Brain Sciences doi: 10.3390/brainsci16090924

Authors: Qiulu Liu Sutong Xu Bei Zhang Chengyu Lv Chenming Liu Yali Wang Haiyue Zhou Yuping Luo Siguang Li

Background/Objectives: Ischemic stroke (IS) induces substantial phenotypic remodeling within the neurovascular unit, and pericytes have been implicated in the cellular responses to ischemic injury. However, the molecular characteristics and regulatory mechanisms underlying pericyte phenotypic remodeling after ischemic stroke remain incompletely understood. Methods: In this study, we used PDGFR-β-CreERT2; ZsGreen lineage-tracing mice and a middle cerebral artery occlusion (MCAO) model to characterize the temporal changes in PDGFR-β-lineage cells following ischemic injury. In vitro, human brain vascular pericytes (HBVPs) exposed to oxygen–glucose deprivation/reperfusion (OGD/R) and subsequently maintained in neurobasal medium to examine ischemia-related phenotypic changes. The involvement of KLF2-associated signaling was further investigated using KLF2 knockdown approaches. Results: We observed increased expression of Nestin in PDGFR-β-lineage cells during the early post-ischemic period, followed by the emergence of subsets co-expressing GFAP or DCX during the subacute stage. These findings indicate the acquisition of neuroglial- and neuronal-associated molecular features, rather than providing definitive evidence of lineage conversion or functional differentiation. The expression of these markers declined at later stages, whereas PDGFR-β-lineage cells were also associated with vascular remodeling during the recovery phase. In vitro, OGD/R-treated HBVPs exhibited increased expression of DCX, MAP2, and NeuN. KLF2 knockdown attenuated these molecular changes. Consistently, OGD/R was associated with increased KLF2, phosphorylated ERK1/2, and MAP2 expression, whereas KLF2 knockdown reduced ERK1/2 phosphorylation and MAP2 expression. These findings suggest that KLF2 is associated with ERK1/2 activation and MAP2 expression during ischemia-related phenotypic remodeling of PDGFR-β-lineage cells. Conclusions: Overall, our results identify transient neuroglial- and neuronal-associated molecular changes in pericytes after ischemic injury and provide evidence for an association between KLF2 and ERK1/2–MAP2 signaling in this process, while further studies are required to determine whether these changes represent stable lineage conversion or functional neuronal differentiation.

Brain Sciences doi: 10.3390/brainsci16090923

Authors: Edwin J. Burns John R. Towler

Background/Objectives: Prosopagnosia is characterised by severe difficulties recognising facial identity. While many self-identified developmental cases fail to meet widely used cognitive task-based criteria for inclusion in research, the extent to which this is an issue in acquired prosopagnosia is unknown. We therefore assessed the sensitivity of widely used inclusion cutoffs and face-processing tests in 14 self-identified British acquired prosopagnosia cases. Results: We found the −2 SD cutoff did not detect impairment in 9/11 (82%) individuals on the Cambridge Face Perception Test, 5/11 (45%) of cases on the Cambridge Face Memory Test, and 2/14 (14%) on the Famous Faces Test. Requiring impairments on two memory tasks at −2 SD or −1 SD resulted in at most 8/14 (57%) and 5/14 (36%) of cases not meeting the criteria, respectively. A more liberal approach, which additionally allowed for inclusion using a single test score at −2 SD, performed better by excluding at most 2/14 (14%). Given that the Famous Faces Test alone at the −2 SD level performed identically to our liberal approach, we suggest it could be used if an objective assessment is deemed necessary. Conclusions: We extend the recent suggestions in the literature that self-identified prosopagnosia cases who fail to meet cognitive test criteria warrant further investigation to explain the reasons for their self-reported status. We therefore advocate a more inclusive approach to prosopagnosia research.

Brain Sciences doi: 10.3390/brainsci16090922

Authors: Hatice Ayça Kaloğlu Mehmet Ünler Buket Koparal Çisem Utku Nevzat Yüksel

Introduction: Obsessive–compulsive disorder (OCD) is clinically heterogeneous, and the neurocognitive characteristics of autogenous and reactive obsessional presentations remain insufficiently understood. This study compared neurocognitive performance and exploratory clinical–cognitive associations in strictly classified autogenous and reactive OCD presentations. Methods: This cross-sectional study included 67 outpatients with OCD classified as having reactive (n = 35) or autogenous (n = 32) presentations based on clinical evaluation and the Yale–Brown Obsessive Compulsive Scale Symptom Checklist. Patients with mixed presentations were excluded. Executive functioning, attentional control, cognitive flexibility, and verbal learning and memory were assessed using the Wisconsin Card Sorting Test, Stroop Test, and Rey Auditory Verbal Learning Test. Depressive symptoms were assessed using the Beck Depression Inventory. Results: The groups were comparable in age, age at OCD onset, illness duration, and overall OCD symptom severity, whereas depressive symptom scores were higher in the autogenous group. Neuropsychological performance was broadly comparable between groups. The autogenous group showed better RAVLT-6 performance, reflecting recall after interference, with a nominally significant unadjusted group difference. This difference remained significant in an exploratory ANCOVA adjusting for depressive symptoms, education, and age at OCD onset, although it did not survive false-discovery-rate correction. Exploratory within-group correlations were observed; however, formal Fisher’s r-to-z comparisons revealed no significant differences between groups. Conclusions: Strictly classified autogenous and reactive OCD presentations showed broadly similar neuropsychological profiles, with a preliminary group difference in recall after interference. Within-group correlations should be interpreted as exploratory and hypothesis-generating rather than as evidence of presentation-specific clinical–cognitive mechanisms. Replication in larger samples is warranted.

Brain Sciences doi: 10.3390/brainsci16090921

Authors: Wenchao Hu Futai Wang Ziyi Niu Peiyang Liu Zhicheng Tian Ceng Luo Rougang Xie

Background: Peripheral nerve injury drives persistent remodeling of the dorsal root ganglion (DRG) microenvironment, but the cellular states and intercellular signaling mechanisms that sustain neuropathic pain remain poorly understood. Methods: Here, we integrated single-cell transcriptomics with histological, behavioral, and electrophysiological approaches to identify an interferon-responsive state in satellite glial cells (SGCs) of the DRG following spared nerve injury (SNI). Results: This state was distinguished by STAT1-associated interferon-responsive genes’ activation and enhanced chemokine signaling, particularly involving CXCL10 and its receptor CXCR3. These molecular alterations were accompanied by remodeling of intercellular communication among SGCs, sensory neurons, and immune cells. Pharmacological inhibition of STAT1 or blockade of CXCR3 not only reduced sensory-neuron hyperexcitability but also attenuated pain hypersensitivity and improved deficits in hindlimb weight bearing and gait after SNI. Conclusions: Collectively, our findings indicate that interferon-responsive SGCs (IFN SGCs) contribute to the maintenance of neuropathic pain by regulating STAT1-dependent chemokine signaling in the DRG. Targeting this signaling pathway may provide a therapeutic strategy for persistent neuropathic pain.

Brain Sciences doi: 10.3390/brainsci16090920

Authors: Yücel Doğruel Hakkı Oğulcan Babacan Doğan Gündoğan Alper Tabanlı Berk Burak Berker Abuzer Güngör

Background/Objectives: Perirolandic brain metastases are challenging to resect because small deviations from the surgical corridor may cause sensorimotor deficits. This study evaluated the stage-specific value and limitations of general-purpose, non-navigated B-mode intraoperative ultrasonography (iUS) with MRI-based frameless neuronavigation in a consecutive surgical cohort of perirolandic metastases. Methods: In this single-center, single-surgeon retrospective case series, 15 consecutive adults underwent microsurgical resection of perirolandic brain metastases using MRI-based frameless neuronavigation and a general-purpose B-mode ultrasound system, without functional mapping or neurophysiological monitoring. Extent of resection was assessed on contrast-enhanced MRI obtained 24 to 36 h after surgery, and post-resection cavity iUS findings were compared descriptively with early postoperative MRI. Results: Gross-total resection was achieved in 13 patients (86.7%). iUS modified intraoperative targeting in 6 of 15 patients: the entry point was repositioned after findings consistent with intraoperative brain shift in 4, and the lesion was localized in interhemispheric corridors in 2. Post-resection iUS suspected residual tissue in 7 of 14 patients, but only 1 corresponded to residual tumor on MRI; a thin remnant on the motor cortex was not identified as suspicious for residual tumor on iUS. A new or worsened motor deficit occurred in 2 patients (13.3%); at follow-up, this was persistent at 20 months in 1 and partially improved in the other. No patient required reoperation, and there was no 30-day mortality. Conclusions: General-purpose B-mode iUS aided exposure confirmation and trajectory refinement but had limited value for excluding thin residual tumor. When functional mapping or neurophysiological monitoring is unavailable, it may provide accessible real-time anatomical guidance; however, because it lacks functional information, it should not be considered an alternative to these functional adjuncts.

Brain Sciences doi: 10.3390/brainsci16090919

Authors: Alan J. Lincoln

Severe mental illness (SMI) includes neuropsychiatric disorders of adult onset, but also those that begin to show symptoms in adolescence and early childhood. This review treats the psychotic spectrum disorders and autism as neurodevelopmental in origin, each arising from perturbation of early brain development rather than from a process beginning at the age of clinical presentation. Grouping them is a claim about developmental origin and not about shared pathogenesis: they differ in the nature and timing of the perturbation and in the cortical systems being organized when it occurs. The diversity of social, language, behavioral, and cognitive symptoms and traits observed within this class is now well recognized. The language adopted to recognize such diversity has employed the term “spectrum” (e.g., autism spectrum disorder (ASD) and schizophrenia or psychotic spectrum). The substantial expansion of structural and functional connectivity research over the past 40 years has shown that both ASD and psychotic spectrum disorders have also been conceptualized as disorders of brain circuitry. Moreover, and particularly for ASD, this research was developed within a diagnostic time frame that itself underwent six revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), from the third edition (DSM-III; 1980) to the fifth edition, text revision (DSM-5-TR; 2022), with the largest changes involving the elimination of the early language onset requirement and the consolidation of prior subtypes into a single autism spectrum disorder. The present review develops a mechanistic account of cerebral connectivity differences in autistic disorder as defined under DSM-III and DSM-IV, where diagnostic practice, and in particular the exclusion of clinically significant language delay from Asperger’s disorder, enriched cohorts for a subgroup in which cerebellar vermal lobule VI and VII abnormality, posterior callosal reduction, and atypical predictive processing were originally identified. The present account proposes, as a hypothesis rather than as an established finding, that deviation of vermal lobules VI and VII from typical development, in the direction of either hypoplasia or hyperplasia, both reported within the same DSM-III/IV cohort, and on evidence consistent with prenatal origin, initiates a developmental cascade that may shape postnatal cerebral connectivity through disinhibition of deep cerebellar nuclei and altered excitatory drive to thalamocortical circuits during sensitive periods. Cross-condition evidence indicates that vermal abnormality also occurs in conditions with distinct primary diagnoses (Joubert syndrome, fragile X, Rett syndrome, Williams syndrome, schizophrenia), producing the autistic-disorder cluster only when the upstream perturbation also affects cortical context-integration substrates at the relevant developmental window. These conditions are treated as further instances of a common neurodevelopmental class rather than as separate kinds of disorder, with autistic disorder as the focal case because it is where the vermal findings were first identified. Transdiagnostic connectivity evidence spanning autism and schizophrenia cohorts is examined to establish whether the cerebellar account generalizes across the SMI class or is specific to autistic disorder, and the regional and directional distribution of the cerebellar findings in each condition is treated as the discriminating variable. The framework proposes the cerebellum as a substrate for predictive internal models scaffolding auditory, social, and contextual learning, and is empirically testable through infant connectivity and event-related potential studies and through stratified re-analysis of multisite samples.

Brain Sciences doi: 10.3390/brainsci16090918

Authors: Hanife Yılmaz Abaylı Ezgi Şişman Fatma Seher Kocaayan Aslıhan Polat

Background: Neurocognitive functioning in transgender adults remains understudied and is predominantly derived from Western samples, often treated as universally applicable. Evidence from non-Western contexts is limited, despite the potential influence of structural stigma and minority stress on cognition and research participation. Türkiye represents a sociopolitical setting where transgender individuals face significant barriers to healthcare and research. To date, no study has systematically examined the neuropsychological profile of transgender adults in Türkiye using a four-group design. Methods: This retrospective, cross-sectional study was conducted at a multidisciplinary university-based gender identity clinic. Eighty-one adults were included: transgender women (n = 14), transgender men (n = 39), cisgender women (n = 13), and cisgender men (n = 15), with cisgender groups matched for age and education. Participants completed a standardized neuropsychological battery assessing visuospatial abilities, executive functions/processing speed, working memory, and verbal fluency. Group differences were analyzed using nonparametric methods, with additional aggregated transgender–cisgender comparisons. Results: Group differences were observed in visuospatial functioning (Judgment of Line Orientation, Rey–Osterrieth Complex Figure; all p ≤ 0.05) and executive control (Trail Making Test Part B, p = 0.048; B–A difference, p = 0.014). Group-level differences were domain-specific: both transgender groups scored below both cisgender groups on the visuospatial measures, whereas the ordering on executive-control measures differed, and distributions overlapped substantially throughout. Processing speed, working memory, and verbal fluency did not differ significantly (p > 0.05). No clear association between hormone therapy status and performance was detected in this small sample. Conclusions: The observed distributions were domain-specific and substantially overlapping, and should not be interpreted as indicating correspondence between cognitive performance and either gender identity or sex assigned at birth. Differences were domain-specific, with substantial overlap across groups. Findings support a context-sensitive, non-pathologizing interpretation emphasizing sociocultural factors rather than inherent deficits. Longitudinal and cross-cultural studies incorporating psychosocial variables are needed.

Brain Sciences doi: 10.3390/brainsci16090917

Authors: Luigi De Gennaro

Each year, Brain Sciences identifies the most downloaded, viewed, and cited articles for each section and invites the Section Editor to compile a selection based on originality, methodological rigor, relevance to current research trends, and overall scholarly impact [...]

Brain Sciences doi: 10.3390/brainsci16090916

Authors: Joyce Wu Ahmed M. Afifi Hong Xie Lila E. Mahmoud Sulaiman D. Aldoohan Xin Wang Cha-Hao Shih Stephen R. Grider

Background: Mild traumatic brain injury (mTBI) may rapidly alter neurocognitive function and has been associated with an increased risk for post-traumatic stress disorder (PTSD). However, neuroimaging investigations during the acute post-trauma phase remain sparse. We previously reported greater left anterior insular cortex (aIC) activation during the cognitive appraisal of fearful versus neutral emotional faces in survivors who did and did not exhibit probable PTSD at 3 months, but not at 2 weeks, after a motor vehicle collision (MVC). Given previous studies suggesting that mTBI may lead to increased cortical activation in the early post-trauma period, we hypothesize that aIC activation within 2 weeks post-MVC may be elevated among probable PTSD survivors who sustained an mTBI compared to those who did not sustain mTBI. Methods: In this secondary hypothesis-driven analysis, previously reported task-related activation at both 2 weeks and 3 months after trauma was extracted from the aIC region of interest and compared among groups of survivors diagnosed with probable PTSD at 3 months with (n = 5) and without (n = 11) mTBI in the emergency department. An exploratory analysis of change over time included two time points and additional groups of survivors without probable PTSD with (n = 10) and without (n = 12) mTBI. Results: At 2 weeks, aIC activation was significantly greater in the probable PTSD with mTBI group than in the probable PTSD without mTBI group (mean = 0.125, SD = 0.053 vs. 0.014, SD = 0.111) (Welch’s t (13.86) = 2.71, two-sided p = 0.017). aIC activation in probable PTSD survivors with and without mTBI was not significantly different at 3 months after MVC. The time and time × group interactions were not significant in brain activation and post-traumatic stress symptoms, but within-group tests suggest that decreases in post-traumatic stress symptoms over time were significant in groups without mTBI. Conclusions: These preliminary results are consistent with the hypothesized association between mTBI and greater aIC activation to negative emotional stimuli in the early post-trauma period among survivors with probable PTSD, but do not support post-trauma brain changes in survivors with mTBI, probable PTSD, both conditions, or neither condition. These preliminary findings warrant further investigation into the relationship between mTBI and probable PTSD-related cortical alterations during the acute post-trauma period.

Brain Sciences doi: 10.3390/brainsci16090915

Authors: Tianyuan Niu Ruoyan Li Mengfan Li

Background/Objectives: Electroencephalography (EEG), with its high temporal resolution, non-invasiveness, and cost-effectiveness, provides a suitable modality for investigating task-related signal patterns associated with Visual Sustained Attention (VSA) and Visual Internally Directed Cognition (VIDC), but cross-subject generalization remains challenging in reduced-channel settings. This study evaluated PDC-Net under an offline GPU setting. Methods: PDC-Net uses a Temporal Representation Adaptation Block (TRAB) for local temporal transformation and feature-channel recalibration and a Cross-Branch Gated Mamba Interaction (CGMI) module for input-dependent bilateral information exchange and long-range sequence modeling. Results: Under the strict LOSO cross-validation setting, PDC-Net achieved an average decoding accuracy of 76.76%, representing the highest mean accuracy among the 11 evaluated models. The model also maintained a favorable balance between cross-subject decoding performance and computational cost under the evaluated offline GPU setting. Conclusions: These findings support the feasibility of offline, subject-independent VSA/VIDC decoding from dual-channel Fp1/Fp2 EEG under the evaluated controlled conditions and provide a basis for subsequent external, cross-session, online, and hardware-specific evaluation.

Brain Sciences doi: 10.3390/brainsci16090914

Authors: Boon Khai Teoh Trang Thi Hoai Nguyen Kotha Peddanna Tran Van Bao Quach Jaung-Geng Lin Yi-Hung Chen

Background: Neuropathic pain (NP) is a debilitating chronic condition driven by maladaptive neuroimmune interactions in the spinal cord, with microglia playing a central pathological role. Electroacupuncture (EA) has shown analgesic effects in clinical and preclinical studies, but the microglia-centered mechanisms underlying these effects remain incompletely integrated. This review aims to provide a comprehensive mechanistic synthesis of how EA modulates microglia-associated neuroinflammatory pathways in neuropathic pain. Methods: This systematic search-narrative review used systematic search and screening procedures to identify English-language animal studies published between 2015 and 2025 in PubMed, CINAHL, Web of Science, and Cochrane Library. Twenty-six animal studies investigating EA effects on microglia-associated signaling pathways in neuropathic pain models met the inclusion criteria. Because of substantial heterogeneity in neuropathic pain models, EA parameters, molecular endpoints, and behavioral outcomes, findings were synthesized narratively, and no meta-analysis was performed. Results: The reviewed evidence revealed four convergent mechanistic categories through which EA modulates microglial activity: (1) attenuation of purinergic microglial activation via downregulation of IRF8, P2X4R, P2X7R; (2) suppression of innate immune sensing and inflammasome pathways, including TLR4/MyD88/NF-κB and NLRP3 signaling; (3) inhibition of downstream inflammatory amplification through p38 MAPK, PI3K/AKT, and COX-2 pathways; and (4) promotion of pro-resolution mechanisms involving IL-10/β-endorphin, PD-L1, GRK2/TREM2/DAP12, α7nAChR, GLP-1R, and GABAergic signaling. Conclusions: The available preclinical evidence suggests that EA modulates multiple microglia-associated pathways, attenuating inflammatory signaling while enhancing selected pro-resolution mechanisms. These findings provide a mechanistic framework for understanding EA-induced analgesia in neuropathic pain and highlight microglial signaling networks as important targets for future experimental and translational investigation.

Brain Sciences doi: 10.3390/brainsci16090913

Authors: YoungSoon Yang Jaeho Kim Youngsuep Kang Seungho Choi Jeonghyeon Seo SangYun Kim

Background: Low-intensity ultrasound (LIUS) has been proposed as a non-invasive approach to modulate cerebrospinal fluid movement, glymphatic–lymphatic clearance, and amyloid-beta (Aβ) handling in Alzheimer’s disease (AD). However, clinical comparisons in amyloid biomarker-confirmed patients receiving standard pharmacotherapy remain limited, and the short-term cognitive domains most likely to change after LIUS remain uncertain. Objective: The objective of this study was to compare 4-week changes in cognitive function, executive function, quality of life, and neuropsychiatric symptoms between amyloid PET-positive patients receiving add-on LIUS with donepezil-based standard treatment and those receiving donepezil-based standard treatment alone. Methods: This retrospective exploratory comparative cohort study included amyloid PET-positive patients with mild cognitive impairment or early AD who received donepezil-based standard treatment. The treatment cohort received 4 weeks of add-on LIUS at Dongtan or Bundang centers, whereas the comparator cohort received donepezil-based standard treatment alone at Soonchunhyang. Outcomes were changes from baseline to 4 weeks in Trail Making Test A (TMT-A), Trail Making Test B (TMT-B), Mini-Mental State Examination, Second Edition (MMSE-II), Quality of Life in Alzheimer’s Disease (QoL-AD), and Neuropsychiatric Inventory (NPI). Group differences were examined using unadjusted change-score comparisons and stabilized inverse probability of treatment weighting (IPTW). Results: The full analysis set included 51 amyloid PET-positive participants receiving donepezil-based standard treatment: 20 who additionally received LIUS and 31 who received standard treatment alone. Compared with controls, the add-on LIUS group showed greater improvement in TMT-A completion time in unadjusted analysis (−20.0 ± 31.3 s vs. −0.1 ± 5.6 s; p = 0.011), and this association remained significant after IPTW adjustment. TMT-B showed a favorable but less robust pattern, with borderline findings in the primary Fail-excluded analyses and a significant result in the Fail = 300 sensitivity analysis. MMSE-II change did not differ between groups. NPI improved more in the add-on LIUS group in unadjusted analysis, although this finding was exploratory. Conclusions: In amyloid PET-positive patients receiving donepezil-based standard treatment, 4 weeks of add-on LIUS was associated with short-term improvement in TMT-A performance compared with standard treatment alone, while MMSE-II remained unchanged. The findings suggest a preliminary signal for processing-speed or visual-search improvement and support prospective randomized sham-controlled studies with harmonized cognitive testing and biomarker endpoints.

Brain Sciences doi: 10.3390/brainsci16090912

Authors: Akshay Bhuvaneswari Ramakrishnan Nithish Kumar NavaneethaKrishnan William Mahler Adrian Schoech Meenalosini Vimal Cruz

Background/Objectives: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently co-occurring neurodevelopmental conditions with partially overlapping neurophysiological profiles. Electroencephalography (EEG) provides non-invasive access to candidate biomarkers, yet the literature remains largely organized around single-diagnosis frameworks, limiting comparison across conditions and constraining translation into intervention selection. This review compares EEG signatures across ASD and ADHD from a transdiagnostic perspective and examines how such signatures might inform the selection of non-pharmacological interventions. Methods: A structured search of PubMed, Scopus, IEEE Xplore and Web of Science identified peer-reviewed studies published between 2010 and 2026 reporting EEG findings in ASD and/or ADHD, spanning resting-state, task-based, connectivity, event-related potential, machine learning and intervention studies. Sixty-eight sources were synthesized thematically. Given substantial heterogeneity in acquisition parameters and analytic pipelines, evidence was integrated interpretively rather than pooled quantitatively, and no formal risk-of-bias assessment was undertaken. Results: Shared features across both conditions frequently included low-frequency theta excess, reduced alpha modulation under cognitive load, and flattened aperiodic (1/f) slopes—a pattern compatible with, though not a direct measurement of, altered excitation/inhibition balance. While substantial heterogeneity exists, disorder-specific signatures often comprised the ASD “U-shaped” spectral profile alongside elevated epileptiform activity, and frontally pronounced theta/beta ratio elevation in subsets of individuals with ADHD. Machine-learning studies increasingly emphasize interpretable, multidomain feature sets over binary classification. Mindfulness-based and neurofeedback interventions converge on theta reduction and alpha enhancement, although reported effects are frequently conditional on responder status, task context, or outcome-rater blinding. Conclusions: Convergent EEG features support a transdiagnostic account of neurodevelopmental dysregulation. A biomarker-informed framework for intervention selection is proposed, which requires prospective validation before clinical application.

Brain Sciences doi: 10.3390/brainsci16090911

Authors: Renming Liu Aung Aung Kywe Moe Zhen Zheng Shapour Jaberzadeh

Background: Motor evoked potential (MEP) amplitude elicited by single-pulse transcranial magnetic stimulation (TMS) is widely used as an indirect index of corticospinal excitability (CSE). Averaged MEP amplitudes are commonly used to improve measurement stability, but averaging may obscure some trial-level information across the recording sequence. As trial-level and hierarchical modelling approaches become increasingly common, it remains important to determine how averaged and trial-level MEP amplitudes should be interpreted as measures of CSE. Objective: This study compared the intra-session and inter-session reliability of averaged and trial-level MEP amplitudes, with exploratory block analyses used to examine whether trial-order structure was obscured by averaging. Methods: Twelve healthy adults completed two sessions with three CSE assessments at T1, T2, and T3 (T1 and T2 20 min apart; T3 at least 48 h later). At each time point, 25 single-pulse MEPs were elicited at 120% resting motor threshold and recorded from the right first dorsal interosseous muscle. Reliability was assessed using intraclass correlation coefficients (ICC), coefficients of variation (CV), minimal detectable change at the 95% confidence level (MDC95), Bland–Altman analysis, linear mixed-effects models, exploratory sequential block analyses, and Bayesian variance decomposition. Results: Average MEP amplitudes remained stable across T1, T2, and T3. Average-level reliability was good across all timepoints (ICC = 0.899) and excellent within session (T1 vs. T2: ICC = 0.992, CV = 4.935%, MDC95 = 0.191 mV). Inter-session average-level reliability remained good (ICC = 0.844–0.852). In contrast, trial-level analyses revealed substantial within-participant variability, with low ICCs, high CVs, and large MDC95 values. Bland–Altman analyses showed minimal mean bias but substantially wider limits of agreement for trial-level data. Exploratory sequential block analyses showed that, in the late block, T1 differs significantly from T3. Bayesian modelling indicated that residual trial-level variability exceeded between-subject variability, with a posterior ICC of 0.336. Conclusions: Averaging 25 MEPs provides a reliable estimate of corticospinal excitability, but it masks variability. Trial-level and exploratory block analyses suggest that this variability may contain meaningful temporal structure, supporting trial-level modelling as a complementary approach for validating and interpreting averaged MEP estimates.

Brain Sciences doi: 10.3390/brainsci16090910

Authors: Sitong Liu Guangyu Zhang Cunwei Wu Wenjia Li Yanan Zhang Boao Wei Yunfei Ma Hongkai Wang Xiaohong Huang

Background/Objectives: Existing motor imagery (MI) EEG decoding is often limited by small datasets, affecting generalization reliability. This study aims to robustly decode multi-limb MI intentions. Methods: We collected an MI-EEG dataset from 292 participants (242 young adults, 50 older adults) performing left/right-arm and left/right-leg imagery. After extracting time-, frequency-, and channel correlation features, we proposed an SE-EEG-Inception model for classification. Results: Evaluated under a strict intra-subject cross-validation protocol, the model achieved a mean 4-class accuracy of 89.4%. For binary tasks, accuracies reached 88.3% (left vs. right arm) and 90.0% (left vs. right leg). Conclusions: The model successfully distinguishes predictive EEG features across different and symmetric limbs. Crucially, this high classification performance demonstrates data-driven predictive utility rather than mechanistic proof of neural differences, providing an offline proof-of-concept for multi-limb BCI control.

Brain Sciences doi: 10.3390/brainsci16090909

Authors: Han Wang Zhaoming Liu Xianjie Li Lin Fu Tingxin Lu Dantong Wang Guanzhen Lin Caixia Wu

Background: Depression-like phenotypes in animal models often show graded behavioral variation rather than uniform group-wise changes, yet treatment effects are still commonly evaluated using categorical comparisons. In particular, it remains difficult to determine whether treated animals retain model-like behavioral features or shift toward a more control-like state. Here, we developed a continuous behavioral phenotyping framework based on multidimensional open-field-test (OFT) features to quantify model-like behavioral states and treatment-associated behavioral shifts. Methods: In the present dataset, untreated CUMS- and LPS-induced mice jointly defined a shared model-like behavioral state characterized by reduced locomotor activity and altered spatial exploration. By integrating principal component analysis with k-nearest-neighbor-based behavioral inference, we derived two complementary indices: Δd, representing the relative distance of an animal from the model-like versus control-like behavioral centroids, and p_depression, a kNN-derived score representing similarity to the untreated model-like reference state. These indices were used to position individual animals along a spectrum between control-like and model-like behavioral states. Results: Higher p_depression and lower Δd indicated OFT phenotypes more similar to untreated model mice. Using this framework, NSC-treated animals showed treatment-associated shifts away from model-like behavioral patterns and toward more control-like states, while preserving substantial inter-individual variability. Behavioral scores also showed group-level correspondence with neuroinflammatory markers, suggesting preliminary biological relevance. Because the primary model-specific biological comparisons were based on a limited subgroup size (n = 4 per group), the observed NSC-associated treatment effects should be regarded as exploratory and require confirmation in larger, prospectively powered cohorts. Conclusions: Together, these findings support continuous OFT-based behavioral phenotyping as a promising exploratory approach for evaluating treatment-associated behavioral change and phenotypic heterogeneity in preclinical depression research.

Brain Sciences doi: 10.3390/brainsci16090908

Authors: Matteo Lupi Alessandro Carano Eros Rossi Maria Carlucci Angelomarco Barioglio Marco Giri Domenico De Berardis Umberto Volpe Giovanni Martinotti

Background/Objectives: The aim of this systematic review is to assess the efficacy, effectiveness, and safety of LAI antipsychotics in patients with schizophrenia and comorbid SUD, providing useful information for clinical decision making and guiding future research in the management of this complex patient population. Methods: The search was conducted on 1 July 2026 and produced 87 results in total; after the screening process, 78 articles were excluded based on the predefined eligibility criteria. The full texts of the remaining 9 studies were retrieved and thoroughly evaluated for inclusion in the qualitative synthesis. Results: The 9 articles that met the criteria for inclusion included 2062 patients in total with follow-up periods varying between 6 months and 3 years. Several studies reported favorable clinical outcomes associated with LAIs; however, not all studies demonstrated clear superiority of LAIs over oral antipsychotics. Conclusions: The present review suggests that LAIs may represent a valuable therapeutic strategy for patients with schizophrenia and comorbid SUD, although the available evidence remains heterogeneous in terms of study design, patient populations, and outcome measures.

Brain Sciences doi: 10.3390/brainsci16090907

Authors: Federica Teutonico Irene Puma Aglaia Vignoli

Background/Objectives: Post-stroke epilepsy represents one of the most frequent and impactful long-term sequelae of pediatric arterial ischemic stroke. Children are particularly vulnerable to developing seizures and epilepsy after stroke, likely because the immature brain responds differently to ischemic injury than the adult brain. The purpose of this narrative review is to summarize the current evidence regarding the epidemiology, risk factors, mechanisms, and clinical implications of post-stroke epilepsy following pediatric arterial ischemic stroke. Methods: We conducted a narrative review to examine the incidence, determinants, risk stratification, and long-term outcomes of post-stroke epilepsy following childhood arterial ischemic stroke beyond the neonatal period. Results: The reported incidence of post-stroke epilepsy in children varies considerably across studies, ranging from approximately 7% to over 40%. However, recent data suggest that roughly one in four children who experience an arterial ischemic stroke will eventually develop epilepsy, highlighting the substantial long-term burden of this condition. Acute symptomatic seizures, particularly very early seizures and acute status epilepticus, consistently emerge as the strongest predictors of subsequent epilepsy, with recent pediatric meta-analytic data suggesting an approximately fourfold increased risk of post-stroke epilepsy. Cortical involvement and persistent neurological deficits also represent robust predictors of post-stroke epilepsy (PSE), whereas younger age at stroke onset, multifocal infarctions, greater infarct burden, anterior circulation involvement, and focal cerebral arteriopathy have been associated with an increased risk. Emerging evidence further suggests a possible contribution of genetic susceptibility and potentially modifiable biological factors, such as vitamin D deficiency, to epileptogenic risk. Conclusions: This narrative review summarizes current evidence regarding the incidence, determinants, and pathophysiological mechanisms of post-stroke epilepsy following childhood arterial ischemic stroke, highlighting established and emerging risk factors and their implications for long-term risk stratification, clinical management, and future preventive strategies.

Brain Sciences doi: 10.3390/brainsci16090906

Authors: Diego Santos García Pablo Campo Prieto Carmen M. Breijo García Lucía Dafonte Gil Juan Pereiro Nogueira Jessica Blanco López Francisco Doblas

Objectives: Non-pharmacological therapies are a cornerstone of Parkinson’s disease (PD) treatment, but there is not enough evidence of their benefit when delivered altogether online. Our objective was to analyze the efficacy and safety of an online comprehensive care therapy program (OL-CCTP) in people with PD (PwP). Material and methods: This was a proof-of-concept experimental, prospective, 6-month interventional study comparing a PD treatment group (PwP-T) with a control group (PwP-C). The OL-CCTP included group sessions of physical therapy/therapeutic exercise, nutrition, speech therapy, cognitive stimulation, and psychological support (126 sessions over 6 months). The primary outcome was the change in quality of life at 6 months, as measured by the PDQ-39 questionnaire. Mood (Beck Depression Inventory-II [BDI-II]), the non-motor symptom burden (Non-Motor Symptoms Scale [NMSS]), and disability (Schwab and England Activities of Daily Living Scale [ADLS]) were also assessed. Results: Sixty patients (36 PwP-T and 24 PwP-C) completed the assessments. A reduction of 12.9% (from 78.4 ± 17.9 to 68.3 ± 18.7; p < 0.0001) was observed in the PDQ-39 total score in the PwP-T group (p < 0.0001), compared to 1.5% (from 77.8 ± 22.2 to 76.6 ± 27.9; p = 0.438) in the PwP-C group (p = 0.009). The BDI-II and NMSS scores decreased significantly by 13.1% (p = 0.001) and 20.3% (p = 0.046), respectively, in the PwP-T group but not in the PwP-C group. There were no significant changes in ADLS in either group. No adverse events were reported. Conclusions: After 6 months of OL-CCTP, an improvement of 12.9% was observed in the quality of life of patients with PD.

Brain Sciences doi: 10.3390/brainsci16090905

Authors: Sigfus Kristinsson Sophia Coolsen Saeed Ahmadi Leonardo Bonilha

Background/Objectives: Speech-language treatment improves recovery in chronic post-stroke aphasia, but whether individuals continue to benefit from repeated treatment exposure remains unclear. We tested whether successive treatment episodes were associated with continued naming improvement and whether gains were reduced in later episodes relative to earlier episodes. Methods: We analyzed retrospective longitudinal data from 35 participants with post-stroke aphasia who completed at least two aphasia treatment studies. Philadelphia Naming Test scores were obtained before and after each treatment study. The primary analysis used a linear mixed-effects model with fixed effects for timepoint, treatment study, and their interaction, with random intercepts for participants and participant-specific treatment studies. Secondary analyses examined candidate predictors and compared within-treatment with between-treatment change while accounting for elapsed time. Results: Naming improved significantly from pre- to post-treatment across studies 1–3 (estimated mean gain = 5.56 points, 95% CI [3.44, 7.67], p < 0.001). The timepoint-by-treatment-study interaction was not significant (p = 0.384), providing no evidence that gains were attenuated across successive studies. Naming improved faster during treatment than between treatments (adjusted difference = 2.18 points per 30 days, p = 0.013). Conclusions: Repeated treatment opportunities were associated with continued naming improvement in chronic post-stroke aphasia, supporting a longitudinal view of aphasia rehabilitation.

Brain Sciences doi: 10.3390/brainsci16090904

Authors: Min Yan Sen Zhang Zigui Zhou Changzhi Yang Xuewen Tian Peijie Chen

Objectives: The pathological progression of Parkinson’s disease (PD) involves alterations across multiple neural cell types, and glial–neuronal communication substantially influences neuronal function. Oligodendrocytes (OLs) have been implicated in PD pathology, but the underlying regulatory mechanisms remain incompletely understood. Methods: In this study, single-nucleus RNA sequencing and spatial transcriptomics were used to characterize OL-associated changes and explore potentially relevant mechanisms in the substantia nigra pars compacta (SNpc) of MPTP-induced parkinsonian mice. Molecular validation was subsequently performed in an exercise intervention cohort. Results: These analyses revealed a significant reduction in OL abundance in the SNpc, accompanied by enrichment of ferroptosis-related pathways. Aerobic exercise partially restored the expression of the OL marker gene Plp1 and the antioxidant pathway-related molecules Nrf2 and Gpx4, while reducing ferroptosis-related oxidative stress. These changes were associated with improvements in PD-like pathological phenotypes. Exploratory untargeted metabolomics further identified candidate alterations in metabolites and pathways related to redox homeostasis, energy metabolism, and myelin-associated processes after MPTP treatment and exercise intervention. Conclusions: Collectively, exercise-associated improvements in MPTP-induced PD-like phenotypes coincided with reductions in OL/myelin-related injury and ferroptosis-related stress. These findings suggest that OL-associated ferroptosis-related stress may represent one of several processes contributing to neuronal injury in PD and may be responsive to aerobic exercise. This study provides a theoretical basis for further investigation of exercise-based rehabilitation strategies and potential therapeutic targets for PD.

Brain Sciences doi: 10.3390/brainsci16090903

Authors: Chenxi Bao Wenqing Li Kangkang Chu Qingxiang Liu Ya Wang Xiaoyan Ruan Huimin Lü Xi Liu Xiaoyan Ke

Background/Objectives: This study aimed to investigate the clinical characteristics associated with psychiatric hospitalizations in children with ASD and to evaluate changes in blood-based Inflammatory Indices following treatment. Methods: A retrospective study of 269 children and adolescents with ASD (≤18 years) admitted to Nanjing Brain Hospital between 2012 and 2023 was conducted. Electronic medical records were reviewed for demographic characteristics, primary reasons for hospitalization, ASD-specific clinical scale scores, and routine laboratory parameters. The systemic immune–inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and non-enzymatic antioxidant indicators (uric acid, total bilirubin, direct bilirubin, prealbumin) were calculated. Results: The mean age at admission was 12.13 years, and 80.3% of admitted patients were male. The leading reasons for hospitalization were aggression (76.21%), psychosocial stressors (48.32%), and ADHD-related symptoms (46.09%), with distinct patterns observed by intellectual disability status, sex, and developmental stage. Multiple regression analyses revealed that age, sex, and specific admission indications were significantly associated with baseline inflammatory indices (SII, NLR, PLR, WBC, NEU, PLT; all p < 0.05) and antioxidant indices (UA, TBIL, DBIL, PA; all p < 0.05). Among 196 patients with 4-week follow-up data, significant post-treatment reductions were observed in SII, WBC, NEU, UA, TBIL, and DBIL, alongside increased prealbumin (all p < 0.05). Conclusions: Psychiatric hospitalizations of Chinese children with ASD are driven by distinct behavioral and neurodevelopmental profiles. Concurrently, accessible blood-based inflammatory and antioxidant indices show significant baseline clinical associations and post-treatment alterations, suggesting their potential as adjunctive biological markers in acute psychiatric settings. These findings are limited by the retrospective single-center design, absence of a control group, and lack of post-treatment clinical severity assessments.

Brain Sciences doi: 10.3390/brainsci16090902

Authors: Yaqiang Che Chunting Wan Wenhao Yang Dongyi Chen

Background: Major depressive disorder (MDD) is a common psychiatric disorder. Electroencephalography (EEG) provides physiological information for depression detection, but many existing methods rely on dense multichannel recordings, limiting their use in lightweight EEG screening. Frontal sparse-channel EEG reduces acquisition burden but provides limited spatial information, requiring effective within-window representation learning and cross-window temporal modelling. Methods: We propose FSC-BiMamba, a dual-branch bidirectional Mamba network for subject-independent window-level MDD classification from frontal sparse-channel EEG. For each window, a Time–Frequency Map Encoder (TFME) learns local time–frequency patterns, while a Frequency-Domain Statistical Descriptor Encoder (FSDE) encodes complementary frequency-domain statistical descriptors. An Adaptive Dual-Token Fusion (ADTF) module integrates the resulting tokens through feature-wise gating to form a unified window representation. Representations from eight consecutive windows are then processed by a bidirectional Mamba (BiMamba) module to capture cross-window context. Finally, a softmax classifier converts each contextualized representation into a window-level class prediction. Results: Performance was evaluated using stratified subject-independent five-fold cross-validation. FSC-BiMamba achieved window-level accuracies of 82.70 ± 2.37% and 84.55 ± 8.01% on MODMA and Mumtaz2016, respectively. Together with its compact architecture, these results indicate a favourable balance between classification performance and model size. Conclusions: FSC-BiMamba effectively integrates complementary window-level representations with cross-window temporal context. It achieved the highest accuracy among the compared models on both datasets, demonstrating a favourable performance–size trade-off for lightweight EEG-based MDD screening.

Brain Sciences doi: 10.3390/brainsci16090901

Authors: Marcin Karol Setlak Bartłomiej Błaszczyk Maciej Wojtacha Adam Rudnik

Background/Objectives: Transcranial magnetic stimulation (TMS) initiates a cascade from intracranial electric-field exposure through neural recruitment and plasticity to distributed network responses. Neuronavigation improves the geometric reproducibility of delivery but does not guarantee equivalent cortical exposure or target engagement. This narrative review integrates these levels within an operational framework for precision TMS. Methods: Six domain-specific PubMed searches covering 1 January 1985 to 31 July 2026 were supplemented by Google Scholar and citation tracking. A documented rerun on 17 August 2026 yielded 6430 records (5617 unique after cross-query deduplication). Evidence was synthesized narratively; no quantitative synthesis or formal risk-of-bias assessment was performed. Results: Neuronavigation improves geometric precision by stabilizing target definition and coil pose, whereas individualized electric-field models estimate intracranial exposure. Neither establishes biological precision, which also depends on neuronal orientation, brain state, circuit architecture, medication, and behavior. Motor-system measures are not validated as universal biomarkers for nonmotor cortex, and no single validated biomarker captures TMS-induced plasticity. Convergent, controlled multimodal evidence may strengthen inference about target engagement; adaptive and closed-loop approaches remain experimental. Conclusions: Geometric delivery, modeled exposure, biological engagement, and durable functional or clinical benefit require separate validation. Spatial accuracy alone does not establish clinical value.

Brain Sciences doi: 10.3390/brainsci16090900

Authors: Raed Al Ruwaili Ekramy M. Elmorsy Mohamed M. Abdel-Daim Eida M. Alshammari Aly A. M. Shaalan Ola A. Habotta Manal S. Fawzy Mai Salem

Background/Objectives: Manganese (Mn) is a neurotoxic trace element whose excessive accumulation in the brain can induce hippocampal damage via oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. This study investigated whether honokiol (HNK) and its liposomal nanoformulation (HNK-LNPs) can ameliorate Mn-induced hippocampal neurotoxicity by modulating key antioxidant and mitochondrial regulatory pathways. Methods: Male Wistar rats were subjected to Mn exposure to induce hippocampal neurotoxicity and were treated with HNK or HNK-LNPs. We assessed oxidative status via NRF2/HO-1 signaling, antioxidant defenses (glutathione, GPx, SOD, CAT), and oxidative indices (ROS, MDA). Neuroinflammatory markers (NF-κB, TNF-α, IL-1β, IL-6, Iba-1), mitochondrial respiratory chain function and ATP levels, SIRT1/PGC-1α signaling, and neurotransmitter homeostasis were evaluated. We analyzed apoptosis using Bax, Bcl-2, caspase-3, and cytochrome c, along with histopathological and ultrastructural examination of the hippocampus. Results: Mn exposure was associated with NRF2/HO-1 downregulation, depleted endogenous antioxidants, increased ROS and MDA levels, and increased NF-κB–driven neuroinflammation and microglial Iba-1 expression. Mn was further associated with reduced ATP synthesis, dysregulation of SIRT1/PGC-1α signaling, and disrupted neurotransmitter balance, with a pro-apoptotic shift (elevated Bax, caspase-3, cytochrome c; reduced Bcl-2) and neuronal degeneration. Co-treatment with HNK, and more prominently with HNK-LNPs, was associated with reversing these alterations, restoring antioxidant and mitochondrial pathways, dampening inflammatory cascades, normalizing neurotransmitters, and favoring neuronal survival, with many indices approaching control values and consistently surpassing free HNK. Conclusions: Liposomal encapsulation significantly enhances honokiol’s neuroprotection against Mn-induced hippocampal neurotoxicity, likely via improved CNS bioavailability and coordinated modulation of NRF2/HO-1 and SIRT1/PGC-1α pathways. These findings support HNK-LNPs as a promising multi-mechanistic therapeutic strategy for metal-induced and related neurotoxic brain disorders.

Brain Sciences doi: 10.3390/brainsci16090899

Authors: Alex Marson Giorgia Cona

Background: Future-oriented cognition involves several neurocognitive processes putatively supported by the dorsolateral prefrontal cortex (DLPFC) and beta-band oscillations. This study aimed to corroborate the role of beta oscillations in the DLPFC during three future cognition tasks: mental time travel (MTT), delay discounting (DD), and time-based prospective memory (PM). Methods: Thirty-three participants (22–29 years) completed the three tasks under two conditions—active and sham stimulation—administered in a counterbalanced within-subjects design, one week apart. Beta-frequency transcranial alternating current stimulation (tACS; 22 Hz, 1.5 mA) was applied bilaterally over the DLPFC (F3–F4). Results: Beta-tACS was associated with dissociable effects across domains. In MTT, stimulation selectively improved accuracy for ordinality judgements anchored to past and present reference points (2014, 2024), without affecting future projections (2034) or reaction times. In DD, beta-tACS did not modify the steepness of temporal discounting in a statistically significant way. In PM, stimulation enhanced both dichotomous accuracy and continuous temporal precision, with no changes in clock-checking behavior. Conclusions: These findings provide preliminary evidence that suggests a possible role of DLPFC beta oscillations in supporting the maintenance and utilization of more concrete temporal representations across distinct temporal domains, resulting in anchoring in more available representations (MTT) and focus on temporal information (PM), challenging unitary accounts of prefrontal beta function and highlighting task-dependent neuromodulation effects within the future temporal domain.

Brain Sciences doi: 10.3390/brainsci16080898

Authors: Monika McAtarsney-Kovacs Raju Sapkota Ian van der Linde Shahina Pardhan

Background: Literature suggests that both the Stroop task and visual short-term memory (VSTM) binding tasks can differentiate individuals with Mild Cognitive Impairment (MCI) from cognitively normal older adults. These cognitive processes have rarely been examined together. This study investigated how Stroop-like color-word incongruency and directional incongruency between arrow orientation and motion affect memory accuracy and reaction time (RT) measures during a VSTM binding task in cognitively normal adults and individuals screening positive for MCI. Methods: A total of 115 adults participated: 34 healthy young adults (mean age = 24.7 ± 3.0 years), 61 cognitively normal older adults (mean age = 70.5 ± 6.3 years), and 20 older adults screening positive for MCI (mean age = 73.9 ± 5.9 years), i.e., MCI-indicatives. Participants completed two non-speeded VSTM binding tasks under low (two items) and high (four items) memory load conditions. Experiment 1 used color words displayed in congruent or incongruent ink colors, while Experiment 2 used arrows whose orientation and motion directions were congruent or incongruent. Results: In Experiment 1, overall % memory accuracy was significantly lower in the MCI-indicative group than in the cognitively normal older group and the young healthy group (p < 0.001); the difference between the young and cognitively normal older group was, however, not significant. In Experiment 2, % memory accuracy in the cognitively normal older group was significantly lower than in the young group but better than in the MCI-indicative group (p < 0.01). Across both experiments, the MCI-indicative group showed slower RTs overall. Incongruency did not affect accuracy but significantly increased RTs in older adults and the MCI group in Experiment 1 (p < 0.001), with no significant effect in young adults. Conclusions: The MCI-indicative group showed significantly decreased overall accuracy and longer RTs during VSTM tasks involving Stroop-like colored word-location and directional binding. While Stroop-like incongruency and directional incongruency did not affect memory accuracy, they selectively increased RT in older and MCI-indicative groups, suggesting that executive processing demands may uncover subtle cognitive changes associated with normal aging and early MCI.

Brain Sciences doi: 10.3390/brainsci16080897

Authors: Eryk Latoch Natalia Sufin Weronika Samełko Michał Płoński

Background: Isolated sphenoid sinus disease (ISSD) in children is an uncommon but clinically significant condition that may present primarily with neurological or neuro-ophthalmological symptoms rather than typical sinonasal complaints. Owing to the anatomical proximity of the sphenoid sinus to the optic nerves, cavernous sinus, and multiple cranial nerves, even localized sphenoid pathology may produce symptoms that mimic primary neurological, neuro-ophthalmological, or headache disorders, contributing to diagnostic delay. Objective: To characterize the spectrum and frequency of neurological and neuro-ophthalmological manifestations, diagnostic pathways, treatment strategies, and reported clinical outcomes in pediatric ISSD, with particular emphasis on diagnostic delay and persistent neurological sequelae. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed and Web of Science were searched from database inception to 3 January 2026. Observational studies reporting pediatric patients aged ≤18 years with radiologically confirmed ISSD were included. Single-patient case reports, reviews, and studies without extractable pediatric data were excluded. Owing to substantial clinical and methodological heterogeneity, findings were synthesized descriptively. Risk of bias was assessed using Joanna Briggs Institute (JBI) critical appraisal tools. Results: Eleven studies comprising 136 pediatric patients were included. Most cases were inflammatory lesions (n = 121, 89%), followed by mucoceles (n = 10, 7.3%) and tumors (n = 5, 3.7%). Headache was the most frequent neurological manifestation reported in 129 patients (94.9%). Ocular manifestations were present in 33/136 patients (24.2%), whereas otolaryngological symptoms were reported in 25/134 patients (18.7%). Cranial nerve involvement was documented in 10 out of 54 patients with available data (19%), most commonly affecting cranial nerves III, V, VI, and VII. Among 79 reported initial diagnoses, primary headache disorders were the most common (49.4%), whereas sphenoid sinusitis was correctly identified in only 20.3%. Diagnosis was established using CT and/or MRI in all included cases. Antibiotic therapy was the most common treatment for inflammatory lesions, while all patients with mucoceles and tumors underwent surgical management. Full recovery was reported in 81% of inflammatory cases and in all patients with mucoceles, although follow-up reporting was heterogeneous. Conclusions: Pediatric ISSD frequently presents with neurological and neuro-ophthalmological manifestations, whereas sinonasal symptoms may be absent or subtle. Persistent or atypical neurological symptoms, particularly headache accompanied by ocular symptoms or cranial nerve deficits, should prompt consideration of sphenoid sinus pathology and early cross-sectional imaging.

Brain Sciences doi: 10.3390/brainsci16080896

Authors: Arun Yadawa Sufang Liu Feng Tao

Chronic pain is a major global health burden and often remains difficult to treat with current therapies, which frequently provide incomplete relief and may cause systemic side effects. As essential organelles in eukaryotic cells, mitochondria facilitate ATP synthesis and serve as key regulators of calcium homeostasis and apoptosis. Evidence points to mitochondrial dysfunction not merely as a result of trauma, but as a fundamental factor in why pain becomes persistent. On the other hand, the endoplasmic reticulum (ER) is more than just a structural component of the cell; it is a multi-functional organelle responsible for protein quality control, including folding and degradation, as well as lipid production and calcium signaling. ER dysfunction is a primary driver of various pathologies, such as cardiovascular disease, cancer, and neurodegenerative disorders. The organelle’s ability to execute its vital functions is strictly dependent on sufficient levels of ATP. Because mitochondrial and ER functions are closely interconnected through calcium exchange, ATP-dependent protein homeostasis, oxidative stress, and mitochondria-associated ER membranes, their dysfunction may act together to amplify nociceptive sensitization and pain chronification. In this review, we summarize current evidence linking mitochondrial dysfunction, ER stress, and ER-mitochondrial crosstalk to the pathogenesis of chronic pain and discuss their potentials as therapeutic targets.

Brain Sciences doi: 10.3390/brainsci16080894

Authors: Charles Bouzou Marta Fernández-Ledesma María Cuesta Pedro Cobo

Background/Objectives: The aim of this study was to apply data-driven clustering techniques for the subtyping of tinnitus severity to a retrospective cross-sectional cohort of 564 subjects. Additionally, the response of the resulting phenotypes to an enriched acoustic environment (EAE) treatment was investigated. Methods: A hierarchical decision cascade was applied to classify the measured audiograms of participants into six hearing loss (HL) patterns. K-clustering techniques were applied to demographic (gender), hearing (average audiometric threshold, HL pattern), tinnitus (tinnitus onset age, duration, severity, lateralisation, type of sound, aetiology) and emotional variables. Subjects received customised EAE stimulus to be listened to for one hour daily over four months. Results: Five phenotypes were found by applying K-clustering techniques to numerical and categorical variables. EAE provided an average tinnitus severity reduction of 24.3 points, which was clinically relevant and statistically significant, in 78% of subjects who completed the four-month treatment. Conclusions: Analysis of the performance of EAE treatment in the different phenotypes afforded clear differences in the composition of excluded, dropped out, and not improved subjects. Absolute mean improvement of both severity and emotional scores was larger in phenotypes PH3 and PH4, as they had higher tinnitus distress and emotional symptoms at baseline. Nevertheless, relative change of severity score was notably smaller in PH4.

Brain Sciences doi: 10.3390/brainsci16080895

Authors: Saqer Alshehri Bartu Atabek Terry Heiman-Patterson Hasan Ayaz

Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease increasingly recognized for extra-motor manifestations, including cognitive dysfunction involving frontal cortical systems. Conventional clinical assessments are primarily behavioral and may not capture subtle alterations in the neural systems that support cognitive performance. This pilot study examined whether wearable functional near-infrared spectroscopy (fNIRS) could detect task-evoked prefrontal hemodynamic differences during the King-Devick Task (KDT), a rapid oculomotor number-naming task that engages visual scanning, attention, processing speed, and verbal response production. Methods: Sixteen participants, including seven individuals with ALS and nine age-matched healthy controls (HC), completed four progressively difficult KDT conditions while prefrontal cortical activity was recorded. Results: As task difficulty increased, response times became slower across participants, while accuracy remained preserved and behavioral performance did not differ significantly between groups. Prefrontal oxygenated hemoglobin (HbO) responses increased with task difficulty across all prefrontal optodes, supporting task-evoked cortical engagement. In contrast, deoxygenated hemoglobin (HbR) responses showed a group-specific pattern in the left dorsolateral prefrontal cortex: individuals with ALS demonstrated progressively increasing HbR responses across difficulty conditions, whereas HC showed relatively stable responses, with group differences emerging at higher difficulty levels. Conclusions: These findings suggest a dissociation between preserved behavioral performance and altered prefrontal hemodynamic regulation in ALS. The observed HbR pattern may reflect differences in cortical recruitment, neurovascular coupling, oxygen extraction, vascular responsiveness, or the efficiency of cortical resource allocation during increasing cognitive-motor demands. Wearable fNIRS may therefore complement behavioral assessments by revealing task-evoked neural alterations that are not evident from performance measures alone.

Brain Sciences doi: 10.3390/brainsci16080893

Authors: Mirjana Perkovic Benedik Tanja Loboda Katarina Benedik Kafol Jan Kafol Neli Bizjak

Background: Juvenile-onset Huntington disease (JoHD) is a rare form of Huntington disease characterized by symptom onset at or before 20 years of age. Early manifestations are often non-choreic and may be attributed to developmental, psychiatric, movement, metabolic, or epileptic disorders. We described three molecularly confirmed cases and examined early manifestations, diagnostic pathways, and epilepsy. Methods: We conducted a retrospective case series and a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 systematic review of PubMed, Scopus, and Web of Science Core Collection through 5 July 2026. The strict patient-level synthesis required attributable onset at or before 20 years, patient-specific molecular confirmation of a pathogenic HTT repeat expansion, and extractable clinical data. Complementary aggregate or linked reports using closely aligned JoHD criteria were retained for context but excluded from patient-level calculations. Results: The cases included childhood-onset JoHD with drug-resistant epilepsy, adolescent-onset JoHD with progressive motor-cognitive decline and epilepsy in a known Huntington disease pedigree, and childhood-onset JoHD without available family history, in whom status epilepticus prompted renewed diagnostic evaluation. Ninety-three reports were included; of these, 81 contributed 228 unique patients and 12 provided complementary data. Early manifestations were heterogeneous and broadly consistent with previously described childhood-onset JoHD phenotypes. Diagnostic delay was extractable in 180/228 patients; among 172 with point estimates, the median was 4.0 years. Definite epilepsy was reported in 60/145 patients with ascertainable seizure status and was descriptively more frequent in childhood-onset (<10 years) than adolescent-onset (10–20 years) JoHD (49/84 [58.3%] vs. 11/57 [19.3%]). Conclusions: JoHD should be considered in children and adolescents with progressive multisystem neurological involvement, particularly when epilepsy occurs with developmental regression, gait or speech deterioration, pyramidal or extrapyramidal signs, basal-ganglia abnormalities, or a compatible family history.

Brain Sciences doi: 10.3390/brainsci16080892

Authors: Dongyang Zhou Hongyi Yan Lei Guo Shuo Yang Tingting Wang Ling Guan Yilong Wang

Background/Objectives: Cerebral small vessel disease (CSVD) is an important contributor to motor impairment. Cortical cerebral microinfarct (CCMI) is an emerging imaging marker of CSVD. Although its association with cognitive impairment has been well established, its relationship with motor function remains unclear. We explored associations of CCMI with motor performance at baseline and 1-year follow-up in this secondary analysis of data from the China Imaging-based Biobank of Cerebral Small Vessel Diseases. Methods: CCMI was assessed on baseline brain magnetic resonance imaging. Motor function was assessed at baseline and at 1-year follow-up. Outcomes were gait speed, poor balance performance (Short Physical Performance Battery balance score ≤ 2), abnormal gait (Scale for the Assessment and Rating of Ataxia gait score ≥ 2), and repeated chair-stand time. Gait speed was the primary outcome and all other motor outcomes were secondary. Multivariable linear and logistic regression models were used, with Benjamini–Hochberg correction applied to secondary outcomes. Results: The analysis included 192 patients, of whom 74 had 1-year follow-up motor data. At baseline, 55 patients (28.65%) had CCMI. Compared with patients without CCMI, those with CCMI had lower gait speed [0.92 (0.75–1.12) vs. 1.05 (0.87–1.16) m/s]. They also had higher prevalences of poor balance performance (29.09% vs. 14.60%) and abnormal gait (63.64% vs. 36.50%). However, fully adjusted analyses provided no conclusive evidence of baseline associations. At 1-year follow-up, CCMI was associated with slower gait speed after adjustment for demographic factors, baseline gait speed, and total CSVD burden (adjusted β −0.16, 95% CI −0.24 to −0.08; p < 0.001). CCMI was also nominally associated with longer repeated chair-stand time (adjusted β 2.07, 95% CI 0.39–3.75; nominal p = 0.02; adjusted p = 0.06), but this association did not survive correction for multiple comparisons. Conclusions: CCMI was associated with slower gait speed at 1-year follow-up in patients with CSVD. This finding is hypothesis-generating and requires confirmation.

Brain Sciences doi: 10.3390/brainsci16080891

Authors: Yasemin Adalı Ümit Akın Dere

Background: Trigeminal neuralgia is a chronic neuropathic pain disorder characterized by severe recurrent facial pain and substantial impairment in quality of life. Although microvascular decompression (MVD) is an established surgical treatment for medically refractory cases, routine clinical data integrating clinical characteristics, previous interventional treatment history, and early postoperative outcomes remain limited. This study aimed to describe the clinical profile and early postoperative outcomes of patients undergoing MVD for trigeminal neuralgia in a single-center retrospective cohort. Methods: This single-center, single-surgeon retrospective cohort study included 62 adult patients who underwent MVD at Pamukkale University Hospitals between 4 September 2019 and 9 July 2026. Demographic and clinical characteristics, previous interventional procedures, trigeminal nerve division involvement, vascular compression status, surgical opening approach, postoperative Barrow Neurological Institute (BNI) pain intensity scores, visual analog scale (VAS) pain scores, wound-related complications, and exploratory perioperative inflammatory markers were retrospectively collected. Favorable postoperative outcome was defined as BNI Grade I–II. Results: The mean age was 51.9 ± 12.8 years, 66.1% were female, and vascular compression was identified in 87.1%. A previous interventional procedure was documented in 35.5%. Favorable BNI outcomes occurred in 74.2% (95% CI, 62.1–83.4%), and complete pain relief (VAS = 0) in 88.7% (95% CI, 78.5–94.4%). Wound-related complications occurred in 9.7%. No evaluated baseline characteristic was significantly associated with either pain outcome. Paired analyses showed no significant perioperative change in CRP (p = 0.353), whereas NLR increased significantly (p = 0.001). Conclusions: MVD was associated with favorable early postoperative pain outcomes in most patients. However, the retrospective design, modest sample size, and symptom-driven longer-term follow-up limit conclusions regarding prognostic determinants and durability of pain relief.

Brain Sciences doi: 10.3390/brainsci16080890

Authors: Kate Erin Harris Gerassimos Lascaratos Kai-Yin Chau

Background/Objectives: Mitochondrial Complex V (Complex V [CX-V], or ATP synthase) is the terminal enzyme of oxidative phosphorylation and is responsible for the majority of cellular ATP production. An increasing body of evidence suggests that CX-V dysfunction may contribute to mitochondrial impairment observed in neurodegenerative disease. This review evaluated current research on the structure, regulation, and function of CX-V, examined the consequences of CX-V dysfunction, and assessed its proposed role in neurodegenerative disorders. Methods: A comprehensive review of the published literature was carried out, with emphasis on primary research investigating CX-V structure and function, inherited CX-V disorders, and experimental evidence linking CX-V dysfunction to neurodegenerative disease. The reviewed studies used a range of experimental approaches, including structural biology, biochemical studies, patient-derived cellular models, animal models and post-mortem human tissue. Results: Current evidence demonstrates that disruption of CX-V impairs ATP production, alters mitochondrial membrane potential, and oxidative phosphorylation, and that pathogenic variants cause primary mitochondrial disease. Across Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis/frontotemporal dementia, glaucoma and inherited optic neuropathies, alterations in CX-V activity, regulation and structural integrity are consistently associated with mitochondrial dysfunction. Direct evidence supporting CX-V as a primary driver of neurodegeneration remains very limited, with many observations originating from broader studies of general mitochondrial dysfunction. Conclusions: CX-V dysfunction represents a recurring feature of mitochondrial impairment across a variety of neurodegenerative disorders and may exacerbate neuronal vulnerability by disrupting cellular bioenergetics. Current evidence indicates that CX-V may serve as a common downstream target of multiple pathological pathways rather than acting as a primary pathological factor. Future studies require direct assessment of CX-V activity in clinically relevant human models and patient tissues to determine its contribution to disease progression and examine its potential as a therapeutic target.

Brain Sciences doi: 10.3390/brainsci16080889

Authors: Khulud Badawi Abdulrahman Mujalli Wadyan Owaydhah Basma Elsharazly Ping Chen Vic K. T. Sun Ola Negm Raheela Khan Wayne G. Carter

Background/Objectives: Exposure to lead (Pb) is a serious public health concern for which there is no safe level. The aim of this study was to investigate the toxicity of Pb to undifferentiated (uSH-SY5Y) and differentiated (dSH-SY5Y) human neuroblastoma cells and to evaluate gene transcription in response to sub-lethal lead exposure. Methods: Pb was applied to uSH-SY5Y and dSH-SY5Y cells across a concentration range of 0–5 mM for 4, 6, and 24 h, and cell viability was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase assays. Results: Pb induced a significant concentration- and exposure-dependent reduction in cell viability. Pb significantly impacted cellular bioenergetics and reduced ATP production in a concentration- and exposure duration-dependent manner, triggering elevated levels of deleterious reactive oxygen species. Transcriptomic profiling in dSH-SY5Y cells after a sub-lethal 24 h exposure to 1.25 mM Pb revealed 757 upregulated and 2206 downregulated genes. From Gene Ontology and KEGG pathway enrichment analysis, biological processes were predominantly associated with immune and inflammatory processes, including cytokine-mediated signalling. Upregulated differentially expressed genes (DEGs) included those for PI3K/Akt and cytokine signalling, and downregulated DEGs included genes linked to spinocerebellar ataxia, mitophagy, cytokine receptor interaction and cellular metabolism. Protein–protein interaction analysis identified six key hub-upregulated genes with a primarily inflammatory focus (CD44, CXCR4, PTGS2, IL1β, TNF, MMP9) and one downregulated gene (CD4) as potential regulators of Pb-induced cellular responses. Disease association analyses revealed links to chemical carcinogenesis and neurodegenerative diseases. Conclusions: Collectively, these findings provide molecular insights into Pb-induced neurotoxicity and highlight a network of genes that converge on neurological and inflammatory pathways, which are candidates for further mechanistic investigation and possible therapeutic targeting following Pb poisoning.

Brain Sciences doi: 10.3390/brainsci16080888

Authors: Patrick Haas Lucas Moritz Wiggenhauser Johannes Spang Leonie Zerweck Christian Volz Marcos Tatagiba Nadia Khan Philipp T. Meyer Till-Karsten Hauser Constantin Roder

Background: Assessment of cerebrovascular reserve capacity (CVRC) is central to treatment planning in adult Moyamoya disease. [15O]-water-PET with acetazolamide challenge (PET-ACZ) serves as the reference standard but is resource-intensive and not universally available, whereas breathhold BOLD MRI (bh-fMRI) may offer a practical noninvasive alternative for screening and triage. Methods: This retrospective diagnostic accuracy study compared bh-fMRI and PET-ACZ in 67 adult MMD patients (1072 ROIs across 402 supratentorial vascular territories) to determine correlation and clinically useful MRI thresholds for impaired cerebrovascular reserve. Data were analyzed using Pearson’s correlation and ROC curves (STARD-compliant). Cerebellum-normalized percent signal change (CN-PSC) was referenced against PET-ACZ < 66% for pathological CVRC. Results: Supratentorial territories showed strong correlation (r = 0.71, 95%CI 0.62–0.80). Optimal diagnostic threshold was <28.2% CN-PSC on bh-fMRI (Youden index; sensitivity 83.8%, specificity 80.9%, AUROC = 0.87); screening threshold < 60% CN-PSC yielded sensitivity 94.6% and NPV 91.1%. No patient factors (age, Suzuki stage, etc.) influenced agreement (univariate/multivariate analyses). Conclusions: Bh-fMRI supplements PET-ACZ as a screening and diagnostic tool for cerebrovascular reserve impairment in adult MMD. PET remains the reference standard for confirmation, especially in intermediate or discordant cases, and the proposed thresholds (<30% CN-PSC: impaired CVRC; 30–60%: confirm with PET-ACZ; >60%: monitor) require prospective validation before routine decision-making use.

Brain Sciences doi: 10.3390/brainsci16080887

Authors: Badr Hafiz Thamer Alsharif Faisal Sukkar Fahad Okal Maryam Enani Moaath Alghamdi Abdulrazag Ajlan Mohammed Aref Mohammed Binmahfoodh Saleh Baeesa

Background/Objectives: Expanded endoscopic endonasal approaches (EEAs) provide direct ventral access to adult intradural skull base tumors; however, postoperative complications are variably defined and reported in the literature. This review aimed to synthesize the overall spectrum of adult intradural EEA complications and distinguish pathology-specific evidence from large mixed EEA complication cohorts. Methods: A PRISMA 2020 systematic review and meta-analysis searched PubMed/MEDLINE, Embase, and Web of Science from database inception through July 2026. Eligible studies included adults or adult-separable subgroups undergoing expanded EEAs for intradural skull base tumors. The primary outcomes were CSF leak, meningitis or intracranial infection, new neurological deficit or vascular injury/stroke, hydrocephalus, mortality, and postoperative seizures. Pathology-specific adult intradural series with exact counts were quantitatively synthesized when appropriate, and large mixed EEA cohorts were summarized separately when the eligible subgroup was not separable. Results: After full-text eligibility assessment, 48 reports were retained in the extraction-status set. Three strictly adult-only exact-count reports contributed to the primary CSF leak meta-analysis, yielding a random-effects incidence of 23.0% (95% CI, 10.5–43.1%; I2 = 78.7%). A sensitivity analysis adding one mixed-age cohort yielded 23.8% (95% CI, 14.5–36.6%; I2 = 68.9%), while a broader sensitivity analysis including both mixed-age reports yielded 21.1% (95% CI, 12.2–33.8%; I2 = 69.4%). Meningitis was reported in 6/166 patients across four studies (3.6%; 95% exact CI, 1.3–7.7%), and new neurological deficit/vascular injury/stroke was reported in 4/166 patients across four studies (2.4%; 95% exact CI, 0.7–6.1%). Postoperative seizures were reported in 4/652 patients across two studies (0.6%; 95% exact CI, 0.2–1.6%). Large mixed EEA cohorts were summarized separately because adult intradural tumor subsets could not be separated. Conclusions: CSF leak was the most consistently reported complication after expanded EEAs for adult intradural skull base tumors. The strict adult-only random-effects estimate was 23.0%, but it was based on only three studies and showed substantial heterogeneity, limiting its generalizability. Meningitis, neurological/vascular events, and seizures were uncommon in the extractable data and were summarized descriptively rather than being meta-analyzed. Large mixed EEA cohorts provide important safety context but cannot substitute for standardized adult intradural, pathology-specific reporting.

Brain Sciences doi: 10.3390/brainsci16080886

Authors: Nana Matsuo Kazuma Mikata Nagomi Okumura Wataru Inoue Kyoka Matsui Takayuki Kodama

Background: Cognitive control is the ability to adapt to varying cognitive demands. Alpha neurofeedback (α-NFB) training is reported to affect neural activity, but little is known about whether neurophysiological responses to auditory α-NFB differ across cognitive tasks with different cognitive load. This exploratory pilot study examined the neurophysiological effects of a single session of auditory α-NFB during cognitive tasks with different cognitive loads. Method: Fifteen healthy young adults participated in the study. Participants completed Tasks 1 and 3 of the New Stroop Test I before and after the intervention. Neural oscillations and task-performance measures were assessed before and after the intervention. Pre–post changes were compared between the intervention and control groups. Results: For Task 1, the intervention group exhibited a significantly greater pre–post intervention change in the α/β ratio than the control group. However, the increase in alpha oscillatory power did not remain statistically significant after Holm correction for multiple comparisons. For Task 3, no significant between-group differences were observed in any neurophysiological or behavioral measure. Conclusions: These exploratory findings suggest that auditory αNFB may influence neurophysiological responses during Task 1, whereas no significant neurophysiological effects were observed during Task 3. This pattern is consistent with the possibility that neurophysiological responses to auditory αNFB may differ according to cognitive load; however, this interpretation remains preliminary and requires confirmation in larger studies. However, no corresponding differences in task performance were observed, and the findings should be interpreted as preliminary and hypothesis-generating.

Brain Sciences doi: 10.3390/brainsci16080885

Authors: Sara Kierońska-Siwak Hanna Mackiewicz-Nartowicz Anna Sinkiewicz Agata Kozakiewicz-Rutkowska Alina Jaroch Marietta Bracha Beata Zwierko Dariusz Grzanka

Background: The frontal aslant tract (FAT) is a white matter pathway associated with language and executive functions. The aim of the study was to identify and analyze this tract using DTI tractography. Methods: The study included 26 healthy adults. Probabilistic multi-fiber tractography and deterministic single-fiber tractography were applied. The seed region (ROI) was defined in the inferior frontal gyrus, and the target region in the superior frontal cortex. FA, MD, and tract volume were analyzed. Results: The FAT was reconstructed in all participants using probabilistic analysis. The left FAT showed higher FA (p = 0.012), greater volume (p = 0.008), and lower MD (p = 0.021) than the right. Probabilistic tractography demonstrated greater tract volume compared to deterministic tractography. Conclusions: The FAT can be identified using DTI tractography. Probabilistic tractography produced more extensive FAT reconstructions than deterministic tractography; however, anatomical accuracy was not directly assessed.

Brain Sciences doi: 10.3390/brainsci16080884

Authors: Fufeng Zheng Song Zhang Xiaoying Tang Guangfei Li

Objective: Depressive symptoms exist on a continuum in the general population, yet the underlying neurobiological mechanisms, particularly the interplay between resting-state networks and task-evoked social cognitive responses, remain elusive. Methods: Leveraging the Human Connectome Project (HCP) dataset, we included 867 participants. With depression scores as the independent variable and age/sex as covariates, we systematically examined associations with sleep quality, negative emotions, sensory scores, gray matter volume (GMV), fractional amplitude of low-frequency fluctuations (fALFF), multi-seed resting-state functional connectivity (rsFC), as well as brain activation and behavioral performance during working memory, emotion recognition, social cognition, relational reasoning, language comprehension, and gambling tasks. The statistical threshold was set at voxel-level p < 0.001 (uncorrected) combined with cluster-level FWE correction at p < 0.05. Results: (1) Depression scores were positively correlated with sleep disturbances, negative emotions (anger/fear), and pain. (2) In resting-state, depression scores negatively correlated with ventral striatum (VS)–cerebellum/parahippocampal gyrus/fusiform rsFC, yet positively correlated with pregenual anterior cingulate cortex (preACC)–supplementary motor area (SMA) rsFC. (3) In task-fMRI, only the social task showed a positive association with task accuracy and regional activation in bilateral pre/postcentral gyri, superior temporal gyri, left middle frontal gyrus, and SMA/paracentral lobule. Conclusions: Elevated depression scores are linked to a pattern that may reflect relative decoupling between reward and perceptual systems, along with enhanced connectivity in cognitive control circuits. Socially, high scorers exhibit a pattern suggestive of compensatory hypervigilance, accompanied by enhanced behavioral performance. This study provides multidimensional evidence for the dimensional neural representation of depressive symptoms.

Brain Sciences doi: 10.3390/brainsci16080883

Authors: G. Lorenzo Odierna Christopher F. Sharpley Vicki Bitsika

Background/Objectives: Depression and anxiety disorders exhibit significant clinical heterogeneity, which complicates diagnosis and treatment. This study investigated whether tripartite interactions between biological sex, the serotonin transporter gene promoter region (5-HTTLPR), and brain-derived neurotrophic factor (BDNF) G196A polymorphisms explain specific symptom-level variations. Methods: A community sample of 271 Australian adults was genotyped for common 5-HTTLPR (short/long) and BDNF (G/A) variants. Participants completed self-reported measures of anxiety (SAS), depression subtypes (SDS; clinical content scales), and psychological resilience (CDRISC). Morning salivary cortisol, BMI, and substance use were assessed as potential confounds. Statistical analyses utilised a three-way factorial ANCOVA to test for interactions on raw scores, controlling for age. Significant omnibus interactions were decomposed via planned stratified ANCOVAs within each 5-HTTLPR stratum. Results: The BDNF GA genotype exerted opposite effects on anxiety and anhedonia depending on sex and 5-HTTLPR background. In females, GA was associated with increased symptoms on an ss background, whereas in males, GA was associated with increased symptoms on an ll background. These effects were highly specific to anxiety and anhedonic depression, while depressed mood, cognitive, and somatic subtypes remained unaffected. Findings were independent of cortisol, BMI, smoking, alcohol use, and psychological resilience. Conclusions: The findings reveal a complex, sex-dependent genetic interaction that selectively influences anhedonia and anxiety. They should be interpreted in the context of modest subgroup sizes following genotype stratification and require replication in larger independent cohorts. Nonetheless, this study highlights the value of considering sex-stratified genetic backgrounds and symptom specificity to advance personalised precision medicine in psychiatry.

Brain Sciences doi: 10.3390/brainsci16080882

Authors: Jeremy Kalfus Devin Ward Borys Wróbel Andrew T. McKenzie

Background: Global cerebral ischemia initiates a cascade of pathophysiological changes that progressively impair subsequent perfusion of brain tissue. Some authors have proposed that adequate cerebral perfusion becomes impossible after approximately 10–30 min of global ischemia. However, the extant evidence base for this threshold and its variations across studies has not yet been systematically examined. Objective: To synthesize the literature on post-ischemic cerebral perfusion success as a function of ischemia duration. Methods: We searched PubMed (11 February 2026) for studies of global cerebral ischemia in animal or human models that reported quantitative or categorical measures of perfusion quality. Eligible studies included those assessing perfusion via restoration of blood flow, via external perfusion of non-blood solutions, and/or via tracer injection following reperfusion. Studies of focal ischemia were excluded. Data extracted included species, ischemia duration, temperature during ischemia, ischemia model, perfusate type, and perfusion quality assessment method. The perfusion quality outcome was operationalized as either the average percentage of brain tissue perfused or the percentage of brains in a group that was adequately perfused. Study quality was assessed using a custom domain-specific checklist. Results: We included 60 studies with 192 study arms reporting on the perfusion of the brains of rabbits, rats, pigs, dogs, cats, and humans. Studies differed in the model of ischemia, the perfusate, the perfusion parameters, the quality assessment methods, and other factors. Longer ischemia was associated with lower perfusion quality, but substantial heterogeneity across studies prevented identification of a consistent sharp temporal threshold. Some studies found that at least partial perfusion was possible after longer periods. Within-study dose–response curves were more consistent than the pooled cross-study pattern. Conclusions: How long the brain remains perfusable after circulatory arrest has not yet been definitively established. On average, perfusion quality clearly declines rapidly as the duration of global cerebral ischemia increases. However, some studies, often using interventions such as hypothermia or vasopressors, have reported at least partial perfusion of the brain even after 30 or 60 min of ischemia. Moreover, at least partial perfusion has been reported in human brain banking studies after postmortem intervals of several hours or days in some donors. Limitations of this review include substantial heterogeneity in study methods and outcome measures, which precluded formal meta-analysis. Future research may benefit from more thorough and precise measures of perfusion quality.

Brain Sciences doi: 10.3390/brainsci16080881

Authors: Luis Ley Urzaiz Rodrigo Carrasco Moro

Background: Trigeminal neuralgia associated with multiple sclerosis (TN-MS) is a secondary facial pain syndrome whose clinical and therapeutic features differ substantially from those of classical TN. Although the literature comparing treatment outcomes between TN-MS and classical TN is relatively abundant, evidence on the impact of treatment on quality of life in TN-MS is scarce. In patients with MS—already vulnerable owing to the course of their disease and the burden of its treatments—therapeutic success cannot be defined by pain scales alone, because even modest analgesic improvement and, in particular, a reduction in medication burden may represent meaningful gains. This review aims to reappraise the therapeutic goals in TN-MS. Methods: We provide a critical narrative review of the evidence, explicitly distinguishing direct evidence from indirect evidence extrapolated from the MS and classical-TN literature, across medical therapy, percutaneous procedures, stereotactic radiosurgery, and microvascular decompression (MVD). Results: First-line pharmacotherapy remains standard but is largely extrapolated from classical TN, and tolerability is frequently limited by sedative and motor adverse effects in already polymedicated patients. Percutaneous procedures and radiosurgery provide clinically meaningful relief in selected patients, but recurrence is common and patient-centered outcomes are poorly documented. Surgical exploration of the cerebellopontine angle—including MVD, neurolysis, and combined techniques—should not be categorically excluded on the basis of an MS diagnosis in carefully selected patients, although outcomes are generally less favorable than in classical TN and the direct evidence is limited and vulnerable to selection bias. Conclusions: Future studies should assess treatment impact on additional outcomes such as medication burden, quality of life, fatigue, cognition, and functional status.

Brain Sciences doi: 10.3390/brainsci16080880

Authors: Vladimir Lipatov Anna Rebreikina Olga Sysoeva

Background: Sensorimotor (mu) rhythms reflect the functional state of sensorimotor cortical networks and are of increasing interest for understanding typical and atypical neurodevelopment. However, the developmental trajectories of mu rhythm modulation in preschool and early school-age children remain poorly characterized. Objectives: We studied age-related changes in alpha (8–13 Hz) and beta (13–30 Hz) sensorimotor rhythms in children aged 3 to 10 years using a mixed longitudinal design and investigated their relationship with language development. Methods: EEG was recorded twice (interval ~1 year) in 44 typically developing children during three conditions: passive hand movement (PHM), video hand movement observation (VHM), and a control condition (video fractal movement, VFM). Language was assessed with the Preschool Language Scales—Fifth Edition (PLS-5) in a subset of 32 of the 44 participants at the first time point. Modulation indices (log10(experimental/control)) were computed, and repeated-measures ANOVAs and Spearman correlations were performed. Results: PHM elicited desynchronization in both alpha and beta bands, while VHM induced alpha synchronization only. Alpha desynchronization showed contralateral lateralization during right- and left-hand movements, without age-related changes. Beta desynchronization showed no lateralization. Beta desynchronization during PHM correlated negatively with Auditory Comprehension and Total Language scores (ρ up to −0.62, FDR-corrected p < 0.05), indicating that more pronounced desynchronization of sensorimotor rhythms relates to better language abilities. Conclusions: These findings support the involvement of sensorimotor networks in auditory language comprehension and suggest that beta mu rhythm may serve as a sensitive marker of individual differences in language development, though replication in larger samples is warranted.

Brain Sciences doi: 10.3390/brainsci16080879

Authors: Haibo Zhou Yaru Yang Liangliang Yi Xinxin Xiang Yutong Liu

Background: The role of socioeconomic status (SES) in individual intertemporal decision-making has received widespread research attention. However, findings regarding its underlying psychological mechanisms remain inconclusive. This study investigates not only the association between SES and intertemporal decision-making but also the underlying cognitive neural mechanisms from both behavioral and electrophysiological perspectives. Methods: Individuals with high and low SES were recruited. In Experiment 1, a behavioral experiment used the Monetary Choice Questionnaire to measure delay discounting rates using the Kirby method and hierarchical Bayesian modeling, as well as choice consistency using the inverse temperature parameter of the softmax function, to examine differences in decision-making between the two groups. In Experiment 2, event-related potential techniques were employed to examine differences in dynamic neural activity during an intertemporal choice task between the high- and low-SES groups. Results: The behavioral results revealed that, in Experiment 1, the low-SES group exhibited a larger delay discounting rate than the high-SES group. The hierarchical Bayesian modeling further indicated that the low-SES group had lower choice consistency. Experiment 2 found that the low-SES group showed a significantly higher proportion of smaller-sooner (SS) choices than the high-SES group. Electroencephalographic results revealed that, compared with the high-SES group, the low-SES group exhibited larger P200 amplitudes but smaller N2 and P300 amplitudes. Within the high-SES group, the larger-later (LL) option elicited more negative N2 and larger P300 amplitudes than the SS option. Conversely, in the low-SES group, P300 amplitudes did not differ significantly between the SS and LL options during the later stage of intertemporal decision-making. Conclusions: The results showed that the low-SES group was more inclined toward immediate gains, made more random choices, displayed higher variability, relied more on intuitive heuristic strategies, and exhibited weaker cognitive control and reduced cognitive resource allocation during intertemporal decision-making. However, at the later stage, the absence of a significant difference between SS and LL options provided preliminary EEG evidence consistent with the possibility that individuals in the low-SES group did not completely disregard future outcomes.

Brain Sciences doi: 10.3390/brainsci16080878

Authors: Yibing Zhang Liu Tu Kei Omata Guanying Chen Xiaojin Liu Tsunehiko Takamura Lihan Zhang Noritaka Wakasugi Caiyan Zou Hiroki Togo Jinqiao Zhang Zhongshi Li Dongsong Li Takashi Hanakawa

Background/Objectives: In bilinguals, experience-based inter-individual differences, including language acquisition age, influence the functional and structural organization of the brain. Although many studies have explored the effects of age of acquisition on non-tonal languages, only a few studies have investigated the relationship between the age of tonal language acquisition and brain networks. Therefore, the aim of the study is to investigate how the age of language acquisition affects the topological organization of structural brain networks in proficient Japanese-Chinese/Chinese-Japanese speakers. Methods: A total of 33 proficient Japanese-Chinese/Chinese-Japanese speakers were recruited and divided into an early group into early and late groups according to their age of Chinese acquisition (AoCA). Sixteen of them constituted the early group, with AoCA at birth, whereas the late group consisted of 17 participants whose AoCA was after age 6. In addition to AoCA, the the age of second language acquisition (AoA-L2) was significantly younger in the early group than in the late group. All participants underwent diffusion MRI scanning. Structural brain networks were reconstructed, and graph-theoretical metrics were computed to compare topological properties between early and late groups. Results: Higher local efficiency and global clustering coefficient were found in the late group. For nodal parameters, the early group, compared to the late group, showed a higher nodal clustering coefficient in the right precuneus and higher betweenness centrality in the right Heschl’s gyrus (HG). Conclusions: Alterations in the right precuneus may be associated with earlier AoA-L2, consistent with its involvement in cognitive control processes required for managing multiple languages. Changes in the right HG could be related to earlier Chinese acquisition, particularly lexical tone learning, given the right HG’s role in pitch processing. This study showed how the linguistic environment, particularly language acquisition age, influences the topological properties of the structural connectivity, shedding light on its far-reaching effects on brain networks responsible for language processing and executive control.

Brain Sciences doi: 10.3390/brainsci16080877

Authors: Yasunobu Nakai Sakura Kurosu Taisuke Akimoto Go Ikeda Tomoko Chujo Midori Kusakabe Takuma Hara Kazuya Uemura Tetsuya Yamamoto

Background/Objectives: This study aimed to explore whether perioperative changes in cognitive function following carotid artery revascularization, including carotid endarterectomy (CEA) and carotid artery stenting (CAS), are associated with subsequent clinical outcomes, focusing specifically on the Standard Verbal Paired Associate Learning Test (S-PA). Methods: This prospective, single-center study enrolled 69 patients who underwent CEA or CAS between June 2018 and June 2024. Neuropsychological assessments (Raven’s Colored Progressive Matrices (RCPM), Kohs Block Design Test for IQ (Kohs-IQ), the Trail Making Test (TMT)-A/B, and the Standard Verbal Paired Associate Learning Test (S-PA)) were conducted preoperatively and within seven days postoperatively. Patient characteristics and diagnostic imaging results, including magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and single-photon emission computed tomography (SPECT), were evaluated. Multivariate Cox proportional hazards models and Kaplan–Meier survival analyses were used to identify predictors of adverse outcomes, defined as recurrent stroke, restenosis, or mortality, during outpatient follow-up. Results: Fifteen patients experienced adverse outcomes during follow-up. Perioperative neuropsychological assessment showed that 36 patients experienced S-PA decline, indicating a tendency towards lower mean cerebral blood flow. Receiver operating characteristic (ROC) curve for perioperative ΔS-PA decline associated with adverse outcomes. The area under the curve (AUC) was 0.728. The optimal cutoff determined by the Youden index was a decline of 2 points (ΔS-PA ≤ −2), yielding a sensitivity of 73.3% and specificity of 68.5%. In a time-to-event analysis, S-PA decline was associated with adverse outcomes in an unadjusted analysis. A similar trend was observed in limited multivariable models; however, effect estimates were imprecise (HR = 4.01, 95% CI: 1.01–15.91, p = 0.048). Conclusions: This study indicates that perioperative decline in S-PA may reflect underlying cerebrovascular vulnerability and may be associated with subsequent adverse outcomes. However, given the limited number of events and potential for residual confounding, these findings should be interpreted with caution. Larger multicenter studies are required to validate these findings.

Brain Sciences doi: 10.3390/brainsci16080876

Authors: Silke Vos Rowena Van den Broeck Diego Ruiz Callejo Olivier Collignon Bart Boets

Background/Objectives. Human voices convey critical socio-affective information, including emotional states. Although autism has frequently been associated with difficulties in processing vocal emotional cues, findings remain inconsistent, particularly in adults. This study investigated neural and behavioral sensitivity to vocal emotion expressions in autistic adults using an objective auditory frequency-tagging EEG paradigm. Methods. Twenty-five autistic adult men and 25 age- and IQ-matched non-autistic men completed an auditory frequency-tagging EEG task and an auditory and multimodal emotion-recognition assessment. During EEG recording, neutral vocal utterances were presented at 4 Hz, with emotional utterances (fear, anger, happiness, or sadness) inserted every third stimulus, generating an oddball frequency of 1.333 Hz indexing vocal emotion discrimination. Results. No significant group differences were observed in neural or behavioral measures of emotion processing. Robust oddball EEG responses were present in both groups, indicating automatic discrimination of emotional from neutral vocalizations. Fearful and angry vocalizations elicited the strongest neural responses. On the behavioral task, autistic and non-autistic participants showed comparable performance in the auditory modality as well as in the visual and audiovisual modalities, with auditory emotion recognition being the most challenging condition for both groups. Conclusions. These findings provide converging neural and behavioral evidence for intact vocal emotion processing in autistic adult men and are consistent with the view that socio-affective processing differences may attenuate across development. Auditory frequency-tagging EEG shows promise as a sensitive tool for studying individual differences in socio-affective processing.

Brain Sciences doi: 10.3390/brainsci16080875

Authors: Joel Abraham Velazquez-Castillo Victor Ramzes Chavez-Herrera Martin Paredes-Cruz Pedro Adrian Gonzalez-Zavala Miguel Adolfo Abdo-Toro Rabindranath Garcia-Lopez Ivan Tellez-Medina Eduardo Ichikawa-Escamilla Blas Ezequiel Lopez-Felix

Background: The diagonal earlobe crease (DELC), or Frank’s sign, has been associated with systemic vascular degeneration. Whether this cutaneous marker correlates with intracranial aneurysm (IA) instability remains unclear. Methods: We conducted a hospital-based observational registry study including 186 consecutive patients with IA. DELC was dichotomized into absent/low-grade versus high-grade creases. Associations between DELC and aneurysm rupture, rupture at small sizes (<7 mm), and clinical outcome were analyzed using multivariate logistic regression models adjusted for demographic and vascular risk factors. Results: High-grade DELC was significantly associated with overall aneurysm rupture (adjusted OR 3.42, 95% CI 1.39–8.41, p = 0.007). Patients with high-grade DELC harbored ruptured aneurysms at significantly smaller mean sizes than those without the sign (6.11 mm vs. 7.94 mm, p = 0.015). High-grade DELC was also associated with a distinct anatomical shift toward the anterior communicating artery complex (p = 0.021) and was independently associated with rupture at <7 mm (adjusted OR 2.08, 95% CI 1.03–4.21, p = 0.041), even after adjustment for aspect ratio and clinical covariates. DELC was not independently associated with post-hemorrhagic clinical outcome. Conclusions: Frank’s sign may represent a readily observable clinical marker associated with IA instability and rupture at conventionally low-risk sizes (<7 mm). These findings support further investigation into DELC as a potential adjunct for individualized risk stratification in patients with small incidental intracranial aneurysms to prevent catastrophic subarachnoid hemorrhage.

Brain Sciences doi: 10.3390/brainsci16080874

Authors: Iana Andreieva Justyna Wiśniowska Natalia Salata Beata Tarnacka

Background/Objectives: Our aim was to evaluate sleep quality and excessive daytime sleepiness in complex regional pain syndrome (CRPS) and explore their associations with pain characteristics, functional impairment, depressive symptoms, and pain coping strategies. Methods: This pilot exploratory, cross-sectional observational study was conducted at a single tertiary rehabilitation center using a convenience sample of 21 adults with CRPS Type I (n = 17) or Type II (n = 4). Sleep quality and daytime sleepiness were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Pain was assessed with the Numeric Rating Scale (NRS), Short-Form McGill Pain Questionnaire (SF-MPQ), and PainDETECT Questionnaire (PDQ). Limb-specific disability was measured using the Disability of the Arm, Shoulder and Hand (DASH) questionnaire for upper-extremity CRPS (n = 10) and the Lower Extremity Functional Scale (LEFS) for lower-extremity CRPS (n = 11). Psychological factors and central sensitization were assessed via BDI-II, CSQ, and CSI. Results: Poor sleep quality (PSQI > 5) occurred in 81.0% (17/21) of participants (mean PSQI: 10.1 ± 4.1). ESS-defined excessive daytime sleepiness was identified in 47.6% (10/21) of patients (mean ESS: 9.6 ± 5.8). In unadjusted bivariate correlation analyses of the full cohort (n = 21), global PSQI score significantly correlated with NRS pain intensity (ρ = 0.445, p = 0.0431), SF-MPQ sensory pain (ρ = 0.468, p = 0.0325), SF-MPQ affective pain (ρ = 0.461, p = 0.0354), and SF-MPQ total score (ρ = 0.504, p = 0.0199. Conclusions: Sleep disturbances and excessive daytime sleepiness are highly prevalent in CRPS patients in tertiary care. Exploratory unadjusted analyses link sleep quality with pain severity, particularly sensory and affective dimensions. Given the exploratory design and small subgroup sample sizes, larger prospective studies are needed to confirm these findings.

Brain Sciences doi: 10.3390/brainsci16080873

Authors: Wenwen Chang Hesam Akbari Muhammad Tariq Sadiq Renjie Lv Rab Nawaz

Background: Performance estimates in motor-imagery electroencephalography (MI-EEG) can depend strongly on how observations are partitioned for training, model selection, and testing. Random sample- or window-level splitting may place data from the same participant in different folds and therefore does not answer the same question as evaluation on previously unseen participants. Methods: We evaluated a previously developed Gramian angular field–phase-locking value (GAF–PLV) classifier on the retained full cohort (N=105) using binary left-versus-right MI and leave-one-subject-out cross-validation (LOSO). Separately, a predefined, outcome-independent subset (N=30) was used for a matched sensitivity analysis of eight classifiers, binary and four-class tasks, and three validation strategies: random five-fold cross-validation, LOSO, and nested LOSO with subject-grouped inner model selection. Results: In the full-cohort GAF–PLV analysis, mean accuracy was 58.07% ± 8.27% and Macro-F1 was 53.48% ± 11.19%, with substantial between-subject variability. In the predefined matched subset, performance estimates and numerical model rankings changed across validation strategies. For example, the numerically highest binary-accuracy model was ShallowConvNet under random five-fold cross-validation, DeepConvNet under LOSO, and ATCNet under nested LOSO. Conclusions: Random within-cohort classification and generalisation to previously unseen subjects are distinct evaluation targets. MI-EEG reports should state the cohort, partition unit, validation design, and model-selection procedure. Rankings in the multi-model analysis are conditional on the predefined 30-subject subset and common 0.4 s input setting and are not presented as definitive full-cohort or architecture-optimal rankings.

Brain Sciences doi: 10.3390/brainsci16080872

Authors: Jian Yan Renzhou Gui Hao Liang Yaqi Wang

Background: Major depressive disorder (MDD) affects 332 million people worldwide, yet diagnosis remains reliant on subjective clinical interviews with substantial inter-rater variability. Objective neuroimaging model-attributed regions offer a path toward precision psychiatry, but existing computational approaches often lack clinical interpretability. Methods: We propose HDGNN-Mamba2, a Mamba-based spatiotemporal heterogeneous dynamic graph neural network. A hybrid Mamba2-GNN block with cross-attention fusion is developed to capture individual spatiotemporal contextual features and identify model-attributed regions. A heterogeneous global graph block with dynamic edge updating is constructed, integrating individual brain features with non-imaging phenotypic information (sex, age, education) to extract embeddings through inter-individual relationship modeling. Heterogeneous Graph Supervised Contrastive Learning is integrated to enhance discriminative capacity. Results: Evaluated on 533 subjects from the REST-meta-MDD dataset, HDGNN-Mamba2 achieved 83.88% accuracy, 86.52% sensitivity, and 80.85% specificity in ten-fold cross-validation. The identified model-attributed regions include the anterior cingulate cortex, parahippocampal gyrus, and thalamus. Conclusions: HDGNN-Mamba2 demonstrates competitive performance as an algorithmic framework for MDD classification, offering complementary architectural advantages in spatiotemporal fusion and interpretable region identification.

Brain Sciences doi: 10.3390/brainsci16080871

Authors: Eduardo Villamil-Cabello Elvira Molinero-Martín Noa Fogelson Antonio Luque-Casado Miguel Ángel Fernández-del-Olmo

Background/Objectives: Gait impairment and reduced handgrip strength are common in Parkinson’s disease (PD), but their relationship remains unclear. This study examined whether associations between handgrip force and gait reflect PD-specific impairment or broader functional capacity. Methods: In this cross-sectional study, 45 individuals with PD and 51 healthy older adults completed unilateral maximal isometric handgrip testing and overground gait assessment at preferred and maximal speed. Handgrip variables included peak force (PF), rate-of-force development (RFD), and impulse. Gait speed, cadence, and step length were recorded. Results: PF was significantly associated with gait speed and step length in both groups, especially under maximal-speed conditions. RFD and impulse were not significantly associated with gait performance in either group. Compared to controls, participants with PD showed poorer gait performance, with lower preferred walking speed and shorter step length in both gait conditions. Within the PD group, PF was lower on the more-affected side than on the less-affected side, whereas most RFD and impulse variables showed no side differences. Conclusions: Maximal handgrip strength, but not upper-limb RFD or impulse, was associated with key gait outcomes in both PD and healthy older adults. These findings suggest that handgrip strength may reflect general functional capacity rather than a PD-specific neuromuscular mechanism and support its use as a practical clinical indicator of mobility-related function.

Brain Sciences doi: 10.3390/brainsci16080870

Authors: Albert Le Floch Guy Ropars

In the published publication [...]

Brain Sciences doi: 10.3390/brainsci16080869

Authors: Yuzeng Xu Sho Otsuka Seiji Nakagawa

Background/Objectives: This study proposes Diffusion Inverse Filtering (DIF), a spatially informed transformation designed to counteract spatial smoothing in functional-connectivity representations (i.e., functional networks) and thereby enhance their discriminative power for pattern recognition. Spatial smoothing in electroencephalography (EEG) signals and derived features, such as functional connectivity, is largely attributed to volume conduction. Functional connectivity has been increasingly used in brain–computer interface (BCI) studies; however, this spatial smoothing can introduce spurious connections and distort functional-connectivity patterns. Methods: DIF approximates spatial smoothing in functional connectivity, which is potentially associated with volume conduction, as a diffusion-like process and applies a regularized inverse operation to transform the observed functional networks into networks with enhanced discriminative representations. The effectiveness of DIF in enhancing the discriminative power of functional-connectivity representations in pattern recognition was evaluated using emotion recognition as the paradigm task, which is a critical component of BCI systems. Experimental results show that DIF generally improves emotion-recognition performance relative to the originally observed functional networks under electrode-sparsification conditions, with the most consistent improvements observed for Pearson correlation coefficient (PCC) estimation. Both signal-level processing, which operates on EEG signals before functional-connectivity estimation, and function-al-connectivity-level transformations, including graph signal processing (GSP)-based filtering applied after functional-connectivity estimation, were included as comparators. Under this framework, DIF is also considered a functional-connectivity-level transformation, but does not rely on a GSP framework. Results: The performance of DIF demonstrates the potential of functional-connectivity-level transformation as a complement or alternative to signal-level processing for enhancing connectivity-based pattern recognition. Overall, DIF improves classification performance and offers strong compatibility with modern functional-connectivity-based BCI pipelines.

Brain Sciences doi: 10.3390/brainsci16080868

Authors: Boya Lu Meng Zhang Zihao Ren Tianjiu Wang Zixuan Wang Chong Ding

Background/Objectives: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulatory approach with potential therapeutic value for cognitive impairment in Alzheimer’s disease (AD). Ferroptosis-related oxidative injury has been implicated in AD-associated neuronal dysfunction, but whether rTMS-induced functional improvement is accompanied by changes in ferroptosis-related oxidative injury remains unclear. This study evaluated the effects of high-frequency rTMS on cognitive function, hippocampal neuronal excitability, and ferroptosis-related oxidative injury in amyloid precursor protein/presenilin-1 (APP/PS1) mice, using Ferrostatin-1 (Fer-1) as a pharmacological comparator. Methods: Six-month-old female mice were used, including age-matched C57BL/6J controls and APP/PS1 mice assigned to the AD + Sham, AD + rTMS, and AD + Fer-1 groups (n = 6 per group). After 14 days of intervention, cognitive performance was assessed using behavioral tests. Whole-cell patch-clamp recordings were performed in hippocampal dentate gyrus granule neurons to evaluate neuronal excitability and voltage-gated sodium (Na+) and potassium (K+) channel properties. Biochemical assays and transmission electron microscopy were used to assess oxidative, iron-related, and mitochondrial changes, and mitochondrial ultrastructure was examined in an independent cohort (n = 3 per group) using transmission electron microscopy. Results: Compared with AD + Sham mice, high-frequency rTMS improved cognitive performance, increased evoked action potential firing, lowered the elevated action potential threshold, partially restored voltage-gated Na+ and K+ current amplitudes, and accelerated recovery of Na+ currents from inactivation. Fer-1 produced partially overlapping, but not identical, effects across behavioral, electrophysiological, biochemical, and ultrastructural outcomes. Both interventions increased hippocampal glutathione (GSH) levels, reduced malondialdehyde (MDA) and total iron levels, partially restored superoxide dismutase (SOD) activity, and improved mitochondrial ultrastructure and reduced the prevalence of mitochondrial profiles with small cross-sectional areas. Conclusions: High-frequency rTMS improved cognitive and hippocampal neuronal outcomes in female APP/PS1 mice. These improvements were accompanied by biochemical and mitochondrial changes compatible with attenuation of ferroptosis-related injury. However, the findings do not establish ferroptosis inhibition as either necessary or sufficient for the effects of rTMS.

Brain Sciences doi: 10.3390/brainsci16080866

Authors: Zhilei Lan Xiaoli Li He Chen

Background/Objectives: Consciousness fluctuations involve brain network reorganization, yet the underlying neural synchronization mechanisms remain unclear. This study examined the static and dynamic characteristics of alpha-band functional connectivity during propofol sedation from two dimensions: phase synchrony and amplitude coupling. Methods: Electroencephalography data from 20 healthy volunteers across baseline, mild sedation, moderate sedation, and recovery were analyzed. Source-level signals for 68 cortical regions of interest were reconstructed using sLORETA. Dynamic functional connectivity matrices for both weighted Phase Lag Index (wPLI) and amplitude envelope correlation (AEC) were computed using 5 s sliding windows. Dynamic connectivity states were identified through clustering analysis, and state occurrence rates were compared between drowsy and responsive participants across sedation levels. Results: Static analysis revealed a dissociation between the two metrics: during moderate sedation, wPLI showed significant suppression in posterior parieto-occipital regions, whereas AEC exhibited widespread whole-brain coupling enhancement. Dynamic clustering identified three wPLI states and five AEC states. Critically, although the two metrics exhibited spatially distinct dynamic reconfiguration patterns, with deepening sedation, the occurrence rate of the ventral connectivity pattern in wPLI and that of the medial prefrontal pattern in AEC both increased significantly, and these two patterns showed synergistic co-occurrence. This effect was more pronounced in the drowsy subgroup, with greater increases in both patterns. Conclusions: Propofol-induced alterations in consciousness are not characterized by linear attenuation along a single neural synchrony dimension, but rather by differential reorganization of phase- and amplitude-based functional connectivity across spatial configurations and temporal dynamics.

Brain Sciences doi: 10.3390/brainsci16080867

Authors: Lindokuhle Thela Bongani Nkambule Zama Msibi Vuyokazi Ntlantsana Saeeda Paruk Andrew Tomita Khethelo Richman Xulu Bonginkosi Chiliza

A pro-inflammatory state, characterized by elevated levels of pro-inflammatory cytokines, is frequently reported among individuals presenting with primary first-episode psychosis (FEP), particularly those with environmental risk factors such as maternal infections and early childhood traumatic experiences. These findings suggest that immune system disturbances may play a crucial role in the onset of psychotic disorders. Building on this, cytokines may contribute to the risk of FEP from the stage of neurodevelopment, where they can induce aberrant changes in neuronal growth. During early childhood, these cytokine-mediated processes may disrupt normal neuronal maturation and lead to brain alterations that increase vulnerability to primary psychotic disorders. Furthermore, pro-inflammatory cytokines exhibit strong bidirectional modulatory interactions with dopamine, a key neurotransmitter implicated in the pathogenesis and persistence of psychosis. Notably, these cytokines may also influence the clinical presentation and severity of psychosis. In addition, antipsychotic medications can partially modulate cytokine levels, and this modulation has been correlated with the efficacy of antipsychotics in treating various psychotic symptoms. Frequently reported cytokines in this context include interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ). We conducted a non-systematized literature search on Google Scholar and PubMed for studies looking at cytokines in primary psychotic disorders during FEP. In this narrative review, we provide an overview of the literature on immune dysregulation in FEP, with a particular emphasis on cytokines.

Brain Sciences doi: 10.3390/brainsci16080865

Authors: Ping-Chen Tsai Kea-Tiong Tang Asangaedem Akpan Heba Lakany

Background: Falls among older adults are linked to central nervous system deterioration and executive function deficits. Objectives: This study evaluates the feasibility of a gamified EEG-based neurofeedback intervention combined with adaptive working-memory training, targeting neural processes associated with attentional inhibition and working memory in older adults, and characterises, as exploratory secondary outcomes, the oscillatory and functional measures that change over the training period. Methods: Twenty healthy older adults (65.0±3.3 years) completed a 24-session longitudinal training programme. The intervention combined real-time alpha-band neurofeedback (NF), targeting left-frontal alpha activity associated with inhibitory control, with an adaptive N-back task engaging theta-band working memory processes. Behavioural outcomes included the Colour Trail Making Test A and B (CTMT-A/B), the Berg Balance Scale short form (BBS-3P), and the four-item Dynamic Gait Index (DGI-4). EEG was recorded at the Early, Middle, and Later stages to characterise training-related neural and behavioural changes. Results: The programme proved highly deliverable: adherence was 100% across all 24 sessions, no session was terminated early, and no severe adverse events occurred. Participants acquired control of the trained signal, with left-frontal alpha power rising across training at the neurofeedback target site, and frontal theta increased bilaterally under adaptive working memory load, consistent with the reduced hemispheric asymmetry characteristic of this age group. Scores changed in the direction of improvement on all four behavioural measures; however, functional changes were small, and cognitive changes cannot be separated from repeated-testing effects. Of sixteen candidate EEG–behaviour associations, four showed moderate-to-large participant-level coefficients and were retained as candidate associations: right-frontal alpha with balance (r=−0.64) and with gait adaptability (r=−0.48), and bilateral frontal theta with processing speed (r=−0.53 and −0.51). Several associations that appeared strong when observations were pooled across stages did not survive participant-level modelling, indicating that repeated-measures methods are needed in this literature. All associations are exploratory, uncorrected for multiplicity, and reported with effect sizes and confidence intervals. Conclusions: The gamified neurofeedback and working-memory training programme was feasible, well tolerated, and fully adhered to in a supervised experimental setting by community-dwelling older adults and was accompanied by measurable modulation of the targeted frontal rhythms. This study delivers a shortlist of candidate EEG features, with the effect-size estimates needed to power a confirmatory trial. Because the design is single-arm, both functional scales approached ceiling, and the same test forms were repeated at each stage, practice effects cannot be separated from intervention effects, and these associations are hypothesis-generating; a sham-controlled trial in a fall-prone population is the appropriate next step.

Brain Sciences doi: 10.3390/brainsci16080864

Authors: Paula Albusac-Olivares Sara Chami-Peña José M. Gutiérrez-Pastor Alberto Caballero-Vázquez Miguel Quesada-Caballero Nora Suleiman-Martos Guillermo A. Cañadas-De la Fuente José Luis Romero-Béjar María José Membrive-Jiménez

Background: Acute confusional state, or delirium, is a common neuropsychiatric disorder in older adults, particularly in emergency departments. It is associated with high morbidity and mortality, as well as difficult detection. Its early identification is crucial to prevent complications and improve prognosis. This study aims to identify and analyze available strategies for the early diagnosis of delirium in geriatric patients in emergency departments. Methods: A literature review and meta-analysis were conducted between 2020 and 2026 using the PubMed, Scopus, Web of Science, CINAHL, and Cochrane databases (PRISMA 2020). To estimate the prevalence of patients with delirium in emergency departments, a meta-analysis was performed using Stats Direct statistical software (Version 4). Methodological quality was evaluated according to the Oxford Centre for Evidence-Based Medicine levels of evidence. Results: Eleven studies were included, demonstrating that delirium in emergency departments is highly prevalent among older adults, particularly those with dementia, polypharmacy, or functional impairment. The 4AT scale was the most frequently used screening tool, notable for its strong sensitivity. Hypoactive delirium emerged as the most common subtype and carried the poorest prognosis. Furthermore, its presence was associated with longer hospital stays, increased complications, and higher mortality rates, while a lack of training among healthcare staff continues to limit early detection. The meta-analysis detected no publication bias and revealed a 20.6% prevalence of delirium among patients in emergency departments. Conclusions: One in five patients attending the emergency department presents with delirium. Delirium in geriatric emergency care demands a structured clinical response grounded in prevention, early detection, and professional training. Integrating validated diagnostic tools and reinforcing the role of nursing professionals are key to improving patient outcomes and safety.

Brain Sciences doi: 10.3390/brainsci16080863

Authors: James V. English

Intimate partner violence-related brain injury is the most recent condition in a 150-year arc in which biological brain injury has been misattributed to psychological or moral causes before formal clinical recognition emerged. Earlier conditions in this pattern were each recognized only after decades of delay. In each prior case, that delay was constrained by limits in available diagnostic technology. Intimate partner violence-related brain injury is the first condition in which diagnostic technology, including computed tomography, magnetic resonance imaging, diffusion tensor imaging, and neurocognitive assessment, has been continuously available throughout the period of non-recognition. This review identifies three structural barriers that sustain this recognition gap: a diagnostic barrier that leaves the injury without formal criteria, an administrative coding barrier that leaves it absent from ICD architecture, and a population surveillance barrier that leaves it indistinguishable from broader assault categories. Each barrier reinforces the others, limiting visibility, resource allocation, and access to care. Across these conditions, this review argues that deferred recognition reflected an institutional dynamic that shaped which injured populations became clinically legible. Recent neuroimaging and cognitive studies make the biological imperative explicit. A cognitive entrapment framework reframes the reduced capacity to engage the cognitive and material resources leaving requires as injury-driven rather than as ambivalence or motivational deficit. The framework offers a mechanistic account of how brain injury may disrupt the multistep planning that leaving demands. Intimate partner violence-related brain injury is not only underdiagnosed but structurally underserved; correcting the mechanisms of recognition failure is necessary for access to treatment and rehabilitation.

Brain Sciences doi: 10.3390/brainsci16080862

Authors: Anza B. Memon Anas Z. Nourelden Mouhamad Hammami Basil Memon Ahmed Hashem Fathallah Farid Ahmed Badar Mirela Cerghet Lonni R. Schultz Susan M. Bowyer

Background/Objectives: Cognitive impairment and neurological dysfunction in Multiple Sclerosis are increasingly understood as consequences of altered brain network connectivity. Magnetoencephalography offers high temporal resolution for investigating functional connectivity patterns, which may underlie various clinical symptoms. This exploratory pilot study aims to characterize preliminary FC patterns at rest and during cognitive processing in MS patients with a high fatigue burden compared with healthy controls using MEG, complemented by a systematic review of existing MEG literature in MS. Methods: In this pilot study, MEG was utilized to investigate connectivity in MS patients and HCs. Data were acquired during resting-state and a digitized version of the Symbol Digit Modalities Test. A systematic review was also conducted following PRISMA guidelines to synthesize the current evidence on frequency-specific MEG connectivity in MS. Results: MS patients exhibited a connectivity pattern paralleling the directionality of neuronal slowing, described in the spectral power MS literature, during resting-state, characterized by reduced interhemispheric coherence in alpha and beta bands alongside region-specific increases in frontal–parietal and parietal–occipital alpha coherence, reflecting a bidirectional spatial reorganization. Conversely, during the SDMT task, the MS group demonstrated significant compensatory recruitment with increased coherence in theta and gamma bands (specifically in frontal and striatal circuits). The systematic review of 44 MEG studies corroborated these findings, highlighting a consistent trend of frequency-dependent dysconnectivity that aligns with clinical load and disease pathology. Conclusions: We found that in MS, network alterations are state-dependent, shifting from reduced connectivity at rest to increased coherence during cognitive effort. These preliminary findings suggest that MEG-based connectivity may serve as a functional neuroimaging biomarker of underlying network reorganization, for monitoring early cognitive disease progression in MS.

Brain Sciences doi: 10.3390/brainsci16080861

Authors: Ting Fan Chengzhen Liu Yang Liu Geng Li

Background/Objectives: Cognitive training provides a framework for examining how repeated practice relates to changes in cognitive performance and task-related brain activation, yet age-stratified patterns of neural effects remain unclear. Methods: We conducted a three-level behavioral meta-analysis and a coordinate-based Seed-based Mapping (SDM) meta-analysis of task-based neuroimaging studies to jointly examine behavioral improvement and task-related activation convergence following cognitive training. Results: Cognitive training was associated with reliable behavioral improvement at the aggregate level (Hedges’ g = 0.546, 95% CI [0.414, 0.678]) and within both children/adolescents and young adults. SDM results indicated that task-related activation changes were spatially heterogeneous and included both increases and decreases across distributed brain regions. In age-stratified analyses, spatial convergence within children/adolescents involved occipital and frontoparietal regions; within young adults, it involved cingulo-insular and posterior midline regions. Exploratory behavioral moderator analyses indicated outcome-dependent variation, with smaller effects for transfer outcomes and larger effects in studies with greater training exposure. Conclusions: Behavioral improvements across included designs were observed in both age groups, whereas task-related activation convergence exhibited spatially heterogeneous, age-stratified patterns. These findings suggest that training-related neural effects are better characterized as spatial convergence patterns across studies rather than as a single uniform activation change. The age-stratified maps describe spatial convergence within each age group and should not be interpreted as statistically established developmental differences.

Brain Sciences doi: 10.3390/brainsci16080860

Authors: Ali Alhazmi

Background/Objectives: Automatic sleep staging from polysomnography (PSG) is particularly challenging in clinical cohorts with neurological disorders. Methods: This study presents SleepStageNet, a compact model (1.075M parameters) that integrates a dual-branch convolutional epoch encoder, feature gating, a bidirectional gated recurrent unit, and multi-head self-attention for five-class staging from five PSG channels (C3, C4, EOG1, EOG2, and chin EMG). The individual operations are adapted from established architectures; the study contribution is their compact integration and controlled evaluation in an Indian acute stroke cohort. Results: Of the 100 recordings in the Indian Sleep Polysomnography (iSLEEPS) resource, 95 satisfied the five-channel extraction criteria, yielding 78,323 annotated epochs. Subject-independent 10-fold stratified group cross-validation produced an accuracy of 73.91 ± 2.24%, a macro F1-score of 67.29 ± 1.96%, and a Cohen’s κ of 0.634±0.029 (sample standard deviations). A matched single-branch encoder obtained κ=0.635 (full minus single branch: Δκ=−0.001, Holm-adjusted p=0.846), while matched C4-only input obtained κ=0.600 (full minus C4-only: Δκ=0.033, Holm-adjusted p=0.008). Grad-CAM and temporal attention visualizations provided qualitative evidence of physiologically plausible focus, while channel occlusion quantified the contribution of each signal. Without fine-tuning, a 10-model ensemble obtained κ=0.614 on ISRUC-SLEEP Subgroup III (10 healthy subjects; 8889 epochs). Conclusions: These results establish a reproducible reference for this clinical cohort while identifying the need for broader external and prospective validation.

Brain Sciences doi: 10.3390/brainsci16080859

Authors: Albert Le Floch Guy Ropars

In the published publication [...]

Brain Sciences doi: 10.3390/brainsci16080858

Authors: Nicola Loi Damiano Sottana Mohammed Zeroual Mattia Solinas Matteo Spinelli Francesca Ginatempo Franca Deriu

Background: The cerebellum has recently been proposed as a key contributor to facial expression (FE) processing, although the neural pathways underlying its involvement remain poorly understood. This study investigated whether cerebellar modulation of FE processing preferentially relies on motor or perceptual circuits. Methods: Sixteen healthy young participants underwent cerebellar cathodal transcranial direct current stimulation (tDCs) and sham stimulation in a randomized crossover design. Cerebellar–motor cortex interactions were assessed using cerebellar brain inhibition (CBI) measured by a paired-pulse transcranial magnetic stimulation protocol, while early perceptual processing was evaluated through P100 and N170 event-related potentials (ERPs). Behavioral performance was assessed using a task involving recognition of neutral, happy, and fearful faces. Results: Cerebellar tDCs selectively modulated the cerebello–thalamo–primary motor cortex pathway, producing a significant reduction in CBI during the passive viewing of emotional (happy and fearful) expressions while exerting no significant effects on occipitotemporal ERP components associated with early face perception or on behavioral measures of emotion recognition, including recognition accuracy and reaction times. Conclusions: These findings indicate that cerebellar contributions to facial emotion processing are predominantly mediated through motor rather than early perceptual pathways. The cerebellum appears to modulate motor network activity during emotional face observation without directly influencing occipitotemporal perceptual mechanisms, although this physiological modulation was not accompanied by measurable changes in behavioral performance. These findings support the hypothesis that cerebellar involvement in social cognition is primarily related to the optimization of emotion-related motor processing.

Brain Sciences doi: 10.3390/brainsci16080857

Authors: Thierry Paillard Aurélien Speller Alex Rizzato Giuseppe Marcolin Julien Maitre

Background/Objectives: Walking-induced fatigue disrupts postural balance, but the differentiated effects of walking uphill and downhill remain unclear. The aim was to compare the impact of two walking sequences, either uphill (+10%) or downhill (−20%), with an identical number of steps (7000 steps) on a treadmill at 5.5 km·h−1 on postural balance. Methods: Nineteen healthy young participants performed the two walking sequence sessions (56 and 57 min) eight days apart. Eyes-closed bipedal postural balance (in three randomized conditions: an unmanipulated condition, a tendon vibration manipulation condition—TV—and a galvanic vestibular stimulation manipulation condition—GVS), maximal voluntary contraction and central activation ratio were assessed before (PRE), immediately after (POST) and 20 min after (POST20) each walking sequence. Results: Walking uphill and walking downhill sequences generated similar muscular and central fatigue in the POST and POST20 conditions. In the unmanipulated postural condition, postural balance was disrupted after both walking sequences in the POST condition, with no difference between walking downhill and walking uphill. In the manipulated postural conditions, postural balance was modified by the walking sequences. It was disrupted in the presence of GVS in the POST condition with no difference between walking downhill and uphill, whereas it was not disrupted in the presence of TV and was even improved after walking uphill. Conclusions: Although the postural alteration was broadly similar between the two walking sequences, their disruptive factors would differ at the muscular, metabolic and sensory levels.

Brain Sciences doi: 10.3390/brainsci16080855

Authors: Jeong-In Gong Seo-Hyun Yoo Jin-Hyuk Eom Sung-Yeon Oh Dong-Yeop Lee Ji-Heon Hong Jae-Ho Yu Jeong-Woo Jeon Yeon-Gyo Nam

Background/Objectives: This study aimed to examine the acute effects of a dual-task intervention combining moderate-intensity cycling with a food-related Go/No-Go task on inhibitory control, subjective appetite, and frontal electroencephalogram (EEG) activity in healthy adults. Methods: Forty healthy adults were randomly assigned to an experimental group or a control group in a single-blind design. The experimental group performed cycling combined with a food-related Go/No-Go task, whereas the control group performed only the cognitive task. Outcomes were assessed before and after the intervention, and Group × Time effects were analyzed using repeated-measures ANOVA with correction for multiple comparisons. Results: No significant Group × Time interactions were observed for the primary outcomes, including EEG alpha and theta power (ηp2 = 0.004 and 0.040, respectively) and Stroop reaction time and accuracy (ηp2 = 0.076 and 0.062, respectively). Subjective appetite decreased in the experimental group and increased in the control group, showing a significant interaction at the uncorrected level (p = 0.017, ηp2 = 0.142); however, this interaction did not remain significant after correction for multiple comparisons. The exploratory DEBQ outcomes showed no significant Group × Time interactions. Conclusions: In this single-session study, the intervention did not demonstrate clear intervention-specific benefits across the cognitive, EEG, or eating-related outcomes. Nevertheless, the contrasting descriptive pattern in subjective appetite warrants further investigation in larger studies involving repeated interventions and clinical populations.

Brain Sciences doi: 10.3390/brainsci16080856

Authors: Lu Huang Zheng Hu Zhengnan Zhang Yunyuan Gao

Background/Objectives: Electroencephalography (EEG) connectivity and microstate analysis have shown great potential for Alzheimer’s disease (AD) diagnosis; however, their clinical application remains limited by the low spatial resolution of EEG and the lack of standardized microstate analysis. To address these challenges, this study proposes a multi-domain feature fusion framework, namely Source-localized Microstate and Multi-frequency Synchronization (SMMS), which integrates EEG source localization (ESL)-based weighted phase lag index (wPLI) functional connectivity with EEG microstate features. Methods: Specifically, ESL was employed to improve the spatial resolution of EEG signals for constructing functional connectivity matrices, while multi-frequency-band wPLI features were extracted to characterize functional synchronization among cortical regions. Meanwhile, EEG microstate features were utilized to capture the temporal dynamics of brain functional states. The proposed framework was evaluated on a public OpenNeuro dataset comprising 36 AD patients, 23 frontotemporal dementia (FTD) patients, and 29 healthy controls (HCs), as well as an additional clinical dataset collected from 48 AD patients at Sir Run Run Shaw Hospital, Hangzhou, China. Results: Experimental results showed that the proposed SMMS framework achieved high classification performance on both datasets. Conclusions: These findings demonstrate its effectiveness for EEG-based Alzheimer’s disease diagnosis.

Brain Sciences doi: 10.3390/brainsci16080854

Authors: Dahye Ham Eunyoung Cho Sungwon Choi

Background/Objectives: The Corsi Block Tapping Test (CBTT) is a widely used measure of visuospatial working memory; however, its traditional paper-and-pencil administration is limited by inter-examiner variability in procedure and restricted accessibility. To address these limitations, the present study developed a Korean mobile version of the CBTT and examined its reliability and validity among community-dwelling older adults. Methods: The CBTT was administered to 120 Community-Dwelling older adults. Participants were aged 65 years or older, had no neuropsychiatric disorders or visual impairments, and met the cognitive and depression screening criteria. The CBTT was compared with established standardized measures, including the Spatial Working Memory Test (SWMT), the Korean-Trail Making Test for the Elderly Type B (K-TMT-e Type B), and the Snellgrove Maze Test (SMT). Results: The internal consistency of the CBTT was acceptable (α = 0.767). The backward metrics, particularly the CBTT Backward Correct Responses, showed consistent significant correlations with all three criterion measures, whereas the forward metrics were largely non-significant. Correlation magnitudes were generally small to moderate. Conclusions: These findings provide preliminary evidence supporting the validity of the CBTT, particularly its backward metrics, as a measure of visuospatial working memory in older adults. However, the CBTT should currently be regarded as a preliminary assessment tool rather than a standalone diagnostic or screening instrument.

Brain Sciences doi: 10.3390/brainsci16080853

Authors: Margaret Danielle Weiss Rajendra Aldis Danta D. R. Bien-Aime Taylor Witkowski Peyton Williams Katie E. Holmes Dharma E. Cortés Philip S. Wang Benjamin Lê Cook Eleanor Castine Richards

Background: The objective of this study was to evaluate the preliminary effectiveness of a self-administered digital mental health intervention, COPE2Thrive, in improving symptoms and functional impairment in youth in a diverse community setting. Methods: Outcome measures included self-reported Kiddie-Computerized Adaptive Testing (K-CAT) scores on seven diagnostic domains, and self-reported scores of six domains and the total score of the Weiss Functional Impairment Rating Scale (WFIRS)—Self Report. All youth were eligible to participate unless they were currently in another therapy. Primary analyses followed the stepped-wedge randomized design, comparing participants assigned to one of three randomized intervention sequences. Secondary analyses treated the study as an open-label intervention study and evaluated pre- to post-treatment change among participants who engaged in the intervention, using the last observation carried forward for non-completers. Results: We successfully recruited a majority non-White sample that was 31.5% Black, 31.5% Hispanic/Latino, and 19.6% Asian. Of the eligible participants, 30.5% enrolled in the study, 23.4% completed the intervention, and 12.5% participated in the follow-up. Racial and ethnic minority subjects were less likely to have received outside behavioral health therapies, both in the screening sample and among those who participated in the intervention. There was no statistically significant improvement in the total score or any of the domain scores on the K-CAT or the WFIRS-S, either in the RCT or in the open-label analysis. Conclusions: Given the low acceptability of the program and the absence of clinically significant improvement in this pilot study, the findings suggest that the intervention, as implemented, may have limited utility for addressing youth distress in diverse communities.

Brain Sciences doi: 10.3390/brainsci16080852

Authors: Egle Milasauskiene Julius Burkauskas Simonas Jesmanas Rymante Gleizniene Vilmante Borutaite Nijole Raskauskiene Kristina Skemiene Virginija Adomaitiene Brigita Gradauskiene Guy C. Brown Vesta Steibliene

Background: Inflammatory mechanisms contribute to major depressive disorder (MDD) in a subset of patients. Lipopolysaccharide (LPS), a potent inflammatory endotoxin, can induce depressive-like symptoms, but its relationship with specific depressive symptom profiles remains unclear. Methods: In total, 95 adults with MDD (mean age was 44 ± 14 years) were recruited from psychiatric inpatient and outpatient services. Depressive symptom severity was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS). Serum concentrations of LPS, IL-10, TNF-α, IL-6, and IFN-γ were measured by ELISA. Associations between inflammatory markers and depressive symptoms were examined using group comparisons, correlation analyses, multivariable linear regression, quantile regression, and mediation analyses adjusted for demographic and clinical covariates. Results: Patients with severe depression exhibited significantly lower circulating LPS levels than those with mild-to-moderate depression (95.6 vs. 165.2 pg/mL, p = 0.007), despite no significant differences in cytokine concentrations. LPS levels were inversely associated with depression severity, anhedonia factor score, and MADRS item 8 (“inability to feel”). Lower LPS concentrations were independently predicted by higher inability to feel, reduced appetite and combined pharmacotherapy use. Quantile regression demonstrated heterogeneity across the LPS distribution, with symptom–LPS associations evident among patients with higher LPS concentrations. Higher LPS levels were associated with greater apparent sadness, concentration difficulties, and reduced sleep, but lower levels of anhedonia, less reduced appetite, less lassitude, lower inner tension, and lower suicidality. Mediation analyses indicated that anhedonia mediated the association between LPS levels and depression severity. Conclusions: Higher circulating LPS may characterize a biologically distinct subgroup of MDD patients with lower symptom severity and less anhedonia, supporting biological heterogeneity within MDD.

Brain Sciences doi: 10.3390/brainsci16080851

Authors: Claudia Taborda Gómez Florencia Fernández Agustín Jara Natalia Borda Franco Moscovicz Yessenia Yauri-Huaman Rodrigo Caceres-Robles Luis F. Pacheco-Otalora Alberto Lazarowski Jerónimo Auzmendi

Introduction. In recent years, cannabidiol (CBD) has been used as an adjunct therapy to anti-seizure medications for the control of seizures in patients with drug-resistant epilepsy. In addition to its anticonvulsant effect, CBD also has well-defined anti-inflammatory properties. Since neuroinflammation can trigger various pro-epileptogenic mechanisms, CBD could play an inhibitory role in this process. Epileptogenesis is the process by which epilepsy becomes a chronic disease following a brain injury, and one of its main characteristics is an increased susceptibility to seizures due to a reduced seizure threshold. However, the role of CBD in modulating this susceptibility remains poorly understood. Methodology. We developed an experimental protocol to discretely measure the seizure threshold (DMST) 7 or 14 days after lithium-pilocarpine-induced status epilepticus (SE) through the administration of small intraperitoneal (i.p.) doses of pentylenetetrazol (15 mg/kg/every 10 min). Results. Using the DMST, we observed a significant decrease in the seizure threshold after SE associated with a hypersensitivity state characterized by irritability and marked weight loss. A separate cohort of rats was treated with CBD (20 mg/kg) for 14 days following SE. Conclusions. Treatment with CBD did not improve the seizure threshold; moreover, it worsened the hypersensitivity state and delayed recovery following SE. Our results suggest that orally administered CBD, at a human-equivalent therapeutic and safe dose, does not improve susceptibility to seizure development after SE.

Brain Sciences doi: 10.3390/brainsci16080850

Authors: Tzu-Pu Chang Hong-Hua Lin Anand K. Bery

Background: Skew deviation, a vertical ocular misalignment caused by brainstem or cerebellar dysfunction, is strongly associated with central lesions in acute vestibular syndrome but has not been systematically studied in outpatient settings. This clinic-based study evaluated the prevalence of video-oculography (VOG)-guided skew deviation, its diagnostic value for posterior fossa lesions, and the accuracy of an automated VOG algorithm for skew detection. Methods: Consecutive dizzy patients attending a neurology clinic over 18 months underwent a VOG-guided alternate cover test. Vertical eye deviation was automatically quantified by the VOG software and validated by expert review of VOG traces and/or videos (expert review constituted the gold standard in this study). We analyzed the prevalence and diagnostic performance of skew deviation for posterior fossa lesions. Receiver operating characteristic analysis and area under the curve (AUC) were used to evaluate the automated algorithm. Results: Among 226 dizzy patients, skew deviation was identified in 5.3% (95% CI 3.1–9.1%). For predicting posterior fossa lesions, skew deviation showed a sensitivity of 23.7% (95% CI 13.0–39.2%), specificity of 98.4% (95% CI 95.4–99.5%), positive predictive value of 75.0% (95% CI 46.8–91.1%), and negative predictive value of 86.4% (95% CI 81.2–90.4%). The automated VOG algorithm demonstrated promising performance for detecting skew deviation, with AUCs of 0.88 for the right eye (95% CI 0.77–0.99) and 0.94 for the left eye (95% CI 0.91–0.97). Conclusions: Skew deviation is uncommon in outpatient dizzy patients, but its high positive predictive value supports its utility as an adjunctive predictor of posterior fossa lesions. Although the automated VOG algorithm showed promising performance, expert review of traces and/or video remains necessary because false-positive results may occur.

Brain Sciences doi: 10.3390/brainsci16080849

Authors: Shenghui Liu Xiaohan Fan Zhiyuan Tan Jinfa Gu Qing Huang Hansen Li Lewis J. Macgregor Hengzhi Deng

Background/Objectives: Ammonia inhalants, commonly known as smelling salts, are widely used in sport as an acute arousal strategy, yet their ergogenic value remains uncertain. This systematic review and three-level meta-analysis examined the acute effects of ammonia inhalation on physical performance and selected psychophysiological outcomes. Methods: Controlled human studies involving healthy adults, physically active individuals, or athletes were included when they compared ammonia inhalation with placebo, sham, or no-inhalation control conditions. Physical performance was the primary outcome, with heart rate and selected subjective responses analyzed as exploratory secondary outcomes. Results: Ten studies were included. The primary analysis showed no statistically significant effect of ammonia inhalation on overall physical performance (k = 47, g = 0.11, 95% CI [−0.06, 0.28]). Heart rate and subjective exertion/fatigue were also not significantly affected. In contrast, subjective activation/arousal increased significantly (k = 9, g = 0.73, 95% CI [0.43, 1.04]), although this finding was based on only two studies. Moderator analyses did not show consistent subgroup differences for performance type, training status, or comparator type, whereas sex-based differences were exploratory and based on limited evidence. Sensitivity analyses suggested that physical performance became significantly improved after removal of influential effects, and power/explosive performance showed a possible benefit; however, these findings should be considered preliminary rather than confirmatory. Conclusions: Overall, ammonia inhalation appears to act primarily as a brief arousal stimulus rather than a consistent ergogenic aid. Potential benefits may depend on task demands, with explosive or repeated high-intensity tasks appearing more plausible targets than maximal strength or precision-based skills. Current evidence remains limited by small samples, heterogeneous protocols, and low certainty.

Brain Sciences doi: 10.3390/brainsci16080848

Authors: Tom Mercer

Background/Objectives: Proactive interference (PI) occurs when existing memories make it harder to retrieve newer information, and visual working memory in older adults may be impacted by increased vulnerability to PI. However, evidence supporting age-sensitive PI in the recent-probes task—a major technique for measuring PI—is mixed. Additionally, features of this procedure may have exaggerated or distorted the effect, so the current study reassessed the recent-probes task. Methods: Throughout trials in an online experiment, adults aged 18–29 and 64–80 memorized four images over a brief delay and then had to choose between a current target and a foil depicting an item from the previous trial (a recent negative probe) or a more distant trial (a non-recent negative probe). Participants were cued to respond either immediately or after a pause, and targets came from a small, extensively repeated set or a unique set. Results: PI was present, with slower and less accurate responding to RN than NRN foils, and errors notably increased when stimuli were unique and an immediate response was required. However, there was little evidence for age differences in PI. Conclusions: The present study did not suggest that older adults are more vulnerable to PI than younger adults, at least in this task and with this sample.

Brain Sciences doi: 10.3390/brainsci16080847

Authors: Sarfaraz K. Niazi

Human societies depend on prestige hierarchies that confer status on demonstrated competence, alongside the dominance hierarchies that rely on coercion and that humans share with other primates. The same neural processes that support cooperative learning under prestige are hypothesized to participate in rivalry, polarization, and ideological hostility when their operating environments depart from those in which they evolved. This selective narrative review proposes a candidate integrative framework, the Hypothesized Neural Integration Model of Prestige and Pride, drawing on converging but largely indirect evidence from affective neuroscience, neuroeconomics, evolutionary psychology, and social neuroscience. The framework groups five categories of functionally pluripotent processing, each understood as engaging nodes within overlapping large-scale brain networks rather than as a localized regional mechanism: valuation-related processing implicating orbitofrontal and ventromedial prefrontal cortex, reward-learning signals indexed in the ventral striatum, self-referential and identity-relevant processing engaging medial prefrontal cortex within the default-mode network, threat- and salience-related processing involving the amygdala and anterior cingulate cortex within the salience network, and neuroendocrine output regulated through the hypothalamic–pituitary–adrenal axis and modulated by gonadal and neuropeptide systems. Consistent with Poldrack on reverse inference and with Marr on levels of analysis, the framework is presented at an integrative implementational level with candidate algorithmic mappings specified for each category, not as a computational specification of the constructs themselves, and treats high-level constructs such as prestige, status, and sacred value as emergent phenomena arising from dynamic network interactions, bodily states, cultural contexts, and historical contingencies rather than as properties localized to single regions. Because few neuroimaging paradigms isolate freely conferred deference from generic social rank, claims specific to prestige are deliberately restricted throughout, and the evidence base is presented as one concerning social rank unless a paradigm operationalizes prestige directly. Material ownership, sacred values, religious belief, and digital prestige metrics are treated as candidate domains of application, with explicit separation of direct neural evidence, behavioral evidence, and theoretical extrapolation. Symbolic escalation in consumer markets, sacred-value absolutism, and amplified social feedback on digital platforms are interpreted as candidate environmental amplifiers of ancestral status mechanisms rather than demonstrated causal pathways. Nine operational study designs are proposed to guide future preregistered tests, including one designed to establish whether a prestige-specific neural claim can be made at all. Intervention strategies are mapped to candidate processing and network targets using an explicit evidence-grading scheme, with structural and institutional measures weighted equally alongside cognitive and contemplative ones. The framework relies on correlational neuroimaging subject to reverse-inference constraints, draws primarily from samples from Western, educated, industrialized, rich, and democratic populations, and should be evaluated as a hypothesis-generating account rather than as a confirmed neural architecture.

Brain Sciences doi: 10.3390/brainsci16080846

Authors: Galina Portnova Guzal Khayrullina Emily Bainbridge Olga Martynova

Background: The autonomic nervous system (ANS) in individuals with obsessive–compulsive disorder (OCD) is often characterized by heightened sympathetic tone and reduced parasympathetic flexibility. This exploratory pilot study aimed to provide a detailed, dynamic portrait of autonomic dysregulation. Methods: Heart rate variability (HRV), galvanic skin response (GSR), and oculomotor measures (pupil size, fixations, saccade velocity) were recorded in 31 participants with OCD (obsessive–compulsive disorder) and 46 healthy controls while viewing 18 videos, half of them designed to trigger specific OCD dimensions and half neutral or positive. Results: The OCD group exhibited a state of sympathetic hyperactivation, evidenced by significantly lower mean NN intervals (average interval between normal heartbeats) and a distinct GSR (galvanic skin response) pattern marked by a rising tonic component across the experiment. Healthy controls exhibited increases in SDNN (standard deviation of NN intervals) and RMSSD (root mean square of successive differences) following pleasant videos, whereas this response was less pronounced and emerged later in the OCD group, suggesting reduced autonomic flexibility. Oculomotor data revealed faster saccade velocities during video viewing in the OCD group; however, unlike controls, their eye movements did not correlate with the pleasantness of the content. Conclusions: These results support the theory that individuals with OCD may exhibit greater sympathetic activation and delayed parasympathetic engagement. The findings suggest that autonomic inflexibility may be a core, measurable feature of OCD.

Brain Sciences doi: 10.3390/brainsci16080845

Authors: Vikas Chauhan Fareena Khan

Ketamine produces clinical states ranging from subanesthetic analgesia and dissociation to anesthetic-dose behavioral unresponsiveness. Its electroencephalographic (EEG) effects differ from the slow-delta and frontal-alpha patterns commonly observed with GABAergic-dominant anesthetics and vary with exposure, administration kinetics, and co-administered agents. After anesthetic bolus dosing, ketamine may produce alternating slow-delta and gamma activity; at lower exposures, spectral and connectivity findings are more heterogeneous. When ketamine is added to propofol or volatile anesthesia, bispectral index and spectral-entropy values may remain elevated or increase, limiting their interpretation as stand-alone measures of hypnotic state. Prior syntheses have largely addressed molecular, cellular, and cortical-circuit mechanisms of dissociation; this narrative review instead synthesizes human EEG, connectivity, imaging, and selected mechanistic evidence using a dose–state framework. We distinguish behavioral responsiveness, environmental connectedness, and conscious experience; assess which network measures are technically derivable from clinical scalp recordings; and consider implications for operating-room and critical-care monitoring. Available evidence supports a cautious interpretation of processed indices and greater attention to the raw EEG, spectrogram, background hypnotic, administration pattern, and clinical context. Validated ketamine-specific EEG biomarkers and prospective monitoring algorithms are not yet available. Potential links between acute EEG effects and antidepressant mechanisms are discussed as shared upstream pathways rather than a single electrophysiological state.

Brain Sciences doi: 10.3390/brainsci16080844

Authors: Charlotte Heremans Inês Alves Martins Siqi Yang Jolien Gooijers Jean-Jacques Orban de Xivry Geert Verheyden

Background/Objectives: Upper limb rehabilitation in chronic stroke is often suboptimal, and somatosensory integration is frequently neglected. The aim of this study was to investigate the feasibility and potential effects of an integrated sensorimotor therapy. Methods: Individuals with chronic stroke and persistent sensorimotor and functional upper limb deficits were included. For four weeks, participants received standard care (control), followed by 48 h of integrated sensorimotor upper limb therapy (ROBUST) over four weeks in addition to their standard care (intervention). ROBUST combined robotic, therapist-led, and home exercises. Feasibility was assessed through adherence, motivation, experiences, and adverse events. Potential effects of the intervention were evaluated via a multimodal assessment approach at baseline (T1), post-control (T2), and post-intervention (T3), with the Action Research Arm Test (ARAT) as the primary outcome. Results: Ten participants were included in this study, of whom nine completed the protocol. Therapy session adherence was 100%, and home program adherence 67%. Motivation remained stable over the intervention period, participants were positive, and no adverse events occurred. Six participants (67%) improved more than the minimal clinically important difference for ARAT, with further relevant improvements in clinical, kinematic, and patient-reported outcomes observed. Conclusions: The novel integrated sensorimotor upper limb therapy (ROBUST) is feasible and shows promising potential for people after stroke in the chronic stage. A randomised controlled trial is warranted. Trial registration: (identifier: NCT06870682).

Brain Sciences doi: 10.3390/brainsci16080843

Authors: Ivana Stanković Ljiljana Jeličić Jelena Đorđević Nela Ilić Mirjana Sovilj Slavica Maksimović Maša Marisavljević Miško Subotić

Background/Objectives: Neurofeedback (NFB) modulates electroencephalographic activity and has been proposed to enhance cognitive performance. This study investigated the effects of repeated sensorimotor rhythm (SMR; 12–15 Hz) neurofeedback training on selective auditory attention in healthy adults aged 25–40 years, utilizing both electrophysiological and behavioral assessments. Methods: A prospective, controlled factorial design with repeated measures was employed, including a sham NFB intervention to control for placebo effects. Electrophysiological evaluation measured the amplitudes and latencies of event-related potentials (N100, N200, and P300) during an auditory Go/No-Go task. Speech-in-noise perception, which demands a higher level of selective auditory attention, was further assessed using the QuickSIN test. Results: Electrophysiological results revealed that SMR training statistically significantly reduced latencies of the N200 component at the Cz and Pz electrodes, and the P300 component at the Fz, Cz, and Pz electrodes, in a dose-dependent manner. No significant amplitude effects were observed for any ERP component. Behavioral results demonstrated a linear improvement in speech perception in noise (QuickSIN test) in the experimental group, a task that indirectly engages auditory selective attention mechanisms, as a function of training sessions, with significant group differences favoring the experimental group. These effects were maintained at the one-month follow-up. Conclusions: These findings indicate that SMR-based NFB modulates neural activity and improves selective attention, supporting its potential as an effective intervention for improving attentional performance and auditory processing in healthy populations, with effects persisting at least one month post-training.

Brain Sciences doi: 10.3390/brainsci16080842

Authors: İlkay Ceylan Serpil Ekin Nur Panik Buket Özyaprak Derful Gülen

Background: Systemic inflammation plays a critical role in secondary brain injury after spontaneous intracerebral hemorrhage (ICH). The pan-immune-inflammation value (PIV) has recently emerged as a novel composite inflammatory biomarker; however, its prognostic significance in critically ill ICH patients remains unclear. Methods: This retrospective cohort study included 111 consecutive adult patients admitted to the intensive care unit (ICU) with spontaneous ICH between January 2020 and December 2024. PIV, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and conventional clinical predictors were evaluated at ICU admission. The primary outcome was 28-day mortality, while the mechanical ventilation (MV) requirement was assessed as a secondary outcome. Receiver operating characteristic (ROC) analysis and logistic regression models were used to evaluate prognostic performance. Results: MV was required in 78 patients (70.3%), and 41 patients (36.9%) died within 28 days. Patients requiring MV had significantly higher PIVs than non-ventilated patients (p = 0.013), whereas PIVs did not differ significantly between survivors and non-survivors (p = 0.539). For predicting MV requirement, GCS score demonstrated the highest discriminative performance (AUC = 0.922), followed by ICH score (AUC = 0.874), procalcitonin (AUC = 0.861), and NLR (AUC = 0.832), whereas PIV showed modest discrimination (AUC = 0.650). For 28-day mortality, procalcitonin achieved the highest AUC (0.800), while PIV showed poor predictive performance (AUC = 0.535). In multivariable analysis, NLR and procalcitonin remained independently associated with both MV requirement and 28-day mortality. PIV was not included in the final multivariable models because of its overlap with NLR; moreover, it did not provide meaningful incremental prognostic value when added to the reference models. Conclusions: In this single-center cohort of ICU-admitted patients with spontaneous ICH, PIV did not add meaningful prognostic value beyond established clinical and inflammatory predictors. These findings do not support the routine use of PIV for early risk stratification in this specific population; simpler markers, particularly NLR and procalcitonin, may be preferred when interpreted alongside established clinical severity measures.

Brain Sciences doi: 10.3390/brainsci16080841

Authors: Xiao He Bohan Cheng Hui He Li Zhao Yan Li

Background: Chronic insomnia can impair recovery and performance in athletes. Continuous theta-burst stimulation (cTBS) is a brief neuromodulatory intervention, but its effects in athletes with chronic insomnia remain unclear. This study evaluated whether right dorsolateral prefrontal cTBS improves sleep quality and athletic performance and alters resting-state EEG microstate dynamics. Methods: In this randomized, sham-controlled trial, 35 male athletes with chronic insomnia received active cTBS or sham stimulation once daily for 7 days; usable EEG data were obtained from 32 participants. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Countermovement jump, 50 m sprint, and Illinois Agility Test performance were assessed before and after intervention. Resting-state electroencephalography (EEG) microstate temporal parameters and directional transition probabilities were analyzed. Results: Active cTBS produced a greater reduction in PSQI global score than sham stimulation. Active stimulation increased microstate C duration and contribution and reduced microstate A occurrence. Directional transitions among microstates B, C, and D were also altered, with largely concordant findings in ΔTM sensitivity analyses. Active cTBS improved countermovement jump height, 50 m sprint performance, and agility, whereas sham stimulation improved sprint performance only. Conclusions: A 7-day course of right dorsolateral prefrontal cTBS improved subjective sleep quality and sport-related performance in athletes with chronic insomnia. These improvements were accompanied by selective changes in resting-state EEG microstate temporal parameters and transition probabilities. Given the exploratory nature of the EEG findings, these microstate changes should be interpreted as potential electrophysiological correlates of treatment response rather than evidence of a causal mechanism.

Brain Sciences doi: 10.3390/brainsci16080840

Authors: Karmen Aslankurt Hanna Schenck Sander M. J. van Kuijk Govert Hoogland Inger de Ridder Onno Teernstra Jim Dings Marcel Aries Michael Veldeman Hans Vink Yasin Temel Rick van Lanen Roel Haeren

Background: An aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurovascular emergency. Among survivors, the most dreaded complication is delayed cerebral ischemia (DCI), affecting approximately one third of aSAH patients. Several mechanisms contributing to DCI have been described, yet the pathophysiology remains unclear. Disruption of the endothelial glycocalyx plays a key role in these pathomechanisms and is therefore of particular interest. This study aimed to explore changes in plasma glycocalyx breakdown products following aSAH and in relation to the development of DCI. Methods: In this prospective study, plasma samples were collected during a two-week follow-up period after aSAH diagnosis. Baseline plasma samples were collected within 72 h after ictus, followed by two additional samples in the first week and three samples in the second week. In patients who developed DCI, additional daily samples were obtained. DCI was defined using its clinical definition. Glycocalyx breakdown products syndecan-1 and hyaluronan concentrations were measured using enzyme-linked immunosorbent assays (ELISA) kits. Results: Twenty-nine aSAH patients were included, of whom six developed DCI. Overall, median syndecan-1 concentrations increased significantly from baseline (33.72 ng/mL, IQR 23.29–42.55 ng/mL) to the day 14 measurements (44.83 ng/mL, IQR 32.52–62.68) (p = 0.002). This increase was more prominent in the DCI group (baseline: 34.35 ng/mL, IQR 33.77–50.99, final measurement: 52.31 ng/mL, IQR 44.98–170.62, p = 0.031) compared to the non-DCI group (baseline: 33.07 ng/mL, IQR 23.29–42.32, final measurement: 37.97 ng/mL, IQR 32.52–52.14, p = 0.028), and mainly occurred at DCI onset. Median baseline hyaluronan concentrations were increased at baseline (148.81 ng/mL, IQR 90.61–178.93) and subsequently decreased (final measurement 115.96 ng/mL, IQR 99.15–140.35, p = 0.263). A comparable decrease in hyaluronan levels was noted in the DCI (baseline: 147.82 ng/mL, IQR 80.63–169.63, final measurement: 117.02 ng/mL, IQR 96.73–200.68, p = 0.893) and non-DCI group (baseline: 149.81 ng/mL, IQR 109.16–178.92, final measurement: 114.91 ng/mL, IQR 102.26–136.63, p = 0.156). Conclusions: The results from this explorative study indicate that aSAH is associated with glycocalyx breakdown. While hyaluronan levels were high in the acute phase and decreased thereafter, syndecan-1 levels increased during the first two weeks following aSAH in DCI patients. For syndecan-1, this change was more pronounced in DCI patients. Our findings suggest an involvement of glycocalyx breakdown in the pathophysiology of DCI. This study requires validation in larger cohorts to strengthen our results, and establishes the potential of glycocalyx breakdown products as biomarkers for DCI.

Brain Sciences doi: 10.3390/brainsci16080839

Authors: Chiara Demartini Fabrizio Facchinetti Fabio Blandini Cristina Tassorelli Francesca Malerba Antonino Cattaneo Diana Amantea Bruno P. Imbimbo Rosaria Greco

Objectives: The critical role of nerve growth factor (NGF) in neuroprotection has been demonstrated in preclinical models of neuronal injury. Here, we investigated the neuroprotective effects of intranasal CHF6467, a recombinant mutant form of human NGF lacking algogenic activity, in transient (45 min) middle cerebral artery occlusion (tMCAo). Methods: Male Wistar rats (n = 20 per group) were treated intranasally with CHF6467 (20 µg/kg, 40 µL) or vehicle (0.9% saline, 40 μL). The first dose was administered 15 min after the onset of MCAo and the second dose 24 h later. Neurological behavioral tests were performed 24 and 48 h after tMCAo. Infarct volume was measured 48 h after tMCAo. Additionally, a separate cohort of rats underwent permanent MCAo (pMCAo) and received two intranasal doses of CHF6467 or vehicle, with long-term neurological outcome assessed 7 days later using the De Simoni neuroscore (n = 13–14 per group). CHF6467 levels were measured in intact brain samples from CHF6467-treated rats (n = 5) and vehicle-treated controls (n = 4). Samples were collected 2 h after the last administration. Results: CHF6467 significantly improved neurological and sensorimotor performance compared with the vehicle-treated rats. This functional effect was associated with a reduction in infarct volume that was positively correlated with neurological deficit improvement. In the pMCAo cohort, CHF6467-treated rats were more likely to achieve a favorable neurological outcome at seven days compared with the vehicle-treated animals. Intranasal CHF6467 reached the brain but showed variable and non-uniform distribution across regions. Levels were highest in the olfactory bulbs, while the cortex and striatum had lower concentrations. In vehicle-treated rats, the drug was undetectable. Conclusions: This study demonstrates the neuroprotective effects of CHF6467 against ischemic brain injury, evidenced by both functional improvement and reduction in infarct volume. Although it reaches the brain, its distribution is heterogeneous and assessed only at one time-point. Further studies should examine its longer-term distribution and underlying mechanisms.

Brain Sciences doi: 10.3390/brainsci16080838

Authors: Sandra Tosta Geoffrey Hewitt Adam Anderson

Background/Objectives. Headache and migraine were exacerbated by light during an episode, with light also serving as a diathesis for pain between episodes. Such interictal photosensitivity has been hypothesized to reflect heightened sensitivity to blue-cyan (BC) light, due to activation of melanopsin-based intrinsically photosensitive retinal ganglion cells (ipRGCs). This study examined evidence for wavelength-selective photosensitivity and its relation to headaches/migraine and accompanying functional sequelae. Methods. Individuals with persistent post-traumatic headache (N = 325) were assessed for photosensitivity with an analysis of filtered wavelengths that resulted in relief. A subsample (n = 209) wore precision tinted lenses that matched their individual wavelength photosensitivity profile for over a 1–3-month follow up period and were assessed on a variety of persistent functional complaints. Results. Analysis of wavelengths associated with photosensitivity did not support differential sensitivity to the BC range, revealing greater sensitivity to light below 440 nm and less sensitivity above 680 nm, but with a coefficient of variation of 94.7%, consistent with extremely high individual variation. Individuals who showed near elimination of photosensitivity (97.9%) had decreased self-reported headache frequency (92.6%), as well as reported diminished physical, emotional and cognitive complaints, with these functional outcomes unrelated to the magnitude of BC filtering. Conclusions. These results suggested (1) wavelengths evoking photosensitivity were highly individually variable and (2) interictal exposure to a variety of wavelengths may have contributed to post-traumatic head pain and associated impaired global function, pointing toward common central origins.

Brain Sciences doi: 10.3390/brainsci16080837

Authors: Marta Gómez-Mateos Luis Augusto Silva-Zendron Andrea Calleja-Caballero Vanesa Santos-Rodríguez Beatriz María Bermejo-Gil Fátima Pérez-Robledo

Background/objectives: Thermal asymmetries between the affected and unaffected sides of the body are common after stroke and can be detected using infrared thermography; however, their responsiveness to rehabilitation and its relationship with motor and functional performance remain unclear. This study investigated whether the addition of treadmill training to conventional physiotherapy modifies lower-limb thermal asymmetry and explored its relationship with functional outcomes in individuals with chronic stroke. Methods: A randomized controlled trial was conducted in 22 individuals with chronic stroke randomly assigned to either an intervention group [n = 12] or a control group [n = 10]. All participants received conventional physiotherapy twice weekly for 12 weeks, while the intervention group additionally performed treadmill training. Thermal asymmetry was assessed using infrared thermography, whereas motor function and walking capacity were evaluated using the Fugl–Meyer Assessment for the Lower Extremity and the Six-Minute Walk Test. Results: Both groups showed reduced thermal asymmetry after the intervention, with no significant between-group differences. Significant improvements in motor function (p = 0.016) and walking distance (p = 0.016) were observed only in the intervention group. Between-group analysis revealed greater motor improvement in the intervention group (p = 0.017). Baseline-adjusted analyses confirmed superior motor function and walking capacity outcomes in the intervention group. Conclusions: Infrared thermography detected changes in lower-limb thermal asymmetry following the 12-week physiotherapy program in individuals with chronic stroke, with no significant between-group differences. In contrast, treadmill training produced superior improvements in motor function and walking capacity. These differing patterns suggest that thermographic and functional assessments may provide complementary information regarding recovery after chronic stroke.

Brain Sciences doi: 10.3390/brainsci16080836

Authors: Brigitta M. Beck Michelle M. Pebole Kristiana D. Carrasquillo Colin T. Mahoney Katherine M. Iverson

Background: Between 33% and 75% of women who experience intimate partner violence (IPV) sustain an IPV-related traumatic brain injury (TBI). Although IPV-related TBI is associated with adverse psychosocial outcomes, its impact on response to healthcare-based IPV interventions remains unclear. Methods: Using data from a randomized clinical trial within the Veterans Health Administration, we examined psychosocial outcomes among 60 woman veterans with past-year IPV experiences participating in two brief IPV interventions: Enhanced Care As Usual (ECAU) and Recovering from IPV through Strengths and Empowerment (RISE). Results: At pretreatment, 21 women (35%) reported a history of probable IPV-related TBI. Multilevel modeling revealed no significant main or interaction effects of TBI history for self-efficacy, empowerment, patient activation, depression, physical health symptoms, or resilience. However, there was a significant interaction of time and probable IPV-related TBI history for valued living, such that women with probable IPV-related TBI history demonstrated greater initial gains followed by slight posttreatment decline; F(2, 76.55) = 2.96, p = 0.049. There was also a significant interaction between probable IPV-related TBI history, treatment condition, and pretreatment anxiety symptoms for anxiety symptoms as an outcome, such that women with probable IPV-related TBI history in the RISE condition, who had more severe anxiety symptoms at pretreatment, reported higher anxiety symptoms on average across the study period than women without probable IPV-related TBI history in RISE; F(1, 48) = 5.04, p = 0.029. Furthermore, there was a significant interaction of probable IPV-related TBI history and pretreatment physical health symptoms for physical health symptoms as an outcome, such that women with probable IPV-related TBI histories maintained higher physical symptoms from pretreatment to the last follow-up assessment; F(1, 134) = 8.99, p = 0.004. Conclusions: No evidence of differential treatment response was detected for women with and without probable IPV-related TBI history. Findings related to valued living and anxiety suggest areas where additional support may improve implementation of brief healthcare-based IPV interventions.

Brain Sciences doi: 10.3390/brainsci16080835

Authors: Beomku Kang Da-Eun Yoon Yeonhee Ryu Younbyoung Chae

Background/Objectives: Modern acupuncture research commonly operationalizes acupoints as standardized sites for needling or electrical stimulation. Although this convention has improved reproducibility, it may obscure how classical acupoint and meridian systems have historically organized relationships among intervention sites, sensory phenomena, symptom patterns, and therapeutic responses. This article proposes an operational framework for examining selected acupoint regions as candidate neuromodulation interfaces. It reframes acupoint and meridian systems as relational body maps and operationalizes this perspective through a multidimensional stimulation–engagement–response model that distinguishes intervention features, target engagement, and downstream functional outcomes while accounting for individual context. Methods: The framework was developed to organize existing evidence, identify unresolved causal links, and generate prospective experimental tests, rather than to establish neural or physiological mechanisms that have already been demonstrated. The Baliao region, comprising bilateral BL31–BL34 over the posterior sacral foramina, was selected as the primary case because classical localization and pelvic symptom associations can be examined alongside sacral anatomy and neurophysiology within a single region. Relevant clinical and preclinical findings were evaluated in relation to potential neural targets, physiological engagement, functional outcomes, and alternative explanations. Results: Clinical and preclinical evidence suggests possible engagement of sacral afferent, spinal, autonomic, and pelvic-floor regulatory circuits. However, the evidence remains indirect, heterogeneous, and insufficient to establish equivalence with implantable sacral neuromodulation, a unique BL31–BL34 mechanism, or absolute point specificity. The framework clarifies what current evidence supports, identifies unresolved mechanistic links and alternative explanations, and proposes prospective strategies for testing target engagement and physiological relevance. Conclusions: This approach provides a staged research agenda for moving from descriptive associations toward prospective tests of parameter-dependent target engagement, physiological relevance, and, ultimately, biomarker-guided neuromodulation.

Brain Sciences doi: 10.3390/brainsci16080834

Authors: Sehee Lee Sun Hwa Hong You Jin Nam Yong Hyuk Cho Sang Joon Son Chang Hyung Hong

Background: Dementia develops through the combined influence of genetic vulnerability, biological processes, and environmental exposures. The apolipoprotein E (APOE) ε4 allele is a well-known genetic contributor to dementia risk, and growing evidence links gut microbial alterations to cognitive decline and cerebrovascular-related pathology. Nevertheless, studies jointly evaluating genetic, microbiome, and clinical information remain relatively scarce. This study examined an integrated framework combining APOE genotype and gut microbiome data for cross-sectional dementia classification. Methods: We analyzed 292 participants representing three cognitive stages: subjective memory impairment (SMI), mild cognitive impairment, and dementia. Clinical variables, APOE genotype, and gut microbial metagenomic profiles were examined. Associations among genetic risk, Alzheimer’s disease pathology, and brain structural changes were assessed, and multivariable models were used to distinguish participants with dementia from those with SMI or MCI. Results: APOE ε4 carriage was most frequent among participants with dementia, while no ε4 carriers were observed in the SMI group. Gut microbial profiles differed according to the dementia-related genetic-risk category (mild vs. moderate-to-high). The fully integrated model showed a numerically higher cross-validated AUC than models constructed from fewer data domains. Streptococcus, Akkermansia, and Fusicatenibacter were more abundant in the moderate-to-high genetic-risk group; these taxon-level findings were exploratory and based on nominal p-values. Conclusions: The findings support an exploratory integrated framework for cross-sectional dementia classification based on genetic and gut microbiome information. Independent longitudinal and multicenter validation is required before the framework can be interpreted as predicting future dementia risk or supporting personalized clinical decisions.

Brain Sciences doi: 10.3390/brainsci16080833

Authors: Sujood Kitany Salim Abu-Rabia Rami Arfaiya

Developmental dyslexia is a common neurodevelopmental disorder characterized by persistent difficulties in accurate and fluent word reading despite adequate intelligence, educational opportunity, and intact sensory function. Contemporary neurobiological models have progressively shifted from localization-based explanations toward network-oriented perspectives emphasizing large-scale brain connectivity, developmental maturation, and neuroplasticity. Nevertheless, the developmental mechanisms underlying early right-hemisphere recruitment remain incompletely understood. Although increased right-hemisphere activation has traditionally been interpreted as a compensatory response to left-hemisphere dysfunction, accumulating evidence from longitudinal neuroimaging, intervention, and developmental studies indicates that this explanation alone does not adequately account for the heterogeneity of neurobiological findings observed across individuals with developmental dyslexia. This narrative review synthesizes evidence from developmental neurobiology, network neuroscience, longitudinal neuroimaging, and intervention research to examine the biological processes underlying early right-hemisphere recruitment. Across the reviewed literature, developmental dyslexia is increasingly characterized by atypical maturation of distributed reading networks involving alterations in white-matter development, functional connectivity, hemispheric lateralization, and experience-dependent neuroplasticity. Collectively, these findings suggest that reading networks remain dynamically modifiable throughout literacy acquisition and that multiple developmental pathways may contribute to diverse neurobiological and behavioral outcomes. Building on this evidence, we propose a Developmental Neuroplasticity Framework for Reading Network Reorganization that integrates existing neurobiological models within a unified developmental perspective. Rather than proposing a new neurobiological mechanism, the framework seeks to explain the heterogeneous patterns of early right-hemisphere recruitment that are not fully accounted for by compensation-based interpretations alone. Specifically, it conceptualizes early right-hemisphere recruitment as one possible adaptive developmental outcome emerging from interactions among early neurodevelopmental vulnerability, distributed network connectivity, developmental neuroplasticity, and environmental experience. By integrating evidence that has largely been considered within separate theoretical perspectives, the framework generates empirically testable predictions regarding developmental trajectories, network reorganization, and intervention-related variability, while providing a conceptual basis for earlier identification of children at risk and the development of more targeted, developmentally informed intervention strategies.

Brain Sciences doi: 10.3390/brainsci16080832

Authors: Selami Varol Ülker

Background: Internet Gambling Disorder (IGD) has become an important public health concern, yet relatively little is known about the combined neural, autonomic, and behavioral mechanisms underlying cue reactivity in immersive gambling environments. This study investigated whether individuals with IGD demonstrate altered neurophysiological and psychophysiological responses during a virtual reality (VR) gambling task. Methods: Fifty-seven adults, including 28 participants meeting diagnostic criteria for IGD and 29 healthy controls, completed a standardized VR casino paradigm incorporating predetermined win, loss, and near-miss events. Electroencephalography (EEG), galvanic skin response (GSR), behavioral performance, and post-task craving were assessed simultaneously. Results: Compared with healthy controls, the IGD group demonstrated significantly greater P300 amplitudes during win trials and enhanced late positive potential (LPP) responses following near-miss outcomes, indicating increased attentional allocation and sustained emotional processing of gambling-related cues. Skin conductance responses were also significantly higher in response to near-miss events, whereas overall skin conductance level and reaction time did not differ significantly between groups. Participants with IGD additionally exhibited greater engagement during the VR task and reported substantially higher craving following exposure to the gambling environment. Conclusion: These findings indicate that immersive VR combined with EEG and autonomic recordings provides a sensitive framework for detecting cue-reactivity associated with IGD. Although the findings should be interpreted in light of the relatively modest sample size and the use of a predominantly male sample, they suggest that immersive VR combined with EEG and autonomic recordings provides a sensitive framework for investigating cue reactivity associated with Internet Gambling Disorder. Integrating behavioral, physiological, and neural measures may improve understanding of the mechanisms underlying problematic gambling and inform future research on objective assessment strategies and intervention development.

Brain Sciences doi: 10.3390/brainsci16080831

Authors: Anna Stakhanova Svetlana Zozulya Natalya Kost Olga Voskresenskaya Anastasiya Pozdnyakova Elena Cheremnykh Yulia Chaika Ekaterina Semina

Background/Objectives: According to current concepts, neuroinflammation is one of the putative causes of autism spectrum disorders (ASD) development. However, the role of neutrophils in neuroinflammation remains insufficiently studied. The study was aimed to determine the role of neutrophils in the neuroinflammatory mechanism of ASD development based on a comparative analysis of physiological and behavioral disturbances and the inflammatory response to early postnatal administration of valproic acid (VPA) to Wistar rats. Methods: The study was performed on 38 rat pups of both sexes, half of which were injected intraperitoneally with an aqueous solution of VPA at a dose of 150 mg/kg from 6 to 12 postnatal days (PND); control rats received water. Standard physiological and behavioral tests were used: weight monitoring, pain sensitivity (Hot Plate test) on 25 PND, and social behavior (sib/non-sib test) on 55 PND. Neutrophil elastase (NE) and alpha1-proteinase inhibitor (α1-PI) activity in serum and cerebellum homogenate was measured spectrophotometrically. Complement system (CS) activity was analyzed by the death rate of Tetrahymena pyriformis ciliates in the presence of rat serum. Results: Early postnatal administration of VPA to Wistar rats induces physiological and behavioral changes characteristic of ASD, confirming the validity of the experimental model used. These changes are accompanied by increased activity of inflammatory factors (CS, α1-PI, NE) in the rat serum, indicating the development of inflammation. VPA treatment increased NE activity in the cerebellum, which may indicate neutrophil infiltration of the brain and neuroinflammation development. Conclusions: The data obtained indicate the role of neutrophils in neuroinflammatory mechanisms of ASD development.

Brain Sciences doi: 10.3390/brainsci16080830

Authors: Anna Bernovskis Fina Gießler Franziska Gaidzik Sylvia Saalfeld Naomi Larsen Philipp Berg

Background: The Contour Neurovascular System (CNS) has been established as an effective treatment for wide-neck intracranial bifurcation aneurysms. However, its post-intervention hemodynamic impact remains insufficiently understood. In silico studies investigating the associated hemodynamic changes are limited and rarely consider post-interventional configurations. Methods: Five intracranial aneurysms treated with the CNS were retrospectively analyzed using both pre-interventional and 24 h post-interventional imaging data. CNS-associated morphological changes were assessed, and virtual CNS deployment was performed in pre- and post-interventional configurations. Consequently, 20 high-fidelity, image-based blood flow simulations were performed to evaluate six flow- and shear-related parameters. Results: All cases exhibited an increase in ostium area between pre- and post-interventional configurations (118.7% ± 52.4%), whereas no relevant geometric differences were observed in the surrounding vessels. Hemodynamic analyses revealed that morphological differences were associated with variations in flow characteristics. In particular, most post-interventional configurations showed higher intra-aneurysmal velocities independent of device implantation, although CNS deployment consistently reduced all investigated parameters (reduction in intra-aneurysmal velocity—pre-interventional with CNS: −83.5% ± 14.0%; post-interventional with CNS: −72.4% ± 19.4%). Conclusions: In this exploratory study, the observed CNS-associated morphological differences were accompanied by variations in aneurysmal hemodynamics, potentially influencing the estimated treatment effect. Although validation in larger cohorts is required, these findings highlight the potential value of 3D-DSA follow-up imaging for a more comprehensive assessment of CNS-associated changes and outcomes.

Brain Sciences doi: 10.3390/brainsci16080829

Authors: Weronika Galus Patrycja Romaniszyn-Kania Aleksandra Urantówka Hanna Zielonka Katarzyna Zawiślak-Fornagiel Julia Wyszomirska Urszula Kłosińska Oskar Bożek Daniel Ledwoń Aleksandra Tuszy Andrzej W. Mitas Joanna Siuda

Background/Objectives: Multiple sclerosis (MS) is frequently accompanied by cognitive impairment, yet the neurobiological mechanisms underlying cognitive heterogeneity remain incompletely understood. The choroid plexus (CP), a blood–CSF barrier structure involved in cerebrospinal fluid production and neuroimmune signaling, has recently emerged as a potential MRI marker of inflammatory and neurodegenerative activity in MS. This scoping review mapped evidence on associations between CP features and cognitive functions in adults with MS. Methods: A broad search of PubMed, Scopus, Web of Science Core Collection, and the Cochrane Library identified 1163 records; after deduplication, screening, and full-text assessment, seven studies were included. Results: CP volume or normalized CP volume was assessed in all seven studies, and one study additionally examined the CP T1/T2 ratio. The Symbol Digit Modalities Test was used in six studies, while five applied multidomain cognitive assessment. Larger CP volume was associated in several studies with poorer baseline information-processing speed, visuospatial memory, or multidomain cognition, but longitudinal findings did not show consistent predictive value for CP volume. One study reported that a higher CP T1/T2 ratio predicted faster visuospatial-memory decline. Conclusions: CP-related measures may reflect broader neuroinflammatory and neurodegenerative processes relevant to cognition in MS, but the evidence remains limited and methodologically heterogeneous. Standardized acquisition and segmentation, harmonized cognitive assessment, and adequately powered longitudinal studies are needed to establish their independent and predictive value.

Brain Sciences doi: 10.3390/brainsci16080828

Authors: Shaoshuai Lu Ziyang Chen Yanyan Wang Hongsheng Bian Shuang Yu Lili Huang

O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) is a dynamic, nutrient-sensitive post-translational modification that couples hexosamine biosynthesis pathway flux to protein function in neurons and glia. This reversible cycling, catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), integrates glucose, glutamine, acetyl-CoA, and nucleotide metabolism with synaptic activity, mitochondrial adaptation, transcriptional regulation, proteostasis, and neuroimmune signaling. Dysregulated O-GlcNAc cycling has been implicated in major neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Huntington’s disease (HD), through effects on disease-related proteins, autophagy, mitochondrial function, and inflammatory networks. However, available evidence does not support a universal model in which global O-GlcNAc elevation is uniformly protective or global reduction is uniformly pathogenic. In this mechanistic narrative review, we integrate disease-specific and substrate-focused findings while distinguishing relatively mature translational evidence from model-based or hypothesis-generating observations. We propose a state-resolved framework in which disease-relevant O-GlcNAc states are interpreted across biological contexts, substrate/site specificity, and intervention dynamics. This framework helps reconcile divergent findings across experimental systems and highlights the limitations of indiscriminate global pathway modulation. Although OGA inhibitors represent the most advanced therapeutic strategy, their broad substrate effects underscore the need for pharmacodynamic biomarkers, human validation, brain-targeted delivery, and state-resolved approaches. Moving from bulk O-GlcNAc measurements toward precise correction of disease-relevant O-GlcNAc states across defined biological contexts will be essential for translating this biology into clinically meaningful interventions.

Brain Sciences doi: 10.3390/brainsci16080827

Authors: Mihai Popescu Elena Anda Popescu Thomas J. DeGraba John D. Hughes

Objective: Post-traumatic stress disorder (PTSD) has been linked to reduced functional brain connectivity, but it is unclear if altered local network properties contribute to these disruptions in functional coupling. Computational studies have demonstrated that dynamical states characterized by scale-free local activity optimize the long-range functional coupling in neuronal networks. Our study uses resting-state magnetoencephalographic recordings to investigate if characteristics of scale-free dynamics of local cortical activity are associated with alterations in long-range functional connectivity in PTSD. Methods: Participants (n = 96) were service members with combat exposure and various levels of post-traumatic stress severity (PTSS). We estimated the amplitude envelopes of beta-band cortical activity in 134 cortical regions and we characterized their scale-free dynamics using the power-law scaling exponent determined by detrended fluctuation analysis. We assessed the correlation between PTSS, scaling exponents, and functional coupling between homologous anatomical areas of the two hemispheres. Results: We found negative correlations between PTSS and scaling exponents as well as between PTSS and inter-hemispheric coupling (IHC) predominantly in prefrontal and temporal regions. Positive correlations between scaling exponents and IHC were present in a large number of regions, with high correlations across primary and unimodal association cortices and lower correlations across high-order heteromodal processing areas. Conclusions: Our findings suggest that mechanisms that regulate scale-free dynamics of local cortical activity may contribute to alterations of long-range functional connectivity in PTSD. Significance: Therapies with the potential to normalize local scale-free brain activity may lead to the restoration of functional brain connectivity, offering a promising avenue for PTSD treatment.

Brain Sciences doi: 10.3390/brainsci16080826

Authors: Alessandro Frolli Maria Carla Ricci Francesca Di Carmine Agnese Lombardi Antonia Bosco Emilio Saviano Luisa Franzese

The journal retracts the article titled “The Impact of COVID-19 on Cognitive Development and Executive Functioning in Adolescents: A First Exploratory Investigation” [...]

Brain Sciences doi: 10.3390/brainsci16080825

Authors: Qian Wang Shiyu Wan Meng Liu Weijun Li

Advice-giving during social interaction is not a one-way flow of information. Instead, it constitutes a dynamic process that includes offering advice, receiving feedback, and adjusting subsequent behaviors. Few studies have examined how advisees’ facial attractiveness and feedback type together shape advisors’ willingness to keep providing advice, as well as the corresponding neural temporal patterns. In this study, we adopted an advice-giving game paradigm. We recorded event-related potentials (ERPs) when 28 participants received feedback and made subsequent advice decisions, to explore the interaction between facial attractiveness and feedback type. Behavioral results showed that both high facial attractiveness and acceptance feedback significantly increased advisors’ willingness to continue giving advice. Moreover, an interaction effect was observed: compared with rejection feedback, the influence of facial attractiveness on willingness to continue advising was relatively weaker under acceptance feedback. ERP results revealed that high facial attractiveness evoked greater P300 and late positive potential (LPP) amplitudes at the feedback reception stage. Under acceptance conditions, low facial attractiveness evoked greater feedback-related negativity (FRN) amplitudes. At the advice decision stage, high facial attractiveness similarly elicited larger P300 and LPP amplitudes, while low facial attractiveness produced greater N2 amplitudes in acceptance trials. These findings indicate that facial attractiveness affects static social evaluation and also shapes the dynamic interaction sequence of giving advice, receiving feedback and forming subsequent decisions. Attractive faces and acceptance feedback may possess greater motivational significance and social salience, thereby promoting advisors’ subsequent willingness to provide advice.