Brain Sciences doi: 10.3390/brainsci16111219

Authors: Silvia Canino Erica Dolce Irene Ruffo Daniela Malangone Simona Raimo Liana Palermo

Background: Our representation of the body is multidimensional, involving both the processing of internal bodily signals and representations of the body’s external features. Although interoception (inner) and outer body representations show age-related differences, their trajectories have rarely been examined together across different stages of life. Methods: The present study investigated age- and sex-related differences in three dimensions of interoception—interoceptive accuracy (IAcc), interoceptive awareness (IAw), and interoceptive sensibility (ISe)—and in action-oriented (aBR) and non-action-oriented (NaBR) body representations in a large sample of 561 healthy participants distributed across seven age groups, from childhood to older adulthood. Age- and sex-related differences were examined through comparisons across the seven age groups and linear and quadratic regression analyses. Results: Age-related differences emerged across all bodily dimensions, but with distinct patterns. IAcc, as operationalized by heartbeat-counting performance, showed a positive linear association with age, with generally higher scores in middle-aged and older adults, whereas IAw was higher in emerging and young adults than in younger children. ISe showed a negative linear association with age, with greater self-reported focus on bodily sensations in younger age groups and lower levels in later adulthood. Both aBR and NaBR showed inverted U-shaped age-related performance patterns, with generally poorer performance in childhood and better performance in adulthood, although their patterns did not fully overlap. Sex effects were dimension-specific: males showed higher heartbeat-counting scores (IAcc), although this finding was not consistent across analyses, whereas females reported higher ISe levels and performed better on NaBR. Age-by-sex interactions were not significant. Conclusions: Overall, these findings indicate that different dimensions of inner and outer bodily representations show partially distinct age-related patterns and support a multidimensional account of bodily representations across the lifespan, although the cross-sectional design and measurement limitations warrant caution in interpretation.

Brain Sciences doi: 10.3390/brainsci16111218

Authors: Renata Marchewka Tomasz Trzmiel Maja Górecka Filip Hojan Katarzyna Hojan

Objectives: Extremely low-frequency magnetic field (ELF-MF) stimulation has been investigated as an adjunctive treatment in stroke rehabilitation; however, the influence of stimulation site on functional recovery remains unclear. To our knowledge, no clinical study has directly compared head and pelvic girdle applications. This study aimed to compare the effects of both application sites with rehabilitation alone. Methods: In this randomized study, 112 participants were included in the final analysis: 26 in the head stimulation group, 47 in the pelvic girdle stimulation group, and 39 in the control group. All participants received intensive physiotherapy and occupational therapy. ELF-MF treatment consisted of 10 sessions at 40 Hz and 5 mT. Functional outcomes and inflammatory biomarkers were assessed at three time points through day 35. Results: All functional outcomes improved significantly over time (all p < 0.001). Median FIM gains were 34, 30, and 26 points in the head, pelvic, and control groups, respectively (p = 0.011). A significant group-by-time interaction was observed for FIM scores (p = 0.003; partial η2 = 0.093), with greater improvement in both stimulation groups compared with controls and no significant difference between application sites. Between-group differences in Barthel Index improvement were significant before age adjustment (p = 0.044) but not after adjustment (p = 0.063). No significant between-group differences were observed for other functional outcomes or inflammatory biomarkers. No stimulation-related adverse events were reported. Conclusions: Adjunctive ELF-MF stimulation was associated with greater improvement in functional independence during stroke rehabilitation, without demonstrated superiority of either application site. These findings require confirmation in larger studies with longer follow-up.

Brain Sciences doi: 10.3390/brainsci16111217

Authors: Yuming Peng Ming Ding

Optically pumped magnetometer-based magnetoencephalography (OPM-MEG) enables cryogen-free, on-scalp recordings with wearable, individually configurable sensor arrays. These features may expand access to MEG for patients poorly accommodated by fixed-helmet superconducting quantum interference device (SQUID) systems. This review evaluates current clinical evidence, implementation barriers, and priorities for clinical translation. This narrative review synthesizes OPM-MEG studies in presurgical epilepsy evaluation and functional mapping, alongside exploratory applications in other neurological and psychiatric conditions. Evidence is considered in relation to clinical performance, validation endpoints, and requirements for acquisition, analysis, and implementation across different clinical settings. Patient-based evidence includes comparative and prospective studies of presurgical evaluation in drug-resistant focal epilepsy. Studies support interictal epileptiform discharge detection and localization, with broad concordance with SQUID-MEG and intracranial electrophysiology; early reports also demonstrate ictal recordings. Pediatric and motion-tolerant recordings represent promising applications. Motor mapping has progressed to small patient cohorts with limited intraoperative validation, while language mapping is supported mainly by small studies and case reports. Applications in neurodegenerative, headache, psychiatric, and developmental disorders remain exploratory and currently lack established clinical indications for MEG. Common translational priorities include standardized performance benchmarks, acquisition quality control, motion management, co-registration, analysis, reporting, and personnel training. OPM-MEG shows promise for extending clinical MEG, supported by patient-based feasibility and comparative studies in presurgical epilepsy evaluation. Multicenter prospective studies should establish performance and reproducibility for defined indications. New applications and claims of additional benefit require evaluation of their effects on clinical management and patient outcomes, supported by standardized workflows across systems and centers.

Brain Sciences doi: 10.3390/brainsci16111216

Authors: Meng Dai Ayodele Sasegbon Wanqi Li Ivy Cheng Shaheen Hamdy

Objectives: To determine whether preconditioning with 1 Hz repetitive transcranial magnetic stimulation (rTMS) alters the effect of subsequent pharyngeal electrical stimulation (PES) on corticobulbar excitability. Methods: Fourteen healthy adults completed three conditions in randomised order in a within-subject crossover design: C1, active 1 Hz rTMS followed by real PES; C2, sham 1 Hz rTMS followed by real PES; and C3, active 1 Hz rTMS followed by sham PES. Bilateral pharyngeal motor evoked potentials (PMEPs) and thenar motor evoked potentials (TMEPs) were recorded at baseline and at 0, 15, 30, 45, and 60 min post-PES. Results: C3 reduced dominant PMEP amplitude relative to its own baseline (overall −12.7%, 95% CI −22.7 to −2.7, p = 0.017). Adding PES after active rTMS raised amplitude relative to C3 (C1 versus C3 +39.5%, p = 0.008). C2 versus C3, which compares two different active protocols rather than isolating the effect of PES, also differed (+15.7%, p = 0.004). Only C1 increased above its own baseline (+26.8%, 95% CI +3.1 to +50.5, p = 0.029) whereas C2 did not (+3.0%, p = 0.525), but the direct C1 versus C2 contrast was not significant overall (+23.8%, 95% CI −5.4 to +52.9, p = 0.101) and reached nominal significance only at 45 min (+32.4%, unadjusted p = 0.023; Bonferroni p = 0.068). Sustained excitation across three or more consecutive timepoints occurred in 8/14 participants after C1, 4/14 after C2 and 0/14 after C3 (Cochran Q = 8.73, p = 0.011), although the direct C1 versus C2 comparison was not significant (exact McNemar p = 0.344). Non-dominant PMEP latency showed a condition effect (p = 0.034); non-dominant amplitude and thenar control responses did not. Conclusions: PES applied after inhibitory rTMS was associated with higher corticobulbar excitability than sham PES. Any additional benefit of preconditioning over PES alone remains exploratory and requires a larger trial.

Brain Sciences doi: 10.3390/brainsci16111215

Authors: Giuseppe Barbato Dario Morra

The modern science of sleep was born in 1953, when Aserinsky and Kleitman [...]

Brain Sciences doi: 10.3390/brainsci16111214

Authors: Berra Bilgin Mustafa Eren Yuncu Meltem Yilmaz Erman Guler Ali Karadag Baran Bozkurt Necmettin Tanriover

Background/Objectives: This study aimed to describe the sequential microsurgical relationships surrounding the lateral mesencephalic sulcus (LMS) through fiber dissection and characterize regional anatomical variation using MRI morphometry in an independent adult cohort. Methods: Eight formalin-fixed adult specimens underwent stepwise fiber dissection. T2-weighted MRI examinations from 100 adults were retrospectively analyzed. Measurements included the inferior colliculus–straight sinus angle (ICSSA), corpus callosum–pontomesencephalic junction distance (CCPJD), LMS–midline angle (LMS-MA), LMS–midline distance (LMS-MD), and LMS–cerebellar surface distance (LMS-CSD). The splenium–mesencephalon relationship (SMR) was categorized descriptively. Comparisons and age correlations were evaluated using Holm-adjusted p values. Results: Dissection documented sequential relationships between the LMS, lemniscal pathways, superior cerebellar peduncle, and deep tegmental structures. The MRI cohort included 50 women and 50 men aged 23–88 years. Mean ICSSA was 29.6 ± 5.3° and CCPJD was 24.17 ± 3.85 mm. Right and left values were 21.9 ± 3.9° and 22.2 ± 4.0° for LMS-MA, 9.77 ± 0.81 and 9.91 ± 0.84 mm for LMS-MD, and 6.12 ± 1.87 and 6.28 ± 1.68 mm for LMS-CSD. No right–left differences remained significant after correction. Males had greater left LMS-MD and right LMS-CSD (adjusted p = 0.002 and 0.004, respectively). Age correlated negatively with CCPJD (ρ = −0.389; adjusted p < 0.001) and positively with right and left LMS-CSD (ρ = 0.268 and 0.379; adjusted p = 0.042 and <0.001, respectively). SMR Types A, B, and C occurred in 70%, 29%, and 1%, respectively. Conclusions: Fiber dissection and MRI morphometry provide complementary descriptive anatomical reference data. The MRI parameters characterize regional variation; their correspondence with deep microsurgical boundaries and clinical applicability remain to be established.

Brain Sciences doi: 10.3390/brainsci16111213

Authors: Xue Wang Junjie Liu Ying Li Yanyan Liu Ying Ji Yinlu Wang Mi Zheng

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are prevalent neurodevelopmental disorders in childhood and adolescence in which neuroimmune dysregulation and altered microglial function have been increasingly implicated, albeit with substantially different levels of human versus preclinical evidence. Preclinical (in vitro and rodent) studies indicate that contracting skeletal muscle secretes bioactive exercise-induced factors (exerkines)—including irisin, cathepsin B, lactate, and extracellular vesicles—that can directly cross or indirectly signal across the blood–brain barrier, modulate microglial inflammatory states, and support synaptic plasticity. However, whether this complete peripheral-to-central cascade operates to normalize synaptic pruning in children and adolescents with ASD or ADHD remains unconfirmed. In this review, we propose the developmental muscle–microglia axis as a hypothesis-generating conceptual framework and specifically focus on its intersection with pubertal maturation. We critically synthesize in vitro, animal, and human evidence on how key exerkines and multi-pathway brain-derived neurotrophic factor (BDNF) regulation may interact with surging sex hormones during the pubertal transition to influence microglial activity and neuroepigenetic states. Furthermore, we frame modality-specific exercise parameters (FITT-VP model) and multimodal wearable/biomarker closed-loop monitoring as candidate hypotheses and conceptual proposals for future clinical trials in youth with ASD and ADHD, while highlighting methodological limitations, safety considerations, and translational gaps.

Brain Sciences doi: 10.3390/brainsci16111212

Authors: Maria Teresa Sindelar Bruno Sales Santina Patané

Background: Hypo- and hyperreactivity to sensory input are included in the DSM-5 diagnostic criteria for autism spectrum disorder (ASD). While deep pressure contributes to the development of the body schema, motor organization, and affective regulation, behavioral responsiveness to sustained deep pressure has rarely been quantified directly, and most available evidence derives from caregiver-report instruments. Objective: This study aimed to compare behavioral response thresholds to deep pressure between autistic and neurotypical (NT) children, to test whether group differences were replicated across two independent samples recruited in ecologically comparable regions (southern Italy and southern Argentina), and to evaluate the feasibility of a standardized, low-cost protocol based on a pediatric aneroid sphygmomanometer. Methods: A total of 511 children aged 3–14 years participated (174 autistic and 337 NT children). ASD diagnoses were established according to DSM-5 criteria by specialized clinicians. Two independent samples of Italian and Argentine children were examined. Graduated pressure was applied using a pediatric cuff at four limb sites, and the behavioral response threshold was recorded when the child first signaled detection. Mean behavioral response thresholds were compared between the ASD and NT groups, across age groups within the ASD samples, and across language-status categories. Results: Mean composite behavioral response thresholds were higher in ASD than in NT children across all four age bands in both countries, and these differences persisted after adjustment for exact age and recorded sex. Higher thresholds in ASD were also observed at each anatomical site. Within the Italian ASD sample, verbal children had lower thresholds than minimally verbal and nonverbal children, while in the Argentine sample, only the nonverbal–verbal contrast remained statistically significant after correction. No statistically significant nonverbal–minimally verbal difference was found. Conclusions: Autistic participants showed markedly higher behavioral response thresholds than NT participants. Verbal participants in the Italian sample had lower response thresholds than minimally verbal and nonverbal children. A standardized sphygmomanometer-based protocol may offer a feasible approach for research and, pending further validation, for clinical use in low-resource settings.

Brain Sciences doi: 10.3390/brainsci16111211

Authors: Wioletta Pawlukowska Krzysztof Wietrzyński Agnieszka Wasilczyk-Kryger Tatiana Lewicka Ewa Maciorowska Karolina Sempruch-Machowska Danuta Wojtas-Kłucińska Weronika Żmuda Lilla Zakariás Marta Masztalewicz Monika Mak

Background/Objectives: This study developed a Polish adaptation of the Hungarian Aphasia Screening Test (HAST-PL) and evaluated its internal structure, internal consistency, and screening accuracy. Methods: Following translation and expert-led adaptation, 173 stroke survivors (130 with clinically confirmed aphasia and 43 without aphasia) were analysed. Clinical status was established before HAST-PL through neurological and speech-language assessment supplemented by medical records. Analyses included ordinal confirmatory factor analysis (CFA), internal consistency, group comparisons, ROC analysis, and 20,000 stratified bootstrap resamples with repeated cut-off selection. CFA was also performed in the aphasia group. Results: The one-factor model yielded CFI = 0.991, TLI = 0.981, RMSEA = 0.086, and SRMR = 0.051; the aphasia-only analysis showed a similar pattern. Internal consistency was acceptable (α = 0.805; ω = 0.834). All five tasks differentiated the groups (p ≤ 0.028). AUC was 0.88 (95% CI [0.83, 0.93]). Screen-positive scores ≤16 yielded 66.2% sensitivity and 97.7% specificity; ≤17 yielded 77.7% and 86.0%, respectively. The apparent maximum Youden index of 0.6383 decreased to 0.6141 after bootstrap correction. The ≤16 and ≤17 rules were selected in 51.265% and 47.950% of resamples, respectively. Conclusions: HAST-PL shows initial promise for aphasia screening. Internal validation supports evaluating both neighbouring thresholds rather than adopting either as a definitive clinical rule. Negative results cannot exclude clinically suspected aphasia, and independent external validation remains necessary.

Brain Sciences doi: 10.3390/brainsci16111209

Authors: Aymen Balıkçı Teresa A. May-Benson İzgi Miray Demirbağ Gamze Çağla Sırma Kübra Önerge Sevda Asqarova Gül İlbay Nazif Ekin Akalan

Aims: Idiopathic toe walking (ITW) is persistent forefoot walking without identifiable neurological or orthopedic causes. Emerging evidence suggests sensory–motor contributions, yet performance-based evaluations are limited. This study aimed to compare sensory integration and praxis in children with ITW and typically developing (TD) peers. Methods: This case–control study included 60 children (4–8 years 11 months): 30 with ITW and 30 TD. Diagnosis was confirmed using the Idiopathic Toe Walking Tool–Turkish Version. Sensory integration and praxis were assessed with the Sensory Integration and Praxis Tests (SIPTs). Group differences were analyzed using univariate analyses with Bonferroni correction, and dysfunction patterns were identified. Results: Children with ITW showed significantly poorer performance on several SIPT subtests, including Manual Form Perception, Graphesthesia, Postural Praxis, Praxis on Verbal Command, Oral Praxis, Bilateral Motor Coordination, and Standing and Walking Balance (p < 0.001). Figure–Ground perception also differed (p = 0.003), while kinesthesia and postrotary nystagmus did not. Somatodyspraxia was identified in 86.7% of the ITW group; other patterns were less frequent. No TD child met dysfunction criteria. Conclusions: Children with ITW exhibit sensory integration and praxis impairments, supporting a sensory–motor basis and the need for performance-based assessment.

Brain Sciences doi: 10.3390/brainsci16111210

Authors: Stanisław Szlufik Olga Stodulska Mikołaj Raźniak Paweł Gutowski Aleksandra Koźmińska Marta Betka Łukasz Milanowski Monika Figura Mirosław Ząbek Dariusz Koziorowski

Background/Objectives: MR-guided focused ultrasound (MRgFUS) Vim thalamotomy targets medication-refractory tremor in essential tremor (ET) and tremor-dominant Parkinson’s disease (PD). We examined longitudinal patient-reported outcomes alongside early motor changes. Methods: This retrospective cohort included 30 patients (12 ET, 18 PD). PDQ-39, PDQ-8, and EQ-VAS were analyzed using random-intercept mixed models. Multiplicity correction covered 16 visit contrasts, including four contrasts for a secondary. A sensitivity analysis included 11 participants with confirmed pretreatment W1 dates and numeric patient-reported data. Results: The paired motor analysis showed a median 12-point TRS reduction and median individual tremor improvement of 64.7% (n = 23; p < 0.001). Median original UPDRS Part III reductions in PD were 5 points OFF (p = 0.010) and 9 points ON medication (p = 0.004). Patient-reported outcomes were available for 25, 21, and 10 participants at W1, W2, and W3. No categorical-visit contrast met the corrected significance threshold in either the full-cohort or restricted analysis. Conclusions: MRgFUS was followed by substantial early tremor reduction and PD motor-score reductions compatible with clinically meaningful improvement against external benchmarks. This post hoc interpretation provides clinical context for motor change; the patient-reported analyses did not establish a consistent or durable quality-of-life benefit. Safety outcomes were not evaluated in this study.

Brain Sciences doi: 10.3390/brainsci16111208

Authors: Polya Ivanova Lambeva Plamen Stoyanov Bozhinov Pencho Tonchev Stoyan Plamenov Bozhinov

Objective: The objective of this study is to evaluate three-month changes in corticomotor excitability, assessed by motor-evoked potential (MEP) amplitudes, following accelerated high-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) in patients with refractory trigeminal neuralgia (TN), and to determine whether chronological age modifies neurophysiological and clinical outcomes. Methods: This prospective, non-randomized, parallel-group comparative cohort study enrolled 192 patients with refractory classical TN, diagnosed according to the International Classification of Headache Disorders, third edition (ICHD-3). The active rTMS group (n = 108) received 10 intensive sessions over five consecutive days (two sessions per day, 40 min interval) using combined 10 Hz and 20 Hz sub-protocols targeting the M1 facial motor representation contralateral to the symptomatic side, guided by international 10/20 electroencephalography (EEG) landmarks and functional MEP optimization. The control group (n = 84) received optimized standard pharmacological care (carbamazepine and/or gabapentin). We assessed Brief Pain Inventory (BPI) and Quality-of-Life Pain (QoLp) scores at baseline (T0), one month (T1), and three months (T3) in both cohorts to evaluate the sustainability of the analgesic effect without maintenance therapies. Longitudinal MEP monitoring was performed exclusively in the active rTMS cohort to trace trajectories; no direct between-group MEP comparisons were performed, and follow-up was fixed at three months. Results: At 3 months, mean facial MEP amplitudes decreased within the active rTMS group (58.11 ± 12.77 μV to 49.77 ± 12.49 μV; p < 0.001), indicating a temporal association with reduced local cortical excitability. This neurophysiological shift paralleled robust clinical improvements: cumulative BPI scores dropped from 96.60 ± 24.88 to 32.88 ± 24.75 (p < 0.001), representing a 65.96% pain reduction, and QoLp scores rose from 4.32 ± 1.85 to 8.57 ± 1.36 (p < 0.001), indicating substantial elevation in functional independence. The control group showed statistically significant but clinically modest changes (p < 0.001, consistent with tabulated estimates), substantially lower than those in the active cohort (group-by-time interaction, p < 0.001). Mixed-design ANCOVA indicated that therapeutic benefits were not modified by chronological age (age-by-time interaction, p > 0.05), despite the active rTMS group having an older baseline age profile (54.69 ± 16.27 vs. 43.17 ± 17.27 years; p < 0.001) due to protracted clinical pharmacoresistance. Conclusions: Accelerated dual-frequency rTMS over the contralateral M1 facial representation may produce measurable reductions in corticomotor excitability that strongly co-occur temporally with clinical remission at 3 months among patients with refractory TN. Significance: These findings may indicate preserved cortical neuroplastic capacity in older, highly treatment-resistant populations, potentially supporting accelerated M1 rTMS as an age-resilient therapeutic strategy for chronic neuropathic pain, although a direct causal relationship remains to be established and extensive randomized trials are required.

Brain Sciences doi: 10.3390/brainsci16111207

Authors: David O. Sorensen Jenna A. Sugai Stéphane Maison Kenneth E. Hancock Daniel B. Polley

Background/Objectives: Individuals with chronic tinnitus perceive a phantom sound that imposes either a bothersome and irrepressible distraction throughout waking hours or a relatively mild nuisance that often fades into subliminal awareness. The difference in tinnitus salience may reflect a general difference in inhibitory control over any distracting sound, whether externally or internally generated. In this exploratory study, we tested whether tinnitus burden, assessed using the Tinnitus Handicap Inventory (THI), was associated with behavioral and neural responses to external auditory distraction. Methods: Thirty adults with chronic tinnitus completed behavioral and electroencephalographic (EEG) testing. Participants with lower and higher THI scores were similar in age and hearing thresholds. Data from twenty-three neurotypical adults provided an additional reference cohort. Participants classified sequences of amplitude-modulated tones as random or repeating during behavioral testing or combined behavioral and EEG recording sessions. Competing noise or melodic distractors imposed lower and higher levels of distraction, respectively. Results: Melodic distractors reduced response accuracy more than noise distractors, with comparable effects in the lower- and higher-THI groups. Neural synchronization to changes in the target sequence also decreased more with melodic distractors, but this effect did not differ between groups. Other measures of synchronization to target and distractor features showed no significant group differences. Conclusions: Behavioral and neural measures were sensitive to external auditory distraction but did not distinguish participants with lower and higher tinnitus burden. These findings do not support a general deficit in suppressing external auditory distractors as an explanation for greater tinnitus burden under the conditions tested.

Brain Sciences doi: 10.3390/brainsci16111206

Authors: Pierluigi Zoccolotti

Neuropsychological research has the general objective of examining human behavior in relation to the structures and functioning of the nervous system [...]

Brain Sciences doi: 10.3390/brainsci16111205

Authors: Heying Cheng Xin Li Ru Zhang Yunge Zhang Luyang Tao

Objectives: This study aims to investigate the characteristics of event-related potentials (ERP) in patients with traumatic subarachnoid hemorrhage (tSAH) during the clinical stable phase, with the aim of obtaining neuroelectrophysiological indicators that can objectively assess cognitive dysfunction caused by this injury. Methods: A total of 16 healthy volunteers and 33 tSAH patients in the stable phase were recruited. Demographic and clinical data were collected, MMSE assessments were completed, and EEG data for P300, mismatch negativity (MMN), and contingent negative variation (CNV) were recorded using a 32-lead ERP system. ERP analysis was performed by comparing the tSAH group with the healthy control (HC) group and by further dividing the tSAH group into a cognitive impairment subgroup (CI, n = 18) and a normal cognition subgroup (NC, n = 15) based on MMSE scores, with a focus on the mean amplitude and peak latency within specific time windows and their correlation with cognitive behavioral measures. Results: The results showed no significant differences in demographic characteristics between the two groups, while the MMSE scores of the tSAH group were significantly lower than those of the HC group. Compared with HC, the mean amplitude of P300 in response to the target stimuli was significantly reduced in multiple brain regions in the tSAH group and attenuated the negativity of mean CNV amplitudes across multiple brain regions, while no significant differences in mean MMN amplitudes were detected across electrodes and no significant differences were observed in peak latencies of P300 and MMN. The CI group was slightly older than the NC group; after controlling for the effect of age, the Mini-Mental State Examination (MMSE) scores of the CI group were significantly lower than those of the NC group, but no significant differences were found between the two groups in mean amplitudes and peak latencies of P300 and MMN or in mean CNV amplitudes. Conclusions: This study indicates that tSAH may be one of the relevant risk factors for post-traumatic cognitive dysfunction. ERP findings suggest that the allocation of relevant cognitive resources is attenuated in this population, but no differences were detected in the temporal sequence of neural processing. No significant abnormalities were observed during auditory deviance detection corresponding to the MMN time window, and no significant differences in ERP characteristics were found among the subgroups. This study found that tSAH can cause selective cognitive electrophysiological impairment, but ERP electrophysiological changes do not fully match cognitive impairment classified based on clinical scales.

Brain Sciences doi: 10.3390/brainsci16111204

Authors: Davide Mascioli Matteo Conti Tommaso Schirinzi Alessandro Stefani

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are increasingly viewed as regions of a single α-synuclein continuum rather than separate entities. Neuropathology shows that Lewy pathology rarely occurs alone: Alzheimer-type amyloid-β and tau, transactive response DNA-binding protein 43 kDa (TDP-43) inclusions, and cerebrovascular lesions accompany it as the rule rather than the exception, and this co-pathology contributes to the clinical heterogeneity observed across the continuum without mapping onto its clinical divisions. The open problem is no longer whether co-pathology matters but how to measure it in living patients and integrate that information for individualized care. This review is organized by proteinopathy (α-synuclein as the primary lesion, then amyloid-β, tau, and TDP-43/vascular co-pathology) and, within each, follows the modalities that interrogate it: molecular imaging, fluid and tissue biomarkers, and their downstream structural, metabolic, functional, and electrophysiological correlates. No single technique captures the co-pathological landscape. Profiling an individual’s proteinopathy burden in vivo requires a deliberate combination of methods, and precision management of the PD–DLB continuum depends on this multimodal integration.

Brain Sciences doi: 10.3390/brainsci16111203

Authors: Jakub Malkiewicz Piotr Wiśniewski Florentyna Matejko Gabriela Zielińska Marta Pencko Katarzyna Jakubiec Wiktoria Skowron Mateusz Toś Joanna Siuda

Background/Objectives: In 2020, a clinical score to predict the risk of cerebral vein thrombosis was published. The score classifies patients into risk categories: low (<3 points), moderate (3–5 points) and high (>5 points). The low-risk result of the score combined with D-dimer level could potentially exclude cerebral vein thrombosis. The main aim of our study was to assess utility of the score in a group of patients with confirmed cerebral vein thrombosis in a real-world setting. Methods: A retrospective assessment of patients with a confirmed diagnosis of cerebral vein thrombosis admitted to a department of neurology was performed. Data on patients’ demographics and medical history, including the components of the score, were collected. Based on the inclusion criteria from the original publication, the number of patients eligible and ineligible for using the score was calculated. Next, the patients were assessed with the score. Results: Thirty-seven patients with newly diagnosed cerebral vein thrombosis were included. Twenty-three (62%) were eligible according to the inclusion criteria of the original study. The sensitivity of the score alone for this group was 52% at a cutoff of three points, and in combination with D-dimer level it was 92%. Two patients were classified as low-risk according to the score and had low D-dimer level. In the remaining symptomatic patients, the score had a sensitivity of 44% without D-dimer testing, and 89% with D-dimer. D-dimer level alone had a sensitivity of 87% and 67%, respectively. Conclusions: The score in combination with D-dimer level had higher sensitivity than D-dimer testing alone. However, the score combined with D-dimer level could not exclude cerebral vein thrombosis in the low-risk patients.

Brain Sciences doi: 10.3390/brainsci16111202

Authors: Xubin Guo Haochuan Yang Qingquan Liu Cheng Lu Taolei Zhang

Background: Previous research on psychosocial interventions for children and adolescents with attention-deficit/hyperactivity disorder (ADHD) has primarily focused on overall symptom severity, with less attention to treatment effects across core symptom dimensions. This systematic review and meta-analysis evaluated the effects of cognitive behavioral interventions on overall ADHD symptoms, inattention, and hyperactivity/impulsivity and explored the influence of intervention type, treatment duration, and weekly session frequency. Methods: PubMed, Web of Science Core Collection, Embase, and CENTRAL were searched from inception to 30 June 2026 for randomized controlled trials. Risk of bias was assessed using RoB 2. Effect sizes were calculated as Hedges’ g and pooled using random-effects models, with sensitivity and exploratory subgroup analyses conducted. The review was registered in PROSPERO (CRD420261376097). Results: Ten randomized controlled trials involving 849 participants were included. Cognitive behavioral interventions significantly reduced overall ADHD symptoms (g = −0.389, 95% CI −0.773 to −0.005), inattention (g = −0.415, 95% CI −0.749 to −0.082), and hyperactivity/impulsivity (g = −0.366, 95% CI −0.658 to −0.075). Inattention showed the numerically largest pooled effect. Exploratory subgroup analyses showed numerical differences across intervention type, treatment duration, and weekly session frequency, but formal moderator tests found no statistically significant between-subgroup differences. Conclusions: These findings support the potential benefits of cognitive behavioral interventions for ADHD symptom management, with the most consistent results observed for inattention. Future randomized controlled trials should compare intervention components and treatment schedules while assessing actual treatment exposure, including home practice, to inform more targeted cognitive behavioral interventions.

Brain Sciences doi: 10.3390/brainsci16111201

Authors: Peter Walla

For over a century, affective neuroscience has labored under an intractable epistemological crisis: what, precisely, is an emotion [...]

Brain Sciences doi: 10.3390/brainsci16111200

Authors: Isah Salim Ahmad Tian Yu Qiang Zhang Xingyang Wu Zhao Liao Hekai Wang Xia Zhao Bixia Yuan Rongbo Lin Cailei Zhao Jianxiang Liao Benqing Wu Haifeng Wang Zhanqi Hu

Objective: To evaluate brain microstructural alterations in children with tuberous sclerosis complex (TSC) using neurite orientation dispersion and density imaging (NODDI) and to investigate associations between NODDI parameters and clinical phenotypes including epilepsy, early-onset epilepsy, infantile epileptic spasms, status epilepticus, and drug-resistant epilepsy. Methods: This prospective cross-sectional study enrolled 68 children with TSC and 39 healthy controls (sex-matched; the groups differed significantly in age, which was adjusted for in all analyses, with spline modeling and pediatric-range sensitivity analyses) who underwent multi-shell diffusion MRI. NODDI parameters neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (FISO) were computed. Group differences were assessed using Mann–Whitney U tests, with additional analyses adjusting for age. Logistic regression examined associations between NODDI parameters and clinical variables. Receiver operating characteristic analysis evaluated discriminative performance within the derivation cohort, with bootstrap and cross-validated internal validation. Results: The TSC group demonstrated significantly reduced whole-brain NDI, ODI, and FISO compared to controls after adjusting for age (all p ≤ 0.001). TSC patients with epilepsy showed significantly lower NDI (p < 0.001), ODI (p = 0.001), and FISO (p = 0.003) versus controls, whereas patients without epilepsy showed no significant differences. Early-onset epilepsy and infantile epileptic spasms were associated with marked NDI reductions (16.7% and 19.0%, respectively; p < 0.001). In a parsimonious model, NDI was associated with epilepsy (p = 0.008; bootstrap-corrected AUC 0.712); in an exploratory multivariable model, NDI (p = 0.008) and ODI (p = 0.035) were associated with epilepsy after adjustment. NDI achieved an AUC of 0.739 (95% CI 0.617–0.861) with 65.5% sensitivity and 78.8% specificity at a cutoff of 0.095, reflecting discrimination within the derivation cohort. Conclusions: NODDI sensitively detects widespread brain microstructural alterations in children with TSC. NDI, and to a lesser extent ODI after adjustment, show significant associations with epilepsy and may serve as quantitative imaging markers of epilepsy-associated microstructural burden; however, the cross-sectional design cannot establish whether these alterations are caused by epilepsy or reflect the underlying TSC disease process, and whether they predict future epilepsy onset or outcome requires longitudinal, externally validated studies. The significant age difference between groups, which statistical adjustment cannot fully resolve, is a key limitation. NODDI is best viewed as one component of a multimodal biomarker framework that also incorporates molecular, immune and electrophysiological measures.

Brain Sciences doi: 10.3390/brainsci16111199

Authors: Michael A. Tollefsrud Matthew G. Wisniewski

Background/Objectives: Misophonia is characterized by disproportionate emotional and physiological responses to specific “trigger” sounds, often accompanied by self-reported difficulty maintaining focus. Here, we seek to provide objective evidence of such cognitive disruptions by combining behavioral measures of auditory working memory with electroencephalographic (EEG) indices of neural processing. Methods: Fifty-five participants (23 misophonic, 32 control) completed a pitch-matching working memory task under three distractor conditions: individualized trigger sounds, neutral sounds, and silence. EEG was analyzed using a time-frequency approach to assess alpha (8–12 Hz) oscillatory activity during working memory retention at the source level; this was carried out using Independent Component Analysis (ICA). Results: Behaviorally, misophonic participants exhibited reduced overall working memory performance compared to controls, with no difference between neutral and trigger conditions, suggesting a general deficit in distractor inhibition. In exploratory analyses, EEG results showed lower alpha power across all conditions in the misophonia group, consistent with diminished ability to inhibit sound processing rather than trigger-specific effects. This lower alpha appeared to occur for sources in parietal and somatomotor areas, with group differences becoming apparent via alpha suppression around distractor onset. Conclusions: The results are consistent with claims made in the literature that misophonics show impaired attentional control and motor regulation, but conflict with findings that suggest that these issues are specific to triggers.

Brain Sciences doi: 10.3390/brainsci16111198

Authors: Emir Begagić Mirza Pojskić Hakija Bečulić Kenan Arnautović

Background/Objectives: Postoperative superior sagittal sinus thrombosis (SSST) is an uncommon neurosurgical complication with variable clinical severity. This scoping review summarized its frequency, mechanisms, clinical presentation, management, and outcomes. Methods: MEDLINE/PubMed, Scopus, Web of Science Core Collection, and Google Scholar were searched up to 11 May 2026. Original studies reporting postoperative SSST were included and synthesized descriptively. Results: Twenty-four studies comprising 1084 patients were included, with 79 postoperative SSST cases with confirmed or extractable SSS involvement. Among studies with operative denominators, SSST frequency ranged from 0.8% to 10.0%. Reported mechanisms included local sinus injury or manipulation, cerebrospinal fluid loss or diversion, infectious/inflammatory conditions, and systemic prothrombotic factors. Clinical presentation ranged from incidental thrombosis to neurological deterioration with edema, venous infarction, or hemorrhage. Management included observation, anticoagulation, and, in selected severe cases, surgical or endovascular treatment. In small, heterogeneous cohorts with SSST-specific outcomes, mortality ranged from 0% to 33.3% and should be interpreted as a descriptive, not pooled, estimate. Conclusions: Postoperative SSST is heterogeneous in mechanism and severity. Current evidence is predominantly retrospective and case-based, limiting firm treatment recommendations.

Brain Sciences doi: 10.3390/brainsci16111197

Authors: Helena Q. Saven Adrian Raine Olivia Choy Andrea L. Glenn Robert Schug

Background. Brain imaging research on psychopathy and other clinical conditions has largely focused on identifying risk factors, with virtually no research on neural protective influences. Increased striatal volume has been identified as a risk factor for adult psychopathy, but possible protective influences have not been considered. We addressed this gap by using a trichotomization analytic framework in two independent samples to examine both protective and risk effects of striatal subregional volumes on psychopathic personality. Methods. Study 1 consisted of 119 male and female participants and Study 2 consisted of 87 male and female participants, all recruited from temporary employment agencies. In both studies participants were administered a structural MRI to evaluate striatal subregional volumes and psychopathy was assessed using the Psychopathy Checklist—Revised. Results. Study 1 established that low volume of the caudate acted as a putative protective factor for psychopathy. Study 2, which allowed for the differentiation of the caudate into the head and body, showed that putative protective effects for the caudate were found for the body of the caudate but not the head. No evidence was found for high caudate volume acting as a risk factor. Conclusions. Findings highlight the importance of differentiating protective versus risk factors in neurobiological research on psychopathy. It is recommended that future brain imaging research on clinical disorders conduct follow-up analyses based on the trichotomization approach to further probe whether a functional or structural abnormality represents either a protective factor or a risk factor.

Brain Sciences doi: 10.3390/brainsci16111196

Authors: Egemen Mancı Erdem Uylas Fırat Özdalyan Merve Demir Benli Emre Eskicioğlu Çağdaş Güdücü Erkan Günay Cem Şeref Bediz

Objectives: This three-wave longitudinal study examined intra-seasonal cognitive trajectories across a competitive basketball season in youth basketball players and age-comparable non-athlete controls. Methods: Ninety-one youth basketball players (U12, U14, U16) and 30 non-athlete controls completed computerized cognitive assessments at pre-season, mid-season, and post-season. Visuospatial attention (Change Detection Test [CDT]), motion anticipation (Timewall Test), and inhibitory control with processing speed (Flanker Task) were evaluated under standardized laboratory conditions. Primary athlete-control analyses combined the U12 and U14 cohorts (~U13), whereas U16 analyses were exploratory and included basketball players only because no age-comparable U16 control group was available. Results: Basketball players and non-athlete controls showed small, nominally significant differences in competitive seasonal change in visual attention and change-detection ability (p = 0.046, η2 = 0.017) and response time (p = 0.020, η2 = 0.025). Basketball players also showed within-season improvements in temporal estimation and motion anticipation (p < 0.001). Processing speed improved similarly in both groups, with no significant Time × Group interaction (p = 0.92), whereas Flanker accuracy (p = 0.40) and interference control (p = 0.82) showed no significant differential seasonal change. Exploratory U16 analyses showed no significant seasonal changes across the assessed cognitive domains (all p > 0.05). Conclusions: Cognitive performance changed selectively across the competitive season. Differences between basketball players and non-athlete controls were most evident in the seasonal pattern of change-detection performance. At the same time, basketball players also showed within-group improvements in temporal estimation and motion anticipation. Processing speed improved in both groups. Overall, the findings indicate domain-specific longitudinal cognitive changes but do not establish basketball-specific causal effects.

Brain Sciences doi: 10.3390/brainsci16111195

Authors: Ozan Deniz Guven Asim Armagan Aydin

Background/Objectives: Diffuse gliomas can reach grade 4 disease through markedly different temporal trajectories, yet prognosis after transformation is generally assessed from the characteristics of the transformed tumor itself. Whether the duration of the preceding disease course retains prognostic information after grade 4 transformation remains incompletely understood. Methods: We conducted a retrospective cohort study of patients with an antecedent WHO grade 2 or 3 diffuse glioma who subsequently underwent histopathologically confirmed grade 4 transformation. Transformation interval was defined as the time between the antecedent diagnosis and grade 4 transformation and was modelled continuously per 12-month increments. The primary endpoint was overall survival (OS) from transformation; progression-free survival (PFS) was secondary. Multivariable Cox models were adjusted for age, Eastern Cooperative Oncology Group performance status, antecedent grade and IDH status. Functional form, molecular context, landmark robustness and incremental prognostic information were additionally examined. Results: Fifty-one patients were included; 33 (64.7%) had antecedent grade 2 and 18 (35.3%) grade 3 disease. Median transformation interval was 51.6 months. Median post-transformation OS and PFS were 20.9 and 14.1 months, respectively. Each additional 12 months before grade 4 transformation was associated with lower mortality in univariable analysis (hazard ratio [HR], 0.845; 95% CI, 0.755–0.946; p = 0.003) and remained independently associated with OS after multivariable adjustment (HR, 0.858; 95% CI, 0.748–0.983; p = 0.028). No evidence of nonlinearity was observed (p = 0.407). The corresponding association with PFS was weaker and not statistically significant (adjusted HR, 0.943; 95% CI, 0.840–1.060; p = 0.327). Exploratory interaction analysis indicated that the inverse transformation interval–OS association was concentrated in IDH-mutant tumours (adjusted HR per 12 months, 0.758; 95% CI, 0.630–0.912), whereas no significant inverse association was demonstrated in IDH-wildtype tumours (adjusted HR, 1.225; 95% CI, 0.923–1.626; interaction p = 0.007). Adding transformation interval improved overall model fit but did not materially improve optimism-corrected discrimination. Conclusions: In this retrospective, single-centre cohort, a longer transformation interval was associated with improved post-transformation OS after adjustment for selected clinical and molecular factors, whereas the association with PFS remained inconclusive. The exploratory IDH interaction and the absence of meaningful improvement in optimism-corrected discrimination warrant cautious interpretation. These findings are hypothesis-generating and require validation in larger, molecularly defined longitudinal cohorts before clinical prognostic utility can be established.

Brain Sciences doi: 10.3390/brainsci16111194

Authors: Teng Xue Qian Liu Tao Jiang Yuxin Qi Yifan Lu Dingding Yang Yan Zhao Xueyan Jia Anan Li Hui Gong Shengxi Wu

Background: Shank3 knockout (KO) mice recapitulate core autism spectrum disorder (ASD)-like behaviors and are widely regarded as a reliable model for autism. Although dysfunction of GABAergic neurons is closely associated with ASD-like phenotypes, it remains unclear how Shank3 deficiency leads to whole-brain structural remodeling of GABAergic neurons. Furthermore, there is currently a lack of systematic methodologies for the comprehensive statistical analysis of GABAergic neurons across the entire brain. Methods: By combining rAAV/B10-mGAD65-EGFP virus labeling with fluorescence Micro-Optical Sectioning Tomography (fMOST), we constructed a mesoscopic whole-brain atlas of GABAergic neurons in Shank3 KO mice, enabling systematic quantification of soma numbers and comprehensive morphological profiling across multiple brain regions. Results: We systematically analyzed soma counts and morphology across multiple brain regions in Shank3 KO and WT mice. Soma counts did not differ significantly between the two groups in any of the analyzed brain regions. However, morphological changes were region-specific, exhibiting increased neurite complexity in the anterior cingulate cortex (ACC) and entorhinal cortex (ENT), but reduced neurite complexity in the retrosplenial cortex (RSP). Conclusions: Viral-fMOST enables whole-brain quantification of GABAergic neurons and provides a reference for imaging other neuronal subtypes. In Shank3 KO mice, neurite changes reveal a mesoscopic map of GABAergic alterations relevant to ASD research.

Brain Sciences doi: 10.3390/brainsci16111193

Authors: Mohamed Hesham Khalil

Background/Objectives: Time spent in unchanging environments is associated with poorer brain, cognitive and mental health outcomes, while environmental enrichment for humans is measured by how much nature is present rather than how it changes. Methods: This study quantified nature’s changing visual complexity using a large-language-model scoring method validated against a deep-learning complexity metric previously tested using event-related potentials. Photos were taken of a natural scene, a tree, and the sky across minutes, days, and seasons (1115 photographs; 2024 to 2026). Results: The analysis identified seven quantitative properties describing nature’s dynamic environmental enrichment in changing visual complexity: Dichotomy, Inclination, Unpredictability, Renewal, Net balance, Amplitude, and Level (DIURNAL). A quantitative simulation then showed that a natural view offers more change than indoor and urban views, consistent with the argument that unchanging environments are detrimental to the brain, which is hypothesised here to act through a dopaminergic pathway. Conclusions: DIURNAL raises questions for biophilic design and for how neurotypical and neurodivergent brains respond to change in visual complexity in nature, digital environments and built environments.

Brain Sciences doi: 10.3390/brainsci16111192

Authors: Jiawei Zhang Yanjiao Zhai Yuefei Li Yonggang Fan Jianwei Li Jie Guo Qiong Tang Tianwei Sun Xin Jin

Background: Ependymal cells are located around the central canal of the spinal cord. Although previous studies have suggested that certain ependymal cell subpopulations may contribute to astroglial scar formation following spinal cord injury (SCI), their potential involvement in post-injury inflammatory responses remains incompletely understood. Methods: In this study, single-cell RNA sequencing (scRNA-seq) identified an inflammation-associated ependymal cell subpopulation characterized by elevated expression of multiple inflammatory genes. Results: Receptor–ligand interaction analysis further predicted enhanced ligand–receptor interactions between ependymal cells and monocytes, particularly through the Thbs1-Sdc4 and Fn1-Sdc4 signaling axes at 1 day post-injury (dpi). Conclusions: These findings suggest previously underappreciated heterogeneity within ependymal cells and imply that specific subpopulations may participate in the neuroinflammatory microenvironment after SCI. Moreover, the Thbs1-Sdc4 and Fn1-Sdc4 pathways may represent potential targets for future immunomodulatory strategies following spinal cord injury.

Brain Sciences doi: 10.3390/brainsci16111191

Authors: Syed Murtoza Mushrul Pasha Shahidur Rahoman Sohag Hossny Ghanem

Background: Deep learning classifiers trained on structural magnetic resonance imaging (MRI) are increasingly proposed for early detection of Alzheimer’s disease (AD) and mild cognitive impairment (MCI), yet the pipelines that produce these models depend on shared datasets, pre-trained weights, and federated updates that an adversary can poison. A backdoored diagnostic model behaves correctly on ordinary scans but collapses to an attacker-chosen label whenever a hidden trigger is present, which turns a prognostic instrument for cognitive aging into a silent source of misdiagnosis. Methods: This article proposes MedBackdoorGuard, a defense framework that detects and mitigates backdoor attacks in MRI-based AD and MCI classifiers without prior knowledge of the trigger. The framework couples spectral latent screening of training data with latent trigger isolation in activation space, then immunizes the model through trigger-sensitive neuron pruning and fine-tuning under an anatomical attention consistency constraint that anchors the decision on medial temporal structures. A runtime inference guard adds superimposition entropy and anatomically informed reconstruction to purify suspicious scans at deployment. Results: Across ADNI, OASIS-1, and a public four-class dementia MRI benchmark under patch, blended, warping, and frequency triggers, MedBackdoorGuard reduces the mean attack success rate from 96.4% to 3.0% while holding clean accuracy within 0.6 percentage points of the undefended model, reaches a poisoned-sample detection AUROC of 97.4%, and identifies 59 of 60 backdoored models. Compared with the strongest defense baseline, attack success rate falls by 15.1 percentage points and clean accuracy rises by 1.7 percentage points. Conclusions: The framework restores MCI recall on triggered scans from 3.9% to 88.3%, which is the outcome that matters for early detection in cognitive aging.

Brain Sciences doi: 10.3390/brainsci16111190

Authors: Rongxiang Liang Bo Wang Zhiwei Ke Song Wang

Impaired brain energy metabolism is an early pathological hallmark of Alzheimer’s disease (AD) and persists throughout disease progression. Regular physical exercise has been shown to restore energy homeostasis and improve cognitive function. However, advanced age, frailty, and multiple comorbidities substantially often limit the ability of patients to engage in sufficient physical activity. These limitations underscore the need for alternative approaches capable of reproducing the systemic benefits of exercise. Consequently, exercise mimetics, a class of bioactive compounds that reproduce these benefits, have attracted growing attention. This review examines how exercise mimetics ameliorate AD-associated pathologies by modulating energy metabolism. Particular emphasis is placed on specific mechanisms, including irisin and metformin, and the molecular pathways through which they regulate energy homeostasis and confer neuroprotective effects.

Brain Sciences doi: 10.3390/brainsci16111189

Authors: Caroline Hallal Anthony Kassab Marc Louak Youssef El Toum Lynn Abi Khalil Faysal Zahran Elina Dirani Rami Bou Khalil

Background: Attention-deficit/hyperactivity disorder (ADHD)-related symptoms overlap with bipolar presentations, but associations between individual ADHD-related symptom dimensions and suicidality remain uncertain. Methods: In this exploratory cross-sectional study, adults previously hospitalized for bipolar disorder at Hôtel-Dieu de France, Beirut, between 2017 and 2025 completed a post-discharge online survey. Retrospective childhood ADHD-related symptoms were screened using the Wender Utah Rating Scale-25 (WURS-25), current adult ADHD symptoms using the Adult ADHD Self-Report Scale (ASRS), and suicidality using the P4 screener and reported previous suicidal behavior. Neither the interval since discharge nor current mood state was systematically assessed. Results: Forty-nine participants completed the survey (mean age 35.9 ± 11.9 years; 71.4% women). The composite suicidality outcome was present in 73.5%; 34.7% had a positive WURS-25 screen and 22.4% a positive ASRS Part A screen. Categorical ADHD screening positivity was not significantly associated with suicidality. Participants with suicidality were younger and more frequently reported increased alcohol or substance use since hospitalization. In exploratory age-adjusted models, the associations involving inattentiveness and impulsivity varied with the included WURS-25 subdimensions: higher inattentiveness scores were associated with lower odds of suicidality, whereas higher impulsivity scores were associated with higher odds when the negative mood subdimension was excluded. Conclusions: These preliminary findings highlight the potential clinical relevance of examining individual ADHD-related symptom dimensions alongside categorical screening results when investigating suicidality in bipolar disorder. However, the observed associations between retrospective ADHD-related symptom dimensions and suicidality in this small bipolar disorder sample were exploratory and sensitive to model specification. They require replication with larger samples, diagnostic ADHD assessment, and concurrent mood-state measurement.

Brain Sciences doi: 10.3390/brainsci16111188

Authors: Gabriel Mendes Costa Áquilla Henrique Gonçalves Teixeira Therency Kamila dos Santos

Background/Objectives: Diffuse glioma surgery requires balancing tumor removal, brain function, and the patient’s priorities. We propose a patient-oriented, resource-adaptive framework and a testable hypothesis about postoperative functional recovery. Methods: A targeted narrative synthesis informed three domains: network characterization, patient priorities, and therapeutic decision. A graph model compares connected resections within clinically selected corridors. It separates modeled tumor-target volume, direct functional cost, structural disruption, and residual connectivity. Results: The framework relates the lesion and baseline function to activities valued by the patient, the consequences of losing them, and acceptable operative boundaries. An exploratory classification combines functional importance with radiological evidence of tract involvement. Indispensable connections remain protected. Trajectory intersections with the proposed resection or access corridor determine connection loss, including fibers of passage and partial bundle interruption. Maximum flow then audits the remaining structural capacity between protected pairs. A fully specified synthetic example shows how spatial injury, patient priorities, and connectivity requirements change the selected plan. We hypothesize that the resulting measures add prognostic information beyond conventional predictors. Topological compensation is a possible mechanism, and IDH status is an exploratory modifier. Conclusions: The framework provides a transparent way to document priorities and compare plans under uncertainty. Its classification, input estimates, and clinical predictions require validation. Services without the necessary individual network data can use the clinical framework to document uncertainty and adapt objectives or referrals.

Brain Sciences doi: 10.3390/brainsci16111187

Authors: Vincens Kälin Arieta Pinto Berisha Alexis Paul Romain Terrapon Anna-Maria Zeitlberger Lauren Wiebe Oliver Bozinov Marian Christoph Neidert Isabel Charlotte Hostettler

Background/Objectives: Unruptured intracranial aneurysms (UIAs) affect 2.3–6.6% of the population. Traditional complication classification systems focus solely on therapeutic interventions, underweighting the burden of neurological deficits in neurovascular patients. This study applied the multidimensional Therapy-Disability-Neurology (TDN) grade to a consecutive cohort of patients treated for UIA in order to characterize the distribution, severity and clinical correlates of adverse events (AEs); the comparison between treatment modalities was a secondary, exploratory objective. Methods: We retrospectively analyzed 296 patients treated for UIA between 2016 and 2025 (microsurgical treatment n = 135, 45.6%; endovascular treatment n = 161, 54.4%). The TDN grade, a three-domain assessment incorporating the therapeutic resources required to treat an AE, functional disability and neurological deficits, was assigned for all AEs occurring during the index hospitalization. AEs were defined as any deviation from the expected post-treatment course, including minor events not usually reported as complications. The primary endpoint was the TDN grade; secondary endpoints included individual AE categories, severe AEs (TDN ≥ 4), functional outcome and length of stay. Results: AEs occurred in 89 patients (30.1%); 37 patients (12.5%) were graded TDN 1 or 2 and 52 (17.6%) TDN 3 to 5, the range corresponding to morbidity as conventionally reported. Four patients (1.4%) died during the index hospitalization or within 30 days of treatment. Median TDN grades were 0 in both groups (microsurgical IQR 0–2; endovascular IQR 0–1; and p = 0.575). The spectrum of AE categories differed between treatment modalities. The TDN grade correlated with GOSE and KPS at discharge and with length of hospital stay (all p < 0.001); length of stay was explained better by the three subgrades together than by the therapy subgrade alone (R2 0.18 vs. 0.13). Treatment modality was not associated with the TDN grade in unadjusted analysis; exploratory adjusted associations with any AE depended on model specification, and no association was found for severe AEs. Conclusions: In this cohort treated for UIA, the TDN grade captured the clinical severity of AEs and may serve as a component of multidimensional outcome assessment in future prospective studies, provided its domains are defined a priori.

Brain Sciences doi: 10.3390/brainsci16111186

Authors: Selim Polat Şengül Kocamer Şahin Ali Emre Hepsağ Esra Aybal Nurdan Ünlü Antonio M. Esquinas

Background/Objectives: Psychological symptoms are common after intensive care. Early distress, dissociation, and disturbing ICU memories may contribute to later post-traumatic stress symptoms. This prospective observational study examined these relationships in adult ICU patients. Methods: Peritraumatic distress, dissociation, anxiety, depression, and ICU memories were assessed during the ICU stay. PTSD symptoms and HADS scores were assessed one month later. Sixty-eight patients were enrolled. Thirteen died before follow-up and two could not be reached. Follow-up data were available for 53 patients. Result: The mean one-month PCL-5 score was 16.1 ± 11.4. No participant reached the selected PCL-5 screening threshold of 47; this does not exclude clinical PTSD. Higher baseline PDI scores were associated with higher PCL-5 scores (r = 0.288, p = 0.037). Delusional ICU memories were also associated with higher PCL-5 scores (r = 0.326, p = 0.018). PDEQ scores were not significantly associated with PCL-5 scores. In the combined regression model, PDI, PDEQ, and delusional memories explained 17.1% of the variance in one-month PCL-5 scores (R2 = 0.171, p = 0.028). No individual predictor was significant in the primary three-predictor model. In a post hoc exploratory model additionally adjusting for baseline anxiety and depressive symptoms, PDI (p = 0.012) and delusional ICU memories (p = 0.027) were significant. Thus, the individual associations differed according to model specification. Conclusions: Early peritraumatic distress and delusional ICU memories may provide potentially informative indicators of subsequent post-traumatic stress symptom burden. These model-dependent findings require cautious interpretation and do not establish independent predictive utility.

Brain Sciences doi: 10.3390/brainsci16111185

Authors: Gemma Almario Ainhoa Molina Martín David P. Piñero

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that, in addition to its characteristic cognitive decline, may be associated with impairments in visual and oculomotor function. The aim of this study was to characterize and compare a battery of visual, binocular, and oculomotor skills in patients with moderate AD and age-comparable older adults without a known diagnosis of cognitive impairment or neurodegenerative disease. Methods: A cross-sectional comparative observational study was conducted in 16 patients with AD and 20 age-comparable controls. Monocular and binocular visual acuity at distance and near, near point of convergence (NPC), stereopsis using the Randot® test, ocular alignment, fixation, and clinical oculomotor function using the NSUCO test were assessed. In a subgroup of patients with AD, an objective assessment was also attempted using GazeLab® video-oculography. Results: No between-group differences in age were observed (p = 0.757). The AD group showed worse binocular distance visual acuity (0.16 ± 0.13 vs. 0.01 ± 0.05 logMAR, p = 0.003), a trend to more remote NPC (16.50 ± 5.35 vs. 10.80 ± 4.56 cm, p = 0.466), poorer stereopsis (188.5 ± 64.14 vs. 80.00 ± 24.48 arcseconds, p = 0.004), and lower NSUCO scores for saccadic and pursuit movements (p < 0.001). Video-oculography was feasible in a subgroup of patients with AD and yielded exploratory, descriptive observations; equivalent recordings were not obtained in control participants. Conclusions: The patients with moderate AD showed poorer performance across several visual, binocular, and oculomotor measures. These findings support the relevance of incorporating visual assessment into the functional characterization of AD.

Brain Sciences doi: 10.3390/brainsci16111184

Authors: Adela G. Buciuc Mark S. Gold Brian Fuehrlein

Substance use disorders remain a leading cause of preventable death, and existing care is better described as disease management than as cure. Medications for opioid, alcohol, and tobacco use disorders reduce substance use, and opioid agonist treatment reduces mortality, yet retention is poor and functional recovery is rarely measured. This review asks whether psychedelics treat addiction, or temporarily create a brain state in which treatment, learning, and recovery work differently. By evaluating each pharmacologically unique compound individually, we align cellular mechanisms, animal studies and human trial data across the full spectrum of substance use disorders. Relapse prevention is not a single construct: conditioned place preference, operant reinstatement, extinction learning, and clinical abstinence index different processes, and agreement at one level does not imply agreement at another. Translational concordance is therefore indication- and compound-specific rather than a class property, with the strongest human signals for psilocybin in tobacco and alcohol use disorders, though even the alcohol signal rests on two small randomized trials with discordant results. Risk is compound-specific too: ibogaine is gated by cardiotoxicity, and ketamine carries reinforcing properties and organ toxicity of its own. Plasticity is an opportunity, not an outcome.

Brain Sciences doi: 10.3390/brainsci16111183

Authors: Agnieszka Wosiak Emilia Stodulska Katarzyna Żykwińska

Background: Cognitive workload classification from electroencephalography is affected by interindividual variability in EEG signals and subjective workload responses. We propose participant-specific adaptive label smoothing, in which the change in perceived workload between resting and task conditions controls the target confidence, while the experimental class remains unchanged. Methods: The method was evaluated on the STEW dataset and compared with five alternative supervision strategies. Two classification models were used: a feature-based convolutional neural network and a multi-scale Swin Transformer network (MST-Net) operating on time-frequency representations. Global and participant-specific stratified normalization were evaluated using participant-disjoint cross-validation. The participant-specific approach used normalization statistics estimated from each unseen participant’s own unlabeled EEG data. Results: Under stratified normalization, adaptive label smoothing produced the highest macro F1 for both models, with values of 0.768 and 0.796, and ROC AUC values of 0.844 and 0.878, respectively. It also maintained high recall for both classes. Conclusions: The findings suggest that participant-specific subjective workload responses can be used to modulate target confidence, with the most consistent benefit observed under participant-specific normalization. As the strategies differ in target definitions and no hard rest/task or fixed label-smoothing control was evaluated, the differences are descriptive.

Brain Sciences doi: 10.3390/brainsci16111182

Authors: Xiaoying Huang Binyue Gao Yoshimichi Ejima Yinghua Yu Jinglong Wu Jiajia Yang

Background/Objectives: Surrounding stimuli affect the visual processing of a target; however, whether this effect varies across stimulus types when peripheral targets do not need to be actively discriminated remains unclear. Methods: We recorded EEG activity from 20 participants during a central color judgment task while they viewed peripheral Gabor patterns, vertical stripes, letters, and numbers that were irrelevant to the task. Flankers appeared 1000 ms before targets in the flanked condition, providing an existing visual background. In the unflanked condition, only the fixation point was present before target onset. We compared event-related potentials (ERPs) and beta power between these conditions. Results: A spatiotemporal cluster permutation test revealed a significant interaction between stimulus type and flanker condition in the ERP results, with a cluster spanning 146–252 ms after target onset. Further comparisons revealed that flanker effects on ERP amplitude differed between Gabor patterns and vertical stripes. Within each stimulus condition, ERP changes were observed over different time ranges and scalp locations. Beta power was lower in the flanked condition for Gabor patterns, vertical stripes, and numbers, but no significant interaction was detected for beta power. Central color judgment responses were faster in the flanked condition, whereas accuracy did not differ significantly between conditions. Conclusions: These findings suggest that an existing flanker background can affect EEG responses after target onset without active discrimination of peripheral targets. Differences in flanker effects across stimulus types were supported by the ERP results, while beta power provided additional evidence of changes within stimulus conditions.

Brain Sciences doi: 10.3390/brainsci16111179

Authors: Lingling Shen Huaqing Chen Chuhuai Wang

Objectives: Long-term physical activity patterns may be associated with cognition through distinct mechanisms, yet direct comparisons between accumulated moderate-to-vigorous exercise and daily ambulatory activity remain scarce. This study aimed to examine whether regular exercise time and daily step count show distinct patterns of association with executive function and cortical functional connectivity in healthy young adults, and to characterize the extent to which the two activity indices overlap. Methods: In this cross-sectional study, 48 healthy young adults were stratified by their physical activity over the preceding six months into high versus low regular exercise time groups (cut-off: ≥150 min/week) and high- versus low-daily-step-count groups (cut-off: ≥10,000 steps/day). All participants completed the Stroop task to assess response inhibition and information processing speed, while 63-channel functional near-infrared spectroscopy (fNIRS) was used to monitor cortical functional connectivity. Results: A high regular exercise time (≥150 min/week) was associated with a higher incongruent-to-congruent accuracy ratio in the word test of the Stroop task (t = 2.318, p = 0.0250, η2 = 0.1046), which is consistent with reduced Stroop interference; this association was not accompanied by differences in cortical functional connectivity. Conversely, a high daily step count (≥10,000 steps/day) was associated with shorter reaction time in the Stroop word test (t = 2.048, p = 0.0463, η2 = 0.0836) and with higher connectivity across the sampled cortical regions (HbO: t = 2.104, p = 0.0409, η2 = 0.0878; HbR: t = 2.431, p = 0.0190, η2 = 0.1139), including stronger left precentral–right occipital connectivity at the HbO level (t = 4.837, FDR-corrected q = 0.0295) and right parietal–left inferior frontal connectivity at the HbR level (t = 4.983, FDR-corrected q = 0.0181). Regular exercise time correlated specifically with the word-test accuracy ratio (Spearman ρ = 0.337, p = 0.019), whereas no significant correlations were found between daily step count-related behavioral and brain activity measures. Conclusions: In this cross-sectional sample, physical activity was associated with cognitive performance in a pattern-specific manner: regular exercise was associated primarily with response inhibition, whereas daily walking was associated primarily with processing speed, with the latter accompanied by more extensive connectivity across the sampled cortical regions. These associations are compatible with, but do not demonstrate, dissociable neural mechanisms and should be tested in longitudinal and intervention designs.

Brain Sciences doi: 10.3390/brainsci16111180

Authors: Riley McNaboe Kona Glenn Youngsun Kong Jeffrey Bolkhovsky Ki Chon Hugo Posada-Quintero

Background/Objectives: Acute sleep deprivation impairs cognitive performance in safety-critical occupations, highlighting a demand for effective countermeasures. Transcranial direct current stimulation (tDCS) has been explored as an alternative noninvasive neuromodulatory approach to mitigating performance decline. Groups have also capitalized on the ability of biosignals like heart rate variability (HRV) to continuously track performance decline during extended wakefulness, but whether fatigue interventions like tDCS shift the autonomic measures used in such tracking during sleep deprivation remains unknown. This study examined whether tDCS affects autonomic function and cognitive performance during sleep deprivation. Methods: Nineteen participants underwent 26 h of continuous wakefulness with repeated cognitive assessments and electrocardiogram monitoring. After 19 h awake, participants received 30 min of verum (n = 10) or sham (n = 9) tDCS targeting the right dorsolateral prefrontal cortex in a double-blind design. Performance and HRV were analyzed with linear mixed-effects models with false discovery rate correction, including 5 min windowed analyses of the Multi-Attribute Task Battery-II (MATB). Results: Stimulation had no significant main effect on any cognitive performance or HRV outcome. Exploratory analyses revealed stimulation × window interactions within the MATB for system monitoring reaction time, resource management performance, and absolute high-frequency HRV power. Verum participants reported lower sleepiness at a single post-stimulation round without a corresponding performance benefit. Conclusions: In this exploratory sample, a single tDCS session produced no detectable group-level effects on cognitive performance or HRV, and apart from one exploratory within-task interaction, no systematic stimulation-related shift in autonomic measures was observed. Effect size estimates and exploratory findings within tasks provide a basis for adequately powered studies examining individual variability in tDCS response.

Brain Sciences doi: 10.3390/brainsci16111181

Authors: Misuzu Oishi Kei Sasaki Noriko Sakurai Ryo Kawamura Naoki Kodama

Background: Autonomous sensory meridian response (ASMR) is a pleasant tingling sensation elicited by specific sensory stimuli. Neuroimaging studies of ASMR have mainly involved young adults. This study explored whether the functional connectivity difference between ASMR trigger and white-noise listening differed between older and young adults. Methods: Thirty young and 34 older adults underwent functional magnetic resonance imaging while listening to a single auditory ASMR trigger and white noise. Seed-to-voxel connectivity was analyzed for 32 seeds, and the ASMR-minus-white-noise contrasts were directly compared between age groups. Results: The direct age-group comparison revealed no significant difference after correction for multiple comparisons, including among participants reporting ASMR-related tingling. Within-group analyses identified condition-related differences in specific connections: medial prefrontal–right lateral parietal connectivity was greater during ASMR than white-noise listening in older adults, whereas left anterior insula–left supramarginal gyrus connectivity was lower during ASMR than white-noise listening in young adults. No significant association between the ASMR-minus-white-noise functional connectivity contrast and tingling ratings was detected in either age group. Conclusions: No significant age-group difference was detected in the ASMR-minus-white-noise functional connectivity contrast. The within-group findings indicate localized differences between two acoustically dissimilar listening conditions but do not provide evidence of age-specific or ASMR-specific neural responses.

Brain Sciences doi: 10.3390/brainsci16111178

Authors: Shuying Lin Lir-Wan Fan Yi Pang

Encephalopathy of prematurity (EoP), a complex neurodevelopmental disorder encompassing brain injury and dysmaturation in preterm infants, has undergone a major conceptual shift over the past several decades. While early neuropathological studies emphasized focal cystic periventricular leukomalacia (PVL), contemporary cohorts predominantly present with diffuse white matter injury (DWMI). The hallmark features of DWMI include hypomyelination or delayed myelination driven by differentiation failure of oligodendrocyte (OL) lineage cells, accompanied by axonopathy and reactive gliosis. Recent insights have broadened this framework beyond isolated white matter abnormalities, demonstrating widespread dysmaturation of neurons, glia, and neural circuits across both white and gray matter structures. At the cellular and molecular levels, diffuse injury is underpinned by the selective vulnerability of pre-OLs to oxidative stress, excitotoxicity, and proinflammatory cascades, which cause differentiation arrest and persistent hypomyelination rather than progenitor cell depletion. Concurrently, activated microglia and astrocytes interact with these oxidative, excitotoxic, and inflammatory pathways, resulting in the disruption of dendritic arborization, interneuron migration, and synaptic pruning, thereby impairing neural circuit assembly. Consequently, EoP is increasingly conceptualized as a multi-factorial neurodevelopmental disorder shaped by the dynamic interplay among destructive injury, developmental dysmaturation, compensatory neuroplasticity, and endogenous repair. These mechanistic insights provide critical implications for therapeutic development. While conventional neuroprotective and neurorestorative strategies remain essential, targeting inhibitory signaling and extracellular matrix barriers to promote OL differentiation and myelination, while concurrently fostering neural plasticity through multimodal interventions, such as gut–brain axis modulation and environmental enrichment, offers unprecedented opportunities to improve functional outcomes.

Brain Sciences doi: 10.3390/brainsci16111177

Authors: Oswaldo Andrés Bolaños Ladinez Geovanny Gabriel Garcia Cox Paula Olivos Massa Maria Gabriela de la Cruz Novoa Fernando Roosemberg Sérgio Brasil

Objective: To analyze the correlation between the hemodynamic indices of the carotid siphon (CS), the middle cerebral artery (MCA) and the optic nerve sheath diameter (ONSD) among patients with acute brain injuries. Materials and methods: An observational, analytical, and cross-sectional study was conducted. Pulsatility indices (PI) of the CS and MCA were recorded using transcranial Doppler, and ONSD was measured using ocular ultrasound. Pearson’s and Spearman’s correlation coefficients were applied, considering statistical significance at p < 0.005. Results: A total of 75 neurocritical patients were enrolled during 2024. A strong positive correlation was observed between the CS PI and the MCA PI, in both the right (r = 0.643; p < 0.001) and left (r = 0.702; p < 0.001) hemispheres. A weak but significant positive correlation was found between the left CS PI and left ONSD (r = 0.242; p = 0.039). Patients with a PI greater than 1.2 had a larger ONSD than those with a PI of 1.2 or lower (t = −2.29; p = 0.025). The mean difference was approximately 0.44 mm, based on the 95% confidence interval from −0.830 to −0.057. This association was observed only in the left hemisphere and showed a moderate effect size (Cohen’s d = −0.61). Conclusions: In this cohort of neurocritical patients, the carotid siphon pulsatility index showed a strong correlation with the middle cerebral artery pulsatility index, suggesting concordant hemodynamic behavior between both sites of insonation and supporting the potential of the carotid siphon as an alternative for Doppler evaluation when the acoustic window is limited. An optic nerve sheath enlargement may be associated with higher pulsatility index; however, invasive ICP monitoring is needed to evaluate the reliability of this association.

Brain Sciences doi: 10.3390/brainsci16111176

Authors: Sofia Kasradze Rashmi Parajuli Giorgi Lomidze Lasha Epremidze Mukesh Dhamala

Background/Objectives: Precise localization of seizure-onset zones (SOZs) from noninvasive electroencephalography (EEG) remains challenging in the presurgical evaluation of drug-resistant focal epilepsy. We investigated whether cortical source reconstruction combined with multiscale spectral Granger causality (GC) analysis of preictal scalp EEG could identify candidate SOZ regions. Methods: Sixteen participants underwent presurgical evaluation; two were excluded for excessive EEG artifacts, leaving 14 participants (seven resected with Engel class I outcomes and seven unresected). A clinically representative 20 s preictal EEG segment was cleaned using independent component analysis, EEG source solutions were reconstructed with sLORETA on a template head model, and the EEG source activities were then parcellated into 68 Desikan–Killiany cortical regions. Nonparametric GC using Janashia–Lagvilava spectral matrix factorization was estimated in four bands (1–12, 13–30, 30–45, and 55–95 Hz). Regional causal inflow, outflow, and net flow were calculated. Candidate SOZ regions were defined as those exceeding the 95th percentile of absolute net-flow values. Concordance was assessed against clinically determined SOZ localization and, in resected cases, postoperative surgical outcome. Results: Using beta (13–30 Hz) as the primary band, we found that candidate SOZ regions were concordant with clinical localization in 6/7 resected participants (85.7%; exact 95% CI, 42.1–99.6%) and 3/5 scorable prospective participants (60.0%; 14.7–94.7%), yielding 9/12 overall (75.0%; 42.8–94.5%). Two prospective participants lacked sufficient clinical localization for assessment. Three resected participants with left mesial temporal epilepsy showed reproducible left parahippocampal dominance across beta, gamma, and high-gamma bands, with variable entorhinal co-involvement. Top-ranked candidate SOZ regions consistently exhibited net causal inflow. Conclusions: In this small, heterogeneous cohort, source-level net-flow mapping of preictal scalp EEG identified clinically plausible candidate SOZ regions; these exploratory findings suggest a potential noninvasive adjunct to presurgical evaluation. The inflow-dominant pattern supports a receiver-like role of the SOZ. Larger prospective studies with individualized head models, multiple seizures, and intracranial EEG validation will help establish robustness and clinical utility.

Brain Sciences doi: 10.3390/brainsci16111175

Authors: Sadettin Erol Özgür Eken Emir Mert Koçoğlu Mertkan Öncü Mert Arabacı Ratko Pavlović Ilona Mihajlović Nikola Radulović

Background/Objectives: Motor imagery is a widely used mental training method in sport, yet basketball-specific evidence is heterogeneous, and its effects under concurrent cognitive load remain largely unexamined. This study examined the effects of eight weeks of PETTLEP-based motor imagery training on two- and three-point successful shot counts under single-task and cognitive-motor dual-task conditions in adolescent male basketball players. Methods: Thirty male basketball players aged 16–17 years from the youth academy of a single nationally competitive club took part in a randomized controlled, two-arm, parallel-group pretest–posttest trial, registered retrospectively at ClinicalTrials.gov (NCT07798843). Participants were allocated to a motor imagery group (IMG, n = 15) or a control group (CG, n = 15) by computer-based simple randomization. Both groups followed the same routine basketball training; IMG additionally completed three structured imagery sessions per week for eight weeks. Dynamic two- and three-point shooting performance and their dual-task versions (concurrent serial-three subtraction aloud from 100) were assessed before and after the intervention. Data were analyzed with 2 × 2 mixed design repeated measures analyses of variance, and dual-task cost (DTC) was computed at the participant level. Cognitive task accuracy and speed were not recorded. Results: Group × time interactions were significant for two-point single-task (F(1, 28) = 35.44, p < 0.001, ηp2 = 0.559), three-point single-task (F(1, 28) = 11.49, p = 0.002, ηp2 = 0.291) and two-point dual-task performance (F(1, 28) = 30.12, p < 0.001, ηp2 = 0.518), but not for three-point dual-task performance (F(1, 28) = 1.50, p = 0.231, ηp2 = 0.051). Between-group differences in change were 1.33 (95% CI 0.87 to 1.79), 0.87 (0.34 to 1.39), 2.13 (1.34 to 2.93), and 0.47 (−0.31 to 1.25) successful shots per 60 s, respectively. Under dual-task conditions, two-point performance in IMG increased in absolute terms (9.73 to 11.07 successful shots), while its relative DTC did not change significantly (14.60% to 13.13%, p = 0.461); DTC increased in CG (11.93% to 19.41%, p < 0.001), and the between-group difference in DTC change was −8.94 percentage points (95% CI −13.92 to −3.96, p = 0.001). Conclusions: Motor imagery training was associated with greater improvements in successful shot counts under both single-task conditions and the two-point dual-task condition. The between-group difference in relative dual-task cost reflected an increase in performance loss among controls rather than a decrease in the imagery group. Because cognitive task performance was not measured, these findings describe motor performance during a dual-task protocol rather than dual-task ability.

Brain Sciences doi: 10.3390/brainsci16111174

Authors: Sara Kierońska-Siwak Patryk Filipiak Andreas Yannopoulos Dariusz Grzanka

Background/Objectives: Diffusion tensor tractography is used to visualize white matter pathways relevant to neurosurgical planning, but manual ROI-based reconstruction may be operator-dependent. This study assessed the inter-rater and intra-rater reproducibility of a standardized deterministic protocol for reconstruction of the frontal aslant tract (FAT). Methods: Diffusion-weighted MRI datasets from 30 neurologically healthy adults were retrospectively reanalyzed. Three independent raters reconstructed the left and right FAT using the same standardized protocol, with identical predefined ROI locations and fixed tracking parameters; however, each rater independently delineated the ROIs. Reconstructions were repeated after 3 weeks. Spatial agreement was assessed using the Dice similarity coefficient and HD95, while reliability of fractional anisotropy (FA), mean diffusivity (MD), and tract volume were evaluated using intraclass correlation coefficients (ICC). Results: FAT reconstruction was successful in 339 of 360 attempts (94.2%), with a higher success rate for the left than for the right FAT (96.7% vs. 91.7%). Mean inter-rater Dice similarity was 0.74 for the left FAT and 0.69 for the right FAT. Inter-rater reliability was highest for FA (ICC 0.88–0.90), followed by MD (ICC 0.85–0.88) and tract volume (ICC 0.79–0.84). Intra-rater agreement was consistently higher than inter-rater agreement. Conclusions: Standardized deterministic FAT reconstruction demonstrated moderate-to-good reproducibility, although operator-dependent variability remained. These findings provide baseline estimates of procedural reliability and support further evaluation of standardized ROI-based tractography approaches.

Brain Sciences doi: 10.3390/brainsci16111173

Authors: Hongbin Wang Huicong Xu Han Liu Shunqiang An Zhenlu Chen Ai Zhang Qing Zhao Shuai Zhang Guizhi Xu

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder in which over 80% of patients experience severe sleep disorders. Understanding the neural dynamical mechanisms underlying these sleep disturbances is essential for developing targeted therapeutic strategies. Methods: We construct a basal ganglia–thalamocortical–pedunculopontine nucleus (BGTC–PPN) network model by combining Hodgkin–Huxley and Izhikevich neuron models to simulate both healthy and PD network dynamics. We systematically compare the discharge patterns, synchronization indices and power spectral densities of key nuclei between healthy and PD conditions. In addition, we use coherence analysis to characterize the frequency-dependent coupling between the PPN and basal ganglia nuclei, and investigate deep brain stimulation (DBS) modulation effects on the PD network using rectangular-wave stimulation at three target nuclei. Results: Under the PD condition, neuronal activity in the GPi and STN is increased but synchronization in the GPe and PPN is enhanced. β band oscillations are increased, and low-frequency activity in the PPN is disrupted. Coherence analysis reveals frequency-dependent coupling between the PPN and basal ganglia during PD-related network states. Comparison of different DBS targets demonstrates distinct effects. Within our 5-Hz-resolution frequency sweep, STN-DBS broadly suppresses β oscillations and, at approximately 70 Hz, minimizes the deviation of both the δ and β bands from the healthy reference; PPN-DBS enhances δ band activity at low stimulation frequencies or suppresses β synchronization at high frequencies, but these two effects do not co-occur within a single frequency window; GPi-DBS yields a larger increase in δ band power relative to the PD baseline near 55 Hz and suppresses β power in the GPi and PPN, yet the STN β deviation remains elevated across the scanned frequencies. Conclusions: PD-related pathological changes extend beyond motor circuitry and alter BGTC–PPN network dynamics that may be relevant to sleep. The target-dependent and frequency-dependent effects of DBS indicate that STN-DBS at approximately 70 Hz concurrently minimizes the deviation of both the δ and β bands from the healthy reference, whereas GPi-DBS and PPN-DBS modulate the two bands in a frequency-decoupled manner within our 5 Hz resolution frequency sweep. These findings provide a computational framework for optimizing DBS intervention strategies for PD-related sleep dysfunction.

Brain Sciences doi: 10.3390/brainsci16111172

Authors: Shunnosuke Shimizu Ryo Kawamura Kei Sasaki Naoki Kodama

Background/Objectives: The effects of changes in speech playback speed on brain activity provide important insights into the development of efficient information processing and learning methods. However, research has predominantly focused on Indo-European languages such as English. This study examined neural responses during Japanese speech listening at two playback speeds using functional magnetic resonance imaging (fMRI). Methods: Forty-two Japanese-speaking adults (mean age: 21.5 ± 1.8 years, 24 female) passively listened to synthesized readings from “Le Petit Prince” at 0.75× (slow) and 1.5× (fast) normal speed, followed by a comprehension test. Results: Both conditions elicited robust bilateral activation centered on the transverse temporal gyrus and superior temporal gyrus. The direct contrast between the conditions yielded no significant voxels, and region-of-interest analyses provided moderate evidence for the point-null model in five of six auditory regions (Bayes factors favoring the null: 3.7–6.0) but were inconclusive in the right Heschl’s gyrus (2.1); multiplicity-corrected tests excluded effects beyond the sensitivity-derived bounds in three of six regions, but classifications depended on motion handling. Responses were leftward lateralized under both conditions, but no significant difference in lateralization between speeds was detected. Nine-item comprehension accuracy was 61.4%; the fast–slow difference was −5.83 percentage points (95% CI [−17.28, 5.61]); 83.3% identified the faster run correctly. Playback speed was confounded with narrative content within participants; speed order was counterbalanced across participants. Conclusions: These findings provide an exploratory baseline for Japanese and indicate that, within this speed range, playback speed is not associated with detectable differences in the magnitude or lateralization of auditory cortical responses.

Brain Sciences doi: 10.3390/brainsci16111171

Authors: Arjun Raj Abdullah Alotaibi Yoko Kato Fuminari Komatsu

Background/Objectives: The incidence of trigeminal neuralgia (TN) rises steeply with age, yet reluctance to offer posterior fossa surgery to patients aged 85 years and older persists, and no series of fully endoscopic microvascular decompression (e-MVD) confined to this group has been reported. To address this, we assessed the technical feasibility, perioperative course, and early pain outcomes of keyhole fully endoscopic microvascular decompression in patients aged ≥85 years with medically refractory TN. Methods: Six patients aged ≥85 years were treated at a single institution between May 2024 and October 2025. Procedures utilized a 3.5–4 cm retrosigmoid incision, a 1.5 cm keyhole craniotomy, a 4 mm 0° endoscope, retraction-free cerebellar relaxation, and continuous brainstem auditory evoked potential monitoring. Pain was graded via the Barrow Neurological Institute (BNI) score. Results: The median patient age was 87 years, the median operative time was 66 min, and estimated blood loss was minimal (0–5 mL) with zero transfusions. Preoperative BNI scores were V in five patients and IV in one. At a median follow-up of 12 months, scores improved to I in five patients and II in one (100% BNI I–II, p = 0.031) with zero recurrences. Conclusions: Fully endoscopic microvascular decompression is technically achievable at ≥85 years with short operative times and excellent pain relief. This demonstrates that chronological age alone is an insufficient reason to withhold definitive decompression from physiologically suitable patients.

Brain Sciences doi: 10.3390/brainsci16111170

Authors: Per G. Farup Knut Hestad Knut Engedal

Background/Objectives: Somatic multimorbidity and mental disorders are associated with impaired cognitive functions, but the clinical importance has rarely been considered. This study evaluated the clinical importance of the associations between cognitive functions and somatic comorbidity. Methods: This cross-sectional study used data from the national research and quality registry “The Norwegian Registry of Persons Assessed for Cognitive Symptoms” (NorCog). Out of 9525 persons in the registry, 3794 (males/females 1789 (47%)/2005 (53%) with a mean age of 74.8 (SD 8.6) years) with mild cognitive impairment (MCI) and dementia had complete registration of age, sex, BMI, years of education, depression (Cornell scale), and somatic diseases and were included in the study. Cognitive functions were assessed with a Norwegian version of Mini-Mental State Examination (MMSE-NR3), Word List Memory Test (WLMT) Immediate and Delayed recall, and Trail Making Test (TMT) A and B. Changes were compared with established limits for minimal clinically important differences (MCID). Twenty-six somatic disorders were registered and grouped into cardiovascular disease, cerebrovascular disease, neurological disease, and metabolic disease. All associations between cognitive functions and somatic diseases were studied using linear regression with the cognitive test scores as dependent variables and somatic diseases as predictors Results: The number of comorbidities and cerebrovascular disease was statistically significantly associated with improved MMSE-NR3 and WLMT Immediate and Delayed test scores. The changes in scores were not clinically important. Neurological disease was associated with improved WLMT Delayed scores and impaired TMT-A scores, but neither change was clinically important. Conclusions: There were statistically significant associations between somatic morbidity and cognitive functions, but none were clinically important. Referral to MCID in addition to statistical differences deserves increased attention in clinical studies.

Brain Sciences doi: 10.3390/brainsci16111169

Authors: Guanxian Li Linlin Gao Jinjin Li Xiaomeng Sun Weihui Wu Xuehua Liu

Objective: This study first established a murine model of pneumonia-induced sepsis-associated encephalopathy (SAE) via intranasal administration of Pseudomonas aeruginosa (PA), aiming to provide a complementary model that more closely mimics the clinical course of pneumonia-derived sepsis, and explored the role of the NLRP3/caspase-1/IL-1β pathway in this model. Methods: Mice were intranasally given PAO1 to induce pulmonary infection-derived SAE, with intraperitoneal lipopolysaccharide (LPS) as a positive control and sham operation as a control. SAE was verified by clinical assessment and histopathology 24 h post-intervention. Hippocampal NLRP3, ASC and caspase-1 were detected by RT-qPCR; serum IL-1β, IL-18, TNF-α, S100B, neuron-specific enolase (NSE) and NT-proCNP were measured by ELISA. Results: Intranasal instillation of 1.2 × 107 CFU PAO1 successfully replicated SAE in mice. Hippocampal mRNA levels of NLRP3, ASC, caspase-1, as well as serum concentrations of the above inflammatory and brain injury markers, were significantly higher in the SAE and LPS groups than in the sham group (all p < 0.05). No significant temporal differences in those serum indicators were observed at 8, 16 and 24 h among groups (all p > 0.05). Conclusions: We successfully established a PA pneumonia-induced murine SAE model. Using this model, we demonstrated that upregulation of the NLRP3/caspase-1/IL-1β signaling pathway is associated with the pathogenesis and progression of SAE.

Brain Sciences doi: 10.3390/brainsci16111167

Authors: Lucília Cardoso Pablo Henrique Moreira Carla Fraga Luiz Moutinho

Background/Objectives: Neuroscience-based research has expanded across neuromarketing and consumer neuroscience, neuroeconomics, neurotourism and neurorobotics, but these domains differ in disciplinary orientation, levels of consolidation and methodological traditions. This study examines the scientific and thematic evolution represented within the analytical corpus across these domains, the position of neurotourism within this broader landscape, and differences in methodological approaches, key constructs and reported research needs. Methods: A scoping review combined structural evidence mapping with structured abstract-level data charting of 981 English-language articles indexed in Scopus. Bibliometric procedures examined scientific production, citation patterns, author-keyword co-occurrence and thematic evolution, while rule-based and human-validated classification supported cross-domain comparison. Abstracts were available for 972 publications. Results: Scientific production increased substantially over time, while the specified author-keyword network remained centred on neuroeconomics and neuromarketing, with neurorobotics occupying a more peripheral technological position. Thematic evolution showed continuity in these domains alongside increasing specialisation in neuroimaging, machine learning, memory, embodiment and spiking neural networks. Within the analytical corpus, the neurotourism-related core comprised eight publications and was methodologically heterogeneous, with only one primary empirical study involving human participants and direct psychophysiological measurement. A broader body of tourism and hospitality research was located mainly within neuromarketing and consumer neuroscience, with more limited contributions from neuroeconomics and neurorobotics. Reported research needs differed, ranging from methodological consistency and conceptual refinement to technological robustness and empirical consolidation. Conclusions: The four domains are connected but are not conceptually or methodologically interchangeable. Distinguishing scientific-domain membership from application context clarifies how tourism-related neuroscience extends beyond the neurotourism label and how related domains may strengthen its empirical and interdisciplinary development.

Brain Sciences doi: 10.3390/brainsci16111168

Authors: Erbil Can Artun Afif Siddiki

Background/Objectives: Sundowning syndrome—recurrent late-afternoon agitation, disorientation and anxiety in people with dementia—is widely attributed to disturbed light exposure. Existing accounts remain qualitative, specifying neither which property of the ambient light field changes nor when, and so yield no prediction varying with latitude, season or sky conditions. This article is a computational hypothesis: it contains no patient data and is intended to make a light-based account specific enough to be tested. Methods: We combine standard solar geometry, an analytic clear-sky radiance model and the CIE photometric and CIE S 026 melanopic weighting functions to compute the spectral composition of the light reaching an observer as a continuous function of time, for single sky directions, for vertical (corneal) planes integrated over the whole sky, for turbidities 2–6, and for an observer indoors near a window, at three European latitudes over a full year. Results: The melanopic daylight efficacy ratio at the eye falls from about 1.33 at solar noon to about 1.02 at a solar altitude of 10° and about 0.89 at 2° (turbidity 2), while modelled total illuminance changes much less (by 3–10%). The decline is a function of solar altitude alone to within 0.005 across sites and dates, is flattened but not removed by aerosol loading and, in a modelled side-lit room with interreflections, by electric light. The Sun passes 10° altitude 51–107 min before sunset, at clock times that vary by 3–6 h over the year. These are model estimates of spectral composition, least certain close to the horizon, and not measures of physiological melanopic stimulation. Conclusions: We propose that afternoon spectral reddening—rather than darkness itself—is a candidate physical cue for sundowning, possibly mediated by the diminished short-wavelength drive to melanopsin-expressing retinal ganglion cells. The proposal yields testable predictions, including an experimental design that separates spectral composition from light level, and implies that lighting interventions should be timed to local solar conditions rather than the clock.

Brain Sciences doi: 10.3390/brainsci16111166

Authors: Dirk Revenstorf Joannes Bernardus Clemens Mertens Martin Schipplick

Background/Objectives: Ketamine has rapid antidepressant effects through NMDA receptor antagonism and downstream neuroplasticity. Combined with structured psychotherapy, it is a promising but still experimental option for patients who have not responded to established treatments. By transiently loosening self-referential processing and habitual evaluative frameworks, psychoactive substances may open a window for therapeutic change. This article outlines the theoretical and neurobiological foundations of altered states of consciousness relevant to this approach. It presents ketamine-augmented hypnotherapy (KAHT) as a specific form of ketamine-assisted psychotherapy. Methods: We review the literature on psychedelic, ketamine-induced, and hypnotic states and describe the KAHT protocol. In KAHT, a single intravenous infusion of racemic ketamine (0.5 mg/kg) is given under hypnotherapeutic guidance, embedded in preparation and integration sessions. Preliminary data from 89 patients include the Mystical Experience Questionnaire (MEQ), pre–post PHQ-9 scores (n = 20), and patient-reported effects. Results: Most patients described the session as calming, euphoric, and psychedelic, with the highest MEQ ratings for transcendence of time and space. PHQ-9 scores decreased significantly (p = 0.048). In the clinically depressed subgroup (n = 14), the reduction did not reach significance (p = 0.09). Of 20 patients, 12 reported lasting positive changes, 6 no change, and 2 negative changes. Conclusions: KAHT appears feasible and may be applicable across diagnostic categories, but responses vary. The uncontrolled design cannot isolate the contribution of the hypnotherapeutic component. Randomized trials are needed to establish efficacy and predictors of response.

Brain Sciences doi: 10.3390/brainsci16111165

Authors: Andrea Garcia-Bitar Sergio Moreno-Jiménez Guillermo Axayacalt Gutiérrez-Aceves Emmanuel Polito-Salazar Ximena Blasco Eduardo Castañeda Laura Crystell Hernández-Sánchez Miguel Ángel Celis-López Jorge Alejandro Torres-Ríos Miryam Ramírez-Ordás Alejandro Rodríguez-Camacho

Neurofibromatosis type 2 (NF2)-related schwannomatosis (NF2-SWN) presents a lifelong challenge in which multiple tumors, evolving functional deficits, and prior interventions complicate decisions about stereotactic radiation. We conducted a structured narrative review of the literature through 12 October 2026, prioritizing NF2-SWN cohorts and separable subgroups and using sporadic-tumor evidence only where NF2-specific data were limited. The synthesis focused on baseline assessment, tumor-growth behavior, radiation outcomes, functional endpoints, salvage and reirradiation, systemic therapy, and longitudinal surveillance. Available evidence supports stereotactic radiosurgery as an important option for selected lesions, particularly when durable local control can be achieved without compromising functional reserve or future treatment options. However, published outcomes are difficult to compare because of heterogeneous populations, imaging and progression definitions, follow-up, functional measures, and potential cohort overlap. Tumor control should not be interpreted in isolation: treatment selection should integrate growth trajectory, anatomical risk, hearing and neurological function, prior surgery or radiation, bilateral disease, patient priorities, and subsequent treatment options. Surveillance remains an active strategy when immediate intervention is unlikely to improve the balance of benefit and harm. We propose a longitudinal framework and core reporting domains to distinguish treated-lesion control from progression elsewhere and support more patient-centered evaluation of treatment sequencing in NF2-SWN.

Brain Sciences doi: 10.3390/brainsci16111164

Authors: Xiao Qin Xiaolian Li Jianhui Jiang Yonghua Pan Biquan Chen Tinglei Huang Wei Duan

Background: Sleep staging is important for assessing sleep architecture and supporting the diagnosis of sleep-related disorders. Manual scoring is time-consuming and subject to inter-scorer variability, while joint modeling of EEG channel relationships and frequency characteristics remains challenging. Methods: We propose DCMG-Net (dual-branch CNN and context-gated multi-view graph network), a frequency-aware network combining multi-view graph convolution with context gating for five-class sleep staging using EEG alone. Multiscale convolutions and attention extract channel features. Functional, globally learnable, and four physiological frequency-band adjacency matrices define six graph views, whose representations are adaptively fused by context gating. Results: On Sleep-EDF-20, ISRUC-S3, and the Sleep Heart Health Study (SHHS), overall accuracies were 91.2%, 90.0%, and 86.3%; macro-F1 scores were 84.4%, 88.7%, and 77.2%; and Cohen’s κ values were 0.88, 0.87, and 0.81, respectively. Macro-F1 exceeded the highest values reported by the compared literature methods by 1.9, 4.2, and 0.7 percentage points, respectively. In the ablation experiments, gating improved macro-F1 over direct concatenation by 6.1 and 2.3 percentage points on ISRUC-S3 and SHHS. Conclusions: Frequency-band topology and context gating jointly exploit EEG frequency information and channel relationships to improve multi-view classification, providing a methodological basis for portable sleep monitoring and computer-assisted clinical scoring.

Brain Sciences doi: 10.3390/brainsci16111163

Authors: Jie Deng Yizhi Yuan Yanxin Ling Yunzhi Liu Yuting Wang Kuan Lu Xin Zhou Yuanyuan Yin Lihua Qiu

Background: Adolescent major depressive disorder (MDD) is common, but the neural mechanisms that underlie it remain poorly understood. Imaging work has been carried out mainly in adults, and data from adolescents with a first, untreated episode are still scarce. In this cross-sectional resting-state functional MRI study, we assessed spontaneous local activity using regional homogeneity (ReHo) together with caudate-seeded functional connectivity (FC), and related both measures to the clinical profile of first-episode, drug-naïve adolescent MDD patients. Methods: The sample comprised 31 adolescents with MDD (aged 10–19 years) and 25 age-matched healthy controls (HC). ReHo and caudate-seeded FC were computed for each participant, and we tested whether these measures were related to symptom severity on the 17-item Hamilton Rating Scale for Depression (HAMD-17). Results: Compared with HC, adolescents with MDD showed significantly increased ReHo in three clusters within a gray-matter mask (cluster-level p < 0.05, FWE-corrected): the right lingual gyrus, the left supramarginal gyrus, and the left insula. No region showed significantly decreased ReHo, and caudate-seeded FC showed no reliable group difference; the increases reported here are therefore presented as exploratory findings. Two regions showed a positive association with symptom severity that withstood Bonferroni correction: the left supramarginal gyrus (r = 0.51, p = 0.007) and the right lingual gyrus (r = 0.49, p = 0.009). Conclusions: In first-episode, drug-naïve adolescent MDD, exploratory analyses showed elevated ReHo in the lingual gyrus, insula, and supramarginal gyrus, pointing to altered synchrony of local BOLD signals in circuits supporting visual processing, interoception, and somatosensory integration. Caudate-seeded functional connectivity showed no robust group difference. Because the design was cross-sectional and the sample modest, these results await confirmation in larger, prospective cohorts.

Brain Sciences doi: 10.3390/brainsci16111162

Authors: Małgorzata Jączak-Goździak Barbara Steinborn Dorota Baum Oliviero Bruni Marcin Żarowski

Background/Objectives: It is unclear whether sleep disturbances differ between epilepsy phenotypes defined by current International League Against Epilepsy (ILAE) criteria. We explored parent-reported sleep disturbances in children with idiopathic generalized epilepsy (IGE) and other epilepsies. Methods: Parents of 127 children with epilepsy completed the Polish Sleep Disturbance Scale for Children (SDSC). We compared IGE (n = 31) with other epilepsies by epilepsy type, etiology, and category, using non-parametric tests with false discovery rate (FDR) correction and linear regression adjusted for age and sex. Results: Children with IGE had lower total SDSC scores than children with other epilepsies (median 39 vs. 44), but this difference was small and not robust in sensitivity analyses. Compared with IGE, structural epilepsy (n = 18) was associated with higher scores for difficulties initiating and maintaining sleep (DIMS; β = 4.3, 95% CI 1.5 to 7.0) and epileptic encephalopathies (n = 15) with higher sleep hyperhidrosis (SHY) scores (β = 1.5, 95% CI 0.33 to 2.7); after FDR correction, both were at or near the threshold of significance (q = 0.053 and q = 0.047). Lower sleep–wake transition scores in IGE were explained by older age. Conclusions: Children with IGE may have milder parent-reported sleep disturbances. The DIMS and SHY findings are exploratory, and age should be considered when interpreting SDSC subscales.

Brain Sciences doi: 10.3390/brainsci16111161

Authors: Woochan Choi Pan-Woo Ko

Background/Objectives: Blood-based biomarkers may help prioritize patients for confirmatory amyloid testing. We compared amyloid positron emission tomography (PET) utilization and diagnostic yield between memory-clinic periods before and after plasma oligomerized amyloid-β (oAβ) testing became routinely available. Methods: This retrospective, single-center, before-and-after cohort study included 1125 index evaluations for cognitive complaints (660 pre-oAβ; 465 post-oAβ). The primary outcome was PET diagnostic yield, defined as the proportion of amyloid-positive scans among patients undergoing 18F-florapronol PET. Secondary analyses assessed PET utilization, PET examinations per amyloid-positive case, and, within the post-oAβ period, the association between oAβ ≥ 0.78 ng/mL and subsequent PET use. Results: PET utilization did not differ significantly between the post- and pre-oAβ periods (10.1% vs. 7.7%; odds ratio [OR], 1.34; 95% confidence interval [CI], 0.89–2.03; p = 0.165). PET diagnostic yield was higher in the post-oAβ period (78.7% vs. 33.3%; OR, 7.40; 95% CI, 2.98–18.37; p < 0.001), including after adjustment for age and sex (adjusted OR [aOR], 6.89; 95% CI, 2.74–17.29). PET examinations per amyloid-positive case were 1.27 and 3.00, respectively. Within the post-oAβ period, oAβ ≥ 0.78 ng/mL was associated with subsequent PET use (aOR, 2.78; 95% CI, 1.49–5.18), with similar estimates after multiple imputation of missing covariates. Conclusions: Amyloid PET yield was higher after routine oAβ testing was introduced than before, without a significant increase in PET use. Because anti-amyloid treatment awareness and referral practices also changed over time, this difference cannot be attributed to oAβ testing itself, and the higher yield does not indicate improved assay accuracy. These findings support prospective evaluation of blood-biomarker-guided triage.

Brain Sciences doi: 10.3390/brainsci16111160

Authors: Irem Tasci Gozde Elidar Sait Albayrak Omer Faruk Goktas Turker Tuncer Mehmet Baygin Fatma Ebru Algul Burak Tasci Sengul Dogan

Background/Objectives: The central vein sign can help characterize multiple sclerosis (MS) lesions on MRI, but reading it takes specialist time and experience. We developed a compact convolutional neural network (CNN) and a deep feature engineering (DFE) pipeline for three-class classification of clinically labeled MR images. Methods: The MS Vein dataset contains 3181 axial FLAIR images from 154 participants in vein-positive, vein-negative, and control classes. MACDIBNeXt (about 6.5 million parameters) combines pooling-based attention downsampling, grouped convolution, and bottleneck and inverted bottleneck blocks. It was pretrained on Stable ImageNet1k and fine-tuned on a participant-level split (98 training, 25 validation, and 31 test participants). The DFE pipeline extracted 768 global average pooling features, selected 47 with CWINCA in participant-grouped folds of the training data, and classified them with tkNN. Results: On 635 held-out test images from 31 participants, the standalone CNN classified 527 correctly (82.99%; participant-cluster bootstrap 95% CI, 77.93–87.66%). DFE classified 571 correctly (89.92%; 85.47–93.82%), with 89.13% macro F1 and Cohen’s κ of 0.83. With participants resampled as clusters, the 6.93-point gain had a 95% CI of 3.33–10.63 points (p = 0.0002), and a cluster-adjusted McNemar test gave p = 0.0021. Grad-CAM activation was intracranial in the displayed examples. Conclusions: MACDIBNeXt with DFE gives promising internal, image-level results. Because the data are retrospective, single-center, and labeled on FLAIR images, external participant-level validation is required before clinical use.

Brain Sciences doi: 10.3390/brainsci16111159

Authors: Ying Yu Peng Zhang Chao Xia Xuemei Ma Fei Xie

Background/Objectives: Glioma diagnosis increasingly depends on the integration of magnetic resonance imaging (MRI), molecular characteristics, and clinical information. Foundation models may support AI-assisted diagnosis through transferable representation learning and multimodal integration, but evidence supporting clinical use remains fragmented. This systematic scoping review maps current applications of foundation models in glioma neuroimaging and evaluates their relevance to tumor delineation, molecular characterization, multimodal diagnostic support, and clinical translation. Following PRISMA-ScR principles, six bibliographic sources were searched through 26 July 2026. Eligible records were categorized by model family, pretraining and adaptation strategy, imaging application, multimodal integration, validation design, and clinical relevance. Among 3688 identified records, 2071 remained after deduplication, 525 underwent detailed eligibility assessment, and 125 were included. Evidence was concentrated in promptable segmentation (n = 47), reusable brain MRI representations (n = 26), vision language and language model applications (n = 22), molecular classification and prognosis prediction (n = 16), and translational or governance studies (n = 14). Foundation models showed potential for tumor delineation, reusable representation learning, molecular phenotype prediction, and multimodal diagnostic support. However, independent external validation, robustness to imaging heterogeneity and missing sequences, calibration, and prospective workflow evaluation remain limited. Foundation models offer promising capabilities for AI-assisted glioma diagnosis, particularly in segmentation, reusable MRI representation learning, molecular characterization, and multimodal support. Current evidence is nevertheless insufficient for routine clinical implementation. Multicenter validation, standardized evaluation, uncertainty assessment, and prospective studies of diagnostic and workflow utility should be priorities for future research.

Brain Sciences doi: 10.3390/brainsci16111158

Authors: Yaru Zhou Xueying Zhang Guijun Chen Haifeng Li Lixia Huang Ying Sun

Background/Objectives: Driven by the neurovascular coupling mechanism, electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) capture shared underlying neural activity from electrophysiological and hemodynamic perspectives and thus complement each other. Emotional processing relies on functional synergy across brain regions recorded via EEG and fNIRS channels. Functionally similar channels are co-activated and adjacent in functional space. Nevertheless, existing EEG–fNIRS emotion recognition methods characterize inter-channel synergy using physical distances or graph structures. They fail to quantify channel-relative positions in functional space and capture synergies between functionally similar channels. Furthermore, these methods overlook dynamic modality contributions during fusion, rendering predictions susceptible to low-quality signals. Methods: To tackle these limitations, we propose the Geometric Positional Encoding and Dynamic Weight Fusion Network (GDWF-Net). The EEG branch adopts functional-space geometric distances as positional cues and embeds them into attention via rotary positional encoding to model inter-channel functional synergy. The fNIRS branch extracts spatiotemporal features using lightweight modules. The fusion module computes dynamic weights from modality contributions, suppresses noisy low-quality modalities via negative learning, and models cross-modal interactions within a mixed-curvature space. Conclusions: Evaluated on the ENTER dataset, GDWF-Net achieves accuracies of 81.63% and 65.71% in subject-dependent and cross-subject settings, surpassing state-of-the-art baselines. Ablation experiments and visualizations verify the effectiveness and interpretability of each proposed module.

Brain Sciences doi: 10.3390/brainsci16111156

Authors: Matthew Crippen

Environmental factors can exacerbate or alleviate affective distress, but not independently of neurobiological mechanisms. This narrative review examines the hypothalamic–pituitary–adrenal axis; threat circuitry (the amygdala, bed nucleus of the stria terminalis, hippocampus and prefrontal cortex); monoaminergic, neurotrophic and glutamatergic signaling; neuroinflammation; the kynurenine pathway; reward circuitry; and the microbiota–gut–brain axis. Each of these responds to features of the environment, or niche. The review proposes a coupling criterion: responses that track current conditions and remain responsive to their own consequences are likely to be adaptive, whereas those that persist after conditions change, or amplify through internal feedback loops, are likely to be pathological. Because a response can track real adversity and still cause harm, this criterion is offered as one dimension of clinical judgment alongside severity, duration and impairment. Two ideas help apply this standard. The first, from ecological psychology and enactive cognitive science, is that bodily processes and capacities shape the action possibilities, or affordances, that a person perceives. The second, selective permeability, describes how the same setting can be supportive for some people and hostile for others. The review compares the proposed account with predictive processing, allostatic load theory and the biopsychosocial model. It sets out candidate indicators and testable predictions and considers possible implications for assessment and care—all offered as hypotheses requiring empirical validation. The account brings the organism–environment relation into judgments of pathology, without implying that all distress is environmentally driven.

Brain Sciences doi: 10.3390/brainsci16111157

Authors: Alejandro Rodríguez-Camacho Andrea Garcia-Bitar Gerardo Yoshiaki Guinto-Nishimura Emmanuel Polito-Salazar Ximena Blasco Juan Marcos Meraz-Soto Jorge Alejandro Torres-Ríos Julia Moscardini-Martelli José Guillermo Flores-Vázquez Laura Crystell Hernández-Sánchez Miguel Ángel Celis-López Guillermo Axayacalt Gutiérrez-Aceves Sergio Moreno-Jiménez

In peri-optic sellar and parasellar tumors, visual preservation requires protection from both radiation injury and progression of inadequately controlled disease. This structured narrative review synthesizes guidelines, systematic reviews, and clinical cohorts identified through targeted PubMed/MEDLINE searches updated through 22 August 2026, covering pituitary neuroendocrine tumors, craniopharyngiomas, and meningiomas. Predominantly retrospective evidence and inconsistent functional reporting limit comparisons between radiation modalities. We propose an anatomy-based framework integrating therapeutic intent, tumor–optic geometry, achievable target coverage, anatomical stability, prior treatment, and baseline visual and endocrine function. Minimum tumor–optic distance alone is insufficient for modality selection. Single-fraction stereotactic radiosurgery is suited to compact, stable targets when disease-specific coverage is achievable within organ-at-risk limits. Hypofractionated stereotactic radiotherapy in three to five fractions may address focal peri-optic dose conflicts, whereas conventionally fractionated precision radiotherapy may accommodate broad contact, complex geometry, or dynamic cystic disease. Automated perimetry, optical coherence tomography, and axis-specific endocrine assessment support longitudinal surveillance; isolated retinal thinning does not establish radiation-induced optic neuropathy. New functional deficits require assessment of tumor status, treatment chronology, spatial dose, and competing causes. The proposed framework requires prospective validation and provides a practical basis for multidisciplinary decisions that jointly evaluate durable tumor control and long-term functional preservation.

Brain Sciences doi: 10.3390/brainsci16111155

Authors: Zhejun Kuang Junyi Wu Dawen Sun Jian Zhao Yifan Wang

Background: Patient-specific seizure prediction remains challenging because preictal EEG patterns and channel relevance vary substantially across individuals. Methods: We propose a CNN-GCN-Diffusion Network (CGD-Net) integrating channel-wise temporal encoding, montage-informed graph modeling, bag-level aggregation, and diffusion-prior-guided soft channel gating. The patient-specific channel prior was estimated exclusively from training data. CGD-Net was evaluated on 19 CHB-MIT recording cases using seizure-group-aware chronological training, validation, and test partitions. Robustness was assessed using random seeds 42, 52, and 62. Results: Across the three seeds, mean accuracy ranged from 74.84% to 75.87%, and mean AUC ranged from 81.82% to 82.01%. In the seed-42 component comparison, the full model achieved the highest mean accuracy, AUC, F1-score, and specificity. Recording-case-level Wilcoxon tests with Holm correction showed significant improvements in accuracy, AUC, and F1-score over the No bag, No diffusion, and No prior configurations, whereas differences from Random graph were not significant after correction. Channel-importance patterns were highly stable across seeds, with a mean pairwise Spearman correlation of 0.9819 and a mean Top-5 Jaccard index of 0.8730, while hub importance showed moderate patient-dependent stability. Conclusions: These results support the combined use of temporal aggregation, montage-informed graph modeling, and prior-guided channel modulation for retrospective preictal-versus-interictal classification. The explanations represent model-level attributions rather than clinically validated seizure-onset regions. Event-level sensitivity and false-alarm rates were not evaluated, and continuous-recording validation is required before clinical warning-system deployment.

Brain Sciences doi: 10.3390/brainsci16111154

Authors: José A. Vega Elda Alba-Suárez Patricia Cuendias Yolanda García-Mesa

Meissner corpuscles are specialized cutaneous mechanosensory end organs primarily located in the dermal papillae of human glabrous skin and specialized mucocutaneous territories. Traditionally regarded as rapidly adapting tactile receptors composed of a sensory axon surrounded by passive lamellar cells, current evidence supports a more complex organization in which the axon, terminal glial cells (TGCs), extracellular matrix, and endoneurial capsule form an integrated mechanosensory unit. This review provides an updated synthesis of the development, anatomical distribution, structural organization, molecular phenotype, mechanotransduction, functional neurobiology, aging, and pathological alterations of human Meissner corpuscles. Particular attention is given to the molecular identity of TGCs and to their emerging role as active components of corpuscular function. PIEZO2 remains the best-established mediator of primary mechanotransduction in the sensory axon, whereas human TGCs express several mechanosensing-associated proteins and experimental evidence suggests a potential glial contribution to corpuscular function. Human studies also demonstrate substantial regional and age-related variability in corpuscular density and phenotype. Importantly, Meissner corpuscles undergo quantitative, structural, immunophenotypic, and molecular alterations in a broad spectrum of peripheral and central neurological disorders. Recent evidence of disease-associated molecular pathology, including intracorpuscular phosphorylated TDP-43 in amyotrophic lateral sclerosis, further expands their potential relevance as accessible peripheral indicators of neurological disease. Finally, emerging three-dimensional imaging, tissue-clearing, spatial molecular profiling, functional imaging, and quantitative digital approaches provide new opportunities for investigating human corpuscular organization. Collectively, current evidence supports viewing the Meissner corpuscle as a dynamic neuro-glial mechanosensory organ whose biological and clinical significance extends beyond its classical role in discriminative touch.

Brain Sciences doi: 10.3390/brainsci16111153

Authors: Evniki Ntinopoulou Panayiotis Patrikelis Theodoros Fasilis Anastasia Verentzioti Athanasia Alexoudi Themistoklis Papasilekas Stefanos Korfias Stylianos Gatzonis

Background: The insula and thalamus are components of the central autonomic network, which supports cardiovascular autonomic regulation and the integration of cognitive and affective processes. Both regions are therefore relevant to understanding the neuropsychological sequelae and cardiovascular autonomic dysfunction following stroke. Objective: This narrative review aimed to synthesize current evidence on the neuropsychological and cardiovascular autonomic consequences of insular and thalamic stroke using a narrative approach and to identify gaps in the integration of these domains. Methods: A structured literature search was conducted in PubMed, Scopus, and Web of Science from database inception through 3 October 2026. Eligible studies investigated domain-specific neuropsychological outcomes and/or physiological measures of cardiovascular autonomic function following thalamic or insular stroke. Data on study design, participant characteristics, assessment timing, outcome measures, main findings, and methodological limitations were synthesized according to lesion location and outcome domain. Results: Fourteen studies representing 13 independent cohorts met the eligibility criteria: 11 studies of thalamic stroke representing 10 independent cohorts and three studies of insular involvement representing three independent cohorts. Thalamic-stroke studies reported heterogeneous impairment across multiple neuropsychological domains, particularly attention, executive function, memory, and language. The three insular-stroke studies reported alterations in physiological measures relevant to cardiovascular autonomic function, including heart rate variability and circulating catecholamines, with heart rate and blood pressure additionally assessed in one study. Cardiac arrhythmias and mortality were additionally reported as secondary outcomes in individual studies. None of the included thalamic-stroke studies assessed cardiovascular autonomic function, whereas none of the included insular-stroke studies assessed domain-specific neuropsychological outcomes. No included study integrated neuropsychological and cardiovascular autonomic assessment within the same patient cohort. Interpretation is limited by the small and methodologically heterogeneous evidence base, particularly for insular stroke, as well as variability in lesion characterization, assessment timing, outcome measures, and longitudinal follow-up. Conclusions: The studies included in this review represent two distinct lines of research addressing neuropsychological outcomes following thalamic stroke and cardiovascular autonomic alterations following insular stroke. Among the included studies, none assessed both neuropsychological and cardiovascular autonomic outcomes within the same patient cohort. Larger prospective, longitudinal, and multimodal studies are needed to determine whether and how these outcomes are associated with lesion characteristics and how they evolve during post-stroke recovery.

Brain Sciences doi: 10.3390/brainsci16111152

Authors: Yun-Juan Chang Philip H. Stavrides Harshitha Pidikiti Kyrillos W. Ibrahim Ju-Hyun Lee Martin J. Berg Kuldeep Sachdeva Stephen D. Ginsberg

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder where early molecular disruptions precede overt pathology and neuronal loss. To identify transcriptional events that bias neurons toward degeneration or resilience, we reanalyzed two single-nucleus RNA-sequencing datasets originally generated to investigate glial responses in an established AD murine model. Methods: Using a neuron-centric analytical framework, excitatory neuronal cells were selected for downstream bioinformatics involving unsupervised clustering, trajectory inference, and functional analyses. Results: This approach revealed neuronal heterogeneity and enabled reconstruction of inferred transcriptional trajectories in a discovery dataset. Three distinct neuronal states along an inferred continuum from stability to degeneration were identified: a homeostatic state, a transitional stress-adaptive state, and an AD-associated state. The transitional state was positioned near a trajectory bifurcation point, indicating divergence toward either partial resilience or an AD-like trajectory. Differential gene expression and pathway analyses revealed RNA-processing dysregulation in the transitional state, suggesting that early alterations in RNA metabolism may play a key role in biasing neurons toward pathological progression. The homeostatic and transitional neuronal states were independently validated, whereas the AD-associated state was not, potentially reflecting differences in brain-region sampling, sequencing strategies, and/or the transient nature of the disease-associated state. Conclusions: This study identified distinct neuronal transcriptional states and inferred trajectories associated with AD-related vulnerability, highlighting RNA-processing dysfunction as a candidate mechanistic contributor of neuronal fate divergence in AD progression. This work provides a foundation for future studies to define cell-type-specific RNA dysregulation in relevant animal models and human postmortem brain tissues to determine whether early RNA-metabolic imbalance and upstream signaling drivers can serve as mechanistic biomarkers or therapeutic intervention points in AD.

Brain Sciences doi: 10.3390/brainsci16111151

Authors: Yu Sun Yuhan Tang Luwei Chen Jiawei Liang Feng Yang Ming Yang

Background/Objectives: Cortical development in children and adolescents shows marked regional heterogeneity, but whether age-related trajectory properties are organized consistently along an externally defined sensorimotor–association (S–A) axis across morphometric phenotypes remains unclear. This study aimed to characterize relative net change, trajectory nonlinearity, and timing centroids across cortical phenotypes and determine how these properties relate to the sensorimotor–association (S–A) axis. Methods: This cross-sectional study included structural MRI data from 936 screened clinical participants aged 6–18 years. Normative age trajectories were modeled for 68 Desikan–Killiany cortical regions using cortical thickness (CT), surface area (SA), cortical volume (CV), and Morphometric INverse Divergence (MIND)-derived nodal degree. Scanner was included as a fixed effect in the model. Relative change (RC), nonlinearity index (NLI), and timing centroid (TC) were extracted from sex-averaged conditional median trajectories within the 6–15-year analysis window. Associations with the S–A axis were tested using Spearman correlations and 10,000 hemisphere-preserving spatial spin permutations, with a two-sided per-test p < 0.05 criterion. Participant-level bootstrap resampling quantified estimation uncertainty. Results: In fitted trajectories, CT, CV, and MIND nodal degree showed net decreases in most cortical regions, whereas SA showed predominantly net increases. Regional distributions of NLI and TC also differed across phenotypes. Of 12 predefined S–A association tests, seven met the two-sided Spin criterion. Toward the association-cortex end, TC increased for CT, CV, and MIND nodal degree, RC increased for SA and MIND nodal degree, and NLI increased for SA but decreased for MIND nodal degree. Conclusions: Cortical age-related trajectories show phenotype- and property-specific spatial associations with the external S–A axis. Concordant gradients of relative net change can coexist with opposite gradients of trajectory nonlinearity, indicating that a common cortical hierarchy is expressed through different age-related properties across cortical phenotypes.

Brain Sciences doi: 10.3390/brainsci16111150

Authors: Xiaoqin Lian Ran Liang Chao Gao Peiyi Wang Wenyang Guan

Background: In most existing EEG-based emotion recognition studies, the spatial configuration of electroencephalography (EEG) electrodes is not adequately preserved, and conventional single-scale convolutional neural networks (CNNs) have limited ability to capture both local and global spatial patterns. To address these limitations, an EEG emotion recognition framework integrating azimuthal equidistant projection (AEP) with a multiscale residual temporal network (MRTNet) is proposed. Methods: Differential entropy (DE) features are first extracted, and the three-dimensional electrode coordinates are projected onto a two-dimensional plane to construct AEP-based DE (AEP-DE) feature maps that preserve the spatial topology of the electrode layout. MRTNet then combines multiscale depthwise separable convolutions with a long short-term memory (LSTM) network to extract spatial features at multiple receptive-field scales and model temporal dependencies across EEG segments. Results: Experimental results show that MRTNet achieves average accuracies of 95.1% for four-class classification on the Database for Emotion Analysis using Physiological Signals (DEAP) and 93.1% for three-class classification on the SJTU Emotion EEG Dataset (SEED). Conclusions: Grad-CAM visualizations further indicate that the model responses are concentrated in spatially localized frontal and temporal regions, providing qualitative support for the spatial interpretability of the proposed method.

Brain Sciences doi: 10.3390/brainsci16111149

Authors: Xiubo Song Yuting Zhang Haiyan Liu Yuntao Gao Yangyang Shen Kaiwen Sun Tingwei Feng Mingxuan Zou Weishan Fan Lingwei Zeng Hui Wang Xiuchao Wang

Background/Objectives: Cognitive control capacity (CCC) describes the maximum volume of information an individual can reliably process per unit time, a key cognitive factor of multitasking performance. While sustained high-load multitasking is known to induce cumulative cognitive impairment, it remains untested whether CCC is associated with vulnerability to this decline across subjective, behavioral, and neural levels. This study systematically characterized how individual differences in CCC relate to multitasking processing ability and examined whether a higher CCC is associated with smaller cognitive fatigue during extended operations. Methods: CCC was assessed in 313 college students via the adaptive MFTA_A paradigm. Participants scoring in the upper and lower 27% of the CCC distribution formed the high-CCC group (n = 42, 3.65 ± 0.33 bps) and the low-CCC group (n = 41, 2.04 ± 0.28 bps). All participants completed a 1 h multitasking information-processing test comprising tracking, instrument monitoring, and listening subtasks. Alertness was measured with the Psychomotor Vigilance Task before and after the test, subjective workload was rated across four Visual Analogue Scale dimensions, and continuous task-state EEG was recorded to analyze spectral power and microstate dynamics. Results: Relative to low-CCC participants, the high-CCC group showed smaller post-test alertness declines, consistently higher multitasking scores across all blocks, and sustained higher theta/alpha ratios and parietal beta power throughout the task. High-CCC participants also exhibited descriptively stronger activation of microstate C and a late rebound pattern in microstate D transitions, while the low-CCC group showed early stabilization of D-state dynamics without compensatory adjustment. Subjective workload ratings rose equivalently across time in both groups, with no significant between-group differences. Conclusions: CCC is strongly associated with multitasking efficiency. Higher CCC is associated with larger information-processing capacity and better sustained performance during high-load work. This association may be supported by more efficient neural resource allocation and more robust cognitive control network engagement, with exploratory evidence of adaptive brain network reorganization under fatigue. CCC is associated with both immediate multitasking performance and alertness maintenance capacity during prolonged operations.

Brain Sciences doi: 10.3390/brainsci16111148

Authors: Sandra M. Mooney Carolyn A. Munson Elena M. Vidrascu Susan M. Smith

Background. Prenatal alcohol exposure (PAE) causes changes in growth, metabolic outcomes, and behavior that can last into adulthood. Treatment with choline has proven efficacious in the short term in animal models and improves some outcomes in people with Fetal Alcohol Spectrum Disorder. Here we tested the hypothesis that maternal supplementation with choline would mitigate behavioral effects of PAE through adulthood. Methods. Pregnant C57BL/6J mice were given alcohol (ALC; 3 g/kg body weight) and choline (Cho; 100 mg/kg) once per day from embryonic day (E) 8.5 through E17.5. Control mice received isocaloric maltodextrin via gavage. Animals that did not receive choline were handled but not injected. Male and female offspring were weighed and tested at 2 months of age (2 mo), 6 mo, 12 mo, and 18 mo on the open field, accelerating rotarod, and fear conditioning tests. Results. Body weight increased with age; however, ALC mice had greater body weight than age-matched controls (CON), and Cho decreased body weight in both CON and ALC mice. Both CON and ALC mice performed better on motor behaviors (open field and rotarod) at younger ages and better on fear conditioning in mid-adulthood (6 and 12 mo). CON mice typically outperformed same-age, same-sex ALC mice, and ALC-Cho mice performed better than ALC mice on fear conditioning but not on motor outcomes. Conclusions. Our data suggest that maternal choline supplementation can modulate body weight increase through later adulthood in both CON and ALC offspring and also confers lasting behavioral benefits in the context of PAE. The similar age-related trends in behavior for both groups suggest that PAE did not accelerate the behavioral decline.

Brain Sciences doi: 10.3390/brainsci16111147

Authors: Rui Li Yulong Wang Chao Yang Ruilong Yan Shuai Zheng Yingqi Xing

Objectives: Microvascular injury after traumatic brain injury (TBI) is the basis for the occurrence of neurological dysfunction. This study aims to dynamically observe cerebrovascular hemodynamics using TCCD to evaluate the stability of the microcirculatory network before and after TBI. Methods: In this study, a moderate TBI model in rats was established, comprising a sham group and TBI groups at days 1 (1 d), 3 d, 5 d, 7 d, 10 d, 14 d, 21 d, and 35 d (n = 5), and each group underwent TCCD and pathological examinations. Examinations were conducted to acquire hemodynamic parameters for every subgroup. Importantly, vessel density (VDnorm), number of endpoints (NEPnorm), and average vessel diameter (AVDnorm) of the injured-side brain tissue to calculate the Microcirculation Structural Score (MSS) were quantified and normalized from histological brain sections, while intracranial vessel hemodynamic indicators including PI, were obtained by TCCD. We analyzed correlations between microcirculation parameters and vessel hemodynamic parameters to validate whether the PI reflects microcirculatory alterations after TBI. Results: This study found that 1–3 days post-TBI was the peak period of vascular injury. From 5 to 14 days, microvascular density and intracranial large vessel blood flow parameters recovered before the microcirculatory structure. From 21 to 35 days, microvessels continued to remodel, with AVDnorm negatively correlated with PI of middle cerebral artery cortical branches (MCAcb-PI) (r = −0.626, p < 0.001). Then, a weighted PI (PIindex) was constructed, which was positively correlated with the microcirculatory injury MSS (r = 0.592, p < 0.001). Conclusions: PIindex can quantitatively assess microcirculatory injury and vascular structural remodeling. TCCD serves as a simple and feasible novel tool to monitor microcirculatory changes after TBI.

Brain Sciences doi: 10.3390/brainsci16111146

Authors: Guido Gainotti

It is generally accepted that emotions are represented more in the right than in the left hemisphere and that temporal and frontal brain structures play a prominent role in functions of representation and control of emotions. It is, however, unclear if the right hemisphere prevalence concerns both the generation and the control of emotions. To clarify this problem, studies dealing with the emotional and behavioural disorders of patients with a right/left and a temporal/frontal variant of frontotemporal degeneration were included in a structured narrative review. A strong prevalence of right-sided atrophy was found in patients with emotion comprehension disorders, but different categories of emotions were affected in patients with temporal and frontal lesions. In the first case, comprehension disorders mainly affected ‘basic emotions’, whereas in the second case they preferentially concerned social and cognitive ‘complex emotions’. A weaker prevalence of right-sided atrophy was found in patients with emotional generation disorders (apathy and empathy) and in those with defects of emotional control (disinhibition). This difference between results obtained on tasks of comprehension and of control of emotions can be due to the fact that ‘apathy’, ‘empathy’ and ‘disinhibition’ can be considered as ‘umbrella terms’, covering behavioural domains larger than those allowed by a strict definition of emotions. The methodological heterogeneity and the observational nature of the evidence proposed suggest to consider the observed temporal–frontal hierarchy as a hypothesis supported by converging but heterogeneous clinical and neuroimaging observations.

Brain Sciences doi: 10.3390/brainsci16111145

Authors: Lucas Moritz Wiggenhauser Patrick Haas Helene Hurth Kateryna Goloshchapova Leonie Zerweck Alexander Debolski Daniel Vogl Marcos Tatagiba Till-Karsten Hauser Nadia Khan Constantin Roder

Background/Objectives: Contralateral disease progression (CDP) in Moyamoya disease (MMD) is a clinically relevant phenomenon, yet difficult to predict. We investigated the association between vessel wall contrast enhancement (VW-CE) and CDP in a European cohort of adult MMD patients with initially unilateral hemodynamic impairment treated with unilateral revascularization. Methods: In this retrospective single-center study, patients with an indication for only unilateral revascularization (based on BOLD fMRI or H215O-PET) were stratified into three subgroups according to contralateral Suzuki grade (0, 1, or ≥2). CDP was defined as secondary contralateral disease progression on imaging with hemodynamic worsening requiring contralateral revascularization during follow-up. Results: Of 158 screened patients, 38 with adequate follow-up were included. CDP occurred in 31.6% (n = 12; 13.6%, 71.4%, and 44.4% in groups 1–3; mean follow-up 2.71 years). In time-to-event analysis, CDP occurred earlier in groups 2 and 3 than in group 1, without reaching significance (log-rank p = 0.078). Patients who later developed CDP more often showed preoperative VW-CE in either hemisphere (90.0% vs. 43.5%, p = 0.021), with consistent but non-significant trends for each hemisphere separately. De novo contralateral VW-CE occurred exclusively in CDP(+) patients (n = 4); contralateral VW-CE overall was significantly more common in CDP(+) than stable patients at the time of CDP (70% vs. 4.3%, p < 0.001). Conclusions: In this exploratory study, contralateral angiographic involvement and preoperative VW-CE were associated with CDP in unilaterally treated MMD patients. De novo contralateral VW-CE may represent a candidate imaging marker of active CDP. Larger multicenter studies are needed to confirm these hypothesis-generating findings.

Brain Sciences doi: 10.3390/brainsci16111144

Authors: Hyoung-Won Cho In-Ae Song Sung-Hee Han Tak Kyu Oh

Background/Objectives: Albumin is commonly given during craniotomy to support intravascular volume and limit cerebral oedema, but randomised data in traumatic brain injury have suggested harm. Its association with survival after craniotomy is unknown. Methods: Using Korean National Health Insurance Service claims, we identified adults who underwent craniotomy in 2022–2023. Exposure was albumin prescription on the day of surgery, and the primary endpoint was 30-day mortality. We used propensity score overlap weighting with hospital fixed effects. Results: Of 25,097 patients, 3168 (12.6%) received albumin. In the overlap-weighted cohort, albumin was associated with higher 30-day mortality (6.6% vs. 3.8%; odds ratio [OR] 1.81, 95% confidence interval [CI] 1.44–2.29; absolute difference 2.9 percentage points, 95% CI 0.9–4.8) and in-hospital mortality (OR 1.96, 95% CI 1.53–2.52). The association was observed for intracranial neoplasm, cerebrovascular disease and traumatic brain injury. Albumin dose was not associated with mortality (OR per 10 g 0.99, 95% CI 0.96–1.01). Conclusions: Perioperative albumin was associated with higher mortality after craniotomy, without a dose–response relationship. Residual confounding by indication and a direct adverse effect could not be distinguished. These findings should not change practice or be cited as evidence of harm, but they provide no support for routine albumin use.

Brain Sciences doi: 10.3390/brainsci16111143

Authors: Rongze Xu Jian Wang Meng Yu Yue Xia Yu Hao Shiyong Ji Cidanzhuoma Xiaolong Tian Zeng Ren Xudong Cao Cidanwangjiu Qianqian Wu Yuhua Zhao Muke Zhou

Objective: To compare the clinical characteristics, treatment timelines, and short-term outcomes of patients with acute ischemic stroke (AIS) who developed stroke at extremely high altitude or in lowland areas and received intravenous thrombolysis, and to investigate factors associated with failure to achieve the recommended door-to-needle time (DNT). Methods: This two-center retrospective cohort study included consecutive patients with AIS treated with intravenous alteplase between January 2019 and February 2026 at Xizang Autonomous Region People’s Hospital and West China Hospital, Sichuan University. Demographic and clinical data, laboratory findings, onset-to-door time, DNT, onset-to-needle time, and in-hospital outcomes were collected. Binary logistic regression was used to identify factors associated with DNT > 60 min. Results: Among 348 patients, 170 were in the high-altitude group and 178 in the lowland group. High-altitude patients were younger, had higher rates of smoking and alcohol consumption, lower oxygen saturation, and higher red blood cell counts and hemoglobin levels (all p < 0.001). DNT was significantly longer at high altitude (p < 0.001). No significant differences were found in discharge NIHSS scores, early neurological improvement, favorable functional outcome, hemorrhagic transformation, or in-hospital mortality (all p > 0.05), although the study was underpowered to detect clinically meaningful differences in hemorrhagic transformation and in-hospital mortality. High-altitude setting remained independently associated with DNT > 60 min after adjustment (aOR, 5.381; 95% CI, 3.068–9.438; p < 0.001), reflecting a composite of altitude-related and center-specific factors. Conclusions: This study provides real-world clinical evidence on intravenous alteplase thrombolysis for patients with AIS at high altitude and helps address the limited efficacy and safety data available for high-altitude populations in previous thrombolysis studies. The comparable short-term neurological outcomes suggest that thrombolysis is feasible in this setting, although the limited statistical power for secondary safety outcomes warrants confirmation in larger studies. The longer DNT observed at the high-altitude center likely reflects both altitude-related and center-specific operational factors, and further research is needed to clarify their relative contributions. These findings may provide a clinical basis for assessing the applicability of reperfusion strategies in the unique high-altitude environment.

Brain Sciences doi: 10.3390/brainsci16111142

Authors: Yasi Jiang Yumei Yue Xiaodan Zhang Dinglai Wu Timothy Hudson Rainer Lihui Yang Weinv Fan Yonggang Hao Ting Shen

Background: Parkinson’s disease (PD) motor subtypes, tremor-dominant (TD) and postural instability/gait difficulty (PIGD), exhibit divergent brain atrophy patterns, yet the transcriptomic basis of this subtype-associated vulnerability remains incompletely understood. We employed an integrative imaging transcriptomics approach to identify both different and shared transcriptomic signatures associated with regional gray matter volume in PD and its clinical subtypes (TD and PIGD). Methods: Ninety-nine PD patients (50 TD, 47 PIGD, 2 indeterminate) and 70 healthy controls (HCs) underwent 3T MRI, regional gray matter volume differences were assessed between PD subtypes and HCs. Partial least squares (PLS) regression linked atrophy patterns to Allen Human Brain Atlas gene expression across brain regions, followed by functional enrichment, pathology-related gene enrichment, cell-type enrichment, and neurotransmitter system mapping. Results: PIGD and TD showed partially overlapping atrophy patterns, with relatively greater cortical and subcortical involvement in PIGD and a narrower pattern in TD. PLS identified 78 shared and hundreds of subtype-associated genes. PIGD-associated genes were tentatively enriched in synaptic pathways and overlapped significantly with alpha-synuclein pathology-related genes, while TD-associated genes were enriched in chromatin regulation and proteostasis. Neurotransmitter mapping revealed broad neurotransmitter involvement in PIGD versus more restricted dominance in TD. Conclusions: PD subtypes exhibit both shared and subtype-associated transcriptomic signatures underlying regional atrophy vulnerability, with PIGD showing relatively more pronounced synaptic disruption and broader neurotransmitter involvement. These findings shed light on the molecular underpinnings that may contribute to the heterogeneity of disease distribution in PD clinical subtypes and may inform the development of targeted therapeutic strategies.

Brain Sciences doi: 10.3390/brainsci16111141

Authors: Nicole J. Braun Danielle E. Mor

Background/Objectives: Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Growing evidence suggests that α-synuclein aggregation may originate in the gut, and dysbiosis of the gut microbiome has been observed in PD patients. Levilactobacillus brevis (L. brevis) is increased in the PD gut microbiome; however, the role of specific host–microbiota interactions and direct causal links with PD pathology remain unclear. We therefore examined the effects of L. brevis on disease phenotypes in PD models driven by α-synuclein toxicity. Methods: Using Caenorhabditis elegans (C. elegans), a rapidly aging and highly genetically tractable model system with simple gut anatomy and orthologs for 60–80% of human genes, we investigated the impact of L. brevis on dopamine neuron structure, dopamine-dependent behavior, and α-synuclein aggregation in PD models. Additionally, we tested candidate regulators of L. brevis-induced effects and conducted dopaminergic neuron-specific transcriptional profiling to gain further mechanistic understanding. Results: In adult C. elegans, feeding with L. brevis protected against pathological features associated with α-synuclein toxicity, including dopaminergic degeneration, dopamine-dependent motor dysfunction, and α-synuclein aggregation. RNAi knockdown of candidate genes vps-35 and ifd-2 in dopaminergic neurons was associated with altered patterns of dopamine-dependent behavior, motivating further investigation of potential genetic contributors. Transcriptional analysis of dopamine neurons revealed changes in gene expression and functional pathways in response to L. brevis. Conclusions: These findings highlight L. brevis as a gut microbial factor capable of protecting dopaminergic neurons in the context of α-synuclein toxicity, and demonstrate the utility of C. elegans for establishing causal roles of host–microbiota interactions in disease. Moreover, this study offers potential therapeutic targets to be validated in vertebrate systems, with the goal of promoting dopamine neuron resilience in PD.

Brain Sciences doi: 10.3390/brainsci16101140

Authors: Grzegorz Załęski Krzysztof Horoszkiewicz Marta Kopańska

Background/Objectives: Video gaming places repeated demands on rapid visual information processing, response selection, and visuomotor coordination. However, it remains unclear whether current gaming in adolescence is associated with broadly enhanced cognitive performance or with selective differences in visual–psychomotor functioning. This study examined associations between current video gaming and visual–psychomotor efficiency, visuomotor coordination, visual search, perceptual performance, and sequential–executive processing in adolescents. Methods: This exploratory secondary cross-sectional reanalysis used an existing dataset of 120 adolescents aged 14–16 years (60 girls, 60 boys), including 92 current and 28 non-current players. Five principal outcomes were analysed using age- and sex-adjusted regression, HC3 standard errors, and Benjamini–Hochberg correction. Sensitivity analyses examined girls, school membership, and all 121 source records. Results: Current gaming was associated with higher PiM (B = 6.92, 95% CI [1.24, 12.59], q = 0.043) and shorter Number Localization time (9.6%, q = 0.042) in the principal models. PiM estimates remained positive across school and sample sensitivity analyses, although not every leave-one-school-out model met the FDR threshold. Inference for visual-search time was more sensitive to analytical specification. The component analyses described overlapping measures underlying PiM. Intensity, tenure, and genre analyses were inconclusive after correction. Conclusions: Current gaming was associated most consistently with greater psychomotor throughput. Visual-search estimates generally favoured current players but were less stable across specifications. These exploratory cross-sectional findings do not establish a causal benefit, a general cognitive advantage, or an optimal gaming dose or genre.

Brain Sciences doi: 10.3390/brainsci16101139

Authors: Karina Yazmín Sánchez-Lastra Rossy Attie-Harari María Fernanda Castillo-Cuadros Carlos A. Cuellar Adriana Cristina Pliego-Carrillo

Spinal cord injury (SCI) significantly reduces both quality of life and life expectancy due to the loss of motor and sensory function, as well as its impact on autonomic dysfunction (AD). Complications related to AD include impaired sphincter control and thermoregulation, orthostatic hypotension, respiratory difficulties, sexual dysfunction, and gastrointestinal complications, among others. These complications limit physical rehabilitation capacities, exacerbating SCI-related challenges and increasing healthcare costs. Currently, no effective clinical treatments exist to restore impaired autonomic neural control. However, invasive and non-invasive neuromodulation strategies such as epidural spinal cord stimulation (eSCS) and transcutaneous spinal cord stimulation (tSCS), respectively, have demonstrated promising results in improving autonomic function. Despite these advances, drawing definitive conclusions remains challenging because studies vary in sample size, stimulation parameters, session numbers, and assessment methods. This narrative review outlines the primary consequences of SCI on the autonomic nervous system (ANS) and evaluates the effects of eSCS and tSCS on cardiovascular, respiratory, gastrointestinal, sphincter control, thermoregulation, and sexual function, while highlighting the diversity of approaches in current studies.

Brain Sciences doi: 10.3390/brainsci16101138

Authors: Chen Chen Yajuan Hu Sifan Wang Xintong Zhang Shuang Zheng Jinying Han Kai Wang

Background: Quantitative electroencephalography (qEEG) facilitates the objective assessment of residual brain function in patients with disorders of consciousness (DOC), which addresses the intrinsic limitations of behavioral assessment methods. Nevertheless, the characteristics of frontoparietal neural oscillation asymmetry between resting state and auditory stimulation state have not been fully elucidated, and its incremental prognostic value for DOC subtype classification and outcome prediction remains to be confirmed. Methods: Fifty-seven patients with DOC and 23 healthy controls completed qEEG recordings at baseline and during auditory stimulation. Interhemispheric asymmetry indices of the frontal lobe and parietal lobe were calculated for the theta band and alpha band. Linear mixed-effects models (LMMs) were adopted to test the main effects and interaction effects of diagnosis, brain region and stimulation condition. The correlations between asymmetry indicators, Coma Recovery Scale-Revised (CRS-R) scores and 6-month Glasgow Outcome Scale (GOS) scores were analyzed. Nested logistic regression and Receiver Operating Characteristic (ROC) analysis were performed to quantify the incremental prognostic value of oscillatory asymmetry beyond conventional clinical variables; odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for all predictive indicators. Internal leave-one-out cross-validation and external cohort validation were performed to assess the generalizability and robustness of the final prognostic model. Results: Significant diagnosis × region interaction effects were observed in both frequency bands. Vegetative state (VS) patients presented with frontal-dominant asymmetry, while minimally conscious state (MCS) patients showed parietal-dominant asymmetry; this dissociative pattern was significantly amplified after auditory stimulation. Only stimulation-evoked theta asymmetry showed consistent correlations with clinical status and prognosis: frontal theta asymmetry was negatively correlated with CRS-R scores, while parietal theta asymmetry was positively correlated with CRS-R scores and 6-month GOS outcomes. Incorporating stimulated frontoparietal theta asymmetry significantly improved prognostic performance, and the area under the curve (AUC) of the optimal model reached 0.930. Conclusions: VS and MCS present distinct frontoparietal oscillatory asymmetry phenotypes, which are specifically enhanced by auditory stimulation. Stimulation-evoked theta band asymmetry can reflect residual conscious function and provides incremental prognostic value for long-term functional recovery, with robust generalizability verified by internal and external validation.

Brain Sciences doi: 10.3390/brainsci16101137

Authors: Xuan Xu Kaige Zhang Luxuan Xia Xiaoxu Liu Liye Wang Yilan Zheng Chengru Jia Nannan Li Zhigang Chen

Background: Cerebral small vessel disease (CSVD) is one of the major causes of cognitive impairment and functional decline in older adults. Instrumental activities of daily living (IADL) may serve as a bridge between cognitive impairment and more basic executive control; however, whether IADL mediates the association between global cognition and anti-saccade inhibitory control in patients with CSVD remains unclear. This study examined the mediating role of IADL between the Montreal Cognitive Assessment (MoCA) and anti-saccade metrics, and exploratorily tested whether years of education moderated this pathway. Methods: A total of 171 patients with CSVD were enrolled. The anti-saccade uncorrected error rate, corrected error rate, and correct rate were collected. Using IADL as the mediator, MoCA as the independent variable, and relevant factors as covariates, mediation and moderated mediation analyses were conducted with PROCESS Model 4, Model 7, and Model 14. The same model specifications were applied to all three anti-saccade outcomes. Benjamini–Hochberg FDR correction was used to address multiplicity across outcome screening and interaction tests. Because no formal direct comparisons of indirect effects among the three outcomes were performed, differences in statistical significance across outcomes were not interpreted as evidence of outcome-specific mediation or distinct neural mechanisms. Results: (1) In Model 4: in the uncorrected analysis, the indirect effect of IADL between MoCA and the anti-saccade uncorrected error rate was significant (95% BootCI [−1.138, −0.003]); however, after Benjamini–Hochberg FDR correction, this indirect effect was no longer significant (Bootstrap p = 0.153, BH-corrected p = 0.212). It should be noted that the unadjusted bootstrap p value was already greater than 0.05; therefore, its non-significance was not solely attributable to FDR multiplicity correction. The indirect effects for the anti-saccade corrected error rate and correct rate remained non-significant after FDR correction (both BH-corrected p = 0.212); no direct comparisons among outcomes were performed in this study. (2) In Model 14: the IADL × years of education interaction term for the uncorrected error rate was significant before correction (p = 0.034), but was no longer significant after FDR correction (BH-corrected p = 0.051). More importantly, the moderated mediation indices for the uncorrected error rate, corrected error rate, and correct rate were all non-significant (uncorrected error rate: 95% BootCI [−0.021, 0.123]; corrected error rate: 95% BootCI [−0.186, 0.016]; correct rate: 95% BootCI [−0.052, 0.119]), suggesting that years of education did not significantly moderate the overall indirect effect. (3) HC3 robust standard error sensitivity analysis showed that in the uncorrected error rate model, path a in Model 4 was no longer significant (p = 0.077), and the Bootstrap 95% confidence interval for the indirect effect was [−1.132, −0.002], with its upper limit close to 0; in Model 14, the IADL × years of education interaction term was also no longer significant (p = 0.211), indicating limited robustness of the above indirect association. Conclusions: In this exploratory cross-sectional analysis, IADL may partially mediate the association between global cognition and the anti-saccade uncorrected error rate in patients with CSVD before correction; however, this indirect effect was not statistically supported after multiplicity correction. It should be emphasized that the unadjusted bootstrap p value was itself non-significant, and this p value was based on a normal approximation and serves as an exploratory reference only; after considering the robustness of the bootstrap confidence interval, this indirect effect did not reach statistical robustness. The findings of this study did not provide evidence for outcome-specific mediation, and the moderated mediation effect of years of education was not statistically supported. These results should be interpreted as exploratory associations and require further validation in independent longitudinal samples.

Brain Sciences doi: 10.3390/brainsci16101136

Authors: Meltem Gönel Corinne Inauen Philip Heesen Martina Sebök Shreyes Paruvacattu Tristan Schmidlechner Elisa Colombo Veronica Percuoco Jorn Fierstra Christoph Globas Susanne Wegener Andreas Luft Luca Regli Giuseppe Esposito

Background/Objectives: Carotid endarterectomy (CEA) is a standard surgical treatment for high-grade symptomatic and asymptomatic internal carotid artery (ICA) stenosis. The Transit Time Flowmeter (TTF) provides an easy-to-use tool to quantify intraoperative ICA blood flow in mL/min. This study aimed to (1) describe post-CEA ICA flow quantified with TTF, (2) identify predictors of post-CEA ICA flow, and (3) examine its association with contralateral steno-occlusive disease. Methods: We queried data from our prospective registry of patients who underwent a CEA between January 2019 and July 2024 and had intraoperative registered post-CEA ICA flow measurements using TTF. Preoperative ICA stenosis was graded according to the NASCET criteria. The clinical data was retrospectively collected. Results: Data from 196 CEAs in 190 patients (median age 74 [67–81]; 25% female) were included. Most patients (86%) had a symptomatic ICA stenosis. The median post-CEA ICA flow was 170 mL/min [IQR 140–242; range 40–800]. Post-CEA ICA flow was not associated with age, sex, comorbidities, symptomatic stenosis, left ventricular ejection fraction (LVEF), or ipsilateral stenosis severity but was significantly higher in patients requiring intraluminal shunt placement during CEA (p = 0.010) as well as in those with contralateral steno-occlusive disease (p < 0.001). Conclusions: TTF is a practical intraoperative tool for quantitative flow assessment during CEA. Higher post-CEA ICA flow in patients with an intraoperative shunt placement or with contralateral steno-occlusive disease may reflect a compensatory hyperperfusion, as the ipsilateral ICA serves as a key supplier when collateral pathways are incomplete.

Brain Sciences doi: 10.3390/brainsci16101135

Authors: Luca Agnifili Davide Celani Matteo Fornaro Alessandro Sferra Rodolfo Mastropasqua Ciro Costagliola

Background/Objectives: This study aimed to compare oral citicoline 500 mg/homotaurine 50 mg/nicotinamide 54 mg/pyrroloquinoline quinone 5 mg (CIT/HOMO/B3/PQQ) with citicoline 500 mg alone (CIT500) for contrast sensitivity (CS), vision-related quality of life (QoL), and reading performance in early, medically controlled primary open-angle glaucoma (POAG). Methods: In this prospective, randomized, active-controlled, two-period crossover study, 40 patients (80 eyes) received one supplement for four months before switching to the alternative for four months without washout. Assessments at baseline, month 4 (M4), and month 8 used the Spaeth–Richman Contrast Sensitivity (SPARCS) test, Glaucoma Quality of Life-15 (GQL-15) questionnaire, and digital MNREAD. Bayesian hierarchical linear mixed-effects models evaluated longitudinal changes and between-sequence differences in change from baseline to M4. Results: SPARCS increased by 2.52 points (95% credible interval [CrI], 1.04–3.99) at M4 in the CIT/HOMO/B3/PQQ-first sequence and by 3.92 points at month 8 after crossover in the CIT500-first sequence. The randomized M4 contrast favored CIT/HOMO/B3/PQQ (+2.24 points; 95% CrI, 0.16–4.32), whereas corresponding intervals included zero for GQL-15 and all four MNREAD parameters. QoL changes were modest. Maximum reading speed and reading accessibility showed potentially favorable longitudinal trajectories, while reading acuity and critical print size changed less consistently. Intraocular pressure, mean deviation, and retinal nerve fiber layer thickness remained stable. Conclusions: CIT/HOMO/B3/PQQ was associated with improved CS and potentially favorable reading-performance trajectories in early POAG. These exploratory findings support further investigation of patient-relevant functional outcomes as complementary measures for evaluating adjunctive therapeutic strategies in glaucoma but require confirmation given the absence of washout and multiplicity adjustment.

Brain Sciences doi: 10.3390/brainsci16101134

Authors: Junho Choi Chun Il Park Shin Tae Kim Jee In Kang Se Joo Kim June-ho Seo

Background: Chronic psychological stress can alter hypothalamic–pituitary–adrenal (HPA) axis activity and inflammatory signaling. However, the biological correlates of specific stress-related emotional experiences and expression patterns remain incompletely characterized in clinical populations. We therefore examined the associations of anger expression and social anxiety with HPA-axis-related and inflammatory biomarkers in psychiatric outpatients. Methods: In this exploratory, single-center cross-sectional study, clinical records of 85 adults attending their initial visit to the study clinic were retrospectively reviewed. Anger expression was assessed with the Korean State-Trait Anger Expression Inventory (STAXI-K; n = 61) and social anxiety with the Korean version of the Liebowitz Social Anxiety Scale (LSAS; n = 63). Fasting early morning serum concentrations of cortisol, dehydroepiandrosterone sulfate (DHEA-S) and interleukin-6 (IL-6) were measured. Hierarchical linear regression and partial correlation analyses were conducted adjusting for age, sex and body mass index. Additional analyses included left-censored Tobit models and cross-equation Wald tests. Results: Higher social anxiety scores were associated with higher log-transformed IL-6 (n = 63; β = 0.400, p = 0.001), which was the only association that remained significant after false discovery rate (FDR) correction across the nine main predictor–biomarker tests (q = 0.013). This association also remained significant in the reported sensitivity analyses. Higher anger-out scores were associated with lower morning cortisol (n = 61; β = −0.311, p = 0.022) and a lower log-transformed cortisol/DHEA-S ratio (n = 59; β = −0.278, p = 0.037), but neither remained significant after FDR correction (q = 0.084 for both); the ratio association was also sensitive to covariate adjustment. In separate mutually adjusted analyses (n = 56), social anxiety remained associated with log IL-6 (partial r = 0.295, p = 0.034), whereas the anger-in association was not statistically significant (partial r = −0.026, p = 0.858). Cross-equation Wald tests did not detect statistically significant differences between associations with cortisol and log IL-6. Conclusions: In this exploratory study, the association between social anxiety and higher IL-6 remained significant after FDR correction across the nine main tests and after separate adjustment for depressive symptom severity. The inverse associations of anger-out with morning cortisol and the cortisol/DHEA-S ratio did not survive FDR correction. These findings warrant longitudinal replication and do not establish causality or distinct biological pathways.

Brain Sciences doi: 10.3390/brainsci16101133

Authors: Meimei Zhang Wei Li Bei Kang Yumei Zhang Tao Feng

Objective: Chronic neuroinflammation is a recognized driver of Parkinson’s disease (PD) pathophysiology, in which systemic inflammation may also participate. This study evaluated composite inflammatory indices in peripheral blood and investigated their associations with disease severity, motor symptoms, and non-motor symptoms. Methods: A retrospective study was conducted using routinely collected clinical and laboratory data. A total of 315 PD patients and 125 healthy controls (HCs) were enrolled. All PD patients underwent motor and non-motor symptom assessments. Differences in peripheral inflammatory indices were compared between the PD and HC groups, and across Hoehn–Yahr (H–Y) stages. Multinomial logistic regression was used for factors associated with disease severity. Multivariable linear regression examined correlations with clinical measures. Benjamini–Hochberg false discovery rate (FDR) correction was applied to PD vs. HC comparisons, H–Y group comparisons, and all symptom-related analyses. Results: Levels of the systemic inflammation response index (SIRI), monocyte-to-lymphocyte ratio (MLR), and monocyte-to-high-density lipoprotein cholesterol ratio (MHR) were significantly elevated in PD after FDR correction. In the multinomial logistic regression model, disease duration was significantly associated with both H–Y < 3 vs. H–Y > 3 (OR = 0.940, 95% CI: 0.894, 0.989; p = 0.016) and H–Y = 3 vs. H–Y > 3 (OR = 0.961, 95% CI: 0.925, 0.999; p = 0.043). Hypertension was associated only with H–Y < 3 vs. H–Y > 3 (OR = 0.468, 95% CI: 0.226, 0.970; p = 0.041). Platelet-to-lymphocyte ratio (PLR) was significantly associated with H–Y = 3 vs. H–Y > 3 (OR = 0.989, 95% CI: 0.980, 0.997; p = 0.012) but not with H–Y < 3 vs. H–Y > 3 (p = 0.167). Systemic immune-inflammation index (SII) was not significantly associated with either comparison. SII × sex (p = 0.496) and PLR × sex (p = 0.048, Bonferroni-corrected p > 0.025) interaction terms were not significant. After FDR correction, no inflammatory indices were significantly associated with motor or non-motor symptom (all q > 0.05). Conclusions: After rigorous adjustment, previously reported associations between peripheral inflammatory indices and PD severity were not replicated. Disease duration and hypertension were the primary correlates of higher H–Y staging. Elevated inflammatory indices should be interpreted with caution, as they may be associated with longer disease duration or vascular comorbidity.

Brain Sciences doi: 10.3390/brainsci16101132

Authors: Benlin Wang Qiaowei He Nan Chi Hongtao Zhang Xicheng Song

Background: The endoscopic endonasal approach (EEA) has been widely applied in the surgical treatment of skull base tumors. However, poor pneumatization of the skull base—such as inadequate sphenoid sinus pneumatization and dense clival bone—can severely obscure key anatomical landmarks, significantly increasing surgical risks. Systematic quantitative studies on endoscopic anatomical landmarks under conditions of poor pneumatization remain limited to date. Methods: Using 10 lightly embalmed adult cadaveric head specimens with red-blue silicone injection, we performed a stepwise dissection of the nasal cavity; sphenoid sinus; cavernous sinus (CS); upper, middle, and lower clivus; craniovertebral junction (CVJ); and lateral skull base regions via the expanded endoscopic EEA with a 0° rigid endoscope. Particular emphasis was placed on observing variations in the landmarks within the sphenoid sinus under conditions of poor pneumatization, and morphometric measurements were obtained for key structures, including the clivus and its adjacent areas, occipital condyles (OC), hypoglossal canal (HC), petrous apex (PA), and vidian canal (VC). Results: In poorly pneumatized specimens, the clival recess (CR) within the sphenoid sinus is often not observable, and the optic nerve prominence and the internal carotid artery (ICA) prominence are indistinct. Quantitative data showed that the total length of the clivus was 28.7 ± 2.1 mm, with gradual widening from superior to inferior (upper clivus: 20.8 ± 2.0 mm; middle clivus: 22.7 ± 2.8 mm; lower clivus: 29.2 ± 3.9 mm). The average drillable area of the entire clivus was 8.6 ± 1.1 cm2, and the PA could be safely drilled by approximately 45–48% (about 1.0 cm3) via the EEA. The length of the VC ranged from 17.1 to 17.8 mm, and its distance from the foramen rotundum (FR) was approximately 7.8–8.0 mm, which may serve as a useful anatomical reference for localizing the horizontal petrous segment of the ICA. Conclusions: In cases of poor pneumatization of the skull base, the osseous and vascular prominences are often obscured under EEA, necessitating coordinate-based localization using quantitative anatomical data. The present study provides segmental clival widths, three-dimensional measurements of the OC-HC complex, the VC-FR interval, and the safe drillable volume of the PA, thereby furnishing a quantitative reference for precise and safe surgery in the poorly pneumatized skull base.

Brain Sciences doi: 10.3390/brainsci16101131

Authors: Stacey Reynolds Lauren Andelin Caterina LaRocca

Ayres Sensory Integration® (ASI) remains one of the most widely used and debated intervention approaches in occupational therapy and related disciplines. Recent advances in rehabilitation treatment specification and reporting frameworks, including the Rehabilitation Treatment Specification System (RTSS) and the Reporting Guideline for Intervention Description in Rehabilitation (GUIDE-Rehab), emphasize the need for precise articulation of treatment ingredients, mechanisms of action, and targets. However, interventions grounded in neurodevelopmental theories, such as Ayres’ theory of sensory integration, are complex, and may present challenges when interpreted within linear causal models. This paper argues that ASI theory is best understood as a treatment theory targeting proximal sensory–motor capacities, while participation-level outcomes may be more comprehensively explained through an enablement framework. Integrating this perspective with data-driven decision making (DDDM) clarifies longstanding ambiguities in the ASI literature and strengthens intervention specification, evaluation, and interpretation.

Brain Sciences doi: 10.3390/brainsci16101130

Authors: Carolina del Pilar Pebe-Muñoz Patricia Alzola Emiliano Díez-Villoria Israel Contador

Background/Objectives: Subjective cognitive decline (SCD) has been proposed as an early symptomatic manifestation of dementia/Alzheimer’s disease. However, its associated brain patterns are not yet fully characterized. In recent years, functional near-infrared spectroscopy (fNIRS) has emerged as a cost-effective technique to detect hemodynamic changes associated with cognitive decline. Therefore, fNIRS may be a valuable tool to investigate SCD neural underpinnings. This systematic review synthesizes current fNIRS evidence regarding the hemodynamic correlates of SCD during both resting-state and cognitive task conditions. Methods: Following PRISMA guidelines, we searched Scopus, PubMed, and Web of Science databases for studies combining keywords (‘subjective cognitive decline’, ‘cognitive complaints’, ‘memory complaints’, ‘fNIRS’, and ‘near-infrared spectroscopy’) with Boolean operators. Results: We identified 181 records, of which 10 studies fulfilled the inclusion and exclusion criteria. All studies were cross-sectional. Furthermore, 33% lacked a healthy control group, 56% lacked a standardized SCD identification protocol, 55% used small or imbalanced samples, and 66% did not clearly differentiate prefrontal subregions. In both resting-state and task conditions, SCD individuals showed heterogeneous hemodynamic responses in prefrontal areas. The severity of SCD and the difficulty of the tasks may be useful moderators of these associations. Conclusions: The limited evidence and methodological differences prevent identifying a specific hemodynamic pattern for SCD. Adopting longitudinal, well-powered, and well-controlled designs will be essential to evaluate fNIRS-derived hemodynamic responses in SCD.

Brain Sciences doi: 10.3390/brainsci16101129

Authors: Tania Akter Mohammad Hanif Ali Md. Imran Khan Md. Shahriare Satu Md. Jamal Uddin Salem A. Alyami Sarwar Ali AKM Azad Mohammad Ali Moni

The journal retracts the article, “Improved Transfer-Learning-Based Facial Recognition Framework to Detect Autistic Children at an Early Stage” [...]

Brain Sciences doi: 10.3390/brainsci16101128

Authors: Qin Yang Xuzi Li Muke Zhou

Background/Objectives: The optimal cervical carotid strategy during thrombectomy for anterior-circulation tandem occlusion remains uncertain. We compared emergent carotid stenting, balloon angioplasty alone, and no targeted acute cervical revascularization. Methods: We searched PubMed, Ovid Embase, Cochrane CENTRAL, Web of Science, and Scopus for comparative studies published from January 2015 to 25 August 2026. A frequentist random-effects network meta-analysis estimated odds ratios (ORs) and 95% confidence intervals (CIs), with outcome-specific cohort-overlap auditing. The event-count network was exploratory; adjusted evidence was analyzed separately. Risk of bias was assessed using RoB 2 or ROBINS-I-aligned domains; confidence was assessed with CINeMA. PROSPERO registration: CRD420261494924. Results: The review included 60 reports representing 49 cohort or report families. Fifteen cohorts contributed 1556 patients for functional independence and 15 contributed 1676 for symptomatic intracranial hemorrhage (sICH). Stenting was associated with greater 90-day functional independence than angioplasty alone (OR, 1.73; 95% CI, 1.22–2.45), without a detected difference in sICH (OR, 1.01; 95% CI, 0.60–1.67). All leave-one-cohort-out functional estimates remained above 1, with 95% CIs excluding 1. Evidence was predominantly nonrandomized. Conclusions: Emergent carotid stenting was associated with greater 90-day functional independence than balloon angioplasty alone, with no detected difference in sICH. Serious or critical risk of bias in all studies in the strict network limits causal interpretation. Imprecision and heterogeneous antiplatelet protocols preclude establishing noninferiority or excluding increased hemorrhagic risk.

Brain Sciences doi: 10.3390/brainsci16101127

Authors: K. K. Mujeeb Rahman M. Monica Subashini

The journal retracts the article “Identification of Autism in Children Using Static Facial Features and Deep Neural Networks” [...]

Brain Sciences doi: 10.3390/brainsci16101126

Authors: Chuan Xue Xiangrui Cai Ziqi Guo Haoran Xu Jiale Xie Rui Ji Lei Cao Jie Jia

Background/Objectives: Systematically elucidating the neural mechanisms of bowel and bladder control is crucial for developing closed-loop brain–computer interface (BCI) neurorehabilitation for patients with spinal cord injury (SCI). This study aims to characterize the spatiotemporal Electroencephalography (EEG) dynamics and compensatory cortical reorganization underlying continence motor intentions across healthy aging and SCI cohorts. Methods: 32-channel EEG signals were collected from healthy young adults, healthy older adults, and SCI patients during motor attempt paradigms of suppressed urination and defecation (SUD) and active urination and defecation (UD). Data were analyzed utilizing event-related spectral perturbation (ERSP) and phase-locking value (PLV) functional connectivity across alpha (8–13 Hz), beta1 (13–20 Hz), and beta2 (20–30 Hz) bands. Results: All cohorts exhibited generally consistent broadband event-related desynchronization (ERD) in the sensorimotor cortex (SMC) during visceral motor attempt. Conversely, the frontal cortex (FC) demonstrated marked frequency-band differentiation. During the SUD task, healthy older adults showed significantly greater SMC beta2 ERD than young adults, whereas SCI patients showed a similar but non-significant trend. Frontal beta2 findings were preliminary and should be interpreted with caution due to potential residual artifacts. Network analysis revealed that physiological aging and SCI are associated with large-scale topological reconfigurations, prominently featuring enhanced long-range frontal functional connectivity to compensate for sensory or peripheral deficits. Conclusions: High-level cortical intentions for continence are preserved after SCI, with frontal high-frequency activity possibly reflecting a compensatory process for sensorimotor disruption. These findings substantiate that visceral intentions exhibit discernible characteristics at the cortical level, establishing a spatiotemporal framework for targeted pelvic nerve modulation via brain–machine interfaces.

Brain Sciences doi: 10.3390/brainsci16101125

Authors: Huihong Ke Wansi Zhong Xiao Zhu Rui Xue Yiting Ge Ying Zhou Yi Chen Min Lou

Background: Most existing digital cognitive assessment tools are simple adaptations of paper-and-pencil tests, lacking adequate validation in older adults and showing poor sensitivity to domain-specific deficits common in high vascular risk populations. This study aimed to evaluate the reliability, convergent validity, and user experience of a gamified Digital Cognitive Assessment Game (DCG) battery developed for adults at high risk of stroke. Methods: This study recruited community dwellers with high risk of stroke. Participants completed the DCG battery, a standardized neuropsychological battery, and a 2-month retest. Reliability was assessed using intraclass correlation coefficients (ICCs). Convergent validity was examined via Pearson correlations and canonical correlation analysis (CCA). User experience was evaluated using Likert-scale questionnaires. Results: A total of 86 participants (mean age 67 years; 60.2% female; mean education 11.37 years) completed baseline assessments. Furthermore, 12/18 DCG tasks showed acceptable-to-high test–retest reliability (ICC range: 0.795–0.883), while the remaining 6 tasks showed marginally acceptable reliability (ICC range: 0.615–0.737). Convergent validity revealed correlations in five domains (r = 0.373–0.582, p < 0.05), with the exception of visuospatial function (r = 0.260, p = 0.063), and a strong correlation for global cognition (r = 0.734, p < 0.001). CCA demonstrated a strong overall association between DCG and conventional batteries (R = 0.86, p < 0.001). The DCG showed good ability for discriminating battery-defined mild cognitive impairment (AUC = 0.91, 95% CI: 0.85–0.97). Participants reported good usability and high acceptance (80% reported having no difficulties completing DCG). Conclusions: The DCG battery demonstrates satisfactory reliability, validity, and user acceptability in adults at high risk of stroke. As a self-administered tool, it represents a promising approach for cognitive screening, particularly in resource-limited settings.

Brain Sciences doi: 10.3390/brainsci16101124

Authors: Songyun Xie Xianghui Liu Xiangming Wang Xinzhou Xie Hao Tang

Background: Electroencephalogram (EEG) signals provide important information for brain–computer interfaces (BCIs) and the diagnosis of neurological disorders but are susceptible to electrooculographic (EOG) artifacts. Traditional methods often rely on multichannel data or relatively long windows, limiting online applicability. Deep learning enables single-channel end-to-end artifact removal, but existing methods may not fully exploit features in the time and frequency domains and may unnecessarily modify relatively clean EEG. Methods: We developed a Wasserstein generative adversarial network (WGAN) integrating reconstruction loss, multi-domain and multi-scale feature extraction, and a gating unit. Reconstruction loss improved waveform reconstruction, yielding a reconstruction-loss-assisted artifact-removal WGAN (rarWGAN). Parallel branches with different kernel sizes extracted multi-scale features, while a multi-domain module combined temporal features with spectral features extracted using complex-valued convolutions. Integrating both modules into rarWGAN produced MDS-rarWGAN. Based on discriminator scores, gating routed inputs classified as contaminated to the generator and retained the others unchanged. Results: On EEGdenoiseNet, MDS-rarWGAN yielded relative root mean square errors (RRMSEs) of 0.189 ± 0.028 and 0.183 ± 0.027 in the time and frequency domains, respectively, with a correlation coefficient of 0.955 ± 0.013. Compared with rarWGAN, RRMSEs decreased by 23.2% and 32.5%, respectively, and the correlation coefficient increased by 1.2%. The gating unit yielded false positive and false negative rates of 1.47% and 0.12%, respectively. For EEG containing artifacts, no statistically significant differences in time domain RRMSE were detected with and without gating (all p > 0.05). On BCI Competition IV 2a, reconstruction metrics measured agreement with a reference derived from independent component analysis (ICA), as artifact-free EEG ground truth was unavailable. Using the same EEGNet classifier, EEG processed by gated-MDS-rarWGAN achieved the highest mean motor imagery classification accuracy among the evaluated deep learning methods. Conclusions: The method suppresses EOG artifacts, reduces unnecessary processing of signals without evident artifacts, and supports motor imagery decoding, offering a feasible preprocessing approach.

Brain Sciences doi: 10.3390/brainsci16101123

Authors: William Mendez Alejandra Bohórquez Ximena Bohórquez Oscar Bohórquez William J. Shelton Edgar G. Ordóñez-Rubiano

Background: Diffusion MRI tractography can support patient-specific neurosurgical planning, but implementation may be limited by workflow complexity, software requirements, and resource constraints. We describe Tractometric®, a diffusion tractography software engine developed for integration with the Surgimetric® neuronavigation planning environment. Methods: Tractometric® was developed through a multidisciplinary, iterative co-design process involving neurosurgeons and neuroimaging specialists. The software uses a modular Model–View–Controller architecture implemented in Python (version 3.11) and supports multiple diffusion reconstruction models, deterministic and probabilistic tracking, patient-specific and atlas-derived regions of interest (ROIs), visualization, and interoperable export. The present study was designed as a technical development and preliminary clinical feasibility report. Technical workflow characteristics were described retrospectively across 30 cases, while preliminary clinical feasibility was explored in 8 patients undergoing tractography-assisted surgical planning. Intraoperative direct cortical and subcortical electrical stimulation was used as a qualitative clinical reference rather than as a formal diagnostic-accuracy test. Results: Tractometric® implemented a complete workflow from diffusion data loading and preprocessing to tract reconstruction, filtering, visualization, and export to Surgimetric®. The 30-case technical series illustrated variation in processing time and user interaction according to operator experience, reconstruction model, registration, ROI strategy, and manual cleaning. In 8 preliminary clinical cases, reconstructed motor and language pathways were qualitatively concordant with positive intraoperative stimulation findings. No formal sensitivity, specificity, spatial agreement, or test–retest reproducibility estimates were calculated. Conclusions: Tractometric® provides an integrated technical workflow for diffusion tractography and neuronavigation planning and was feasible to implement in a preliminary clinical series. The current data support technical feasibility and workflow integration, but do not establish anatomical accuracy, reproducibility, clinical efficacy, or cost-effectiveness. Independent, prospective validation using standardized acquisitions, predefined tractography parameters, quantitative spatial metrics, and systematic intraoperative mapping is warranted.

Brain Sciences doi: 10.3390/brainsci16101122

Authors: Mehmet Celal Kefeli Mehmet Hamamcı

Background/Objectives: Obsessive–compulsive disorder (OCD) severely impacts both patients and their families. This study aimed to compare sleep quality, insomnia severity, and daytime sleepiness in partners of individuals with OCD against a healthy control group. Additionally, it investigated how patient OCD severity and partner depression and anxiety symptoms relate to these sleep outcomes. Methods: This cross-sectional case–control study included 104 spouses of OCD patients (46 females, 58 males; mean age 37.92 ± 8.22 years) and 100 healthy control spouses (48 females, 52 males; mean age 38.40 ± 7.93 years), all married for at least one year. Spouses completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Insomnia Severity Index (ISI). Patient OCD severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: OCD spouses exhibited significantly higher anxiety and depression scores than controls. Poor sleep quality was reported by 57.7% of OCD spouses versus 32% of controls. After adjusting for confounders (age, body mass index, education, sex, marriage duration), OCD spouses demonstrated significantly worse sleep quality and higher daytime sleepiness. Female spouses experienced a significantly more severe burden of insomnia and sleep disturbances than males. Independent of group, higher depression scores correlated with poorer sleep parameters. Furthermore, patient OCD severity positively correlated with all partner sleep scale scores. Conclusions: We conclude that partners of individuals with OCD are particularly vulnerable to complex sleep difficulties, including poor sleep quality and daytime fatigue. By broadening our clinical focus to address these hidden sleep issues and psychological needs, we may help mitigate secondary health risks and improve the overall well-being of affected families.

Brain Sciences doi: 10.3390/brainsci16101121

Authors: Ahmed Najjar Yasir Hassan Elhassan

Background/Objectives: Trigeminal neuralgia (TN) disproportionately affects older adults, in whom medication intolerance, drug interactions, comorbidities, and limited physiological reserve may complicate management. This structured narrative review examines the evidence concerning the selection, effectiveness, durability, and complications of neurosurgical treatments for medication-refractory TN in older adults. Methods: PubMed was searched from database inception through 1 July 2026 using terms related to TN, older age, and neurosurgical treatment. Eligible publications evaluated microvascular decompression (MVD), radiofrequency lesioning, percutaneous balloon compression (PBC), glycerol rhizotomy, or stereotactic radiosurgery (SRS). Titles and abstracts were screened using predefined eligibility criteria, followed by further assessment of potentially eligible publications and standardized data extraction. Studies reporting separately extractable outcomes for defined older populations were classified as direct evidence; mixed-age studies without age-stratified outcomes were treated as indirect evidence and used primarily for procedural and comparative context. Results: The principal search identified 1324 unique records, and 22 publications were included: six provided direct older-adult evidence and 16 provided indirect contextual evidence. Direct evidence was largely limited to MVD and PBC. In selected older adults, MVD was associated with favorable and potentially durable pain outcomes, whereas PBC generally provided rapid initial pain relief. However, differences in outcome definitions, assessment times, follow-up, and patient selection precluded direct comparison. No included study provided separately extractable outcomes for adults aged ≥65 years undergoing radiofrequency lesioning, glycerol rhizotomy, or SRS. GRADE certainty was low or very low for most procedure-specific and comparative conclusions. Conclusions: Favorable observational outcomes in selected older patients suggest that chronological age alone should not automatically exclude an otherwise appropriate patient from consideration for MVD. Treatment should be individualized according to TN subtype, physiological reserve, comorbidity and anesthetic risk, imaging findings, pain urgency, previous interventions, baseline facial sensation, and patient preferences.

Brain Sciences doi: 10.3390/brainsci16101120

Authors: William R. Swindell Aminah Ali Alfredo Iacoangeli Salman Bhai

Background: ALS is characterized by motor neuron failure with potential neurocognitive comorbidity. Cortical neurons, and their support cells, exhibit pathologic features, some of which have been identified in post-mortem transcriptome studies of the cortex from ALS patients and control subjects. These studies, however, have utilized varying technologies with few attempts to reconcile findings. Methods: This study used meta-analysis to evaluate differential gene expression (ALS vs. control) from 16 prior transcriptome studies utilizing multiple technologies (microarray, bulk RNA-seq or snRNA-seq). Normalization with GC content correction was used to mitigate downstream biases impacting differential expression. Results: Approximately one-third of protein-coding genes (5930 of 16,579) exhibited significant between-study effect size heterogeneity (FDR < 0.05), which was frequently associated with variation in average post-mortem interval. Nonetheless, we identified 269 and 273 differentially expressed genes (DEGs) with relatively consistent increased or decreased expression in the ALS cortex, respectively (FDR < 0.05 with SMD ≥ 0.20 or SMD ≤ −0.20). ALS-increased DEGs were associated with transcription (RNA polymerase), cell signaling (TGF-beta, PI3K), interneurons, microglia, endothelial cells, and deep laminar layers (L5, L6). ALS-decreased DEGs were associated with transcription (RNA polymerase), glial cells (astrocytes, oligodendrocytes) and the L1 layer. There was significant overlap between DEGs from the ALS cortex and those previously identified from ALS spinal cord and blood. Conclusions: These findings highlight signaling pathways, cell types and cortical layers associated with robust changes in ALS cortex gene expression. Our results illustrate the importance of meta-analysis as a tool for understanding between-study heterogeneity and identifying repeatable findings across technologies.