive effects were moderated by blink metrics, with significant interactions between rosemary and blink metrics for mean reaction time μ and response variability σ. Rosemary also increased P3a amplitudes, indicative of dopaminergic contribution. The effects of rosemary on cognition and mood were moderated by individual blink profiles, indicating that baseline neurocognitive state plays a role. Although cholinergic accounts are well established, this study highlights the use of proxies of dopamine to investigate broader neurotransmitter involvement in rosemary’s enhancing properties.

NeuroSci doi: 10.3390/neurosci7010014

Authors: Eleftheria Ntalagianni Eleni Katsouli Anna Christakou Dimitrios Chytas Piergiorgio Lochner Epameinondas Lyros

Background: Patients with primary central nervous system (CNS) tumors often experience fatigue and sleep disturbances, significantly impacting their quality of life. Exercise has been shown to improve these symptoms in various cancer populations. The aim of this study is to evaluate the effects of different types of exercise on fatigue and sleep in less-investigated CNS tumor patients. Methods: A literature search was conducted in PubMed, Scopus, Cochrane Library, and CINAHL. Eligible randomized and non-randomized studies evaluating exercise interventions in patients diagnosed with primary brain tumors were systematically reviewed, primarily using a narrative synthesis approach. Cancer-related fatigue and sleep-related outcomes were extracted as variables of interest. Where possible [≥2 Randomized Control Trials (RCTs) available for glioma patients], meta-analyses were conducted to assess the overall effects of physical therapy on the above-mentioned outcomes. Results: A total of 15 relevant intervention studies were identified, either RCTs or other types of studies, such as prospective feasibility cohort studies and case studies. A total of 448 participants were enrolled, with the majority diagnosed with glioma. There were single reports on pituitary adenoma after surgery and meningioma patients. In glioma patients, the overall effect of various modality exercise interventions on fatigue was non-significant, reflecting the heterogeneous characteristics of studies with diverse outcomes. However, meta-analysis focusing on combined exercise interventions (aerobic and resistance training) showed a positive effect on reducing fatigue in these patients [Standardized Mean Difference (SMD) = 0.866, p = 0.03]. Fatigue in glioma patients may also improve through yoga and Pilates. Aerobic but not strength exercise seems to improve sleep in glioma patients (SMD = 1.14, p = 0.02). Sleep quality may also improve through yoga and combined exercise. Conclusions: Certain types of exercise appear to effectively reduce fatigue and improve sleep in patients with CNS tumors. Future, well–controlled, multi-arm, larger-scale studies are necessary to resolve discrepancies, as well as to explore long-term outcomes and define factors influencing individualized exercise responses.

NeuroSci doi: 10.3390/neurosci7010013

Authors: Cindy M. Wozniczka Donald F. Weaver

Alzheimer’s disease (AD) remains an unmet medical challenge, as there are no effective therapies that alter the disease’s progression. While approaches have targeted molecules like acetylcholine (ACh) and glutamate, these strategies have provided only limited benefits and do not address the complex molecular mechanisms underlying AD development. This review suggests that β-alanine (3-aminopropanoic acid) is an underexplored neurotransmitter that could serve as a potential AD drug target. Existing evidence indicates that β-alanine modulates GABAergic and glutamatergic neurotransmission, thereby affecting neuronal hyperexcitability. Additionally, studies suggest that β-alanine has antioxidant effects, reducing oxidative stress caused by reactive oxygen species (ROS). We propose that β-alanine might bind to Aβ/tau proteins, possibly targeting the six-amino acid sequences EVHHQK/DDKKAK, which are involved in protein aggregation. β-Alanine may also influence the release of pro-inflammatory cytokines from microglia, potentially reducing neuroinflammation. We also hypothesize that β-alanine may help regulate metal dyshomeostasis, which leads to ROS production. Taurine, structurally like β-alanine, appears to influence comparable mechanisms. Although structural similarity doesn’t ensure therapeutic effectiveness, this evidence supports considering β-alanine as a treatment for AD. Furthermore, β-alanine and its analogues face challenges, including crossing the blood–brain barrier (BBB) and optimizing structure–activity relationships (SAR). This review includes articles through September 2025, sourced from four databases.

NeuroSci doi: 10.3390/neurosci7010012

Authors: Roberto García-Leal Julio Prieto-Montalvo Juan Guzman de Villoria Massimiliano Zanin Estrella Rausell

Hand representation maps of the primate primary motor (M1) and somatosensory (SI) cortices exhibit plasticity, with their spatial extent modifiable through training. While activation and map enlargement during tapping tasks are well documented, the directionality of information flow between these regions remains unclear. We applied Information Imbalance Gain Causality (IIG) to examine the propagation and temporal dynamic of BOLD activity among Area 4 (precentral gyrus), Area 3a (fundus of the central sulcus), and SI areas (postcentral gyrus). Data were collected from both hemispheres of nine participants performing alternating right–left hand finger tapping inside a 1.5T fMRI scan. The results revealed strong information flow from both the precentral and postcentral gyri toward the sulcus during tapping task, with weaker bidirectional exchange between the gyri. When not engaged in tapping, both gyri communicated with each other and the sulcus. During active tapping, flow bypassed the sulcus, favoring a more direct postcentral to precentral way. Overtime, postcentral to sulcus influence strengthened during non task periods, but diminished during tapping. These findings suggest that M1, Area 3a, and SI areas form a dynamic network that supports rapid learning processing, where Area 3a of the sulcus may contribute to maintaining representational plasticity during complex tapping tasks.

NeuroSci doi: 10.3390/neurosci7010011

Authors: Naoki Yamada Itsuki Sato Shoji Kinoshita Atsushi Muraji Seiki Tokunaga Taro Naka Ryo Okubo

Objectives: This pilot study examined telerehabilitation, which has emerged as a crucial modality in light of recent global challenges such as the COVID-19 pandemic. We examined the effectiveness of a mobile health telerehabilitation intervention developed for older adults with frailty. Methods: Six participants received a telerehabilitation intervention (Rehab Studio) that included exercise training videos. The participants were aged ≥65 years, had no history of dementia or psychiatric disorders, and had mild-to-moderate care needs. For 1 month, the participants received 1 h live online rehabilitation sessions with real-time communication with rehabilitation specialists (physical therapists and occupational therapists: PTs/OTs). The quality of life (QoL) (EuroQol 5 dimensions 5-level [EQ-5D-5L] questionnaire) and self-rated health scores were recorded before and after the intervention, and the data were analyzed using paired t-tests to determine whether the service was effective. Results: Significant differences were found in the total EQ-5D-5L and self-rated health scores (p < 0.05). The mean EQ-5D-5L score increased from 0.63 ± 0.13 before the intervention to 0.77 ± 0.14 after the intervention (p = 0.010), while the mean self-rated health score increased from 66.0 ± 18.0 to 83.3 ± 10.3, respectively (p = 0.019). Conclusions: This study revealed that the mobile health telerehabilitation intervention is safe and can improve QoL for older adults with frailty. However, the effectiveness of the intervention needs to be further investigated in patients with poor performance in daily living activities. Telerehabilitation could help to reduce the burden of nursing care in aging societies with declining birthrates. However, given the extremely small sample size (N = 6), these p-values should be interpreted with considerable caution. Statistical significance in such a small sample does not provide strong evidence for population-level effects, and our findings should be regarded as hypothesis-generating rather than confirmatory.

NeuroSci doi: 10.3390/neurosci7010009

Authors: Mariana Lara Zambetta José Mário Prati Thiago Luiz de Russo Anna Carolyna Lepesteur Gianlorenço

Background: Currently, there is a considerable number of studies addressing vagus nerve stimulation (VNS) for the treatment of different stroke-related outcomes. We aimed to promote a broad view of the outcomes studied and what are the opportune outcomes to be studied involving this therapeutic strategy for the treatment of post-stroke complications. Methods: This is a scoping review that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two investigators conducted independent searches on PubMed/MEDLINE, Scopus, and Embase till July 2025. Randomized clinical trials and preclinical studies using invasive or non-invasive vagus nerve stimulation conducted with a population diagnosed with stroke were included. Results: Forty-one experimental studies and sixteen clinical trials were included. The outcomes found were neuroprotection; motor, functional, and cognitive rehabilitation; dysphagia; comparison of different stimulation intensities; safety, efficacy, and feasibility of the non-invasive approach; comparison between transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS); and comparison between two models of ischemia (permanent and transient). Preclinical studies mostly investigated molecular elements involved in neuroprotection, neuroinflammation, and cellular apoptosis, while clinical studies evaluating the effectiveness of this technique used for rehabilitation and its comparison or combination with other techniques remain scarce. Conclusions: Most studies investigating the effects of VNS on different post-stroke outcomes are experimental studies. Clinical studies are still scarce and with limited analysis of outcomes.

NeuroSci doi: 10.3390/neurosci7010010

Authors: Đula Đilvesi Bojan Jelača Aleksandar Knežević Željko Živanović Veljko Pantelić Jagoš Golubović

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment disorder, with a lifetime prevalence estimated at approximately 10%. This narrative review explores the historical evolution, current management strategies, and emerging trends in CTS diagnosis and treatment. Early recognition of CTS led to the development of conservative interventions, including splinting, corticosteroid injections, and physical therapy, aimed at alleviating median nerve compression and associated symptoms. The advent of open carpal tunnel release established surgery as the definitive treatment for moderate-to-severe CTS, with subsequent refinements—such as mini-open and endoscopic techniques—focused on minimizing tissue trauma and expediting recovery. Comparative studies demonstrate similar long-term efficacy between surgical modalities, though endoscopic approaches often provide faster short-term recovery. Advances in diagnostic imaging, including high-resolution ultrasound, have improved early detection and dynamic assessment of median nerve compression. Emerging therapies, such as regenerative biologics, neuromobilization, and minimally invasive surgical innovations, offer promising adjuncts to current care. Despite substantial progress, further research is needed to clarify optimal patient selection, refine minimally invasive techniques, and explore regenerative interventions. This review underscores the importance of individualized, evidence-based, and patient-centered approaches to CTS management, integrating both established and emerging strategies to optimize functional outcomes and quality of life.

NeuroSci doi: 10.3390/neurosci7010008

Authors: Faisal Aqeel Alsehli Jahad Alghamdi Abdulaziz Homedi Saif Alsaif Kamal Ali Wed S. Alzahrani Nataleen A. Albekairy Aiman A. Obaidat Mohammad S. Shawaqfeh Buthaynah Ahmed Alawad Atheer Abdulaziz Alfulaij Norah Mohammed Almamoon Abdulkareem M. Albekairy

Neonatal seizures are common complications in neonatal intensive care units. They have been noticed to be more common in preterm infants, but they can also affect term infants. Levetiracetam is a broad-spectrum antiepileptic drug that has been studied to manage seizures, yet limited data are available on its use in neonatal seizures. Objectives: Study the effect of levetiracetam on neonatal seizures in terms of maintaining seizure freedom after the initiation of levetiracetam and investigating its safety profile in the neonate population. Method: Retrospective cohort study comparing two groups of patients identified through accessing their medical profiles after searching the following keywords: phenobarbital, levetiracetam, and neonatal seizures amongst all NICU admissions in King Abdulaziz Medical City, Ministry of National Guard Health Affairs, from the period between December 2016 and January 2020. Forty-eight patients were included based on the inclusion/exclusion criteria. The selected sample was further subclassified into 28 neonates who received phenobarbital and 20 who received levetiracetam. Results: Seizure control was significantly observed in neonates with onset <24 h and those born at <37 weeks GA. In the first arm, 22 out of 28 neonates achieved seizure freedom while using phenobarbital; in the second arm, 11 out of 20 neonates achieved seizure control on levetiracetam after failing with phenobarbital. While seizure control was better achieved by phenobarbital, it was found that almost 57% of the first arm developed side effects on phenobarbital; however, only 10% of the neonates on levetiracetam developed side effects. While PB remains effective for acute suppression, LEV demonstrated a superior safety profile with no serious adverse events and a high rate of successful seizure management as an add-on therapy (83% control in combined cohorts). Conclusions: The study concluded that using levetiracetam could result in improved outcomes. LEV is a safe and effective alternative or adjunct to PB. Its use may mitigate the neurotoxic risks associated with GABAergic drugs, though continuous EEG monitoring is essential to ensure electrical seizure cessation and avoid electroclinical dissociation. The number of patients who received levetiracetam initially is not considered a representative sample to reach a conclusion on the use of levetiracetam as an effective monotherapy.

NeuroSci doi: 10.3390/neurosci7010007

Authors: Gonzalo Emiliano Aranda-Abreu Fausto Rojas-Durán María Elena Hernández-Aguilar Deissy Herrera-Covarrubias Luis Roberto Tlapa-Monge Sonia Lilia Mestizo-Gutiérrez

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, and Huntington’s disease represent a major challenge in neuroscience due to their complex, multifactorial nature and the absence of curative treatments. These disorders share common molecular mechanisms, including oxidative stress, mitochondrial dysfunction, proteostasis collapse, calcium dyshomeostasis, chronic neuroinflammation, and the prion-like propagation of misfolded proteins. Together, these processes trigger a cascade of cellular damage that culminates in synaptic dysfunction and programmed neuronal death. This review integrates current evidence on the sequential stages of neurodegeneration, emphasizing the convergence of oxidative, inflammatory, and proteotoxic pathways that drive neuronal vulnerability. Moreover, it explores emerging therapeutic strategies aimed at restoring cellular homeostasis, such as Nrf2 activation, modulation of the unfolded protein response (UPR), enhancement of autophagy, immunotherapy against pathological proteins, and gene therapy approaches. The dynamic interplay among mitochondria, endoplasmic reticulum, and glial cells is highlighted as a central element in disease progression. Understanding these interconnected mechanisms provides a foundation for developing multi-targeted interventions capable of halting or delaying neuronal loss and improving clinical outcomes in neurodegenerative disorders. This work provides an integrative and introductory overview of the convergent mechanisms underlying neurodegeneration rather than an exhaustive mechanistic analysis.

NeuroSci doi: 10.3390/neurosci7010006

Authors: Hiroshi Kataoka Masahiro Isogawa Hitoki Nanaura Hiroyuki Kurakami Miyoko Hasebe Kaoru Kinugawa Takao Kiriyama Tesseki Izumi Masato Kasahara Kazuma Sugie

REM sleep behavioral disorder (RBD) is of increasing interest in Parkinson’s disease (PD). Previous studies exploring the association between REM sleep without atonia (RWA) and clinical PD features or other objective sleep metrics are scarce and have used PSG findings. A mobile electroencephalography (EEG)/electrooculography (EOG) recording system with two channels can objectively measure sleep parameters, including RWA, during natural sleep at home. We investigated whether RWA measured on a portable recording device at home could be associated with clinical PD features or other sleep metrics using baseline data from the ZEAL study. Differences between patients with and without RWA was analyzed using ANCOVA test. REM sleep length was significantly longer in patients with RWA than in those without RWA. A multivariate comparison using ANCOVA showed a significant difference in log-transformed REM sleep duration of patients with RWA after adjustment for potential confounders (adjusted mean difference of 1.203; 95% confidence interval 0.468 to 1.937; p = 0.003). The strength of this study was that it evaluated the association between RWA during natural sleep at home and clinical variables as well as other sleep metrics. The major result was that patients with and without RWA did not differ in their clinical variables, and there was no relation between RWA and objective sleep metrics other than REM sleep. The duration of REM sleep may be associated with RWA during natural sleep at home.

NeuroSci doi: 10.3390/neurosci7010005

Authors: Simon Podnar

In non-vasculitic immune-mediated neuropathies, imaging studies demonstrate an enlargement not only of clinically involved but also of clinically intact nerves. The present study aimed to present a pattern of nerve swelling and its relation to nerve function. In a group of patients with dysimmune motor and sensorimotor mononeuropathies, nerve cross-sectional areas (CSAs) were measured using ultrasonography (US) and compound muscle action potential (CMAP) amplitudes using electrodiagnostic (EDx) studies. Nerve CSAs were compared in (1) clinically involved, (2) swollen and clinically uninvolved, and (3) non-swollen (clinically uninvolved) nerves. Patients’ non-swollen nerves were also compared to those of controls. In swollen nerves, the correlation between nerve CSA and CMAP amplitude was calculated. Twenty-two patients (12 men) and 50 controls (28 men) were included in the study. Clinically involved nerves were thicker than swollen segments of clinically intact nerves (p < 0.001). The patients’ non-swollen (clinically uninvolved) nerves were thicker than the controls’. In swollen nerves, CSA was strongly negatively correlated with CMAP amplitude (r = −0.54, p < 0.001). In patients with immune-mediated mononeuropathies, nerve swelling correlates with clinical and EDx findings. Patients’ clinically uninvolved nerves were also swollen, but to a lesser degree.

NeuroSci doi: 10.3390/neurosci7010004

Authors: Guillermo José Bazarra Castro Carlos Martínez Macho Ricardo Mantecón Zorrilla Enrique Barbero Pablos Cristina V. Torres Díaz Jose Antonio Fernández-Alén Ricardo Gil Simoes

Religious experiences represent a universal and timeless phenomenon that has accompanied humanity since its origins. In recent decades, neuroscience has explored the relationship between temporal lobe epilepsy (TLE) and hyperreligiosity phenomena, describing sudden convictions, states of ecstasy, and spiritual conversions associated with epileptic seizures. This article offers a narrative review of the literature on the relationship between epilepsy and religion, including its clinical manifestations (ictal, postictal, and interictal) and the main neurobiological models proposed to explain it, such as the limbic marker hypothesis and theory of mind (ToM). The possible role of the uncinate fasciculus as an integrative pathway between temporal and limbic regions is also explored, based on recent neuroimaging studies. Finally, we present an illustrative clinical case of a patient with meningioma and TLE associated with episodes of intense religious conviction, in whom a structural alteration of the right uncinate fasciculus was observed. This case reinforces the relevance of considering both neuronal networks and white matter tracts in the study of religious experiences, while underscoring the need for broader and more systematic studies to confirm these findings.

NeuroSci doi: 10.3390/neurosci7010003

Authors: Christopher B. Watson Christopher F. Sharpley Vicki Bitsika

The experience of childhood maltreatment (CM) increases the risk for depressive disorders by two-and-a-half times across the lifespan. Although stress system and immunological models offer some explanation of this vulnerability, further investigation is required to understand the underlying neurophysiological mechanisms and identify potential biomarkers for diagnosis and treatment. Resting-state electroencephalography (EEG) offers a low-cost, non-invasive, and accessible methodology for that purpose. This narrative review synthesizes resting-state EEG findings that are common to CM and depression as a primer for further research and the future formulation of a model that may link these two in a causal manner. Although evidence supports atypical beta and theta band power, frontal alpha asymmetry and altered default mode network functional connectivity as possible indicators of the CM-EEG association, there is a paucity of EEG-based CM research available to complement the extensive depression-focused literature. Large-sample, prospective EEG studies of CM that consider confounding factors and assess the neurophysiological impact of CM independent of psychopathologies are required.

NeuroSci doi: 10.3390/neurosci7010002

Authors: Andrei Gabriel Mangalagiu Bogdan Mircea Petrescu Sorin Riga Octavian Vasiliu

Mild cognitive impairment (MCI) is a nosological entity that requires special attention from a therapeutic perspective, because annual conversion rates to dementia of 5–15% in these cases are considered typical. This narrative review aimed to identify available data supporting the efficacy and tolerability of various pharmacological therapeutic interventions by searching PubMed/MEDLINE, the Cochrane Database of Systematic Reviews, and the Web of Science (WoS) Core Collection for primary and secondary reports published over the last 25 years on the pharmacological treatment of MCI. The retrieved interventions were distributed in five large categories: (1) conventional cognitive enhancers; (2) disease-modifying therapeutic interventions; (3) strategies mitigating vascular risk and management of concomitant medications; (4) adjuvant and nootropic formulations; (5) case management of non-cognitive symptoms in MCI. The most broadly applicable pharmacological strategies in MCI include systematic deprescribing and optimisation of concomitant therapies, reducing anticholinergic and sedative load, avoiding iatrogenic hypoglycaemia and excessive blood pressure lowering, and careful, individualised treatment of vascular risk factors. Based on the randomised controlled trials, meta-analyses, and contemporary guidelines, a pragmatic pharmacological approach to MCI is suggested. Further trials with better design are urgently needed to document the efficacy and safety of pharmacological interventions in patients diagnosed with MCI.

NeuroSci doi: 10.3390/neurosci7010001

Authors: Mohamed Salaheldien Alayat Kadrya H. Battecha Yazeed Saleh Jabr Faisal Zagzoog Baraa Hasaballah Faisal Faleh Saud Alsulami Matuq Abdullah Refaei Osama Saleh Almehmadi

Objectives: The aim of this study was to investigate the effectiveness of Cryoflow cooling on forearm skin temperature and nerve conduction velocity (NCV) in normal subjects. Methods: Thirty male volunteers participated in this study, with a mean age of 20.8 ± 0.74 years. A Cryoflow hose with a nozzle was positioned approximately 10 cm from the forearm and scanned the anterior surface of the non-dominant forearm for 10 min, with temperatures adjusted to −10 °C. Participants’ average skin temperature was measured by using an infrared camera. Motor and sensory NCV for both the median and ulnar nerves were measured from both forearms. The dominant side served as a control side. The level of significance was set at p value ≤ 0.05. Results: Following treatment, the experimental group experienced a reduction in average skin temperature, dropping from 32.94 ± 1.11 °C to 16.92 ± 1.68 °C, while the control group showed no significant change. Both the median and ulnar nerves exhibited significant decreases in motor NCV (−10.37 m/s and −8.79 m/s, respectively), alongside slight increases in distal motor latency. Sensory NCV of the median and ulnar nerves decreased significantly (−5.20 m/s and −8.40 m/s, respectively), accompanied by increased onset latency. No significant changes were found in the control group. Conclusions: Cryoflow air-based cryotherapy to the forearm causes a substantial reduction in local skin temperature and significant slowing of peripheral nerve conduction. Both motor and sensory fibers of the median and ulnar nerves exhibited decreased conduction velocities and increased latencies following cooling.

NeuroSci doi: 10.3390/neurosci6040131

Authors: Elisa Roca Elena Roca Alessandra Cucinella Giorgio Madonia Giovanni Centonze Fiorella Lombardo Licia Martinelli Maria Elisa Damiani Antonio Santo

Background: Innovative treatments for lung cancer patients have significantly improved their lives. Therefore, patients who develop brain metastases are more likely to require management of quality of life (QoL) by reducing pathological decline in brain function. New therapeutic strategies have allowed us to manage brain metastases, thanks to the ability to cross the blood–brain barrier. Moreover, new molecules have been designed as adjuvants to standard treatments for the management of cancer patients with brain metastases. Methods: We implemented a descriptive, observational, retrospective study. Therefore, we consecutively collected the data of eighty-six (N  =  86) patients admitted to our department (April 2020–April 2025) diagnosed with brain involvement in a thoracic neoplasm and treated with silibinin, in association with standard treatment. The main endpoint of our analysis is to define the safety profile of silibinin and to evaluate its eventual benefits in terms of QoL. Results: Silibinin was well tolerated (only one mild adverse event was reported); furthermore, patients taking silibinin had a good quality of life that was maintained over a long period of time, and in some cases, an improvement in neurological symptoms and overall patient well-being was also documented. Conclusions: Our study is the first collection of a large number of lung cancer patients with brain metastasis taking silibinin, which is very well tolerated and allows patients to maintain a good QoL.

NeuroSci doi: 10.3390/neurosci6040130

Authors: Jamir Pitton Rissardo Ana Leticia Fornari Caprara

Background/aim: Vitamin D (VitD) has been implicated in neuroprotection, yet its role in Parkinson’s disease (PD) remains unclear. This systematic review and meta-analysis aimed to evaluate the association between VitD status, supplementation, and vitamin D receptor (VDR) gene polymorphisms with PD risk and outcomes. Methodology: Following PRISMA guidelines, we searched PubMed, Scopus, and Google Scholar through August 2025 for observational studies, clinical trials, and genetic association studies. Primary outcomes included serum VitD levels in PD versus healthy controls (HCs), prevalence of VitD insufficiency/deficiency, and effects of VitD supplementation on motor symptoms. Secondary outcomes assessed associations between VDR polymorphisms and PD susceptibility. Data were synthesized using random- and fixed-effects models, with heterogeneity and publication bias evaluated. PROSPERO (CRD420251133875). Results: Sixty-three studies (n ≈ 10,700 participants) met inclusion criteria. PD patients exhibited significantly lower VitD levels (SMD = −0.46; 95% CI: −0.51 to −0.41) and higher odds of insufficiency (OR = 1.52) and deficiency (OR = 2.20) compared to HC. Cohort data suggested sufficient VitD may reduce PD risk (HR = 0.83). Supplementation yielded modest, non-significant improvements in motor outcomes. Among 20 genetic studies, FokI (rs2228570) was most consistently associated with PD, while other VDR SNPs showed variable or null associations. Conclusions: VitD deficiency is common in PD and may influence disease risk and motor function. Current evidence indicates limited benefit of supplementation for motor outcomes, and genetic associations remain inconsistent.

NeuroSci doi: 10.3390/neurosci6040129

Authors: Maria Pagano Anna Anselmo Giuseppe Micali Fabio Mauro Giambò Francesco Speciale Daniela Costanzo Piercataldo D’Aleo Antonio Duca Alessia Bramanti Marina Garofano Placido Bramanti Francesco Corallo Irene Cappadona

Background: Cardiovascular diseases (CVD) affect the heart and blood vessels. Cardiorenal syndrome (CRS) highlights the interaction between the heart and kidneys, worsening the clinical course. Assessing renal function is essential for risk stratification and guiding therapeutic decisions. Furthermore, cognitive and psychological aspects are often impaired in these patients. Aim: To compare clinical, cognitive, emotional, and quality of life parameters between patients with CRS and those with heart failure (HF) alone, and to assess the agreement between estimated glomerular filtration rate equations (Cockcroft–Gault and CKD-EPI). Methods: This observational study was conducted at the Cardiology Unit of the IRCCS Centro Neurolesi Bonino Pulejo “Piemonte” Hospital (Messina, Italy) between June 2024 and March 2025. Thirty participants aged 45–85 years were enrolled: 15 with type 1 cardiorenal syndrome (CRS group) and 15 with heart failure without cardiorenal syndrome (HF group). All participants had a confirmed diagnosis and provided informed consent. Clinical evaluation and standardized tests (MoCA, BDI-II, BAI, and SF-12v2) were administered. Statistical analyses were performed using t-tests, chi-square tests, and Bland–Altman analysis, with significance set at p < 0.05. Results: The two groups were comparable in body mass index and left ventricular ejection fraction. CRS patients had significantly higher serum creatinine and lower GFR with both equations. The two GFR equations were strongly correlated (r = 0.94; p < 0.0001). Bland–Altman analysis showed a mean difference of 5.80 mL/min (95% limits of agreement: –12.4 to +24.0 mL/min), indicating wide individual variability. No significant differences were found in cognitive performance or quality of life. However, CRS patients exhibited significantly higher depressive symptoms (BDI-II mean 11.33 ± 8.19 vs. 5.40 ± 6.68; p = 0.0384) and a trend toward higher anxiety (BAI mean 8.13 ± 4.73 vs. 4.67 ± 5.79; p = 0.0834). Conclusions: A multidisciplinary approach, including psychological support, is necessary for patients with CRS.

NeuroSci doi: 10.3390/neurosci6040128

Authors: Angelka Pešterac-Kujundžić Una Nedeljković Ivana Sretenović Aleksandar Milosavljević Dragoslav Nestorovic Ivan Vukašinović Vojislav Bogosavljević

This study evaluated participation outcomes one year after aneurysmal subarachnoid hemorrhage (aSAH) compared with matched healthy controls and identified factors associated with participation within the patient group. Forty aSAH survivors and seventy-five controls were assessed 12–14 months post-ictus. Participation was measured with the Utrecht Scale for Evaluation of Rehabilitation–Participation (USER-P), psychological distress with the Hospital Anxiety and Depression Scale (HADS), coping with the Brief COPE, and cognition with the Montreal Cognitive Assessment (MoCA). Compared with controls, patients reported greater participation restrictions (82 vs. 100, p < 0.001), lower frequency (35 vs. 51, p < 0.001), and reduced satisfaction (65 vs. 75, p < 0.001). Anxiety, depression, and avoidant coping independently predicted restrictions (adjusted R2 = 0.48), while satisfaction was predicted by employment, fewer depressive symptoms, and less avoidant coping (adjusted R2 = 0.52). Lower MoCA scores predicted reduced participation frequency (p = 0.032), and patients with cognitive impairment showed significantly greater restrictions and lower satisfaction. One year after aSAH, survivors experience substantial participation limitations associated with psychological distress, maladaptive coping, and cognitive deficits. These results underscore the importance of cognitive and psychological rehabilitation to enhance long-term participation and social reintegration after aSAH.

NeuroSci doi: 10.3390/neurosci6040127

Authors: José J. Jarero-Basulto Yadira Gasca-Martínez Martha C. Rivera-Cervantes Deisy Gasca-Martínez Nidia Jannette Carrillo-González Carlos Beas-Zárate Graciela Gudiño-Cabrera

The journal retracts the article “Cytotoxic Effect of Amyloid-β1-42 Oligomers on Endoplasmic Reticulum and Golgi Apparatus Arrangement in SH-SY5Y Neuroblastoma Cells” [...]

NeuroSci doi: 10.3390/neurosci6040126

Authors: Avital Schurr

Ever since the discovery that neuronal tissue can utilize lactate as an aerobic substrate for mitochondrial adenosine triphosphate (ATP) production, a debate has ensued between those who have questioned the importance of lactate in brain energy metabolism and those who argue that lactate plays a central role in this process. The “neuron astrocyte lactate shuttle hypothesis” has sharpened this debate since it postulates lactate to be the oxidative energy substrate for activated neurons. Those who minimize lactate’s role insist that a non-oxidative process they termed “aerobic glycolysis” supports brain activation, despite oxygen availability. To explain the paradox that the active brain would utilize the inefficient glycolysis over the much more efficient mitochondrial oxidative phosphorylation (OXPHOS) for ATP production, they suggested the “efficiency tradeoff hypothesis,” where the inefficiency of the glycolytic pathway is traded for speed necessary for the information transfer of the active brain. In contrast, other studies reveal that oxidative energy metabolism is the process that supports brain activation, refuting both the “aerobic glycolysis” concept and the premise of the “efficiency tradeoff hypothesis”. These studies also shed doubts on the usefulness of the blood oxygenation dependent functional magnetic resonance imaging (BOLD fMRI) method and its signal as an appropriate tool for the estimation of brain oxygen consumption, as it is unable to detect any oxygen present in the extravascular brain tissue.

NeuroSci doi: 10.3390/neurosci6040125

Authors: Davide Rotondo Laura Lagostena Valeria Magnelli Francesco Dondero

Per- and polyfluoroalkyl substances are persistent environmental contaminants increasingly implicated in neurotoxicity. Establishing causality and mechanisms relevant to Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis requires human-relevant systems that capture exposure, barrier function, and brain circuitry. We review advanced cellular platforms—iPSC-derived neuronal and glial cultures, cerebral and midbrain organoids, and chip-based microphysiological systems—that model disease-relevant phenotypes (Aβ/tau pathology, dopaminergic vulnerability, myelination defects) under controlled PFAS exposures and defined genetic risk backgrounds. Modular, fluidically coupled BBB-on-chip → brain-organoid microphysiological systems have been reported, enabling chronic, low-dose PFAS perfusion under physiological shear, real-time barrier integrity readouts such as transepithelial/transendothelial electrical resistance (TEER), quantification of PFAS partitioning and translocation, and downstream neuronal–glial responses assessed by electrophysiology and multi-omics. Across platforms, convergent PFAS-responsive processes emerge—mitochondrial dysfunction and oxidative stress, lipid/ceramide dysregulation, neuroinflammatory signaling, and synaptic/network impairments—providing a mechanistic scaffold for biomarker discovery and gene–environment interrogation with isogenic lines. We outline principles for exposure design (environmentally relevant ranges, longitudinal paradigms), multimodal endpoints (omics, electrophysiology, imaging), and cross-lab standardization to improve comparability. Together, these models advance the quantitative evaluation of PFAS neurotoxicity and support translation into risk assessment and therapeutic strategies.

NeuroSci doi: 10.3390/neurosci6040124

Authors: Luca Sartori Samuel Luciano Caliri Roberto Colasanti Pietro Dalla Zuanna Nicola Bresolin Valentina Baro Pietro Ciccarino Francesco Volpin Franco Chioffi Luca Denaro Andrea Landi

Background: Glioblastomas (GBMs) in eloquent areas, particularly within the motor system, represent a significant surgical challenge due to the risk of postoperative neurological deficits. This study evaluates the effectiveness of a structured preoperative protocol, including nTMS-guided motor mapping, to optimize surgical outcomes and minimize neurological deficits, with a particular focus on the timing of adjuvant oncological therapy initiation. Methods: A retrospective analysis was conducted on 44 GBM patients, divided into two groups: 11 with motor area lesions (group A) and 33 with non-eloquent lesions (group B). All patients underwent a standardized preoperative protocol. Surgical outcomes (EORs), neurological function (MRC score and KPS index), time to oncological therapy initiation and survival (OS and PFS) were compared between groups. Results: Both groups achieved high rates of GTR without significant differences in EOR (72.7% group A vs. 78.8% group B). Although group A exhibited a higher incidence of postoperative motor deficits, motor function at three-month follow-up was similar between groups. Time to initiation of oncological therapy did not differ between groups (40.6 days group A vs. 41.9 days group B, p = 0.719), highlighting that preservation of motor function helped minimize delays in starting oncological therapy. No significant differences were found in survival outcomes. Conclusions: A structured preoperative protocol incorporating nTMS motor mapping allows for safe and aggressive resection of motor-area GBMs. This approach effectively mitigates the risk of delays in initiating adjuvant oncological therapy, optimizing the patient prognosis. Further studies are needed to explore the long-term benefits of this protocol in both functional and oncological outcomes.

NeuroSci doi: 10.3390/neurosci6040123

Authors: Maurizio Bergamino Lauren R. Ott Molly M. McElvogue Ruchira Jha Cindy Moreno Ashley M. Stokes

Mild traumatic brain injury (mTBI) frequently causes subtle brain changes that are difficult to detect with conventional diagnostic approaches. In this exploratory pilot study, we combined tri-exponential intravoxel incoherent motion (IVIM) and pseudocontinuous arterial spin labeling (pCASL) MRI with Multimodal Canonical Correlation Analysis and joint independent component analysis (mCCA+jICA) to identify imaging signatures distinguishing mTBI patients from healthy controls (HCs) and their associations with clinical function. Cerebral blood flow (CBF) and IVIM-derived metrics were extracted from 90 brain regions in 19 mTBI patients and 24 HCs, and multivariate components were identified using mCCA+jICA. Two independent components (IC2, IC15) showed group differences at the uncorrected level (p < 0.05) but did not survive false discovery rate (FDR) correction. IC2 correlated positively with CBF and perfusion fraction (Fp) and negatively with tissue diffusion fraction (Fs), consistent with reduced vascular integrity in mTBI, while IC15 showed similar trends. One component correlated with Glasgow Outcome Scale–Extended (GOS-E) scores (uncorrected p = 0.046). Although this study is preliminary and limited by a small sample size, our findings suggest that mTBI is associated with perfusion and microstructural alterations, particularly in subcortical regions, and demonstrate the potential value of combining IVIM and ASL within multivariate fusion frameworks to reveal patterns not captured by single-modality approaches.