Brain Sciences doi: 10.3390/brainsci16040400

Authors: Carmen Rubio Héctor Romo-Parra Alejandro López-Landa Moisés Rubio-Osornio

Text Correction [...]

Brain Sciences doi: 10.3390/brainsci16040399

Authors: Sara Masiero Pasquale Arcuri Paolo Boccolari Elena Zorzi Alessandro Vio Tracy Fairplay Davide Zanin Fabio Vita Danilo Donati Roberto Tedeschi

Background: Carpal tunnel syndrome (CTS) is one of the most common entrapment neuropathies. While surgical decompression is widely considered the definitive treatment, conservative options remain clinically relevant, particularly for symptom relief and functional recovery in the short term. Objectives: To update the evidence comparing surgical versus non-surgical interventions for CTS, assessing pain, function, and clinical recovery. Design: Systematic review of randomised controlled trials (RCTs). Data Sources and Methods: Six databases (CENTRAL, MEDLINE, Embase, Cochrane Neuromuscular Register, ClinicalTrials.gov, and WHO ICTRP) were searched for RCTs published between November 2022 and January 2025. Risk of bias was assessed with RoB 2.0 and certainty of evidence with GRADE. Due to clinical heterogeneity, a narrative synthesis was performed. Results: Four RCTs (n = 1158) were included. Corticosteroid injection and percutaneous electrical nerve stimulation (PENS) appeared to provide faster symptom relief than surgery at short-term follow-up. However, surgery was associated with a higher probability of sustained recovery at 12–18 months (RR 1.36; 95% CI 1.19–1.56). Evidence for PENS was limited to one female-only trial, which restricts generalisability. Certainty of evidence was moderate for long-term outcomes and low for short-term results and safety. Conclusions: The available evidence suggests that surgery may offer more durable long-term recovery, whereas corticosteroids and PENS may be useful for short-term symptom relief. These findings should be interpreted with caution given the limited number of trials and the risk of bias in most included studies. Treatment choice should align with patient goals and recovery timelines. Registration: PROSPERO (CRD420250650789).

Brain Sciences doi: 10.3390/brainsci16040398

Authors: Charlotte Copas Abigail D. Astridge Jennifer Makovec Knight Stuart J. McDonald Sandy R. Shultz Georgia F. Symons

Background: Intimate partner violence (IPV) is a pervasive medical concern affecting millions of people worldwide, with the majority being women. IPV is linked to a number of long-term physical and mental health consequences, including brain injuries and associated persistent post-concussion symptoms (PPCS) and post-traumatic stress disorder (PTSD). Despite the high prevalence of these conditions, there is sparse literature assessing accessible and effective therapeutic avenues specific to IPV victim-survivors. Methods: This narrative review had two aims: to identify therapeutic studies addressing PTSD and PPCS in women IPV survivors, and to provide a narrative overview of potential therapeutic categories, including psychotherapy, mindfulness and meditation, exercise, and pharmacotherapy. A comprehensive literature search was conducted using PubMed and Google Scholar. Inclusion criteria required full-text, peer-reviewed articles published in English, conducted in women with a history of IPV, reporting treatment outcomes related to PTSD or PPCS. Where no IPV-specific evidence was identified, findings from closely related populations including military veterans, athletes, and general TBI samples were narratively reviewed to inform potential therapeutic implications. Results: Nineteen studies addressing PTSD in women IPV survivors were identified, predominantly utilizing psychotherapeutic or mindfulness and meditation-based interventions. No intervention studies targeting PPCS specifically in IPV survivors were identified. Consequently, results for PPCS are largely extrapolated from adjacent populations. Although potential therapeutic avenues were narratively identified across psychotherapy, mindfulness and meditation, exercise, and pharmacotherapy, IPV-specific evidence remains limited, and validation for PTSD and PPCS in this population is needed before clinical recommendations can be made. Conclusions: While 19 studies identified promising therapeutic options for IPV-related PTSD, no IPV-specific PPCS interventions were identified, and implications for PPCS management remain largely inferential. Validation and integrated trauma-informed approaches addressing the intersection of PTSD and PPCS are needed for this understudied population.

Brain Sciences doi: 10.3390/brainsci16040397

Authors: Oyku Dinckol Noah H. Wenger Aryanna Copling Bhumiben P. Patel Munir Gunes Kutlu

Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by persistent drug seeking and impaired behavioral control. Dopaminergic signaling has long been recognized as a central regulator of reinforcement learning, motivation, and habit formation. Addictive substances profoundly alter dopamine transmission through multiple mechanisms. These drug-induced changes contribute to the initiation, escalation, and persistence of addictive behaviors. In addition to dopamine, the cholinergic system has emerged as an important modulator of striatal circuit function. Acetylcholine and its receptors interact extensively with dopaminergic pathways, shaping striatal signaling dynamics and influencing learning and action selection, with particularly strong relevance for nicotine dependence. In this review, we discuss how striatal dopamine and acetylcholine contribute to learning, habit formation, and addiction-related behaviors, as well as how these systems interact at the circuit level. By integrating these findings, we propose a framework for understanding how dopamine–acetylcholine interactions may influence behavioral regulation relevant to substance use disorders.

Brain Sciences doi: 10.3390/brainsci16040396

Authors: Pavlos Christodoulides Dimitrios Peschos Victoria Zakopoulou

This study investigated neural oscillatory dynamics underlying visual word recognition in university students with dyslexia using a portable brain–computer interface (BCI) EEG system. The sample included university students with dyslexia (N = 12) and matched controls (N = 14) who completed auditory discrimination and visual word recognition tasks, with and without musical accompaniment. Through these experimental conditions, the researchers assessed (a) the cortical activation across frequency bands, (b) the modulatory effect of background music, and (c) the relationship between emotional states and brain activity. Results revealed significant group differences in oscillatory patterns, with reduced β- and γ-band activity in the left occipito-temporal cortex among participants with dyslexia, confirming disrupted temporal coordination in posterior reading networks. Compensatory right-hemisphere activation was observed, particularly under musical conditions, accompanied by increased α-band power and reduced δ activity, indicating enhanced attentional engagement and reduced cognitive fatigue. Emotional assessment using the DASS-21 revealed higher stress and anxiety scores in the dyslexic group, suggesting that affective factors may modulate oscillatory dynamics. The presence of background music appeared to attenuate these effects, supporting improved emotional regulation and cognitive focus. These findings demonstrate that dyslexia reflects a distributed disruption in neural synchrony and cross-frequency coupling, influenced by both cognitive and affective mechanisms. The integration of portable EEG technology with rhythmic auditory stimulation offers new insights into the neurophysiological and emotional aspects of dyslexia, highlighting the potential of rhythm- and music-based approaches for both diagnostic and therapeutic applications.

Brain Sciences doi: 10.3390/brainsci16040395

Authors: Holger Schulze Achim Schilling

Background/Objectives: Tinnitus and hyperacusis can occur together or in isolation, with hyperacusis being associated with tinnitus much more frequently than vice versa. This striking correlation between tinnitus and hyperacusis prevalence implies that there might be a common origin, such as (hidden) hearing loss, and possibly interrelated neural mechanisms in the pathological development of those two conditions. Here, we propose such interrelated pathological mechanisms. Methods: This is a theoretical work based solely on considerations and published data. Results: We propose a model localized in the dorsal cochlear nucleus (DCN) of the brainstem, based on classical mechanisms of Hebbian and associative plasticity known from classical conditioning. Specifically, our model proposes that hyperacusis results from the synaptic enhancement of cochlear input to the DCN, whereas chronic tinnitus results from the synaptic enhancement of somatosensory input to the DCN. Specific conditions leading to one or the other condition are discussed. Conclusions: Our model predicts that hearing loss leads to chronic tinnitus, while noise exposure (which may also cause hearing loss) leads to hyperacusis. We would like to emphasize that our aim with the proposed model is not to provide a self-contained theoretical construct, but to stimulate thought regarding possible pathological causes of tinnitus and hyperacusis that have not yet been investigated. Individual assumptions that cannot yet be substantiated by the existing literature are intended to provide impetus for future experimental studies.

Brain Sciences doi: 10.3390/brainsci16040394

Authors: Stefania Chiappini John Martin Corkery Amira Guirguis Alessio Mosca Mya Murray Davide Arillotta Luigi Dattoli Giovanni Martinotti Stefania Bonaccorso Fabrizio Schifano Nicolò Schifano

Background/Objectives: Finasteride and dutasteride are 5α-reductase inhibitors that block the conversion of testosterone to dihydrotestosterone, reducing androgenic stimulation of tissues such as the prostate and hair follicles. Used mainly for benign prostatic hyperplasia and androgenic alopecia, finasteride selectively inhibits type-2 5α-reductase isoenzyme, while dutasteride inhibits both type-1 and type-2. Although sexual adverse effects like erectile dysfunction are well-documented, emerging evidence suggests possible neuropsychiatric reactions—including depression, suicidal ideation, and cognitive decline—potentially linked to reduced neurosteroid synthesis, such as that of allopregnanolone. Causality cannot be inferred from spontaneous reporting data. This study aimed to assess pharmacovigilance signals for psychopathological disorders associated with finasteride and dutasteride in the FAERS database. Methods: Cleaned FAERS data referring to years up to 2025 after deduplication were analyzed, excluding non-serious cases and those without the drug as the sole suspect (MedDra 29.0). Reporting Odds Ratios (RORs) with 95% CIs were calculated to compare psychiatric reactions between finasteride and dutasteride. Python 3.11 was used to screen and summarize relevant cases, accounting for differences in total case numbers. Results: This pharmacovigilance study analyzed FAERS data to assess the neuropsychiatric and sexual adverse reactions associated with finasteride and dutasteride. Depression, anxiety, suicidality, and libido-related issues were reported more frequently for finasteride, especially in younger men using low-dose therapy for alopecia. Potential mechanisms include reduced neurosteroid synthesis, androgen/sex-hormone axis disruption, altered hippocampal neurogenesis, and dopaminergic changes. Conclusions: A baseline psychiatric assessment and the regular monitoring of mood, sexual function, and suicidal ideation are recommended. Limitations include under-reporting, reporting bias, and a lack of incidence data. The findings underscore the need for ongoing surveillance and controlled studies to clarify the clinical significance of these signals.

Brain Sciences doi: 10.3390/brainsci16040393

Authors: Diego Iacono Gloria C. Feltis

The journal retracts the article titled “Idea Density and Grammatical Complexity as Neurocognitive Markers” [...]

Brain Sciences doi: 10.3390/brainsci16040392

Authors: Dan-Alexandru Constantin Denisa Bianca Cristina Florin Gabriel Leașu Andrada-Georgiana Nacu Liliana Marcela Rogozea

Background/Objectives: Tobacco use is a leading cause of preventable death worldwide and is linked to major health and economic burden. Many smokers attempt to quit, yet long-term success rates with current medicines and counseling are still modest. Long-term nicotine exposure distorts brain systems involved in reward, craving, and self-control. These changes weaken inhibitory control and strengthen responses to smoking cues, which increases the risk of relapse. Transcranial magnetic stimulation (TMS) is a non-invasive technique that delivers magnetic pulses to specific cortical regions, most commonly the dorsolateral prefrontal cortex, to influence neural activity. This narrative review explored how transcranial magnetic stimulation may aid smoking cessation by acting on neural circuits linked to nicotine dependence. Methods: Five major databases were searched for studies published between 2015 and 2026. After removal of duplicates and screening, a total of 34 studies were included in this narrative synthesis. Randomized controlled trials, clinical studies, and neuroimaging investigations involving adults with nicotine dependence were included. A thematic narrative method was employed to synthesize findings due to the differences in study designs, protocols, and outcome measures. Results: TMS has been shown to attenuate cravings, decrease daily cigarette consumption, and decrease nicotine dependence in various studies. Several trials reported higher abstinence rates with active stimulation compared with sham treatment. Meta-analytic findings indicate stronger effects with 10 Hz stimulation and treatment courses of 20 sessions or more. Neuroimaging studies report changes in functional connectivity within reward, executive control, and salience networks, suggesting partial restoration of disrupted circuits. Treatment response varies according to age, educational level, baseline dependence, and stimulation parameters. Conclusions: These findings support transcranial magnetic stimulation as a promising brain-based approach for smoking cessation, while further well-designed trials with longer follow-up are still needed.

Brain Sciences doi: 10.3390/brainsci16040391

Authors: Yeonsu Kim Seounghun Lee Seong-Eun Kim Yeojung Kim Xianshu Ju Yulim Lee Tao Zhang Juyeon Kim Sungho Choi Jun Young Heo Woosuk Chung Jiho Park

Background/Objectives: Alterations in excitation/inhibition (E/I) balance, involving both inhibitory and excitatory signaling, have been implicated in the pathophysiology of autism spectrum disorder (ASD). Volatile anesthetics, including sevoflurane, act on multiple molecular and network targets, and anesthetic sensitivity may therefore differ in ASD. This study investigated whether sevoflurane sensitivity is altered in BTBR T+Itpr3tf/J (BTBR) mice, a widely used mouse model of ASD. Methods: Sevoflurane sensitivity was compared between BTBR mice and C57BL/6J (B6) control mice using behavioral and electroencephalographic (EEG) analyses. The minimum alveolar concentration required to abolish nociceptive responses (MACsevo) and the sevoflurane concentration associated with recovery of the righting reflex (RRsevo) were measured. Dose-dependent EEG changes, including burst suppression and theta power distribution, were also evaluated. Results: MACsevo did not differ significantly between BTBR and B6 mice. However, RRsevo was significantly lower in BTBR mice (1.10 ± 0.10%) compared with B6 mice (1.65 ± 0.13%; p < 0.001). EEG analyses demonstrated that burst suppression occurred at lower sevoflurane concentrations in BTBR mice (2.0%) than in B6 mice (2.4%). In addition, topographical mapping revealed distinct theta power dynamics between the two strains during anesthesia. Conclusions: BTBR mice exhibit increased sensitivity to sevoflurane during emergence from anesthesia and show distinct EEG patterns compared with control mice. These findings suggest altered anesthetic responsiveness in a mouse model of ASD and support the possibility that network-level neurophysiological differences may influence anesthetic responses. Further studies are needed to clarify whether similar alterations are present across other ASD models and human ASD populations.

Brain Sciences doi: 10.3390/brainsci16040390

Authors: Giovanni Umberto Borin Marta Aventaggiato Cristina Bittante Vittorio Cacciatori Alessia Segatti Elisa Concon Grazia Devigili Enzo Bonora Giacomo Zoppini Giovanna Maddalena Squintani

Background: Diabetic neuropathy manifests as symmetric distal and autonomic neuropathy, including cardiovagal dysfunction. Small-fiber involvement can occur, leading to neuropathic pain and dysautonomia. The diagnostic gold standard of these two conditions comprehends skin biopsy and cardiovascular autonomic reflex tests (CARTs), respectively. Non-invasive diagnostic tools, such as laser-evoked potentials (LEPs), show promise in detecting small-fiber damage, though correlations between LEP abnormalities and cardiovascular autonomic dysfunction remain poorly investigated. Methods: We retrospectively evaluated LEPs (from hands and feet stimulation) in 33 diabetic patients, comparing them to a cohort of 33 age-matched healthy subjects, to highlight any significant abnormalities in the diabetic cohort. We further analyzed the LEP results in T2DM cohort with clinical, laboratory variables and CARTs to explore potential correlations and to assess whether any association between LEPs and CARTs could be identified. Results: N2/P2 complex amplitude was significantly reduced in diabetic patients compared to healthy subjects, with greater involvement in the lower limbs. While no association between LEP abnormalities and abnormal CARTs was observed, LEP amplitude reductions were notably associated with elevated glycated hemoglobin levels and longer disease duration, which appeared to be the strongest predictor of LEP reduction. Conclusions: Our findings corroborated literature data regarding length-dependent LEP alterations detectable even in initial diabetic stages. The lack of correlation between LEP abnormalities and autonomic dysfunction may stem from the predominant involvement of C fibers in autonomic neuropathy, which are not adequately assessed by currently used LEPs.

Brain Sciences doi: 10.3390/brainsci16040389

Authors: Evgenia Gkintoni Apostolos Vantarakis

Background: The global burden of mental disorders continues to escalate, necessitating scalable, evidence-based interventions. Artificial intelligence (AI)-delivered health promotion programs represent a promising approach to addressing treatment gaps by targeting the neuropsychological mechanisms that underlie mental health outcomes. This meta-analysis synthesizes evidence on the effectiveness of AI-delivered interventions in improving executive function, emotion regulation, and clinical outcomes across diverse populations. Methods: A systematic search identified 186 studies (n = 22,755 participants) published between 2020 and 2025. Random-effects meta-analyses estimated pooled effect sizes (Hedges’ g, calculated as between-group standardized mean differences with small-sample correction [J = 1 − 3/(4df − 1)]) for primary outcomes. Between-study heterogeneity was quantified using I2 and τ2 statistics. To address dependency among effect sizes from studies reporting multiple outcomes, robust variance estimation (RVE) was employed. Subgroup analyses examined intervention modalities, delivery formats, and clinical populations. Moderator analyses explored sources of heterogeneity, including publication year, sample size, intervention duration, control condition type, risk-of-bias rating, geographic region, and AI sophistication tier, and mediational models tested putative therapeutic mechanisms. Results: AI-delivered interventions demonstrated a significant overall effect on health outcomes (g = 0.68, 95% CI [0.58, 0.78]; τ2 = 0.12; I2 = 73.4%). Executive function outcomes showed moderate effects (g = 0.61, τ2 = 0.08), with working memory improvements being strongest (g = 0.72). Emotion regulation outcomes demonstrated moderate-to-large effects (g = 0.61, 95% CI [0.51, 0.70], τ2 = 0.006); formal subgroup pooled estimates by emotion regulation strategy were not calculated due to insufficient studies per strategy (k < 3 per category); individual study effect sizes ranged from g = 0.27 to g = 1.11. Among 41 studies examining neuropsychological mechanisms, convergent patterns suggested involvement of prefrontal neural circuits (DLPFC), enhanced alpha-band activity, and improved heart rate variability; however, formal mediation was tested in only 18 studies (9.7%). Among clinical populations, interventions for cognitive impairment yielded the largest effects (g = 1.02; this finding should be interpreted cautiously given modest cumulative sample size [n = 482], potential small-study effects [Egger’s p = 0.08], and trim-and-fill adjusted estimate of g = 0.85), followed by mental health conditions (g = 0.72), while other clinical populations showed smaller but significant improvements (g = 0.19). Mobile applications (g = 0.78) and chatbot-based interventions (g = 0.74) demonstrated the strongest effects among delivery formats. Among studies testing formal mediation, analyses suggested mindfulness (β = 0.42), decentering (β = 0.38), and cognitive reappraisal (β = 0.45) as processes associated with therapeutic outcomes. Conclusions: AI-delivered health promotion programs demonstrate significant effectiveness across executive function, emotion regulation, and clinical outcomes, though substantial heterogeneity (I2 = 45–82%) indicates meaningful variability warranting attention to subgroup-specific effects. Given the diversity of intervention types included (chatbots, mobile apps, VR systems, neuromodulation), pooled estimates should be interpreted as characterizing the average effect across this heterogeneous landscape; subgroup-specific estimates provide more precise guidance for clinical decision-making regarding specific modalities. Effects are associated with convergent patterns of neuropsychological mechanisms, though mechanistic conclusions remain preliminary given that only 22% of studies (41/186) examined neuropsychological mechanisms, and formal mediation analyses were conducted in only 18 studies (9.7%); most of the mechanistic evidence is correlational rather than causal. Future research should establish standardized AI taxonomies, optimize adaptive algorithms, conduct adequately powered replication studies in populations with cognitive impairment, prioritize experimental mediation designs to establish causal pathways, and evaluate long-term maintenance effects with a minimum of 6–12-month follow-up periods.

Brain Sciences doi: 10.3390/brainsci16040388

Authors: Lucas Gorial Garmo Sid Osborn Emily Hock Julien Rossignol Gary L. Dunbar

Background/Objectives: Traumatic spinal cord injury (SCI) frequently results in permanent motor and sensory deficits. Tumor necrosis factor-α is rapidly upregulated after SCI and contributes to secondary injury cascades, including microglial activation, cytokine amplification, and blood–spinal cord barrier disruption. Etanercept, a TNF-α inhibitor, has been investigated in modulating post-SCI neuroinflammation. This systematic review synthesizes preclinical evidence evaluating the therapeutic role of etanercept in SCI. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. The review was not prospectively registered. PubMed, Scopus, and Web of Science were searched through 9 December 2025. Eligible studies included original investigations of etanercept administered for in vivo mammalian models of SCI. Non-English articles, preprints, conference abstracts, case reports, and reviews were excluded. Risk of bias was assessed independently by at least two reviewers using the SYRCLE tool. Due to heterogeneity in models and dosing strategies, meta-analysis was not performed. Results: Of 119 records identified, 36 duplicates were removed. After screening 83 titles and abstracts, 67 were excluded. One additional study was excluded after full-text retrieval. Thus, 15 articles were included. Primary outcomes varied between studies, including inflammation, histopathology, and functional recovery. Conclusions: Preclinical evidence suggests that etanercept may attenuate early neuroinflammation after SCI; however, methodological heterogeneity and limited data warrant further investigation. This work was supported by the College of Medicine at Central Michigan University, the John G. Kulhavi Professorship in Neuroscience, and the E. Malcolm Field and Gary Leo Dunbar Endowed Chair in Neuroscience at Central Michigan University.

Brain Sciences doi: 10.3390/brainsci16040387

Authors: Hanzhen Zhang Chunjing Tao

Background/Objectives: SSVEP-BCI has broad application potential in mobile human–computer interaction due to its high information transfer rate and stable signal characteristics. The introduction of deep learning technology has significantly advanced SSVEP decoding performance, offering novel approaches for processing short-duration signals and tackling complex classification tasks. The establishment of the Tsinghua Benchmark dataset provides a standardized benchmark for evaluating algorithm performance, accelerating the development of deep learning-based SSVEP decoding. However, a summary of SSVEP deep learning decoding technologies for real-time mobile applications is lacking. Methods: We conducted a comprehensive literature review of SSVEP deep learning decoding studies published since 2023, using the Tsinghua Benchmark dataset. This review focuses on technical developments targeting real-time performance, low computational complexity, and high robustness. Results: We summarize the key technologies developed for real-time mobile SSVEP decoding. Our analysis thoroughly examines how these techniques address core challenges in the engineering implementation of mobile brain–computer interfaces, including real-time processing requirements, resource constraints, and environmental robustness. Conclusions: This review provides a comprehensive overview of SSVEP deep learning decoding technologies for mobile applications, establishing a technical foundation to advance mobile brain–computer interfaces from laboratory settings to practical deployment.

Brain Sciences doi: 10.3390/brainsci16040386

Authors: Oscar Arias-Carrión Emmanuel Ortega-Robles Elías Manjarrez

Consciousness presents a structural puzzle: a unified, context-sensitive, globally integrated mode of experience emerging from distributed neural dynamics. While classical neuroscience has mapped synaptic, oscillatory, and network-level mechanisms with increasing precision, debate persists as to whether classical formalisms fully capture the integrative and contextual features of conscious processing. This review examines whether quantum principles offer explanatory leverage in two distinct senses: as formal mathematical frameworks for modeling contextual cognition, and as mechanistic hypotheses proposing biologically instantiated non-classical states. We surveyed empirical and theoretical developments spanning zero-quantum-coherence in MRI signals, entanglement-structured learning paradigms, quantum-inspired computational models, and proposed neural substrates, including microtubules, nuclear spins, and photonic architectures. Although certain findings have been interpreted as consistent with a non-classical structure, no study to date has demonstrated entanglement, long-lived coherence, or collapse dynamics in neural tissue under operational criteria comparable to those used in controlled quantum systems. Replication remains limited, biological entanglement witnesses are not yet established, and nonlinear classical dynamics can reproduce many putative quantum signatures. Accordingly, the decisive question is not whether the brain is quantum, but whether its dynamics exceed the explanatory reach of rigorously defined classical models. Progress hinges on replication, adversarial scrutiny, and operational criteria precise enough to discriminate genuine non-classical correlations from classical complexity. Whether quantum mechanisms ultimately prove necessary or refined classical models remain sufficient, this inquiry compels a deeper understanding of integration, contextuality, and the physical constraints shaping conscious experience.

Brain Sciences doi: 10.3390/brainsci16040385

Authors: Jocabed Mendoza-Martínez Fiacro Jiménez-Ponce Karla Nayelli Silva-Garcés Sergio Rodrigo Méndez García Adolfo Angel Casarez Duran Christopher René Torres-SanMiguel

Background/Objectives: Freezing of gait (FoG) is a disabling motor manifestation of Parkinson’s disease (PD) associated with impaired neural control of locomotion and increased gait variability. Quantitative characterization of gait kinematics may provide biomechanical insight into FoG-related instability, particularly under different dopaminergic states. Methods: This pilot study evaluated sagittal-plane knee kinematics in healthy individuals (n = 27) and patients with PD. (n = 8) under OFF and ON dopaminergic medication conditions using two-dimensional videogrammetry (Kinovea®). Knee flexion–extension trajectories were time-normalized to 0–100% of the gait cycle, and group ensemble profiles (mean ± SD) were computed. Results: Phase-specific range of motion (ROM), within-subject variability, and interlimb coordination were quantified. Interlimb coordination was assessed using Pearson’s correlation coefficients (r) and cross-correlation lag analysis computed per subject and summarized statistically across groups. Compared with healthy participants, PD patients in the OFF state exhibited significantly reduced knee ROM during stance and swing (p < 0.05), accompanied by increased kinematic variability and disrupted temporal coordination. Interlimb correlation was significantly lower in PD OFF compared to healthy gait groups (p = 0.010), with larger temporal lags, indicating impaired bilateral synchronization. Following medication intake (ON state), knee excursion increased and interlimb coordination partially improved; however, correlation values and timing symmetry did not fully normalize to healthy levels. Conclusions: These findings demonstrate that sagittal-plane knee kinematics and interlimb coordination metrics derived from low-cost 2D videogrammetry are sensitive to the dopaminergic state and reveal persistent neuromotor deficits in PD. The proposed framework provides an interpretable and accessible approach for characterizing gait organization in Parkinson’s disease and supports future integration with clinical assessment and longitudinal monitoring.

Brain Sciences doi: 10.3390/brainsci16040384

Authors: Yanis Mouheb Mélanie Louras Jean-François Maillart Olivia Gosseries Claudia Charry Aminata Bicego Audrey Vanhaudenhuyse

Background: Port-a-catheter (PAC) placement is a common procedure in oncology that, despite local anaesthesia, can induce patient discomfort, procedural pain, and anxiety. Virtual reality hypnosis (VRH), combining immersive virtual reality with clinical hypnosis, has been proposed as a non-pharmacological adjunct to reduce peri-procedural distress. Objectives: This pilot study aimed to explore the suitability of VRH during PAC placement and its potential effects on pain, anxiety, and VRH-related experiences, while investigating psychological variables associated with VRH engagement. Methods: In this single-arm interventional monocentric prospective pilot study, twenty oncology patients undergoing first-time elective PAC placement received a VRH intervention delivered via a medical-grade head-mounted display throughout the procedure. Pain, anxiety, and VRH-related dimensions—including absorption, dissociation, automaticity, arousal, and sense of presence—were assessed pre- and post-procedure using self-reported numerical rating scales and questionnaires. Non-parametric Wilcoxon tests evaluated pre–post changes, and correlational analyses (Pearson’s and Spearman’s when necessary) explored associations between variables. Results: VRH was well tolerated by most participants, although three patients required additional pharmacological support, and four could not complete the session due to intolerance or technical issues. Anxiety scores decreased significantly following VRH, whereas pain showed a non-significant trend toward reduction. Post-procedural absorption and dissociation were positively associated with presence, and higher absorption traits were linked to greater immersive engagement and prior VR/hypnosis experience. Cybersickness was negatively associated with absorption. Older age was correlated with lower post-procedural pain, and females reported higher state anxiety. Conclusions: In this pilot, VRH was feasible, well tolerated, and associated with a significant exploratory reduction in procedural state anxiety. Given the single-arm design, these findings constitute directional evidence warranting controlled trial evaluation rather than proof of efficacy. These preliminary results support the rationale for randomised controlled trials to evaluate VRH efficacy, underlying mechanisms, and potential role as a non-pharmacological adjunct in oncology perioperative care.

Brain Sciences doi: 10.3390/brainsci16040383

Authors: Caleb Barcenas Pamela Klonoff Alexandra Theodorou Jon Van Doren Samuel Schaffer Edward Koberstein Joseph Murthy Matty del Pino Luna Santiago Palmer Cancel

Background/Objectives: After an acquired brain injury (ABI), caregiver burden in family members is a clinical concern. Prior research has demonstrated that improved self-awareness in survivors of an ABI reduces caregiver burden. We examined the relationship between caregiver burden and ABI survivors’ levels of self-awareness across a span of injury chronicity following discharge from outpatient holistic milieu neurorehabilitation. Method: This retrospective observational study analyzed data on 59 individuals with heterogeneous ABIs who participated in an outpatient holistic milieu neurorehabilitation program from 2021 to 2025. This study utilized the discrepancy model of the Mayo-Portland Adaptability Inventory-4 (MPAI-4) to measure self-awareness in survivors of an ABI by calculating a discrepancy score from the self- and caregiver-rated MPAI-4 total score. Demographic information (age, education, race/ethnicity), injury history (injury type, age at injury, chronicity), program variables (length of program participation), functionality (MPAI-4), and caregiver burden (Zarit Burden Interview) at discharge were collected. Results: In order to predict caregiver burden based on self-awareness of an ABI survivor and time since injury, a multiple linear regression analysis was used. Although the multiple regression model significantly predicted caregiver burden, only self-awareness added significantly to the prediction and accounted for a modest proportion of the variance in caregiver burden. Conclusions: Self-awareness, as measured by utilizing the MPAI-4 discrepancy model, explained a modest proportion of the variance in caregiver burden regardless of time since injury. Among family members of survivors of an ABI, self-awareness of the survivor is a predictor of burden experienced by the family and would be beneficial to address as part of neurorehabilitation.

Brain Sciences doi: 10.3390/brainsci16040382

Authors: Soon Lee Christina B. Welch Karen Zinka Michael Evans Hea Jin Park Valery V. Lozada-Fernandez Franklin D. West

Background/Objectives: Mental health conditions, including stress, anxiety, depression, and sleep problems, represent a significant health concern globally. Mounting evidence suggests a link between mental health and the gut microbiome via the gut–brain axis. However, discrepancies in human microbiome data exist due to the heterogeneity in study design and analytical approaches. Thus, this study aimed to explore the gut microbial characteristics associated with self-reported mental health symptoms using multiple analytical methods. Methods: A total of 44 healthy adults, defined as individuals without any major chronic medical conditions, were assessed for mental health symptoms using self-reported questionnaire data. To evaluate gut microbial characteristics, stool samples were collected at six time points over 28 days and underwent 16S rRNA gene sequencing. Differential abundance was assessed via ANCOM-BC, and a random forest classifier was implemented to rank features important for the classification of mental health symptoms. Participants who did not report anxiety, stress, depression, or sleep problems served as the reference group for microbiome comparisons. Results: The proportion of participants with self-reported mental health symptoms was 11.4% (stress), 27.3% (depression), 31.8% (anxiety), and 15.9% (sleep problems). Participants reporting mental health symptoms showed differences in gut microbiome composition compared to asymptomatic participants, including variation in alpha- and beta-diversity. Differential analysis identified specific taxa with higher or lower relative abundance in participants reporting specific mental health symptoms. Random forest feature ranking identified partially overlapping taxa across methods, suggesting candidate associations warranting further investigation. Conclusions: These exploratory findings suggest that self-reported mental health symptoms in otherwise healthy adults are associated with differences in the gut microbiome. The taxa identified in this study represent candidates for validation in larger, independent cohorts.

Brain Sciences doi: 10.3390/brainsci16040381

Authors: Marli Appel da Silva Guilherme Welter Wendt

Background/Objectives: Fibromyalgia is increasingly viewed as a disorder of central sensitization, involving altered nociceptive processing and dysregulated stress and affective neural systems. Evidence supports shared neurobiological mechanisms linking chronic pain, emotional distress, and affect regulation, including corticolimbic and hypothalamic–pituitary–adrenal axis alterations. However, predictive models evaluating psychological distress as markers of these brain-based processes remain scarce. This study aimed to internally validate a preliminary model of fibromyalgia diagnosis using self-reported distress indicators as proxies of central dysregulation. Methods: A case-control design study with 180 participants was performed. Medically diagnosed fibromyalgia cases were recruited via a pain facility or referrals, alongside geographically matched controls from the general population. Psychological variables were conceptualized as neurobehavioral indicators reflecting central sensitization and stress-system dysregulation. Predictors were selected using LASSO penalized regression with 10-fold cross-validation. Retained variables were re-estimated using logistic regression. Model performance was evaluated through Nagelkerke’s pseudo-R2, a likelihood ratio test, and area under the curve (AUC). Internal validation was conducted via 1000-bootstrap resampling with calibration-slope-based shrinkage. Results: The final model included global psychological distress, positive affect, sex, and age (R2=0.359, with good discrimination [AUC = 0.81; optimism-corrected AUC ≈ 0.79]). Higher distress and age were associated with increased odds of fibromyalgia. Conclusions: Self-reported psychological distress, particularly global distress and reduced positive affect, combined with sex and age, showed internal validity in predicting fibromyalgia diagnosis. These findings support the hypothesis that behavioral markers of emotional dysregulation may reflect underlying central sensitization and stress-system alterations implicated in chronic pain. Future research integrating psychological measures with neuroimaging and neuroendocrine markers may further clarify the neural mechanisms linking affective dysregulation and chronic pain vulnerability.

Brain Sciences doi: 10.3390/brainsci16040378

Authors: Monan Wang Jiujiang Guo Xiaojing Guo

Background: The recognition of autism spectrum disorder (ASD) has been a challenge due to the heterogeneity in symptoms and complex variations in brain function. Resting-state functional magnetic resonance imaging (rs-fMRI) has become instrumental in studying these disorders by accessing underlying abnormal neural activity and connectivity. Recently, deep learning approaches have shifted the analysis of brain networks by capturing spatiotemporal information from fMRI sequences. Nonetheless, most existing studies are limited by relying on a single representational scale, typically restricting analysis to either voxel-level spatiotemporal patterns or static connectivity matrices. Additionally, the dynamic reconfiguration of functional coupling and its variations across different anatomical parcellations are often ignored, which obscures neurobiologically meaningful dynamics. Methods: In this regard, we propose a multi-atlas dynamic connectivity transformer fused with 4D spatiotemporal modeling for ASD recognition (MADCT-4D). Specifically, the framework comprises two complementary branches. The 4D spatiotemporal branch encodes raw rs-fMRI volumes to learn hierarchical representations of evolving neural activity, while the dynamic-connectivity branch models time-resolved functional connectivity sequences constructed from multiple atlases, enabling the network to capture dynamic reconfiguration at the connectome level under different parcellation granularities. Moreover, we perform late fusion by combining the branch-specific decision scores with a learnable gate, allowing the model to adaptively weight voxel-level dynamics and multi-atlas connectivity evidence for each subject. Results: Extensive experiments on the publicly available ABIDE dataset demonstrate that the proposed method achieves 90.2% accuracy for ASD recognition, outperforming multiple competitive baselines. Conclusions: The proposed framework yields interpretable biomarkers based on learned dynamic connectivity patterns that are consistent with altered functional coupling in ASD.

Brain Sciences doi: 10.3390/brainsci16040380

Authors: Mohamed Ouardouz Amanda E. Hernan J. Matthew Mahoney Rodney C. Scott

Background/Objectives: Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a triplet repeat expansion in the Fmr1 gene leading to the loss of Fragile X Messenger Ribonucleoprotein (Fmr1 protein). The loss of Fmr1 protein modulates many cell biological processes and leads to the emergence of intellectual disability and autism. FXS is modeled in Fmr1-KO mice that display features consistent with human FXS, including hypersensitivity, cognitive and learning deficits, hyperactivity and audiogenic seizures. Here, we investigated the effect of auditory stimulation during a range of developmental stages on recognition memory and sociability deficits in Fmr1-KO mice. Methods: Fmr1-KO mice were subjected to auditory stimulation for 2 min three times a day at one-hour intervals for 5 days at the nursing, juvenile and adult stages. The animals were tested for social interaction and novel object recognition at 2 to 3 months old. Results: During auditory stimulation, the wild running phenotype was observed in the Fmr1-KO juvenile animals and two animals at the nursing stage experienced status epilepticus and died. Fmr1-KO animals showed social deficits compared to both the control and animals exposed to auditory stimulation at the juvenile stage. In the novel object recognition task, auditory stimulation was more effective at the nursing and juvenile stages. Conclusions: These data show that auditory stimulation may be an effective way to restore cognitive and social deficits in FXS.

Brain Sciences doi: 10.3390/brainsci16040379

Authors: Laura Orsolini Giulio Longo Teresa Cantarini Salvatore Reina Umberto Volpe

Background: The widespread use of Social Networks (SNS), particularly among youths, could promote Feeding and Eating Disorders (FEDs), but could also be a tool for implementing FED prevention strategies. This study aimed to identify which SNS could be most effective for implementing primary and secondary FED prevention. Methodology: A cross-sectional study was conducted via an Italian population-based survey, distributed using a snowball sampling strategy. The survey included 283 participants aged 18–35 by using the Bergen Social Media Addiction Scale (BSMAS), the SCOFF screening tool for FEDs, items from the Body Uneasiness Test (BUT), and the Mukbang Addiction Scale (MAS). Results: The sample was predominantly female (69.3%). Participants screening positive on the SCOFF were more frequently TikTok users. Stepwise logistic regression analysis showed that TikTok use was associated with SCOFF positivity (OR = 1.9) and body image concerns (e.g., spending a lot of time in front of the mirror; OR = 1.9). Instagram use was associated with body image dissatisfaction (OR = 3.9). In the overall sample, the likelihood of screening positive on the SCOFF was associated with TikTok use (OR = 1.7), higher BSMAS scores (OR = 1.1), exposure to body positivity/neutrality content (OR = 1.9), and watching Mukbang videos (OR = 1.8). Conclusions: TikTok and, to a lesser extent, Instagram appear to be widely used by young individuals vulnerable to FEDs and body image dissatisfaction. These platforms may therefore represent strategic channels for delivering educational and preventive interventions targeting eating behaviors and body image among young people. Further longitudinal research is needed to clarify causal relationships and evaluate the effectiveness of SNS-based prevention strategies.

Brain Sciences doi: 10.3390/brainsci16040377

Authors: Dong Huang Lin Xu Yuwen Li

Emotion recognition plays a crucial role in human–computer interaction and mental health applications. Traditional Electroencephalogram (EEG)-based emotion recognition methods are limited in classification accuracy due to their neglect of the spatiotemporal characteristics of the signals and individual differences. This study proposes a novel EEG emotion recognition framework that integrates spatiotemporal features to enhance performance through the following innovations: (1) the use of a Recurrence Plot (RP) to transform one-dimensional EEG signals into two-dimensional images, enhancing the representation of nonlinear dynamic features; (2) the design of a Spatiotemporal Channel Attention Module (TCSA), which combines temporal convolution, channel, and spatial attention mechanisms to optimize the capture of complex patterns; and (3) the integration of the lightweight and efficient network Efficientnet to construct the TCSA-Efficientnet classification model. On the Database for Emotion Analysis using Physiological Signals (DEAP) dataset, the proposed method achieves accuracy rates of 99.11% and 99.33% for valence and arousal classification tasks, respectively. On the Database for Emotion Recognition Using EEG and Physiological Signals (DREAMER) dataset, the method achieves accuracy rates of 98.08% and 97.49%, outperforming other EEG-based emotion classification models on both datasets. This demonstrates its advantages in accuracy, robustness, and generalization.

Brain Sciences doi: 10.3390/brainsci16040376

Authors: Rocco Salvatore Calabrò

Neurorehabilitation has entered a phase of rapid conceptual expansion [...]

Brain Sciences doi: 10.3390/brainsci16040375

Authors: Jian Meng Demi Zhang Yuling Zhong Xiaodong Xu Edith Kaan

Background/Objectives: The processing and evaluation of behavior, actions or events that go against social (moral) norms can be assumed to operate on mental representations of the world and of how people typically behave. These mechanisms and representations may therefore be shared by the processing of meaning in general. The current study investigated whether the processing of deviations of morality can be distinguished from processing of semantic inconsistencies. Methods: Event-related brain potentials (ERPs) were recorded from English speakers while they read short written texts in English for comprehension. Texts contained words that constituted moral violations, semantic violations and neutral controls depending on the context, allowing for a direct comparison. Results: Using trial-based analyses, we found different ERP responses to semantic and moral violations: the moral violation elicited a long-lasting, posterior Late Positive Component (LPC) starting at around 300 ms, whereas the semantic violation elicited a positivity that started later and was descriptively more frontally distributed. Furthermore, the LPC amplitudes could be explained by the moral acceptance scores over and above plausibility scores, but not vice versa. Conclusions: The outcomes are compatible with the view that the processing of moral deviations engages at least some mechanisms that are different from the processing of semantic deviations.

Brain Sciences doi: 10.3390/brainsci16040374

Authors: Ilaria Guarracino Marta Maieron Serena D’Agostini Miran Skrap Paola Cogo Tamara Ius Barbara Tomasino

Background/Objectives: Performing presurgical functional magnetic resonance imaging (fMRI) mapping in young patients is considered a challenge for clinicians, as fMRI maps are the sole source of information about the functional organization of cognitive functions/areas, especially when an awake craniotomy is not possible, as is often the case for pediatric populations. The literature on the fMRI tasks used in pediatric populations with brain injuries shows a certain heterogeneity in the approaches (task-based or resting states) and tasks, with a preference for motor/language mapping: tasks assessing extra-language functions are lacking. Methods: We have designed fMRI tasks focused on language and extra-language functions, which can be easily be applied when clinicians need to perform presurgical mapping. We present a retrospective case series of 17 patients. Results: Seventeen young patients (13.4 ± 2.8 years; range 7–16) were included in the study, for whom fMRI was performed. All underwent successful fMRI mapping by completing fMRI tasks selected based on their lesion site. The number of tasks performed by each patient significantly correlated with their age (r(17) = 0.561, p = 0.019). The patients tolerated the assessment and had good motion control: their movement parameters were minimal (range of rotation of −0.015–0.01 degrees; range of translation of −0.8–0.2 mm). The most administered fMRI tasks were tongue motor localizer (60%) and object naming (70%), with some patients performing extra-language function mapping involving visuo-spatial processing, selective attention, memory, and inhibition. Conclusions: This is an exploratory study given the sample size. fMRI measurements were considered feasible, as patients were able to complete the tasks under clinically realistic conditions. We discuss the clinical implication/usefulness of administering tasks for a personalized functional assessment of the young patient before surgery.

Brain Sciences doi: 10.3390/brainsci16040373

Authors: Shanika Arachchi Ed Daly Anushree Dwivedi Lisa Ryan

In the original publication [...]

Brain Sciences doi: 10.3390/brainsci16040372

Authors: Maria Milioudi Stella Stabouli Dimitrios Zafeiriou Efthymia Vargiami

Attention-deficit/hyperactivity disorder (ADHD), brain–derived neurotrophic factor (BDNF), and enuresis are interconnected in several ways, primarily through their potential links to neurodevelopmental factors and brain function. ADHD is considered a neurobehavioral and neuropsychiatric condition characterized by numerous comorbidities, and it represents one of the most frequently encountered neuropsychiatric disorders in clinical practice. Enuresis constitutes a subgroup of intermittent incontinence occurring during sleep that can be further subdivided into monosymptomatic (MNE) and non-monosymptomatic enuresis (NMNE). BDNF plays a crucial role in neurodevelopment, including neuronal growth, proliferation, survival, differentiation, and synaptic plasticity. This narrative review synthesized available literature identified through a systematic search of PubMed/MEDLINE, Science Direct, and Scopus databases (January 2000–December 2025). However, the evidence base is heterogeneous, and findings regarding BDNF in ADHD are inconsistent. Studies examining BDNF in enuresis often involve urinary BDNF, which reflects local bladder production rather than central BDNF activity. Further research is needed to clarify the specific roles of BDNF in the development and manifestation of these conditions and to fully elucidate the complex relationship between BDNF, ADHD, and enuresis.

Brain Sciences doi: 10.3390/brainsci16040371

Authors: Carlo Reale Giuliana Costanzo Lorella Pasquinucci Carmela Parenti

Background: Neuropathic pain remains a major unmet clinical challenge. Growing evidence identifies sigma receptors (σRs) as pivotal intracellular modulators of maladaptive stress signaling, positioning them as promising non-opioid targets for chronic pain management. Notably, despite the pleiotropic nature of σRs in regulating diverse cellular pathways—which might theoretically suggest a high risk of off-target effects—current selective antagonists have demonstrated remarkable safety and tolerability profiles. Sigma-1 and sigma-2 receptors (σ1R and σ2R) are molecularly and functionally distinct proteins that regulate neuronal excitability, proteostasis, and neuroimmune communication, all mechanisms that characterize neuronal excitability and cellular stress adaptation. σ1R acts as a ligand-operated molecular chaperone at the mitochondria-associated endoplasmic reticulum membrane. Extensive preclinical data demonstrate that σ1R antagonism attenuates peripheral and central sensitization, suppresses neuroinflammation, and restores opioid analgesic efficacy. These findings are supported by the advanced clinical candidate E-52862, which has shown efficacy and a favorable safety profile in neuropathic pain conditions. σ2R, identified as transmembrane protein 97 (σ2R/TMEM97), functions as a regulator of cholesterol trafficking, lysosomal integrity, and integrated stress response (ISR). σ2R modulation alleviates neuropathic pain by restoring proteostatic balance and reducing ISR-driven neuronal vulnerability rather than directly suppressing excitability. Emerging σ2R ligands such as FEM-1689, UKH-1114, and CM-398 provide compelling proof-of-concept for durable, disease-modifying analgesia. Methods: A structured literature search was conducted using PubMed, Scopus, and Web of Science to identify studies published within the last decade describing σ1R and σ2R/TMEM97 biology, ligand development, and their preclinical or clinical evaluation in neuropathic pain. Reference lists were manually screened to ensure comprehensive coverage. Conclusions: This review synthesizes pharmacology, ligand development, and translational evidence supporting σRs as next-generation targets for neuropathic pain therapy, highlighting convergent roles of σ1R and σ2R in pain chronification and outlining future directions for structure-guided therapeutic strategies.

Brain Sciences doi: 10.3390/brainsci16040370

Authors: Mohamed Hesham Khalil

Chronic stress is among the most pervasive health challenges of contemporary urban life, yet its persistence is not simply a matter of external pressure. When adult hippocampal neurogenesis is impaired, the brain loses its capacity to regulate the hypothalamic–pituitary–adrenal (HPA) axis and distinguish new threats from familiar ones through dentate gyrus pattern separation, rendering stress self-perpetuating. Physical activity is widely recognised as a promoter of neurogenesis through brain-derived neurotrophic factor (BDNF), yet the built environments in which most people spend approximately 90% of their time simultaneously suppress BDNF through chronic stress and deny sufficient physical activity intensity to restore it, a condition known as type 2 allostatic overload sustained by architectural impoverishment. This paper proposes architectural enrichment as a theoretical framework designed to resolve this problem at its root through two independent but synergistic mechanisms: architecturally mediated voluntary stair use to elevate peripheral BDNF via metabolic pathways, and neurobiophilic design based on the Neurobiophilia Index to attenuate cortisol and passively support BDNF and neurogenesis. Twelve hypothesised neurobiological profiles are derived in a framework that advances the concept of hippocampal neurosustainability, proposing that buildings can be designed not merely to avoid harming the brain but to actively sustain its capacity for resilience amid the stressors of modern urban living.

Brain Sciences doi: 10.3390/brainsci16040369

Authors: Richard Baird Ryan Harrison Quinn Kennedy Mollie McGuire Dorion Liston

Background/Objectives: Due to their positions, professional baseball catchers are at elevated risk of concussion, which can impair visual processing. There is a need for sensitive sensorimotor monitoring tools to track concussion-related neurophysiological changes more accurately. We investigated whether oculometrics can address this need. Methods: Four Major League Baseball catchers completed an oculometric assessment shortly after suffering a concussion (Time 1) and again after completing vision rehabilitation (Time 2). The assessment produces 10 z-scored measures, including a summary score. Results: Players’ Time 1 summary score tended to be typical of a normal healthy adult (Mean = 0.07 z-scored units). On average, players improved by 1.3 z-score units from their Time 1 summary score (SD = 1.07). Exploratory analyses revealed that sensorimotor recovery was driven by smooth pursuit latency, proportion of tracking comprising smooth pursuit, and the amplitude of catch-up saccades. Conclusions: Our analysis was based on a very small sample of concussion cases, each of which was unique. Despite this limitation, our data show how oculometrics can measure improvements in visual processing following a concussion among baseball players with exceptional perceptual-motor skills. Our data highlight the risk that brain injuries in high-performing individuals go undetected due to standard-of-care tools normed to behavior from healthy control populations; for these athletes, “normal” scores cannot be interpreted as neurologically “healthy”.

Brain Sciences doi: 10.3390/brainsci16040368

Authors: Constantinos Halkiopoulos Evgenia Gkintoni Basilis Boutsinas

Background: Electroencephalography (EEG) provides millisecond-resolution measurements of neural activity, offering a unique potential to identify biomarkers of cognition, emotion, and mental health. However, the proliferation of methodologically diverse studies necessitates systematic synthesis to establish the reliability and clinical utility of proposed EEG biomarkers. Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed, PsycINFO, Web of Science, and Scopus for studies published 2015–2025 examining EEG correlates of cognitive control, learning, emotion regulation, and mental health. From 3847 initial records, k = 210 unique studies (estimated n ≈ 9935 participants across 38 countries; see Methods for sample size derivation) met the inclusion criteria. Random-effects meta-analyses estimated pooled effect sizes for primary EEG markers across five research domains. Results: Frontal-midline theta demonstrated robust effects for cognitive control (k = 12; d = 0.89, 95% CI [0.72, 1.07]; I2 = 0.0%) and learning/memory (k = 10; d = 0.70, 95% CI [0.50, 0.89]). The late positive potential indexed emotional processing (k = 18; d = 0.87, 95% CI [0.75, 1.00]) and regulation success (k = 14; d = −0.65, 95% CI [−0.79, −0.51]). Neurofeedback showed very large effects for PTSD (k = 2; d = −1.98, 95% CI [−2.50, −1.47]) and moderate effects for anxiety (d = −0.62), ADHD (d = −0.60), and depression (d = −0.42). Alpha event-related desynchronization marked cognitive engagement (k = 18; d = −0.70, 95% CI [−0.85, −0.55]). Heterogeneity was negligible (I2 = 0.0%) in most analyses, except for clinical interventions, which showed condition-explained heterogeneity (I2 = 75.4%). Conclusions: EEG biomarkers demonstrate substantial effect sizes and a notable consistency across cognitive and clinical domains, supporting their potential as candidate neurophysiological indicators for diagnostic research, the investigation of treatment response, and intervention monitoring. Causal claims are not warranted from this evidence base alone. A four-phase implementation framework is proposed to facilitate clinical translation. Future research should prioritize methodological standardization, diverse samples, and real-world validation.

Brain Sciences doi: 10.3390/brainsci16040367

Authors: Bo Liu Yuntena Wu Tonglin Jin Zeyu Lei

Background/Objectives: Increased accessibility of suicidal cognitions reflects the cognitive processes underlying the acquisition of suicidal thoughts. Previous research shows that expectation violation reduces the accessibility of life cognitions rather than increasing that of suicidal cognitions, but this may be due to a slowing effect masking an increase in suicidal cognitions. Methods: Beyond the reaction time task, the present study used simultaneous EEG-fNIRS to reveal how expectation violation differentially affects the accessibility of suicidal and life cognitions. In a trial-by-trial cognitive task, participants read sentences that were either semantically consistent (expectation confirmation) or anomalous (expectation violation), followed by a semantic judgment on suicide-related, neutral, and life-related words. Response times for each word type served as a measure of cognitive accessibility for that category. Results: Compared to expectation confirmation, expectation violation reduced the cognitive accessibility of life rather than increasing that of suicide in the reaction time task. However, in neural responses, it led to reduced N1 amplitude, increased P2 amplitude for suicide-related information, and greater hemodynamic response in the left frontopolar region. Conclusions: Expectation violation triggered distinct neural responses to suicidal information, reflecting an attentional bias that may explain how suicidal thoughts emerge within normative cognition.

Brain Sciences doi: 10.3390/brainsci16040366

Authors: Kazuyuki Matsumoto Keita Kiuchi Hidehiro Umehara Masahito Nakataki Shusuke Numata

Background/Objectives: Multimodal depression detection research has traditionally relied on early or hybrid fusion strategies without systematically analyzing how dynamic fusion mechanisms interact with modality-specific pretraining. Although gated and attention-based architectures are increasingly adopted, their behavior is rarely examined within a structured fusion taxonomy framework. Methods: In this study, we conduct a controlled taxonomy-level evaluation of multimodal fusion strategies in a Japanese PHQ-9-annotated depression dataset. We compare four fusion paradigms (concatenation, summation, gated fusion, and cross-attention) across three integration stages, crossed with modality-specific affective pretraining configurations for visual (CMU-MOSI/MOSEI), acoustic (JTES), and textual (WRIME) encoders, yielding 512 experimental conditions. Results: The results reveal strong position-dependent effects of fusion strategy. Cross-attention fusion at the audio integration stage achieved the highest mean AUC (0.774) and PR-AUC (0.606), with statistically significant superiority over gated and concatenation-based fusion (Kruskal–Wallis H=86.28, p<0.001). In contrast, fusion effects at the text stage were non-significant in AUC but significant in PR-AUC, highlighting metric-sensitive behavior under class imbalance. Pretraining effects were modality-specific: SigLIP initialization produced significant positive transfer (Δ=+0.018, p<0.001), whereas audio pretraining on JTES resulted in negative transfer (Δ=−0.014, p=0.004), suggesting domain mismatch effects. Gate analysis further revealed condition-dependent modality dominance, including cases of semantic–geometric reversal under joint auxiliary augmentation. Conclusions: Our findings suggest that multimodal depression detection systems should not be interpreted through static fusion categories alone. Instead, modality contribution appears to be associated with structured interaction effects between fusion strategy, integration position, and affective pretraining. This work provides a controlled empirical bridge between fusion taxonomy and dynamic modality weighting in clinical multimodal modeling.

Brain Sciences doi: 10.3390/brainsci16040365

Authors: Vasileios T. Stavrou Panagiotis Zis

Background: The pain experienced by people with fibromyalgia (FM) is thought to be the result of altered nociceptive processing, impaired descending inhibition and reduced tolerance to physical load. However, the relationship between the amount of exercise and pain reduction remains unclear. Methods: This study synthesized randomized controlled trials of exercise interventions for FM to quantify the combined analgesic effects of different types of exercise. A secondary aim was to standardize exposure using metabolic equivalent of task (MET)-based metrics and examine the association between cumulative intervention dose (MET·h) and analgesic response (Hedges’ g) across intervention arms. Following the PRISMA guidelines, a search was conducted in PubMed for randomized controlled trials published up to 31 December 2025. After screening and a full-text assessment, 15 trials were included. The protocols were converted into MET-defined intensity and weekly MET·min exposure, and the cumulative dose was calculated as the total MET·h accrued over the intervention period. Random-effects models were used to estimate the pooled effects within modality subgroups. Results: Across modalities, exercise was associated with reductions in pain, with effects typically falling within the small-to-moderate range. Larger improvements were observed in structured or supervised programs. The dose-response scatter plot showed wide variability across the dose range, with overlapping confidence intervals. An exploratory fourth-degree polynomial fit explained limited variance (R2 = 0.1615) and did not indicate a monotonic dose-response pattern. This suggests that cumulative workload alone is a weak proxy for therapeutic response. Conclusions: Based on these findings, a pain-responsive algorithm combining weekly Visual Analogue Scale (VAS), ΔVAS and Talk Test thresholds was implemented as a preliminary online calculator to support the prescription of exercise tailored to symptoms.

Brain Sciences doi: 10.3390/brainsci16040364

Authors: Miriam M. Moser Luka Laub Dorian Hirschmann Anna Cho Wei-Te Wang Philippe Dodier Gerhard Bavinzski Karl Roessler Arthur Hosmann

Background: Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating neurological condition, with patients presenting with poor-grade aSAH having a particularly limited potential for recovery. Data on outcome trajectories after microsurgical clipping in this subgroup are scarce. The objective of this study was to analyze the functional outcomes in patients with poor-grade aSAH treated with microsurgical clipping, and to identify clinical factors associated with recovery. Methods: This retrospective study included 38 patients (median age 55 years; 60.5% female) with World Federation of Neurosurgical Societies (WFNS) grades 4–5, who underwent microsurgical clipping at a single tertiary care centre between 2016 and 2023. Functional outcome was assessed using the modified Rankin Scale (mRS) at hospital discharge and 6 months follow-up, and functional outcome was analyzed in relation to clinical variables (delayed cerebral ischemia (DCI), intracerebral hemorrhage (ICH), initial seizures, the need for decompressive craniectomy) using correlation and group comparison analyses. Results: The indication for microsurgical clipping was primarily driven by the need for ICH evacuation (50%) or by aneurysm configuration (47.5%). Microsurgical aneurysm clipping was performed on the day of hemorrhage in 25 patients (65.8%), with 16 patients (42.1%) undergoing immediate surgery following direct transfer from the emergency department to the operating theatre. ICH was present in 60.5% and IVH in 92.1%. Decompressive craniectomy was performed in 42.1%. DCI occurred in 21.6% of patients. In-hospital mortality was 15.8%, increasing to 22.6% at 6 months follow-up. Good functional outcome (mRS 0–2) was observed in 10.5% of patients at discharge and improved to 25.8% at 6 months. At hospital discharge, higher mRS scores were associated with the need for immediate aneurysm repair (p = 0.04), primary decompressive craniectomy (p = 0.02), and DCI (p = 0.006). Primary decompressive craniectomy (p = 0.04), reflecting greater disease severity, and DCI (p = 0.002) remained associated with worse functional outcome at 6 months. Conclusions: In poor-grade aSAH patients undergoing microsurgical clipping, mortality remains substantial; however, functional recovery may extend beyond hospital discharge. The need for immediate surgical intervention and primary decompressive craniectomy likely reflects a particularly severe hemorrhagic burden in patients and is associated with worse early functional outcomes, whereas DCI remains an important factor in overall functional recovery.

Brain Sciences doi: 10.3390/brainsci16040363

Authors: Zhehan Wang Yuliang Ma Yicheng Du Qingshan She

Background: The decoding of motor imagery electroencephalography (MI-EEG) is constrained by core issues including low signal-to-noise ratio (SNR) and cross-session as well as cross-subject domain shift, which seriously impedes the practical deployment of brain–computer interfaces (BCIs). Methods: To address these challenges, this paper proposes a novel end-to-end MI-EEG decoding method named BARN-DA. Two innovative modules, Band-Aware Channel Attention (BACA) and Multi-Scale Kernel Perception (MSKP), are designed: one enhances discriminative channel features by modeling channel information fused with frequency band feature representation, and the other captures complex data correlations via multi-scale parallel convolutions to improve the discriminability of the network’s feature extraction. Subsequently, the features are mapped onto the Riemannian manifold. For the source and target domain features residing on this manifold, a Riemannian Maximum Mean Discrepancy (R-MMD) loss is designed based on the log-Euclidean metric. This approach enables the effective embedding of Symmetric Positive Definite (SPD) matrices into the Reproducing Kernel Hilbert Space (RKHS), thereby reducing cross-domain discrepancies. Results: Experimental results on four public datasets demonstrate that the BARN-DA method achieves average cross-session classification accuracies of 84.65% ± 8.97% (BCIC IV 2a), 89.19% ± 7.69% (BCIC IV 2b), and 61.76% ± 12.68% (SHU), as well as average cross-subject classification accuracies of 65.49% ± 11.64% (BCIC IV 2a), 78.78% ± 8.44% (BCIC IV 2b), and 78.14% ± 14.41% (BCIC III 4a). Compared with state-of-the-art methods, BARN-DA obtains higher classification accuracy and stronger cross-session and cross-subject generalization ability. Conclusions: These results confirm that BARN-DA effectively alleviates low SNR and domain shift problems in MI-EEG decoding, providing an efficient technical solution for practical BCI systems.

Brain Sciences doi: 10.3390/brainsci16040362

Authors: Ismail Altintop Mehmet Tatli Zeynep Soyer Sarica Arzu Hanım Yay Çiğdem Karakukcu

Background: Contrast-induced encephalopathy (CIE) is an uncommon yet clinically significant complication associated with iodinated contrast media, with its mechanisms remaining unclear. Objective: The aims of this study are to examine the neurotoxic effects of contrast media and assess the neuroprotective roles of N-Acetylcysteine (NAC) and sildenafil with regard to HIF-1α expression. Methods: Thirty-six female Wistar albino rats (n = 36) were allocated into four experimental groups (n = 9 each): control, contrast media + saline (CMA + Saline), contrast media + NAC (CMA + NAC), and contrast media + sildenafil (CMA + Sildenafil). NAC (150 mg/kg) and sildenafil (50 mg/kg/day) were administered intragastrically for 48 h before exposure to contrast media. Biochemical, histopathological, and immunohistochemical evaluations were conducted 48 h post-contrast administration. Results: Exposure to contrast media resulted in neuronal death, vascular obstruction, and increased hypoxia-inducible factor-1 alpha (HIF-1α) immunoreactivity. The primary outcome measure, tissue HIF-1α concentration by ELISA, did not differ significantly among groups (p = 0.119). Semi-quantitative immunohistochemical analysis revealed significant group differences in HIF-1α immunoreactivity (p < 0.001), with all injury/treatment groups differing significantly from control. The difference between the contrast media group and the sildenafil-treated group approached but did not reach statistical significance after correction for multiple comparisons (Dunn’s test, p = 0.050). Conclusions: The primary biochemical endpoint did not demonstrate significant group differences. Secondary IHC analysis suggests a potential attenuation of HIF-1α immunoreactivity by sildenafil, though this did not reach statistical significance and requires confirmation in adequately powered studies. HIF-1α immunoreactivity warrants further investigation as a potential biomarker for contrast-induced neural injury.

Brain Sciences doi: 10.3390/brainsci16040361

Authors: Stella Margoni Senad Hasaj Guglielmo Donofrio Georgios D. Kotzalidis Tommaso Callovini Mario Pinto Camilla Scialpi Matteo Bucci Maria Benedetta Anesini Gabriele Sani Lorenzo Moccia Delfina Janiri

Background/Objectives: Schizophrenia is a severe psychiatric disorder frequently characterised by sleep and circadian disturbances, which are closely linked to cognitive dysfunction, symptom exacerbation, and poor functional outcomes. A growing body of evidence implicates the orexin (hypocretin) system—an essential regulator of arousal, sleep–wake stability, metabolic processes, and motivated behaviour—in the pathophysiology and treatment response of psychotic disorders. We aimed to investigate the relationships between the orexinergic system and psychoses. Methods: On 3 March 2026, we searched the PubMed, Scopus, PsycInfo/Articles and Cinahl databases for studies dealing with the orexin system and psychotic disorders and treatment response. Results: We found 20 eligible studies reporting variable and inconsistent alterations in orexin signalling in patients with schizophrenia. Studies were mostly cross-sectional and heterogeneous in design. Antipsychotic medications interfere with orexin-dependent pathways, potentially contributing to both therapeutic effects and adverse outcomes such as sleep disruption and metabolic dysregulation. Conclusions: While evidence from preclinical studies could point to an influence of dopaminergic activity through orexinergic mechanisms, with possible attenuation of antipsychotic-induced motor side effects and improvement of attentional deficits associated with NMDA receptor hypofunction, the utility of dual orexin receptor antagonists (DORAs) in psychoses is unclear. Despite the high prevalence of insomnia in schizophrenia, its pharmacological management remains suboptimal, with current treatments often limited by reduced efficacy or tolerability concerns. DORAs, which are currently approved medications for the treatment of insomnia, represent a novel and mechanistically distinct therapeutic option that may improve sleep while modulating arousal- and cognition-related circuits relevant to psychosis.

Brain Sciences doi: 10.3390/brainsci16040360

Authors: Pardise Elmi Dorsa Mavedatnia Gabriel Berberi Marc Lawrence Angelina Tohmé Xinyuan Hong Daniel Lelli Darren Tse

Background/Objective: Dizziness is managed using various therapies, including lifestyle changes, nutritional supplementation, pharmaceutical therapies, and physical therapy, each offering differing efficacy. With legalization of cannabis in Canada, patients are exploring its use in treating their dizziness and related symptoms. Limited knowledge exists regarding usage patterns, forms, doses, and effects on these symptoms. The current study aims to examine cannabis use in patients experiencing dizziness. Methods: We conducted a cross-sectional study at the Ottawa Hospital outpatient neuro-otology clinic. Eligible participants included new patients presenting with a primary complaint of dizziness and follow-up patients reporting new-onset dizziness. Participants completed a questionnaire capturing demographic data, dizziness and related symptoms, attitudes toward cannabis use, consumption patterns, and its perceived effects on their symptoms. Results: Of 154 participants, 118 (77%) expressed willingness to consider cannabis for dizziness and 78 (51%) reported previous cannabis use. Of those patients, 44 (56%) consumed it recreationally, largely via smoking (29/78, 37%). Approximately 21% of these patients reported a moderate–large subjective relief from dizziness after use of cannabis. The most common diagnoses amongst cannabis users were migraine/vestibular migraine (24%), persistent postural perceptive dizziness (22%), and benign paroxysmal positional vertigo (17%). Other related symptoms relieved by cannabis included sleep (28/78, 36%), emotional difficulties (17/78, 22%), neck pain/stiffness (14/78, 18%) and headaches/migraines (9/78, 12%). Conclusions: There is generally a positive attitude towards cannabis use in treating dizziness amongst patients, with a subset of patients reporting a subjective improvement of dizziness and its related symptoms, such as sleep and emotional difficulties.

Brain Sciences doi: 10.3390/brainsci16040359

Authors: Ju-Hak Kim Myoung-Ho Lee Myoung-Kwon Kim

Background: This paper presents a systematic review and meta-analysis to identify the effects of Rhythmic Auditory Stimulation (RAS) delivered via wearable devices on the gait and balance in patients with Parkinson’s disease. Method: The PICO criteria were established according to the PRISMA 2020 guidelines, and literature searches were performed across five databases covering studies published between 2015 and 2025: PubMed, Embase, Cochrane, Scopus, and Web of Science. After applying the inclusion criteria, eleven randomized controlled trials (RCTs) were selected. The quality of the studies was evaluated using the PEDro Scale and ROB-2. Statistical analyses were performed using Review Manager 5.4 based on the number of samples, means, and standard deviations to calculate the effect sizes. Result: The analysis results showed that wearable RAS significantly improved the gait speed (SMD = 0.49, p < 0.05) and balance ability (SMD = 0.40, p < 0.05), while no significant differences in the gait pattern, FOG-Q, or UPDRS-III were observed. The heterogeneity among studies was low, and the funnel plots were distributed symmetrically, indicating minimal publication bias. The average PEDro score was 7.33, suggesting moderate-to-high methodological quality. Conclusion: wearable RAS was identified as an evidence-based intervention effective in improving the gait speed and balance in patients with Parkinson’s disease.

Brain Sciences doi: 10.3390/brainsci16040358

Authors: Piotr Skalski Katarzyna Pękacka-Falkowska Agnieszka Pluto-Prądzyńska Michał K. Owecki

Background/Objectives: Psilocybin has re-emerged as a promising intervention for neuropsychiatric disorders including major depressive disorder, treatment-resistant depression, anxiety associated with life-threatening illness, obsessive compulsive disorder, and substance use disorders. However, conventional randomized controlled trials (RCTs)—the current gold standard in evidence-based medicine—may not adequately capture the therapeutic complexity of psilocybin, which depends not only on pharmacological action but also on contextual, psychological, and interpersonal factors. This critical narrative review aimed to evaluate the adequacy of existing clinical research frameworks for assessing psilocybin’s therapeutic potential and to explore alternative methodologies that may better reflect real-world clinical conditions. Methods: Using the Web of Science Core Collection database, we identified and analysed the ten most cited clinical studies on psilocybin published between 2015 and 2025 inclusive. Additional literature was included through reference cross-checking, systematic reviews, meta-analyses, and interdisciplinary sources covering neurobiology, history, and real-world evidence (RWE). The review synthesizes clinical outcomes, methodological constraints, and epistemic considerations relevant to psychedelic-assisted therapy. Results: Evidence from highly cited trials demonstrates rapid and sustained antidepressant and anxiolytic effects of psilocybin, with notable benefits also observed in addiction treatment. However, significant methodological limitations were identified, including selection bias, challenges in placebo design and blinding, small sample sizes, and the underrepresentation of diverse populations. Psilocybin outcomes were strongly influenced by subjective experience and contextual factors such as set and setting. Emerging RWE studies revealed heterogeneous patterns of response and provided insights unattainable through RCTs alone. Conclusions: Psilocybin shows considerable therapeutic promise, but current RCT methodologies capture only part of its clinical effects. Comprehensive evaluation will require larger and more diverse clinical trials, long-term follow-up, standardized psychotherapeutic protocols, and the integration of RWE to reflect real-world practice. Psychedelic-assisted therapy should be conceptualized as a complex intervention that combines pharmacological and psychotherapeutic components.

Brain Sciences doi: 10.3390/brainsci16040355

Authors: Maria Cafaro Laura Ambrosecchia Valeria Cioffi Enrica Tortora Raffaele Sperandeo Daniela Cantone

Background/Objectives: This article is a narrative review that examines the development of attachment from intrauterine life to the first thousand days of a child’s life, integrating psychoanalytic, neuroscientific, genetic, and cross-cultural perspectives. Biological, relational, neurological, and cultural factors interact and shape individual differences in socio-emotional functioning. This paper aims to propose a reinterpretation of early attachment, describing it as both a clinical and relational phenomenon and an adaptive process inscribed in human evolutionary history, according to the Four-Domain Integrative Framework described herein. Methods: The review examined three main areas of evidence: early attachment characteristics, cross-cultural caregiving variations, and genetic and epigenetic mechanisms underlying environmental sensitivity. Results: The review first identified seven characteristics of early attachment (proximity seeking, emotional attunement, intrauterine experiences, maternal holding, security patterns, brain plasticity, and maternal stress) which represent developmental mechanisms that generate individual differences in trust, self-regulation, resilience, and psychopathological vulnerability. Second, cross-cultural variations in six distinct caregiving contexts were examined, demonstrating that secure attachment emerges through culturally specific pathways, differentially influencing motor development, sleep patterns, hypothalamic–pituitary–adrenal axis maturation, and social skills. Finally, the differential susceptibility model was provided through the analysis of five genetic and epigenetic systems (oxytocin receptor gene, serotonin transporter gene, dopamine receptor gene, glucocorticoid receptor methylation, and fetal programming) that modulate environmental sensitivity. Conclusions: Biological, relational, neurological, and cultural factors interact and shape individual differences in socio-emotional functioning.

Brain Sciences doi: 10.3390/brainsci16040356

Authors: Giuditta Smith Elisa Bassoli Yagmur Ozturk Emily Arteaga-Garcia Wanjing Anya Ma ROAR Developer Consortium ROAR Developer Consortium I-ROAR Data Collector Consortium I-ROAR Data Collector Consortium Jason D. Yeatman Marilina Mastrogiuseppe Sendy Caffarra

Background/Objectives: With growing waves of migration, children speaking a home language different from the language of school literacy have become increasingly common in Western education systems. In this context, understanding and monitoring bilinguals’ reading development is crucial to inform both educational and clinical practices and ensure equitable services. The present study contributes to the literature by investigating learning patterns in single-word reading across primary school grades. Monolingual and bilingual children learning to read in an alphabetic orthography were examined. Methods: The sample consisted of 565 typically developing monolingual and bilingual primary school children from grades 1–5 (bilinguals = 162). Participants completed a computerised Lexical Decision task (LDT) recording accuracy and response times, and standardised tests of reading and cognition. A parental questionnaire was used to gather socio-demographic and linguistic information. Results: Response bias-corrected accuracy rates in the LDT revealed an increase in sensitivity across school years after correcting for potential confounds (SES, vocabulary, nonverbal intelligence). No significant effect of bilingualism was observed. Response times for correct responses also decreased consistently across grades after controlling for the same confounds. Although no significant main effect of bilingualism emerged, an interaction with grade revealed a greater decrease in response times for second-grade bilinguals compared to monolingual peers. Conclusions: Monolingual and bilingual children showed comparable sensitivity rates and reading times, suggesting similar decoding skill acquisition. However, an earlier decrease in response times for bilinguals points to a facilitatory effect in the early stages of reading development, consistent with a bilingual advantage during skill learning.

Brain Sciences doi: 10.3390/brainsci16040357

Authors: Tiziana Iaquinta Luca Pullano Elena Commodari Francesca Foti

Background/Objectives: Observational learning allows people to acquire new skills by observing the actions of others embedded in their social environment. From childhood, observational learning is a central process in human cognitive development, playing a crucial role in the acquisition of complex skills. Children and adults with autism spectrum disorder (ASD) often exhibit deficits in what are considered prerequisites for observational learning to occur (i.e., attending, imitation, delayed imitation, consequence discrimination). Considering this, the present review examined the literature on the complex and timely question of whether individuals with ASD can learn by observation, while accounting for the social versus non-social nature/content of the tasks. Methods: This work was a narrative review aimed at providing an overview of published studies in which observational learning was analyzed in individuals with ASD. Twenty-two studies met the inclusion criteria and were eligible for this review. Results: The core findings indicate that individuals with ASD may be able to learn by observing others, especially when taught the prerequisites for observational learning. Furthermore, the findings indicate that observation may be an effective way to expand the typically restricted and circumscribed interests of children with ASD and to increase emotion recognition skills. Conclusions: Overall, these findings have significant educational, clinical, social, and economic implications, supporting the use of observational learning strategies for both social and non-social skills to reduce reliance on expensive one-on-one teaching and to address some of the core deficits of ASD.

Brain Sciences doi: 10.3390/brainsci16040354

Authors: Katarzyna Nowomiejska Aleksandra Czarnek-Chudzik Anna Niedziałek Robert Rejdak Radosław Pietura Kamil Jonak

Background/Objectives: To investigate the volume of the lateral geniculate nucleus (LGN) in patients with advanced retinitis pigmentosa (RP). Methods: Nineteen patients with advanced RP (mean age 52 years and mean duration of illness 357 months) and twenty-one age-matched normal subjects have been examined using 7 Tesla MRI of the brain. Brain segmentation was carried out with the “recon-all” function in the FreeSurfer software (version 7.4.1) package. Results: The volumes of the left and right LGN were significantly smaller in those patients with RP, in comparison to the controls. We found a significant positive correlation between the volume of the left LGN and the right eye best-corrected visual acuity in the RP group. Conclusions: Late-stage RP leads to a significant reduction in LGN volume, as measured with 7 Tesla MRI. The volume of the left LGN was correlated with the visual function of the right eye in patients with late-stage RP. The statistical power of the results is limited by there being a low number of RP patients included in this study, which is due to the low prevalence of this rare eye disease.

Brain Sciences doi: 10.3390/brainsci16040353

Authors: Lingping Meng Mingzheng Li Xiao Sun

Background: This study examined age-related differences and interrelationships among psychological symptoms, personality traits, and emotional expression styles in a community sample of 151 participants aged 10–77 years, spanning four age groups: adolescents, young adults, middle-aged adults, and older adults. Methods: Psychological symptoms were assessed using the SCL-90, personality traits using the Big Five Inventory-2 (BFI-2), and emotional expression patterns were derived from facial expression recognition via a convolutional neural network (CNN) model. Kruskal–Wallis H tests were used to examine age-related differences. K-means cluster analysis was applied to identify emotional expression patterns, and logistic regression was used to construct a mental health risk screening model. Results: The young adult group (19–35 years) achieved the highest scores on the depression (M = 1.73) and anxiety (M = 1.61) dimensions, indicating a higher level of psychological distress during this life stage. Personality traits showed a significant developmental trajectory: neuroticism decreased with age (H(3) = 17.09, p < 0.001, η2 = 0.11), declining from 2.69 in the young adult group to 2.17 in the older adult group; conscientiousness increased with age (H(3) = 37.39, p < 0.001, η2 = 0.24), representing the most substantial age-related effect. K-means clustering identified three distinct emotional expression patterns: Cluster 1 was characterised by happiness, Cluster 2 by anger, disgust, and fear, and Cluster 3 by neutrality, sadness, and surprise. Cluster 2 exhibited the highest scores on neuroticism, anxiety, depression, and mood swings, and scored significantly higher than the other two clusters on interpersonal sensitivity, depression, anxiety, and hostility (p < 0.05). Mental health risk screening indicated that 26.5% of participants were classified as high-risk. Logistic regression analysis (AUC = 0.742) showed that neuroticism was the strongest predictor of elevated mental health risk (OR = 4.58), while extraversion (OR = 0.41) and conscientiousness (OR = 0.57) were significant protective factors. Conclusions: These findings provide exploratory evidence regarding age-related patterns of psychological symptoms and personality traits in a convenience sample and offer preliminary support for personality-based mental health risk screening. Notably, the SCL-90 was employed as a screening tool rather than for clinical diagnosis. Given the unequal age group sizes, particularly the small young adult subgroup, generalisability across the lifespan should not be assumed.

Brain Sciences doi: 10.3390/brainsci16040352

Authors: Donald Moss

This review examines what constitutes heart rate variability (HRV), the relationship between HRV and the autonomic nervous system, and the physiology driving HRV. HRV is correlated with vagal nerve activity and parasympathetic nervous activation. Higher HRV is correlated with youth, active lifestyle, adaptive capacity, and good health. Next, the review examines the medical significance of HRV, especially the correlation between lower HRV and the presence of medical and psychological disorders. In general, HRV serves as a biomarker for health and disease, an index of autonomic nervous system dysregulation, an index of prefrontal cortical functionality, and a marker for psychopathology across diagnoses. Higher HRV is associated with several characteristics associated with successful psychotherapy and hypnotherapy: social engagement, compassion, emotional regulation, and cognitive flexibility. Given this association, somatic regulation should be regarded as integral to treatment alongside psychotherapy and hypnosis. Understanding HRV can enable the psychotherapist and hypnotherapist to optimize treatment. In effect, the therapist can harness the power of the brain and nervous system to better prepare the patient for therapy and to enhance the process of therapy. This review encourages therapists to utilize several strategies and interventions to increase patients’ HRV levels prior to and during therapy. The review will be most applicable for those hypnotherapists who integrate hypnosis into counseling and psychotherapy. The review describes the process by which HRV biofeedback training guides the individual to voluntarily increase HRV. It also identifies a number of lifestyle parameters and self-care practices (including self-hypnosis) that increase HRV. Encouraging lifestyle and self-care practices to increase HRV can support a greater response to hypnotherapy and psychotherapy. With additional training, hypnotherapists can integrate HRV biofeedback into a hypnosis practice. Further, several simple interventions already within the scope of most hypnosis practitioners can be utilized to enhance HRV at the beginning of a hypnotherapy process, and again during the process of therapy.

Brain Sciences doi: 10.3390/brainsci16040351

Authors: Jesse Shamsul Alessandro Pesaresi Daniele Starnoni Samia Messaoudi Lorenzo Dolci Hugues Cadas Sami Schranz Sara Sabatasso Vincent Dunet Roy T. Daniel Pablo González-López Lorenzo Giammattei

Objectives: This study aims to define the surgical anatomy, technical feasibility, advantages, and limitations of the TPPA through detailed cadaveric dissection and a representative clinical case, evaluating its potential as a safe and effective alternative to traditional approaches to the mesiotemporal lobe. Methods: A cadaveric dissection was performed on one adult head injected with colored latex, using standard microsurgical instruments and high-definition video documentation. Each procedural step was recorded and illustrated with cadaveric photographs. Additionally, a clinical case of mesiotemporal cavernous hemangioma resected via TPPA is presented, including an operative video. Results: The dissection demonstrated a direct and safe trajectory to the amygdala and hippocampal head, with clear identification of key vascular and white matter landmarks. In the clinical case, the lesion was completely resected with no postoperative neurological deficits. Conclusions: The TPPA represents a novel microsurgical corridor to the mesiotemporal region, minimizing cortical disruption, Sylvian fissure dissection, and manipulation of middle cerebral artery branches. Although its exposure is limited posteriorly, the TPPA could offer an optimal balance between functional preservation and surgical accessibility, constituting a valuable addition to the modern microsurgical armamentarium.

Brain Sciences doi: 10.3390/brainsci16040350

Authors: Xiuli Du Luyao Zhu

Background/Objectives: Emotions can be recognized through external behavioral cues and internal physiological signals. Owing to the inherently complex psychological and physiological nature of emotions, models relying on a single modality often suffer from limited robustness. This study aims to improve emotion recognition performance by effectively integrating electroencephalogram (EEG) signals and facial expressions through a multimodal framework. Methods: We propose a multimodal emotion recognition model that employs a Multi-Scale Dilated Attention Convolution (MSDAC) network tailored for facial expression recognition, integrates an EEG emotion recognition method based on three-dimensional features, and adopts a self-learning decision-level fusion strategy. MSDAC incorporates Multi-Scale Dilated Convolutions and a Dual-Branch Attention (D-BA) module to capture discontinuous facial action units. For EEG processing, raw signals are converted into a multidimensional time–frequency–spatial representation to preserve temporal, spectral, and spatial information. To overcome the limitations of traditional stitching or fixed-weight fusion approaches, a self-learning weight fusion mechanism is introduced at the decision level to adaptively adjust modality contributions. Results: The facial analysis branch achieved average accuracies of 74.1% on FER2013, 99.69% on CK+, and 98.05% (valence)/96.15% (arousal) on DEAP. On the DEAP dataset, the complete multimodal model reached 98.66% accuracy for valence and 97.49% for arousal classification. Conclusions: The proposed framework enhances emotion recognition by improving facial feature extraction and enabling adaptive multimodal fusion, demonstrating the effectiveness of combining EEG and facial information for robust emotion analysis.

Brain Sciences doi: 10.3390/brainsci16040349

Authors: Francesca Scopetta Marta Barbi Gianmarco Cinesi Filippo De Giorgi Alfonso Tortorella Giulia Menculini

Background: Youth mental health services increasingly encounter adolescents and young adults with complex affective presentations and trauma histories. Dissociation has been proposed as a clinically relevant marker within bipolar vulnerability pathways but remains underrecognized in early-intervention settings. This pilot study investigated the prevalence and clinical correlates of bipolar at-risk (BAR) status in a help-seeking youth sample, with specific focus on dissociative symptoms in this vulnerable population. Methods: A pilot study with a cross-sectional design was conducted in a specialized outpatient clinic for 14–25-year-olds. Seventy-six participants without Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision bipolar disorder completed a multidimensional assessment, including dissociative (Dissociative Experiences Scale version 2 [DES-II], Adolescent-DES [A-DES], Structured Clinical Interview for DSM Dissociative Disorders [SCID-D]), affective, anxiety, impulsivity, and prodromal symptom measures. BAR status (BAR+) was determined via clinical interview according to Bechdolf criteria. Clinically significant dissociation (DES+) was defined by established cut-offs at the DES-II and A-DES scales. Group comparisons, binary logistic regression and exploratory mediation analysis were performed. Results: In our sample, 44.7% of the participants met BAR+ criteria and 42.9% displayed clinically significant dissociation. Patients with BAR+ status more frequently reported familiar history of affective disorders, previous antidepressant use, loneliness, and non-suicidal self-injury. They displayed more severe depressive symptoms and impulsivity, as well as higher scores at all the affective temperament subscale except for hyperthymic. BAR+ patients displayed higher prevalence of dissociative symptoms than BAR− (51.6% vs. 24.2%; p = 0.045). Among the BAR+ subgroup, DES+ youths showed greater traumatic burden, depressive symptoms, and anxious temperament scores. Dissociation was associated with BAR+ status (OR 3.2) after adjusting for age, gender, and loneliness, while attentional impulsivity did not mediate this relationship. Conclusions: Dissociative symptomatology is highly prevalent among help-seeking youths and is directly associated with subthreshold bipolar-spectrum vulnerability. A dissociative BAR phenotype, marked by emotional instability and trauma exposure, may delineate a clinically complex subgroup, supporting the integration of dissociation-focused assessment into youth bipolar-risk staging and early-intervention protocols.

Brain Sciences doi: 10.3390/brainsci16040348

Authors: Gökce Hatipoglu Majernik Andreas Öllerer Teresa Lassacher Emre Kaya Dzmitry Kuzmin Andrea Janu Christoph Griessenauer Monika Killer-Oberpfalzer

Background/Objectives: This GLP (Good laboratory practice) study evaluates the MRI compatibility and occlusion performance of the Nuvascular Harbor intrasaccular device for the treatment of bifurcation and sidewall aneurysms in a rabbit aneurysm model. Methods: A total of 27 New Zealand White rabbits with 33 surgically created aneurysms (22 bifurcation, 11 side wall) were included and allocated to 90-day (n = 12) or 180-day (n = 15) follow-up. After exclusion of one aneurysm due to parent vessel occlusion and one aneurysm unsuitable for treatment, 31 treated aneurysms remained for analysis. All animals underwent DSA and 3T MRI, including TOF-MRA, FLAIR, DWI, and SWI sequences. Occlusion status was independently graded using the Raymond–Roy Occlusion Classification (RROC), and intermodality agreement was assessed. Results: MR-based occlusion assessment demonstrated strong agreement with DSA, with exact Raymond–Roy class concordance in 80.6% of cases and clinically relevant agreement (adequate vs. incomplete occlusion) in 96.8%. Agreement analysis showed substantial concordance (Cohen’s κ = 0.65) and a strong positive correlation (r = 0.79). Adequate occlusion rates were comparable between modalities (87.1% on MRA vs. 83.9% on DSA), supporting the reliability of MR imaging for non-invasive occlusion assessment, reflecting consistent device visibility on MR imaging. Conclusions: The Harbor device provides a promising solution for follow up aneurysm occlusion with increased MR visibility, enabling safer, contrast- and radiation-free follow-up. This study emphasizes the need for future endovascular devices to integrate imaging compatibility into their design to enhance long-term patient follow up.

Brain Sciences doi: 10.3390/brainsci16040347

Authors: Janusz Szyndler Zofia Wicik Anna Wierucka Piotr Maciejak Michał Sobstyl Angelika Stapińska-Syniec Piotr Glinka Karol Piwowarski Natalia Chmielewska

Objectives: In this study, we explore the molecular basis of the literature-reported inverse association between brain neoplasms and neurodegenerative disorders, including Parkinson’s disease (PD). As miRNAs are post-transcriptional regulators, we selected them as candidates underlying opposite processes of neurodegeneration and glioma development. Methods: We used bioinformatic analyses for disease-gene extraction, miRNA target prediction, enrichment analyses, and miRNA ranking. We identified 953 shared genes between PD and glioblastoma (GBM) in DisGeNET, then prioritized miRNAs predicted to regulate the largest number of shared targets. Next, we collected peripheral blood from patients with PD (n = 12), patients with gliomas (the most advanced—grade IV, n = 10 and grade III n = 3) and controls undergoing spinal surgery for disk pathology (n = 10). Blood samples were obtained pre-operatively in controls and glioma patients. Tumor and peritumoral tissues were obtained from glioma patients, whereas tissue sampling is not feasible in PD. Brain tissues and plasma were analyzed using RT-qPCR (miRNA) and ELISA (p53). Results: We observed increased levels of miR-16-5p (p < 0.05) and p53 protein (p < 0.05) in tumor tissues compared with peritumoral tissue. Additionally, miR-16-5p and miR-32-5p plasma levels were elevated in glioma patients compared with both PD patients (p < 0.01 and p < 0.001, respectively) and controls (p < 0.01 and p < 0.001, respectively). Plasma levels in PD did not differ from controls. Conclusions: Although these analyses highlight miR-16-5p and miR-32-5p as candidate biomarkers associated with glioma related pathways, the results did not provide evidence for the expected opposite regulation between PD and glioma. Future studies with a larger cohort of patients using high-throughput methods are needed to validate these findings and to elucidate the mechanisms driving neurodegeneration or excessive proliferation.

Brain Sciences doi: 10.3390/brainsci16040346

Authors: Patrick Quercia

Background: Sensorimotor differences have frequently been reported in children with developmental dyslexia, but are often considered secondary or comorbid to phonological deficits. Within an embodied cognition perspective, reading acquisition emerges from dynamic interactions between bodily regulation, multisensory integration, and learning-related neural plasticity. Proprioception contributes to spatial orientation, motor coordination, and perceptual stabilization, while sleep-dependent processes play a critical role in the consolidation and automatization of cognitive and motor skills. Objectives: Building on early clinical observations, including the hypothesis proposed by Martins da Cunha, this review explores whether variations in proprioceptive processing and sensorimotor regulation may influence multisensory stability and the conditions under which reading skills develop in some individuals with dyslexia. Methods: This narrative synthesis integrates clinical observations and experimental paradigms examining proprioceptive function in children with dyslexia, including studies conducted in our laboratory over the past two decades. These investigations address postural regulation under varying attentional demands, laboratory measures of proprioceptive acuity, visuospatial localization tasks, multisensory interactions, and exploratory observations concerning sleep–wake regulation. Results: Across studies, children with dyslexia often show differences in proprioceptive processing associated with variations in postural regulation, visuospatial stability, and multisensory tasks. Laboratory measurements suggest reduced proprioceptive acuity in some individuals, with moderate correlations observed between proprioceptive sensitivity and reading-related measures. Additional observations suggest that nocturnal physiological regulation—including respiratory dynamics and sleep architecture—may interact with daytime sensorimotor stability and attentional functioning. Conclusions: Taken together, these findings support the hypothesis that variations in sensorimotor regulation across the sleep–wake cycle may influence the stability of multisensory processing and attentional conditions relevant for reading acquisition. Within this perspective, proprioception is not proposed as an alternative explanation for dyslexia but as a complementary dimension that may contribute to the heterogeneity of dyslexic profiles. Further longitudinal and controlled studies are required to clarify the relationships between sensorimotor regulation, sleep-dependent plasticity, and learning processes.

Brain Sciences doi: 10.3390/brainsci16040345

Authors: Saleha Redžepi Edin Avdagić Ajša Šahinović Mirza Pojskić

Visual mental imagery, the ability to generate and manipulate internal visual experiences without direct sensory input, links perception with memory, planning, and higher cognition. In this targeted narrative review, we synthesize neuroimaging and lesion evidence on the brain basis of visual imagery, with a focus on neuroradiological correlates of the ventral and dorsal visual pathways. Unlike prior cognitive neuroscience reviews that primarily emphasize functional mechanisms, this review is neuroradiology-oriented and integrates lesion patterns and white-matter disconnection to support clinico-radiological interpretation of imagery complaints. Using a dual-stream framework, we contrast ventral occipito-temporal systems that preferentially support object imagery (appearance-based features such as form, faces/objects, and color, with texture remaining under-studied) with dorsal occipito-parietal systems that preferentially support spatial imagery (relations, transformations, and navigation). Across studies, imagery recruitment is strongly task- and stage-dependent: ventral regions are most often engaged during object-focused imagery, whereas parietal regions are prominent during spatial transformation tasks, with evidence for interaction between pathways when demands require both content and spatial operations. Structural and clinico-radiological findings indicate that imagery impairment can arise from focal posterior lesions and posterior neurodegenerative syndromes but also from network disruption affecting long-range connections that support top-down access to posterior representations. Finally, emerging work on aphantasia and hyperphantasia supports a network-level view in which imagery vividness relates to how effectively higher-order systems engage visual representations. We conclude that standardized, stream-sensitive tasks and multimodal approaches combining functional and structural imaging with lesion-based evidence are key to discovering clinically actionable biomarkers of imagery dysfunction.

Brain Sciences doi: 10.3390/brainsci16030344

Authors: Andrea Calderone Rosaria De Luca Alessio Currò Alessio Mirabile Marco Piccione Rocco Salvatore Calabrò

Background/Objectives: Severe acquired brain injury (sABI) disrupts early rehabilitation because arousal fluctuates, trunk control is fragile, and agitation limits therapy tolerance; land-based practice is frequently constrained by fall risk and staffing. We aim to reframe aquatic therapy as a programmable multisensory environment to stabilize arousal and support axial alignment before conventional impairment targets are feasible. Here, programmable denotes the deliberate titration and reporting of water depth, turbulence or perturbation, temperature, body orientation, and flotation and manual support as intervention inputs. Methods: This perspective integrates principles from neurobehavioral assessment, motor control, and immersion physiology to propose the Arousal–Alignment–Action loop as a falsifiable model and to define manipulable aquatic inputs (water depth, turbulence or perturbation, temperature, body orientation, and flotation and manual support) as dosing parameters. We outline a pragmatic testing ladder (within-session micro-experiments, feasibility studies, and embedded evaluations) and a minimal outcomes and confounder set to support cumulative evidence. Results: The framework links state regulation to alignment and goal-directed behavior, specifies predictions that can fail, and highlights boundary conditions (sedation, autonomic instability, pain, recent surgery or wounds, and cervical or cardiopulmonary constraints). A minimal outcome package spanning arousal/responsiveness, trunk control, behavioral dysregulation, participation/tolerance, and basic physiology is proposed, with optional objective adjuncts for mechanism-oriented studies. Conclusions: Treating water as a measurable and titratable medium, rather than a generic modality, may reduce early intensity bottlenecks and improve implementability and comparability of aquatic neurorehabilitation research in medically stable sABI; however, the model is intended as hypothesis-generating until supported by stronger direct clinical evidence.

Brain Sciences doi: 10.3390/brainsci16030343

Authors: Diego Santos García Inés Legarda Tamara M. González Fernández Ana Rodríguez Sanz Maria Isabel Morales-Casado Alejandro Peral Nuria Caballol María Álvarez Sauco Iria Campos Rodríguez Déborah Alonso Modino Lydia López Manzanares Jesús Olivares Romero Alberto Blanco Ollero

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson’s disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped out for different reasons and started before this LECIG in Spain up to 30 November 2025. Non-parametric tests were applied to evaluate the changes between the pre- (Vpre) and post-treatment (Vpost) (LECIG) periods. Results: Data about 14 patients (57.1% males; 66.6 ± 8.6 years old) from 12 hospitals out of a total of 15 who were treated with LECIG were included. The mean time with fLD/fCD was 98.6 ± 92.3 days, with 92.9% and 57.1% experiencing side effects and lack of response, respectively. Specifically, significant subcutaneous nodules were reported in up to 64.3% of the patients. LECIG was a direct switch from fLD/fCD in 35.7% of the patients. LECIG was well tolerated, with only one dropout due to complications related to dementia. Adverse events were reported in 28.6% and 35.7% of the patients in the optimization and final follow-up evaluation (mean follow-up of 233.7 ± 157.4 days) phases, respectively. From Vpre to Vpost, “Off” time was reduced in 2.9 ± 1.9 h (p = 0.002) and motor symptoms burden improved significantly (p = 0.013), whereas a trend of significance was found for non-motor symptoms burden (p = 0.050) and quality of life (p = 0.126). Conclusions: LECIG could be an alternative therapeutic option in PwP who failed fLD/fCD.

Brain Sciences doi: 10.3390/brainsci16030342

Authors: Mari Bardopoulou Costas Chryssanthopoulos Evgenia D. Cherouveim Evangelia Tzeravini Evangelia Stanitsa Maria Koustimpi Eirini Chatzinikita Irini Patsaki Stelios Poulos John Papatriantafyllou Theodoros Vassilakopoulos Maria Maridaki Christos Consoulas Sokratis G. Papageorgiou Michael Koutsilieris Anastassios Philippou

Background/Objectives: Physical exercise has emerged as a promising non-pharmacological intervention for cognitive dysfunction; however, the most effective mode of exercise remains unclear. This study aimed to investigate the acute effects of two cycling exercise protocols, (a) continuous aerobic/moderate-intensity (CA) and (b) high-velocity/low-resistance (high-cadence) interval (HVI), on cognitive and executive performance in patients with mild cognitive impairment (MCI). Methods: Seventeen patients (10 females and 7 males, age: 65.5 ± 8.85 years) diagnosed with MCI or early-stage Alzheimer’s disease (13 MCI and 4 eAD) participated in a random order in three different conditions: CA, HVI, and control/no exercise (CON). Cognitive parameters were assessed acutely before and after the completion of each condition. Results: Significant condition × time interactions were observed for both Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB) (p < 0.01). Higher scores (p < 0.01) for MoCA and FAB post-intervention were found compared to baseline in both exercise bouts, whereas no changes occurred in CON. Interestingly, when post-intervention scores were compared between conditions, cognitive performance was improved only in HVΙ compared to CON in MoCA (p < 0.01) and FAB (p < 0.001), revealing a stronger acute effect of HVI. Conclusions: A single bout of high-velocity, low-resistance (high-cadence) interval cycling acutely enhanced global cognition and executive function in individuals with MCI, exerting greater improvement compared to continuous aerobic exercise or control condition. These findings emphasize the potential utilization of HVI as an effective non-pharmacological intervention to acutely enhance cognitive performance in older adults with MCI.

Brain Sciences doi: 10.3390/brainsci16030341

Authors: Chiara Valeria Marinelli Emiliano Pizzicannella Marinella De Salvatore Daniela Sarti Vincenza Tommasi Pierluigi Zoccolotti Luca Andreoli Elisa Granocchio

Background and Objectives: Children with specific learning disorders (SLD) often present a history of speech and language deficits. However, systematic evidence on the co-occurrence among distinct learning and communication disorders remains limited. This study aimed to describe the associations among reading, spelling, and math disorders and their relationships with clinically diagnosed speech sound and language disorders and speech sound disorders in a large, well-characterized clinical sample. Methods: 235 3rd- to 8th-grade Italian children with SLD participated in the study. They were categorized in terms of learning (reading, spelling, and math) and comorbid communication disorders (speech sound, and language disorders), according to established diagnostic criteria. Prevalence rates were assessed for each of the resulting subgroups. Results: Comorbidity between the three learning disorders was very frequent; 75.4% of children showed different forms of multiple SLDs, with 47.7% presenting a combined reading, spelling, and math disorder. Communication disorders were reported in 40.4% of the sample. Both language and speech sound disorders frequently co-occurred with spelling disorders, whereas associations with isolated reading or math disorders were more infrequent. Additionally, speech sound disorders frequently co-occurred with isolated spelling disorders, whereas language disorders frequently co-occurred with comorbid spelling disorders. Conclusions: Consistent with previous evidence, the study shows that learning disorders are highly comorbid with communication disorders. Critically, speech and language disorders are most frequently comorbid with spelling disorder, independent of reading and math deficits, highlighting spelling as a potential key interface between phonology, language, and learning.

Brain Sciences doi: 10.3390/brainsci16030340

Authors: Olga Murgina Ksenia Stafeeva Sofya Karaulova Alena Vostrikova Sofya Kononova Daria Chursina Svetlana Pozdeeva Anastasia Makogonova Inna Burakova Svetlana Pogorelova Polina Morozova Yulia Smirnova Mikhail Syromyatnikov Viktor Shutikov Evgeny Mikhailov Artem Gureev

Background/Objectives: The gut–brain axis is increasingly recognized as a critical modulator of cognitive function. This study investigated the neurotoxic effects of combined exposure to bacterial lipopolysaccharide (LPS) and the antiretroviral drug zidovudine (ZDV) in a mouse model, and evaluated the protective potential of two probiotic interventions: Bacillus subtilis and a mixture of lactobacilli. Methods: Cognitive function was assessed using the Morris water maze (MWM). Gut microbiota composition was analyzed by 16S rRNA sequencing, and intestinal morphology was examined histologically. Gene expression of neuroinflammatory markers and mitophagy-related genes in brain tissue was quantified by RT-PCR. Plasma levels of cell-free mitochondrial DNA (cf-mtDNA) were measured as a marker of mitochondrial damage. Results: Combined LPS + ZDV exposure induced systemic inflammation, impaired spatial memory, damaged the intestinal mucosa, and caused dysbiosis characterized by an increase in pro-inflammatory Muribaculaceae. In the brain, LPS + ZDV significantly upregulated Tnfa expression, confirming neuroinflammation. Bacillus subtilis administration prevented cognitive deficits, maintained Tnfa at control levels, and significantly reduced Il1b and Il6 expression compared to the LPS + ZDV group. This was accompanied by activation of the PINK1/PTEN-dependent mitophagy pathway, prevention of cf-mtDNA release, and restoration of gut microbial diversity. In contrast, the Lactobacilli mixture not only failed to improve outcomes but was associated with exacerbated intestinal damage, more pronounced cognitive dysfunction, and no reduction in neuroinflammatory markers. Conclusions: Combined exposure to LPS and ZDV induces gut–brain axis dysfunction characterized by neuroinflammation, cognitive impairment, intestinal damage, and dysbiosis. Bacillus subtilis effectively preserves cognitive function through activation of PINK1/PTEN-dependent mitophagy and suppression of neuroinflammation, highlighting its potential as a therapeutic candidate for cognitive impairments associated with gut–brain axis dysfunction. The contrasting effects of the lactobacilli mixture underscore the critical importance of strain-specificity in probiotic interventions.

Brain Sciences doi: 10.3390/brainsci16030339

Authors: Pablo Rodríguez-Prieto Julia Soler-Vázquez Joaquín A. Ibáñez-Alfonso

Background/Objectives: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood and it tends to remain during adulthood. It not only affects cognitive abilities and behavior but also often presents emotional disturbances and alterations in the perceived quality of life. These symptoms are primarily related to dysfunctions in the ventromedial and dorsolateral prefrontal network. The main objective was to evaluate the feasibility and explore the initial outcomes of an integrated protocol combining neuropsychological treatment and transcranial direct current stimulation (tDCS). Methods: This study presents a single-case experimental A-B design of a 21-year-old woman, diagnosed with predominantly inattentive ADHD, treated at the University Psychology Clinic of Loyola Andalucía University. The treatment was carried out twice a week for 5 weeks (10 sessions in total), with 20 min of anodal tDCS at F3 and cathodal tDCS at F4 (2 mA), while digital neurorehabilitation exercises and psychotherapeutic support were provided. Results: An overall significant improvement was observed in cognitive functions (p = 0.008), with clinically significant gains in cognitive flexibility, visual working memory, and planning. Mixed results were found in inhibition, with improvement in interference control but no change in response inhibition. No significant changes were observed in sustained attention, auditory working memory, or processing speed. In terms of emotional state, an overall improvement was noted (p = 0.046), particularly in depression symptoms and perceived quality of life related to physical and psychological health. However, no significant changes were observed in anxiety symptoms or in areas related to the environment and social relationships. These findings reflect pilot-level evidence of clinical change within a feasibility framework. Conclusions: The combined treatment was found to be safe and feasible, showing promising preliminary improvements in cognitive and emotional domains. As a single-case study, these results serve as hypothesis-generating evidence for future controlled trials.

Brain Sciences doi: 10.3390/brainsci16030338

Authors: Maciej Śliż Wojciech Paśko Francisco Martins Rafał Krupa Élvio Rubio Gouveia Hugo Sarmento Krzysztof Przednowek

Background/Objectives: Reaction time, hand–eye coordination, spatial orientation, and attention play a key role in handball, which is characterized by high intensity as well as high cognitive and motor demands. The level of these abilities may change during the season, potentially reflecting training adaptations and increasing physical fatigue. The aim of the study was to compare the level of psychomotor abilities in professional handball players before the start of the competition round and after the end of the league season. The study included 77 handball players playing in the Polish Handball Super League (average age: 25.6 ± 5.2 years). The players were divided according to position: pivot, center, and wing. Methods: Psychomotor abilities were assessed using the Test2Drive computer system, employing tests of simple and choice reaction time, eye–hand coordination, spatial orientation, perception and attention, and movement anticipation. Results: At the end of the season, a statistically significant reduction in reaction time was observed in the choice reaction (p = 0.001), eye–hand coordination (p = 0.002), and spatial orientation tests (p = 0.003). In terms of motor skills, an increase in time was observed in the SIRT test (p = 0.003), CHORT (p = 0.005) and HECOR (p = 0.011) tests, while the time in the PUT test was shortened for both neutral (p = 0.002) and critical (p = 0.025) stimuli. Positional analysis showed that after the season, the pivot player achieved higher effectiveness in the CHORT test than the wing player (p = 0.020). Additionally, statistically significant differences were observed for correct responses in the SPANT test (p = 0.032). In terms of correct answers in the PAMT test, the pivot player had the lowest effectiveness. Conclusions: Participation in the full season of competition coincided with significant changes in the psychomotor profile of handball players, with a simultaneous improvement in reaction speed and deterioration in movement time parameters.

Brain Sciences doi: 10.3390/brainsci16030337

Authors: Guido Catalano Sara Abbondio Roberta Nicotra Valentina Berselli Marta Guarischi Valentina Vezzali Sabrina Signorini

Background: Eye-tracking (ET) devices are gaining attention in technology-based paediatric rehabilitation through their intrinsic ability to assess patients’ engagement and visual attention within motivating, technology-based environments. We conducted a systematic review of available evidence from 2004 to 2025 on the implementation of ET in rehabilitative trainings targeting paediatric populations with neurological and neurodevelopmental disorders. This paper aims to outline the rehabilitative outcomes pursued in the clinical populations considered. Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three electronic databases (PubMed, Web of Science, and Scopus) were consulted to summarise the state of the art of the last 20 years. Selected articles were categorised according to the type of treated disorder and the rehabilitated function. Results: ET devices have been increasingly integrated into paediatric rehabilitation with promising results across multiple neurodevelopmental conditions (e.g., ASD, ADHD, cerebral palsy). These systems have proven effective not only in training gaze control, but also in enhancing executive functions, social cognition, communication, and participation. Furthermore, they promote personalised and data-driven solutions and support high levels of engagement, feasibility, and user satisfaction. Conclusions: ET represents a promising frontier for paediatric rehabilitation, addressing various neurodevelopmental disorders. The gaze-contingent protocols employed have demonstrated potential effects in promoting adaptive behaviour across multiple developmental areas. Further research is warranted to provide shared guidance and to strengthen practice recommendations.

Brain Sciences doi: 10.3390/brainsci16030335

Authors: Miaomiao Guo Qi Wang Mengfan Li Liang Sun Tian Wang Guizhi Xu Lei Wang

Background: Against the backdrop of global population aging, understanding the mechanisms of age-related cognitive decline has become crucial for improving the health and quality of life in older adults. Methods: This study employed a multimodal approach to investigate the neural modulations induced by a motor cognitive dual task and their relationship with age-related decline. By integrating behavioral assessments, electroencephalography (EEG), and body composition analysis, we comprehensively evaluated performance and neural correlates in 19 younger and 18 older adults. Specifically, EEG analyses focused on comparing pre-task and post-task resting-state recordings to investigate the immediate impact of a single acute cognitive-motor dual-task session on neural oscillations and brain network organization. Results: Key findings include: (1) older adults exhibited significantly inferior performance in task accuracy, reaction time, and composite performance score compared to younger adults (p < 0.001); (2) neural oscillatory analysis of resting-state data revealed a localized increase in gamma-band power at posterior-temporal sites (PO4/T6) in older adults following the dual-task, while younger adults exhibited widespread multi-band (delta to beta) power modulation across frontal, central, and temporal regions in younger adults; (3) brain network analysis demonstrated synergistic enhancement of multi-band (Theta, Alpha, Beta, Gamma) connectivity and optimized topological organization in younger adults post-task, contrasting with network rigidity and localized compensatory patterns in older adults; (4) correlation analyses indicated significant associations between dual-task performance and MoCA-B scores in older adults (r = 0.861, p < 0.001). Conclusions: This study innovatively elucidates the neurophysiological characteristics of brain aging. The motor-cognitive dual-task paradigm proves to be a sensitive tool for capturing early cognitive changes, holding significant promise for clinical screening.

Brain Sciences doi: 10.3390/brainsci16030336

Authors: Zhuoqun Liu Haoxuan Pan Huimeng Lei Xiaohong Sun

Objectives: Females are often underrepresented in preclinical fear research due to concerns over estrous cycle related variability. This study examined whether there were differences between female and male C57BL/6J mice in terms of fear extinction and safety learning, aiming to verify the inclusion of both sexes in fear regulation research. Methods: Mice underwent a 5-day fear conditioning and extinction protocol, with recent (Day 6) and remote (Day 13) retrieval tests. A separate cohort received unpaired tone-shock safety conditioning over two days, followed by recent and remote retrieval. Freezing percentage and locomotor distance, among other measures, were quantified to compare behavioral responses between sexes. Results: During fear acquisition and extinction, females and males showed comparable conditioned fear and progressive extinction, with no sex differences in freezing percentage, bout counts, or locomotor distance. Freezing remained low during both recent and remote retrieval in both sexes. In the safety-conditioning task, the safety cue reduced freezing relative to contextual baseline, contextual freezing declined from recent to remote retrieval, and no sex differences were observed across measures. Conclusions: Female and male C57BL/6J mice exhibit equivalent performance in auditory fear conditioning, extinction, retrieval, and safety learning under matched conditions. These findings support equitable inclusion of both sexes in preclinical fear-regulation studies, enhancing translational relevance without added behavioral variability.

Brain Sciences doi: 10.3390/brainsci16030334

Authors: Jae Hyuk Shim Hyeon-Man Baek

Background/Objectives: Translating brain volumetric biomarkers to individual-level Alzheimer’s disease (AD) diagnosis remains challenging due to difficulty interpreting raw volumes without longitudinal monitoring or matched controls. We tested a classification model using population-referenced volumetric percentiles to distinguish AD from cognitively normal (CN) subjects and evaluated its generalization across independent cohorts. Methods: Brain volumes from 95 regions were extracted using an automated segmentation pipeline and converted to age and sex adjusted percentiles using a reference population (N = 1833). A logistic regression classifier was trained on ADNI subjects (N = 873; AD = 183, CN = 690) split into training (60%), validation (20%), and test (20%) sets. The model was evaluated on two independent validation datasets: the held-out ADNI validation set and an external Korean cohort (N = 72; AD = 36, CN = 36) acquired with different scanner protocols and demographic characteristics. Results: The model achieved excellent discrimination across all evaluation sets: ADNI validation (AUC = 0.963, accuracy = 90.3%), ADNI test (AUC = 0.960, accuracy = 89.7%), and Korean external validation (AUC = 0.981, accuracy = 87.5%). The minimal validation gap (0.018) demonstrated robust generalization. Positive coefficients for ventricular regions reflected AD-associated atrophy patterns, while negative coefficients for medial temporal structures indicated their contribution within multivariate patterns distinguishing AD from normal aging. Conclusions: Population-referenced brain volumetric percentiles enable accurate AD classification with robust generalization across populations and scanner protocols. By contextualizing individual brain structure relative to normative populations while accounting for age and sex, this approach demonstrates potential for clinical translation as an accessible neuroimaging-based diagnostic tool.

Brain Sciences doi: 10.3390/brainsci16030333

Authors: Wenbin Sheng Zihan Gang Liwei Zhang Yongcong Shao Qianxiang Zhou

Background/Objectives: Acute total sleep deprivation (TSD) is known to impair working memory capacity. However, the specific relationship between alterations in the brain’s electrical power spectrum following TSD and working memory deficits remains poorly understood. Methods: In this study, 30 healthy young adults (14 males and 16 females) were enrolled, and 28 participants were finally included in the analysis after excluding EEG data with excessive noise, who underwent a verbal working memory task under two conditions: baseline sleep (BL) and 36 h of TSD. EEG data were recorded concurrently. Results: We observed a significant decrease in working memory accuracy and a significant prolongation of reaction time after TSD. Furthermore, TSD led to a significant enhancement of parietal alpha-ERD (at electrodes P3/Pz/P4) and theta-ERS, accompanied by a reduction in N2 and P3 wave amplitudes. Conclusions: These findings suggest that TSD may impair working memory by weakening parietal alpha-ERD and early conflict monitoring and late attention evaluation processes. The enhanced theta-ERS might represent a compensatory mechanism.

Brain Sciences doi: 10.3390/brainsci16030332

Authors: Irma Hernández-Jasso Denisse Calderón-Vallejo José Ávila-Mendoza David Epardo Jerusa Balderas-Márquez Carlos Arámburo J. Quintanar Carlos Martínez-Moreno

Background/Objectives: Sciatic nerve injuries are among the most common classes of peripheral nerve harm and have a strong impact on quality of life, as well as a significant negative economic impact for patients, society, and governments, since they represent a frequent cause of work-related disabilities and sick leave applications. Following nerve injury, neurons, Schwann, and satellite cells undergo marked changes in phenotype, metabolic activity, neuronal survival, nervous transmission, and an exacerbated activation of the inflammatory response. Leuprolide acetate (LA), a clinically available agonist of gonadotropin-releasing hormone (GnRH), has shown clear neurotrophic properties and is considered a novel potential candidate for treating neural injuries, including sciatic nerve pathologies. This study aimed to analyze the effect of LA treatment on sensory function and dorsal root ganglia (DRG) changes in a rat sciatic nerve full-transection (SNT) model. Methods: Variations in cold and heat sensitivity were assessed using the thermal plate test, while DRG tissue sections were examined for modifications in reactive gliosis by immunofluorescence analysis, and axonal transport using a retrograde tracer. Also, changes in the expression of pro-regenerative genes Stat3, Socs3, Fos, Jun, Atf4, and Limk1 were quantified by qPCR. Results: Our results showed that LA treatment exerted a distinct neurotrophic effect, since it promoted the specific recovery of cold sensitivity, improved axonal transport, regulated the inflammatory response, and modulated the exacerbated expression of pro-regenerative genes in the SNT model. Conclusions: These findings indicate that LA therapy may have the potential to improve sensory recovery in patients with sciatic nerve injuries.

Brain Sciences doi: 10.3390/brainsci16030331

Authors: Yanna Tong Kenneth B. Elkin Changya Peng Jiamei Shen Fengwu Li Longfei Guan Yu Ji Wenjing Wei Xiaokun Geng Yuchuan Ding

In our article “Reduced Apoptotic Injury by Phenothiazine in Ischemic Stroke Through the NOX-Akt/PKC Pathway” [...]

Brain Sciences doi: 10.3390/brainsci16030330

Authors: Cong Zhang Xisheng Li Jiannan Chi Ming Cao Qingfeng Gu Jiahui Liu

Background/Objectives: Emotion classification based on eye-movement features has become a widely adopted approach due to the simplicity of data acquisition and the strong association between ocular responses and emotional states. However, several challenges remain with regard to existing emotion recognition methods, including the relatively weak correlation between eye-movement features and emotional labels and the fact that the key features are not prominently presented. Methods: To address abovelimitations, this study proposes an improved CNN-transformer combined with enhanced deep canonical correlation analysis network (ICTD). The proposed method first performs preprocessing and reconstruction of raw eye-movement signals to extract informative features. Subsequently, convolutional neural networks (CNNs) and transformer architectures are employed to capture local and global feature, respectively. In addition, an incremental feature feedforward network is incorporated to enhance the transformer, enabling the model to assign higher importance to salient feature information. Finally, the extracted representations are processed through deep canonical correlation analysis based on cosine similarity in order to generate classification outcomes. Results: Experiments conducted on the SEED-IV, SEED-V, and eSEE-d datasets demonstrate that the proposed ICTD framework consistently outperforms baseline approaches and attains optimal classification results. (1) On the eSEE-d dataset, the results of three-category arousal and valence classification reach 81.8% and 85.2%, respectively; (2) on the SEED-IV dataset, the emotion four-category classification result reaches 91.2%; (3) finally, on the SEED-V dataset, the emotion five-category classification result reaches 85.1%. Conclusions: The proposed ICTD framework effectively improves feature representation and classification performance, showing strong potential for practical emotion recognition and physiological signal analysis.

Brain Sciences doi: 10.3390/brainsci16030329

Authors: Michal Schulenkowski Chun Khai Loh Michael Back

Background: Current target volume delineation protocols for glioblastoma utilise uniform or isotropic expansion around the surgical cavity and residual tumour, without considering specific sites at risk for infiltration. Tumours arising in different neuroanatomical sites may demonstrate distinct patterns of infiltration. This study aims to review the infiltration and progression sites for the occipital lobe glioblastoma to identify sites potentially at risk. Methods: Patients with occipital lobe glioblastoma managed according to the EORTC-NCIC protocol were identified through a prospective database. Based on MRI analysis, a qualitative description of sites of tumour infiltration and subsequent progression was performed. These were categorised into neuroanatomical subsites adjacent to the occipital lobe: level 1 related to the origin gyrus; level 2 related to adjacent gyral subsites; and level 3 related to subsites that involved distant regions. Patients could be classified in more than one level where multifocal involvement was present at diagnosis or progression. Spatial patterns were assessed in relation to three major white matter tracts: inferior longitudinal fasciculus, cingulum, and corpus callosum. Results: A total of 46 patients were analysed. At diagnosis, 20 patients (43.5%) had medial occipital lobe involvement and 26 (56.5%) had lateral involvement. Level 2 and level 3 infiltration were observed in 33 (71.7%) and 27 (58.7%) patients. Progression occurred in 43 patients (93.5%), with involvement at level 1 in 28%, level 2 in 77%, and level 3 in 98%. Lateral tumours demonstrated proportionately higher progression in the trigone (75% vs. 52.6%) and anterior temporal lobe (50% vs. 15.8%, p = 0.026), while medial tumours more frequently involved the splenium (47.3% vs. 16.7%, p = 0.046). Conclusions: Infiltration and progression of occipital lobe glioblastoma may demonstrate distinct neuroanatomical patterns, with spatial distribution corresponding to major white matter tracts.

Brain Sciences doi: 10.3390/brainsci16030328

Authors: Jesús Pastor Lorena Vega-Zelaya Diego Real de Asúa

The qEEG findings of subjects with Down syndrome (DS) have not been described in the context of bipolar montage. Resting-state EEG (rsEEG) with a bipolar montage was performed in 22 young adults (26.0 ± 1.2 years) with DS but without psychiatric or neurological pathology and matched control subjects of the same sex and age, and the results were conventionally and numerically analyzed. Channels were grouped into frontal, parieto-occipital, and temporal lobes. For every channel, the power spectrum was calculated and used to compute the area for the delta, theta, alpha and beta bands and was log-transformed. Shannon’s spectral entropy (SSE) and coherence by bands were computed. Finally, we also calculated the peak frequency distribution of the alpha band. qEEG revealed alterations in the rsEEG that were not detected visually. Subjects with DS showed a significant generalized increase in the power of the delta and theta bands, along with a decrease in the power of the alpha band in the posterior half of the scalp. This alpha activity also exhibited features corresponding to older euploid subjects, showing interhemispheric asynchrony in one-third of the individuals. The beta band power was significantly increased in the frontal lobes and adjacent regions, such as the parietal and mid-temporal regions. Individuals with DS showed a generalized decrease in parieto-occipital synchronization associated with intelligence quotient. Left temporal synchronization was also lower. The synchronization of specific channel pairs was greater in subjects with DS in the frontal lobe and much lower in the occipital and temporal regions. These results indicate that alterations in band structure and synchronization in subjects with DS are highly specific and can aid in the clinical evaluation of these individuals.

Brain Sciences doi: 10.3390/brainsci16030327

Authors: Najme Soleimani Maria Misiura Ali Maan Sir-Lord Wiafe Jennalyn Burnette Asia Hemphill Vonetta M. Dotson Rebecca Ellis Tricia Z. King Erin B. Tone Vince D. Calhoun

Background/Objectives: Young adulthood is a critical developmental period during which lifestyle behaviors may shape intrinsic brain network dynamics that support cognition. This pilot longitudinal intervention study examined whether variability in physical activity and sedentary behavior during an 8-week exercise and/or cognitive intervention protocol was associated with changes in intrinsic brain dynamics and cognitive and mood outcomes in undergraduate young adults. Methods: Participants (n = 32) completed resting-state functional magnetic resonance imaging (rs-fMRI) at baseline (T1) and post-intervention (T2). Dynamic functional network connectivity (dFNC) was estimated from 53 intrinsic connectivity networks derived using spatially constrained independent component analysis (ICA). Ten recurring dynamic connectivity states were identified and individualized using constrained dynamic double functional independent primitives (c-ddFIPs). State occupancy and dynamic convergence and divergence metrics were computed to characterize network flexibility. Results: Greater moderate-to-vigorous physical activity was modestly but consistently associated with increased occupancy of integrative higher-order states, particularly States 6 and 7, and reduced occupancy of more segregated configurations. More physically active individuals also demonstrated greater divergence between integrative and low-engagement states, whereas greater sedentary time corresponded to increased similarity among segregated configurations. Working memory performance showed parallel associations with more integrative and better-differentiated dynamic patterns. Conclusions: These findings suggest that dynamic functional network reconfiguration may represent a neurobiological mechanism linking lifestyle behaviors and cognitive health in young adulthood. Furthermore, they highlight the translational promise of engagement-driven, low-burden programs for college-aged young adults, showing that even modest variability in habitual physical activity corresponds to greater engagement and differentiation of integrative connectivity states linked to executive and broader cognitive functions.

Brain Sciences doi: 10.3390/brainsci16030326

Authors: Danilo Pesic Dusica Lecic-Tosevski Bojana Pejuskovic Ana Munjiza-Jovanovic Olivera Vukovic

Recent revisions of personality disorder (PD) classifications have moved from categorical diagnoses toward dimensional models, raising renewed questions about the nosological status and clinical utility of borderline personality disorder (BPD). This narrative review traces the development of the borderline construct from early descriptions of patients positioned between neurosis and psychosis, through its theoretical consolidation within the concept of borderline personality organization, to the operationalization of BPD in DSM-III and subsequent diagnostic revisions. A central section summarizes contemporary controversies regarding the validity and utility of BPD features. Arguments for abandoning the diagnosis emphasize the absence of a distinct borderline factor in factor analytic studies, the tendency of the construct to capture fluctuating symptoms and patterns of behaviour rather than stable maladaptive personality traits, the stigmatizing and non-selective use of the label, and the lack of disorder-specific treatment approaches. In contrast, converging evidence supports the view that core borderline symptoms frequently function as markers of general PD pathology and of the severity of impairments in self and interpersonal functioning. The paper integrates the concept of the borderline level of personality functioning, conceptualizing borderline pathology as a dynamic dimension of dysfunction with potential transient regressions, and links this concept to the Level of Personality Functioning (LPF, Criterion A) within the DSM 5 Alternative Model for Personality Disorders (AMPD). Retaining borderline pathology as a dimension may support contemporary PD assessment by offering a clinically recognizable marker of overall dysfunction, a guide for rating severity, an indicator of personality structure and need for psychotherapy, without disrupting continuity with an extensive clinical and research tradition.

Brain Sciences doi: 10.3390/brainsci16030325

Authors: Davide Mazzara Angelo Torrente Paolo Alonge Giulia Gerardi Anna Renda Roberto Monastero

Background/Objectives: Mild cognitive impairment (MCI) is common in Parkinson’s disease (PD) and significantly impacts quality of life. Non-invasive brain stimulation (NIBS) techniques have emerged as potential therapeutic interventions. This systematic review analyzes the current evidence regarding the efficacy of Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES) on cognitive domains in patients with PD-MCI. Methods: A systematic search was conducted across the PubMed, Scopus, Web of Science, and Medline Ultimate databases up to 20 November 2025. We included studies investigating the effects of NIBS compared to sham stimulation on neuropsychological outcomes in diagnosed PD-MCI patients. Results: Eight studies involving different stimulation protocols were included. Interventions primarily used TMS or tES targeting the left dorsolateral prefrontal cortex (DLPFC). Episodic memory and global cognition were the most responsive domains, assessed with specific neuropsychological scales. Findings for executive functions and attention were heterogeneous, while visuospatial abilities generally showed limited immediate response. Conclusions: NIBS represents a promising but low-certainty-evidence adjunctive therapy for PD-MCI, with improvements found in memory and global cognition. Future research should prioritize larger sample sizes, combined interventions (NIBS plus cognitive rehabilitation), and extended follow-ups to evaluate long-term neuroplasticity.

Brain Sciences doi: 10.3390/brainsci16030324

Authors: Mile Vukovic Sladjana Lukic

Background/Objectives: Cross-linguistic studies show that the production of morphosyntactic elements (e.g., clitics) is problematic and often omitted in nonfluent agrammatic aphasia (NFA), with the degree of impairment varying across languages. Serbian, with its rich clitic system, provides a sensitive window into grammatical impairment. This study is the first to examine the production of proclitics and enclitics in Serbian speakers with aphasia and their relationship to short-term and working memory. Methods: Forty-six individuals with stroke-induced aphasia (25 NFA and 21 fluent aphasia [FA]) and 54 healthy controls completed an experimental Serbian clitic production test. Participants were prompted to produce clitic sentences (12 proclitics, such as prepositions or conjunctions, and 18 clitics, such as pronouns or auxiliary verbs) in response to various scenarios. Performances were correlated with sentence repetition and digit span (forward/backward). Results: Both aphasia groups produced significantly fewer clitics than controls (p < 0.001). Participants with NFA produced fewer overall clitics and showed no clitic type effects (p = 0.329), whereas participants with FA produced proclitics more accurately than enclitics (p = 0.028). Clitic production correlated with performance on sentence repetition and digit span tasks, but patterns differed by aphasia group. In NFA, both enclitics and proclitics were associated with sentence repetition and digit span (p < 0.05), whereas in FA, these measures were primarily associated with enclitic production (p < 0.05). Conclusions: Clitics production distinguishes nonfluent from fluent aphasia in Serbian and is differentially supported by working and verbal memory resources. The Serbian clitic production test reveals a selective proclitic advantage that is observed only in fluent aphasia, serving as a sensitive clinical marker in this population.

Brain Sciences doi: 10.3390/brainsci16030323

Authors: Alexander D. Bartkowiak Marie R. Mooney

Background: Neurodevelopmental disorders span a wide spectrum of deficits, often with a known or suspected genetic basis. While some genetic determinants may indicate treatment with selective compounds, more often both the molecular cause of the disorder and the mechanism of action for the therapeutic compound are more ambiguously matched. Due to the polypharmacological nature of most neuroactive compounds, measuring gene expression changes following drug perturbation could be an effective strategy to gain insight into shared therapeutic action downstream of diversity in receptor interaction. High-throughput drug discovery platforms have effectively measured changes in gene expression following drug perturbation in cell cultures, but unfortunately, these platforms often lack specificity for neuroactive compounds, fail to capture the developmental influence of cell–cell interactions, and do not accurately model drug metabolism in an intact system. Methods: In this study, we present a high-throughput, low-cost and cell-type-specific approach for capturing transcriptional changes in neural cell populations following neuroactive compound exposure through the combined use of transgenic zebrafish, cell sorting, and bulk RNA-seq. Results: Our system captures unique transcriptional profiles between neuronal and non-neuronal cell populations and demonstrates specific drug responsiveness within our neuronal cell population. We assessed two known positive allosteric modulators (PAMs) of γ-Aminobutyric acid sub-type A receptors (GABAAR), ivermectin and propofol, as a case study to explore shared pathway and gene expression changes following drug exposure; these chemically distinct agents share a mechanistic signature that dampens the neuronal hyperexcitability characteristic of a broad spectrum of neurodevelopmental disorders. Two shared downregulated genes reflect a core expression module for modulating GABAergic tone: SRC proto-oncogene, non-receptor tyrosine kinase (SRC), and Glutamate decarboxylase 2 (GAD2). Conclusions: We provide this methodology and analysis as a framework for exploring shared changes in gene expression following neuroactive compound exposure in vivo, leading to a more complete and nuanced understanding of therapeutic effects on neurons that can aid in drug repurposing efforts for neurodevelopmental disorders.

Brain Sciences doi: 10.3390/brainsci16030322

Authors: Mario Treviño Nathaly Martín Andrea Barrera Inmaculada Márquez

Background/Objectives: Successful interception of moving targets requires combining predictive control, which anticipates future target states, and reactive control, which compensates for ongoing sensory discrepancies. How these components evolve over time and are distributed across gaze and manual behavior remains unclear. We aimed to explore the time-resolved dynamics of predictive control during continuous interception and to dissociate eye and hand contributions. Methods: Human participants intercepted a moving target in a two-dimensional arena using a joystick while eye movements were recorded. Target speed was systematically varied, and visual information was selectively reduced by occluding either the target or the user-controlled cursor. Predictive control was assessed using two complementary metrics: a geometric strategy index capturing moment-to-moment spatial lead or lag relative to target motion, applied separately to gaze and manual trajectories, and root mean square error (RMSE) computed relative to current and forward-shifted target positions to quantify predictive alignment. Results: Successful interception was characterized by structured, speed-dependent transitions between predictive and reactive control rather than a fixed strategy. Predictive alignment emerged early and was dynamically reweighted as temporal constraints increased. Gaze and manual behavior showed complementary but partially dissociable predictive signatures. Occluding the target decreased predictive alignment, whereas occluding the user-controlled cursor had comparatively minor effects, indicating strong reliance on internal state estimation rather than continuous visual feedback of the effector. Conclusions: Predictive and reactive control are continuously and dynamically reweighted during interception. Their interaction unfolds within single trials and depends on target dynamics and sensory availability. These findings provide quantitative evidence for time-resolved coordination between anticipatory and feedback-driven control mechanisms in goal-directed behavior.

Brain Sciences doi: 10.3390/brainsci16030321

Authors: Alexis Demas

Pareidolia is often framed as a viewer-side illusion: a tendency to perceive meaningful forms—especially faces—in ambiguous inputs. This Concept Paper argues that pareidolia can also be deliberately engineered and therefore provides a tractable entry point into the neurophysiology of visual creativity. We propose a unifying construct in which engineered pareidolia functions as externally scaffolded mental imagery: minimal visual constraints recruit internally generated templates and top-down inference while remaining anchored to sensory input. To strengthen theoretical rigor, we define necessary and sufficient features that distinguish this construct from adjacent accounts (scaffolded cognition; perceptual scaffolding; bistable perception). Using Arcimboldo’s composite portraits and Dürer’s embedded face in View of the Arco Valley, plus a canonical Renaissance example (Leonardo’s Bacchus/Saint John the Baptist), we outline distinct “design regimes” that modulate cue validity, attentional release, and interpretive switching. We then connect engineered pareidolia to creativity research by linking pareidolia design and detection to measurable constructs in divergent/creative perception, including but not limited to Torrance-style domains, and we propose feasible behavioral and neurophysiological paradigms that control for artistic skill and clinical status. Finally, we distinguish benign pareidolia from hallucination, discuss clinical resonance in dementia with Lewy bodies where pareidolia can be quantified, and outline an empirically testable research program that reframes pareidolia as a bridge between imagination, perception, and creativity.

Brain Sciences doi: 10.3390/brainsci16030320

Authors: Jeroen Staudt Yvonne C. M. Rensen Hein A. De Haan Jos I. M. Egger Boukje A. G. Dijkstra

Background/Objectives: Chronic alcohol use accelerates biological and cognitive aging, yet it remains unclear how cognitive aging progresses during abstinence in alcohol use disorder (AUD). It is also unknown to what extent this follows models such as accelerated aging or the age-related decline as proposed by the vulnerability hypothesis. This study examined age-related changes and cognitive recovery during abstinence in patients with AUD. Methods: A total of 197 clinically admitted patients, referred for detoxification and extensive neuropsychological examination, were included. Neuropsychological testing was administered in the second and sixth week of admission using well-normed instruments. Using both multi-assessment and cross-sectional data, relationships between age and normed cognitive outcome scores were examined. Results: After six weeks of abstinence, age-related deviations were observed for perceptual reasoning (PRI), verbal comprehension (VCI), and short-term memory (SMI) but not for ten other cognitive indices. During admission, age significantly influenced the change in belonging to a specific recovery category. Each additional year of age reduced the odds of showing no cognitive impairment by 5% and reduced the odds of cognitive recovery by approximately 4%, compared to non-improvers. Conclusions: Age-related influences appear limited to specific cognitive functions and do not follow a uniform or easily interpretable pattern. Perceptual reasoning seems negatively affected after age 60 for participants with six weeks of abstinence. Older participants showed a reduced likelihood of cognitive recovery and a reduced likelihood of having no cognitive problems at all. The findings do not support accelerated aging and are still too weak to be considered evidence for the vulnerability hypothesis. Implications for future research are discussed.

Brain Sciences doi: 10.3390/brainsci16030319

Authors: Andrew Zaman Caelia Marshall Elizabeth L. Stegemöller

Background: In addition to motor symptoms, persons with Parkinson’s disease (PD) experience several non-motor symptoms with challenges in working memory being particularly common. These cognitive challenges may worsen under stress. The purpose of this pilot study was to examine how physical stress affects working memory in persons with PD. Methods: Eight individuals with PD and 11 healthy older adults (HOAs) completed digit span forward and backward tasks following a socially evaluated cold pressor stressor and a control condition. Results: Under non-stressful conditions, persons with PD had a smaller digit span backward capacity and were slower during the digit span forward task compared to HOAs. However, during the stress condition, individuals with PD performed comparably to HOAs on the backward digit span task. Stress negatively affected response times on the backward task for both groups but did not alter capacity or response time on the forward task. Conclusions: These findings provide an initial step in understanding the effects of physical stress on working memory in PD. Since working memory supports many daily activities, understanding how stress influences this cognitive process may inform interventions that enhance stress regulation and improve cognitive and functional outcomes for individuals living with PD.

Brain Sciences doi: 10.3390/brainsci16030318

Authors: Christodoulos Komiotis Anastasia Tasiou Alexandros G. Brotis Kostas N. Fountas

Background/Objectives: Hydrocephalus is defined as the symptomatic accumulation of excessive cerebrospinal fluid (CSF) within the ventricular system. It has an estimated incidence of 85 cases per 100,000 population annually in adults, making it one of the most common conditions managed by neurosurgeons globally. Many conditions may lead to ventricular dilation and hydrocephalus, such as hemorrhage, tumors, infection, trauma, and idiopathic normal-pressure hydrocephalus (iNPH). Regardless of the cause, the gold-standard treatment for hydrocephalus is CSF diversion, usually via a ventriculoperitoneal (VP) shunt. The goal of the present study is to present our experience regarding the etiology of hydrocephalus, management, and shunt failure characteristics over the last 11 years. Methods: A single-center retrospective cohort study was performed. Our cohort consisted of adult patients who were shunted or required revision surgery in our department over the last 11 years. Data regarding the etiology of hydrocephalus, management, shunt characteristics, revision status, and etiology of revision were collected and retrospectively analyzed. Univariable and multivariable logistic regression models were established in order to explore potential associations between the etiology of hydrocephalus and patient characteristics and risk of shunt revision. Revision-free survival probabilities were estimated using the Kaplan–Meier method, while shunt failure rates were also calculated. Results: Our cohort consisted of 114 patients, the median age was 59 (IQR = 26.5) years, and the male-to-female ratio was 1.04:1. The most common cause of hydrocephalus was iNPH (30.7%), followed by post-hemorrhagic (23.7%) and tumor-related hydrocephalus (21.1%). The 12-month revision rate was 13.6%, with overall revision-free survival of 86.4% at one year. Infection (43.2%) was the most common cause of shunt revision, followed by obstruction (16.2%), and mechanical disconnection and migration (18.9%). Younger age was associated with higher risk of revision, while etiology of hydrocephalus and patient sex were not. Conclusions: Our study adds to the pertinent literature data regarding hydrocephalus etiology, management strategies, and shunt failure rates across different hydrocephalus etiologies. Additionally, it serves as a foundation for future studies that could identify predictors of shunt failure, apart from the etiology of hydrocephalus, such as patient characteristics, surgical factors, or shunt types. Finally, we highlight the importance of comprehensive national and potentially continental registries, which will facilitate large-scale analyses.

Brain Sciences doi: 10.3390/brainsci16030317

Authors: Stefan Stojanoski Katarina Karher Duško Kozić Siniša S. Babović Miloš Vuković Katarina Koprivšek

Background: Frontal lobe involvement represents an important but heterogeneously expressed feature across neurodegenerative and vascular cognitive disorders. While frontal atrophy has been described in Alzheimer’s disease (AD), detailed volumetric assessment of frontal subregions across Alzheimer’s disease, amnestic mild cognitive impairment (aMCI), and vascular dementia (VaD) remains insufficiently characterized. The aim of this study was to evaluate frontal lobe and frontal subregional volumetric alterations across these diagnostic groups using automated MRI-based volumetry. Methods: This cross-sectional study included 120 participants divided into four groups: AD, VaD, aMCI, and cognitively healthy controls (n = 30 per group). All participants underwent standardized neuropsychological assessment and 3T brain MRI. Automated volumetric analysis of the frontal lobe and its subregions was performed using the Vol2Brain pipeline. Group differences in total intracranial volume–adjusted frontal volumes were assessed using analysis of covariance, controlling for age and sex, followed by Bonferroni-corrected post hoc comparisons. False discovery rate (FDR) correction was applied across subregional comparisons. Results: A significant main effect of diagnostic group was observed for total frontal lobe volume, with lower adjusted volumes in patients with AD compared with aMCI and cognitively healthy controls. After correction for multiple comparisons, only total frontal lobe volume remained statistically significant. At the nominal level, group differences were observed in several frontal subregions, predominantly involving prefrontal and orbitofrontal areas. However, these findings did not survive FDR correction and should be interpreted as exploratory. No consistent frontal volumetric pattern was observed in VaD. Receiver operating characteristic analysis demonstrated moderate discriminatory ability of total frontal lobe volume for distinguishing AD from cognitively healthy controls. Conclusions: Automated MRI-based volumetry revealed global frontal lobe reduction in Alzheimer’s disease, whereas subregional findings were exploratory after correction for multiple testing. Frontal volumetric measures did not demonstrate a characteristic pattern in VaD. Global frontal volume may provide complementary structural information within clinically define cognitive disorders.

Brain Sciences doi: 10.3390/brainsci16030316

Authors: Stefanie Bauer Timo Kahles Michael Diepers Gerrit A. Schubert Lukas Andereggen Serge Marbacher

Background/Objectives: Selection of the optimal recipient artery in superficial temporal artery to middle cerebral artery (STA–MCA) extracranial–intracranial bypass surgery is essential to ensure adequate cerebral perfusion. Various pre- and intraoperative tools for target vessel selection have been proposed. Indocyanine green fluorescence video angiography (ICG-VA) enables real-time visualization of cerebral hemodynamics, facilitating recipient vessel selection and anastomotic evaluation. Here, we review the literature and present the use of qualitative ICG-VA to support intraoperative decision-making during double-barrel (DB) STA–MCA bypass surgery. Case description: We report the case of a 68-year-old patient with bilateral steno-occlusive cerebrovascular disease, who developed progressive hemodynamic compromise of the left hemisphere after prior right-sided STA-MCA bypass. Preoperative imaging demonstrated impaired perfusion and posterior-to-anterior leptomeningeal collateralization from the posterior cerebral artery. During the left-sided DB bypass surgery, intravenous ICG-VA was used to assess relative cortical perfusion. Two superficial M4 branches with the most pronounced perfusion delay were selected as recipients based on the ICG-VA and anatomical criteria. Postoperative angiography confirmed graft patency. At short-term follow-up, the patient remained neurologically stable, with complete regression of preoperative symptoms. Conclusions: This case illustrates the application of qualitative ICG-VA for perfusion-oriented recipient vessel selection in DB STA-MCA bypass for steno-occlusive disease. Real-time perfusion assessment may complement conventional anatomical criteria for recipient vessel selection in flow-augmentation procedures. Further studies incorporating quantitative hemodynamic analysis are warranted.

Brain Sciences doi: 10.3390/brainsci16030315

Authors: Daniel J. Morris Susana G. Torres-Platas Karen R. Konkoly John Hirschle Lodoe Sangpo Thabkhe Tenzin Legden Lobsang Pelmo Tenzin Pasang Marcia Grabowecky Robin Nusslock Ken A. Paller

Background/Objectives: Lucid dreaming—dreaming with the awareness that one is dreaming—has been explored from many perspectives, including those of cognitive neuroscience and various ancient cultural traditions. Lucid dreaming appears within the Tibetan-Buddhist literature together with dream yoga, a set of contemplative practices aimed at cultivating lucidity during dreams along with other qualities such as visual imagination, somatic awareness, and cognitive flexibility. These practices include deity visualization, which is the practice of bringing to mind a detailed image of a being whose qualities the practitioner wishes to cultivate. We examined whether it is possible to induce a lucid dream of Chenrezig, the ultimate embodiment of compassion in a Tibetan-Buddhist context. Methods: Five participants slept in the sleep laboratory for 7 overnight sessions with polysomnographic recording and auditory reminders to visualize Chenrezig during REM sleep. Results: Lucid dreams were reported by two participants. A frequent lucid dreamer with no prior Tibetan-Buddhist training experienced a lucid dream that included a visualization of Chenrezig following auditory cueing during REM sleep. A monastic participant with no prior history of lucid dreaming reported their first-ever lucid dream on the night following their laboratory session. Conclusions: This exploratory study illustrates, via collaborative research including monastic scholars trained in neuroscience, that dream content can be intentionally shaped using an approach that integrates contemplative visualization practices with modern techniques of dream engineering.

Brain Sciences doi: 10.3390/brainsci16030314

Authors: Sergio Paolini Anthony Kevin Scafa Roberta Morace Vito Chiarella Rocco Severino Giuseppe Corazzelli

Background: Posterior approaches to intramedullary spinal cord tumors traditionally rely on bilateral laminotomy or laminoplasty to ensure adequate midline exposure and contralateral dissection. Unilateral approaches are seldom applied in this context, due to concerns regarding insufficient visualization and limited working angles across the midline. Objective: To describe a modified hemilaminectomy technique designed to achieve safe midline myelotomy and bilateral tumor dissection through a unilateral corridor, preserving the structural and clinical benefits of minimally invasive posterior access. Methods: Fourteen patients with intramedullary spinal cord tumors underwent resection via a refined hemilaminectomy technique, which incorporated systematic thinning of the spinous process and strategic dural suspension. Pre- and postoperative neurological status was assessed using the modified McCormick scale. Surgical parameters, postoperative outcomes, and radiological follow-up were retrospectively collected. Results: Gross total resection was achieved in 13 of 14 patients (92.9%), with no new permanent neurological deficits. The mean surgical duration was 194.8 ± 55.9 min, and mean hemoglobin decrease was 1.47 ± 0.94 g/dL. Early postoperative improvement in McCormick grade was observed in 50% of cases, with statistically significant overall functional recovery (p = 0.013). No cases of postoperative cord tethering were identified on follow-up magnetic resonance imaging. The approach was technically reproducible and ergonomically favorable, with a shallow learning curve in surgeons experienced with conventional hemilaminectomy. Conclusions: The modified hemilaminectomy technique enables effective bilateral exposure and safe midline myelotomy through a unilateral approach, achieving high resection rates with minimal morbidity. It represents a feasible and reproducible alternative to bilateral approaches and warrants prospective validation.

Brain Sciences doi: 10.3390/brainsci16030313

Authors: Alina Roman Horațiu Catalano Karla Barth Cristina Florescu Mariana Tipei-Voia Dana Rad Olga Chiș Edgar Demeter Regis Roman Raluca Șandru Irina Mihaela Trifan

Background/Objectives: Academic engagement plays a central role in students’ learning outcomes and persistence in higher education. However, the mechanisms through which amotivation influences engagement remain insufficiently understood, particularly within conditional self-regulation frameworks. The present study examined a conditional self-regulation model in which amotivation predicts academic engagement through forethought and self-reflection under different levels of perceived performance control. Methods: Data were collected from 530 university students from Western Romania. A moderated parallel mediation model (PROCESS Model 59) was estimated to test whether forethought and self-reflection mediate the relationship between amotivation and academic engagement and whether perceived performance control moderates these pathways. Results: The results indicated that amotivation maintained a robust direct association with academic engagement across levels of performance control. Perceived performance control moderated the amotivation–forethought pathway, while self-reflection showed conditional indirect effects depending on control levels. Conclusions: These findings suggest that motivational deficits operate within a context-sensitive regulatory architecture in which control beliefs shape the activation of self-regulatory processes. The results contribute to understanding academic adaptation under motivational constraints and highlight the role of perceived performance control in students’ self-regulation systems.

Brain Sciences doi: 10.3390/brainsci16030312

Authors: Shannon M. O’Donnell W. Jack Rejeski Mohammadreza Khodaei Robert G. Lyday Jonathan H. Burdette Paul J. Laurienti Heather M. Shappell

Background: Previous research has found that mindfulness-based techniques are beneficial for reducing stress in heavy-drinking individuals. However, the underlying neurobiology of these stress-reducing effects are unclear. Moreover, much of the research examining neurobiological correlates of mindfulness has used static functional connectivity, suggesting that brain activity goes unchanged for the entire length of an MRI scan. Methods: In the current study, we used a state-based dynamic functional connectivity model to examine brain states during either a 10 min mindfulness session or resting control that followed an individually tailored stress imagery task. Using a hidden semi-Markov model (HSMM), six brain states and the associated dynamics of state traversal were estimated for a population of moderate-to-heavy drinkers (N = 32). We modeled the 36 Schaefer atlas regions spanning the salience and default mode networks, and the HSMM characterized each state by its distinct multivariate pattern of activity and covariance structure. Group differences in dwell times, transition behavior, and overall state dynamics were evaluated using permutation tests and mixed-effects models. Results: Participants that experienced the mindfulness session had more transitions and longer time spent in states in which the salience network was more active. Participants assigned to the control group had more transitions and increased time spent in states in which nodes of the default mode network were more active. Moreover, for control participants, increased occupancy time to SN-dominant states was associated with lower perceived stress. Conclusions: Using HSMM provided a unique insight into network connectivity during mindful states; we believe it offers a novel approach to testing and optimizing mindful-based therapies.

Brain Sciences doi: 10.3390/brainsci16030311

Authors: Cristian Manea Corina Colareza Dana Rad Mușata-Dacia Bocoș Teofil Panc Mona Bădoi-Hammami Gheorghe Mihai Bănariu

Background: Self-transcendence has been described in psychological literature as an orientation toward meaning beyond the individual self. However, because the present study does not directly measure transcendence as a psychological construct, we approach it cautiously as a candidate form of internally oriented attention, operationalized through EEG spectral dynamics. Although this construct has been linked to self-referential cognition and large-scale brain systems supporting internal mentation, electrophysiological evidence remains limited, especially in designs that compare spiritually oriented practices with non-spiritual internal-focus controls. Objective: We examined whether a candidate EEG-derived Transcendence Index (TI) is associated with EEG oscillatory activity across canonical frequency bands and whether prayer and relaxation show descriptively distinct oscillatory patterns. Methods: In a within-subject design, participants completed a psychological assessment battery including personality and anxiety measures and underwent EEG recording during two eyes-closed conditions (Prayer vs. Relaxation). Spectral power features were extracted for delta, theta, alpha (low/high), beta (low/high), and gamma (low/high, where signal quality permitted). We examined associations between TI and band-limited activity and explored condition-related oscillatory patterns across Prayer and Relaxation. Given the modest sample size (N = 39), the study was designed and interpreted as exploratory research. Results: Higher TI was associated with an oscillatory profile consistent with internally oriented attention and reflective self-processing, with the most consistent patterns observed in theta–alpha dynamics (and comparatively lower beta contribution). In addition, Prayer and Relaxation showed descriptively distinct oscillatory patterns, suggesting that prayer engages internal-focus processes that may not be fully captured by relaxation alone. Conclusions: These findings support the feasibility of examining internally oriented attentional dynamics potentially related to “transcendence” as a candidate construct through scalp EEG spectral activity. Integrating theory-informed indices with EEG features may help refine psychophysiological models of self-transcendence and inform digitally supported assessment approaches, pending further construct validation. These findings should therefore be interpreted as exploratory preliminary evidence supporting the feasibility of EEG-based indices of internally oriented attention.

Brain Sciences doi: 10.3390/brainsci16030310

Authors: Girija Kadlaskar Stephanie E. King Jessica R. Stewart

Background: The present study examines sensory differences in children referred for autism evaluations and explores associations between sensory differences, autism symptomatology, and adaptive skills. Using a clinically referred sample, this study captures the heterogeneity of diverse developmental profiles observed in everyday clinical practice and provides a nuanced understanding of sensory differences in an ecologically valid way in the context of autism assessments. Methods: Participants included 238 children (41 females/3–14 years), referred to a university-based autism clinic due to concerns related to autism. Autism diagnoses were confirmed using the Autism Diagnostic Observation Schedule-2, DSM-5 criteria, and expert clinical judgement informed by comprehensive multidisciplinary evaluation. Additional measures were collected to obtain information on sensory processing (Sensory Profile-2/SP-2) and adaptive functioning (Vineland-II/-3). Diagnostic outcomes were classified as autism (n = 121) versus non-autism (n = 117). Results: Non-autistic children scored higher than autistic children in sensory avoiding and sensitivity, with no group differences in sensory seeking or registration as measured by the SP-2. Correlational analysis showed negative associations between sensory differences and both autism symptomatology and adaptive functioning. Regression analysis further indicated that higher sensory differences predicted lower adaptive functioning, with sensory sensitivity showing the most widespread associations across communication, daily living skills, and socialization. Conclusions: Non-autistic children exhibited greater sensory avoiding and sensitivity than autistic children, which may possibly reflect co-occurring concerns such as anxiety or attentional difficulties (e.g., avoiding noisy environments due to anxiety rather than sensory sensitivity). Across groups, higher sensory differences showed consistent associations with lower adaptive functioning, highlighting the importance of assessing sensory behaviors in children with diverse clinical profiles.

Brain Sciences doi: 10.3390/brainsci16030309

Authors: Eda Yılmazer Metin Çınaroğlu Selami Varol Ülker Gökben Hızlı Sayar

Background: Anorexia nervosa (AN) is a severe psychiatric disorder marked by restrictive eating, distorted body image, and high relapse rates. While cognitive-behavioral therapy (CBT) is a widely used treatment, its mechanisms of action in AN remain incompletely understood, particularly beyond self-reported symptom change. This study investigated the effects of a 12-week CBT intervention on both clinical and multimodal laboratory-based outcomes in women with restrictive-type AN. Methods: In a two-arm, pre–post randomized controlled trial (ClinicalTrials.gov: NCT07037017), 59 women with restrictive-type AN were randomized to a CBT intervention (n = 30) or no-treatment control (n = 29). A total of 50 participants (CBT: 26; control: 24) completed baseline and post-intervention assessments and were included in analyses. Outcomes included psychometric measures (eating disorder symptoms, depression, anxiety, body image-related obsessive–compulsive symptoms, and cognitive emotion regulation) and laboratory-based indices: electroencephalography (EEG), galvanic skin response (GSR), and eye-tracking during exposure to food- and body-related stimuli. Group × Time effects were analyzed using repeated-measures mixed-effects models, and statistical analyses were conducted using SPSS (Version 31; IBM Corp., Armonk, NY, USA). Results: Significant Group × Time interactions indicated greater improvements in the CBT group across all psychometric outcomes, including reduced eating disorder symptom severity (p < 0.001, ηp2 = 0.28) and increased adaptive emotion regulation. CBT participants also showed significant reductions in EEG P300 and late positive potential (LPP) amplitudes to body-related stimuli, increased frontal alpha asymmetry, decreased visual fixation on salient body and food cues, and attenuated GSR reactivity (all p < 0.05). Exploratory correlations revealed that symptom improvements were associated with reductions in neurophysiological and attentional reactivity. Conclusions: To our knowledge, this is the first RCT in AN to demonstrate that CBT not only improves self-reported outcomes but also modulates neurophysiological and attentional processes implicated in the maintenance of the disorder. Multimodal laboratory assessments provided mechanistic insight into treatment effects and may inform personalized intervention strategies. CBT appears to facilitate recovery through both cognitive–emotional and physiological recalibration.

Brain Sciences doi: 10.3390/brainsci16030308

Authors: Xiao Yu Roxana Dev Omar Dev Maizatul Mardiana Harun

Background: With advancing age, cognitive control and postural-gait regulation decline, while dual-task interference intensifies, leading to restricted mobility and increased fall risk. Variable-priority cognitive-motor dual-task training (VPDT) enhances attentional flexibility and task integration by systematically shifting attentional allocation during training. However, its effects on cognitive and physical function remain unclear. Objective: To review the effects of VPDT on cognitive and physical function in older adults. Method: A comprehensive database search was conducted in the PubMed, Embase, Cochrane, Web of Science, PsycInfo, and CINAHL databases from inception to April 2025, relevant articles were selected, data were extracted using a PICO framework and synthesized narratively. Result: Eight controlled trials (n = 284) were included. Across studies, VPDT was generally associated with improvements in functional balance and mobility outcomes, while between-group differences versus fixed-priority dual-task training (FPDT) were inconsistent. Cognitive outcomes were sparsely reported (only one trial), and psychosocial outcomes were assessed in only a small subset of studies, precluding firm inferences regarding cognitive or psychosocial benefits. Overall risk of bias was predominantly “some concerns,” with two studies rated “high risk,” and overall certainty of evidence ranged from low to moderate due to risk of bias, small samples, and heterogeneity in protocols and outcomes. Conclusions: VPDT may improve physical function in older adults, particularly balance and mobility, but current evidence does not demonstrate a consistent incremental advantage over FPDT. Confidence in comparative effects remains limited due to small sample sizes, risk-of-bias concerns, and heterogeneity in intervention design and outcome measurement.

Brain Sciences doi: 10.3390/brainsci16030307

Authors: Benedetta Nardi Francesca Parri Stefano Pini Federico Giovannoni Cristiana Pronestì Silvia Tarantino Gabriele Massimetti Ivan Mirko Cremone Liliana Dell’Osso Barbara Carpita

Objectives: Autism Spectrum Disorder (ASD) and psychotic disorders have long been considered separate diagnostic entities, yet increasing evidence highlights shared neurodevelopmental mechanisms and symptom overlap. Psychotic-like experiences have been frequently reported in individuals with ASD, while subthreshold autistic traits (ATs) in first-degree relatives may also confer vulnerability to psychotic symptoms. This cross-sectional study aimed to compare psychotic spectrum manifestations among adults with ASD, their first-degree relatives (BAP), and controls (HCs), to explore associations between psychotic and ATs, and to evaluate whether psychotic symptoms predict diagnostic group membership. Methods: 22 adults with ASD, 22 BAP, and 24 HCs were evaluated with the Psychotic Spectrum–Self Report (PSY-SR) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). Results: ASD participants scored significantly higher on the PSY-SR. BAP individuals showed higher PSY-SR total scores compared to HCs, though less severe than in ASD. All PSY-SR domains positively correlated with all AdAS Spectrum domains, with few exceptions. Multinomial regressions showed that higher PSY-SR total scores significantly predicted ASD and BAP membership, and that the PSY-SR Paranoid domain score specifically predicted inclusion in both groups in relation to HCs. Conclusions: Psychotic spectrum symptoms are elevated not only in individuals with ASD but also among first-degree relatives, supporting a continuum linking autistic and psychotic vulnerabilities. The strong association between paranoid symptoms and ATs highlights a dimension of potential clinical relevance for early identification and assessment. These findings reinforce shared neurodevelopmental pathways between the autism and psychosis spectra and underscore the importance of dimensional approaches across diagnostic categories.

Brain Sciences doi: 10.3390/brainsci16030306

Authors: Amna Khan Patrick J. Ronan Shafiqur Rahman

Background/Objectives: Evidence indicates that aberrant glutamate transporter function and expression are linked to the pathophysiology of comorbid major depressive disorder (MDD) and pain. We have previously reported that cefepime (CFP) attenuates lipopolysaccharide (LPS)-evoked pain and depression by regulating hyperglutamatergic activity in male mice. However, the effects of CFP on LPS-evoked pain, depression-related anxiety, and cognitive impairment in female mice regarding sex-specific glial mechanisms remain unknown. Methods: Using behavioral paradigms, we evaluated the therapeutic potential of CFP in mitigating LPS-evoked pain, depression-related anxiety, and cognitive impairment in female mice. Furthermore, we used Western blot analysis to examine the effects of CFP on ionized calcium-binding adaptor molecule 1 (Iba-1) and glutamate transporter 1 (GLT-1) protein levels in the prefrontal cortex (PFC) and hippocampus (HPC). We also measured tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations in the HPC and PFC after CFP treatment using ELISA. Results: Pretreatment with CFP significantly increased the mechanical threshold and withdrawal latency in female mice. Additionally, systemic treatment with CFP markedly reduced immobility during the forced swim and tail suspension tests. Moreover, pretreatment with CFP remarkably augmented the open arm time during elevated plus maze test and spontaneous alternation between arms during Y-maze test. Western blot analysis indicated that systemic administration of CFP significantly reversed the downregulation of astroglial GLT-1 expression and reduced the microglial Iba-1 protein levels in the HPC and PFC. Furthermore, pretreatment with CFP significantly attenuated the LPS-evoked increase in the production of pro-inflammatory cytokines in the HPC and PFC. Conclusions: These results represent the novel inaugural report of a combined pain-MDD phenotype in female mice. The findings imply that positive glutamate transporter modulator CFP could be a novel treatment for comorbid pain and MDD in female patient population.

Brain Sciences doi: 10.3390/brainsci16030305

Authors: Łukasz Mański Aleksandra Moluszys Anna Góra Eliza Wasilewska Agnieszka Rosa Krzysztof Szczałuba Krystyna Szymańska Jolanta Wierzba

Background/Objectives: Joubert syndrome is a rare neurodevelopmental disorder characterized by congenital cerebellar and brainstem malformations affecting networks involved in predictive motor control, sensorimotor integration, and autonomic regulation, resulting in a heterogeneous motor phenotype. Functional impairment is typically described using global gross motor scores, which may not adequately reflect axial control, postural organization, musculoskeletal alignment, or respiratory–postural interactions. The objective of this descriptive pilot case series was to provide a multidimensional functional characterization of children with Joubert syndrome by integrating standardized motor assessments with postural, musculoskeletal, and thoracoabdominal measures. Methods: Six children with genetically and radiologically confirmed Joubert syndrome underwent a single standardized assessment session conducted by the same examiner. This cross-sectional, non-controlled study was based on feasibility sampling, and no a priori power calculation was performed. Gross motor function and postural control were evaluated using the Gross Motor Function Measure-88 and the Balance Assessment Rating Scale. Additional measures included joint range of motion, sacral inclination angle, thoracic configuration, thoracic excursion during quiet breathing, and respiratory rate. Analyses were limited to descriptive statistics. Results: Gross motor performance varied widely across participants, whereas postural control scores did not parallel gross motor performance levels within the cohort. Inter-individual variability was observed in joint mobility, pelvic alignment, and thoracoabdominal configuration, including among children with relatively preserved gross motor scores. Thoracic excursion during quiet breathing demonstrated a relatively narrow and low within-cohort range. Conclusions: In this small exploratory case series, functional characteristics observed in this cohort extended beyond global motor scores. Axial control, postural organization, and thoracoabdominal configuration may represent relevant descriptive domains of functional presentation within a multidimensional framework. Larger, longitudinal, and controlled studies are required to determine their clinical and neurodevelopmental significance.

Brain Sciences doi: 10.3390/brainsci16030304

Authors: Mehpare Sarı Yanartaş Nurel İnan Aydemir Furkan Donbaloğlu Chakan Tsakir Özlem Yayıcı Köken Burçin Şanlıdağ Şenay Türe Boran Şekeroğlu Aygen Yılmaz Şenay Haspolat

Background: Celiac disease (CD) is a multisystem immune-mediated disorder increasingly recognized to affect sleep and neurobehavioral functioning. Pediatric data remain limited, and no prior study has examined especially for sleep microstructure in this population. This study evaluates the prevalence and patterns of sleep disturbances in children with CD using the Sleep Disturbance Scale for Children (SDSC) and explores potential electrophysiological correlates through N2 sleep spindle analysis. Methods: Children with biopsy-confirmed CD (n = 31) and age-matched controls (n = 25) completed the SDSC. A subgroup of CD patients with SDSC ≥ 35 and healthy controls underwent quantitative sleep spindle analysis (C3, C4, O1, O2) using automated and visual verification methods combined. Results: Clinically significant sleep disturbances were substantially more prevalent in CD than in controls (77.4% vs. 12%). Excessive somnolence, sleep–wake transition disorders, and sleep hyperhidrosis were the most affected domains. Moreover, among children with CD, those noncompliant with a gluten-free diet exhibited higher rates of excessive somnolence and sleep–wake transition disorders. While spindle parameters did not differ between groups, higher SDSC scores (≥35)—particularly in the somnolence and sleep–wake transition disorder domains—are associated with reduced spindle amplitude and density, suggesting that spindle alterations are linked to sleep disturbance severity rather than disease status per se. Conclusions: Sleep disturbances are common in pediatric CD and worsen with poor dietary adherence. Although sleep microarchitecture is largely preserved, reduced spindle activity is evident in children with higher subjective sleep burden, suggesting that spindle metrics may serve as potential objective markers for sleep disturbance. Longitudinal studies are required for validation.

Brain Sciences doi: 10.3390/brainsci16030303

Authors: Liliana Dell’Osso Benedetta Nardi Martina Calvaruso Alina Lohse Cristiana Pronestì Chiara Bonelli Gabriele Massimetti Ivan Mirko Cremone Mario Luciano Stefano Pini Andrea Fiorillo Barbara Carpita

Background: Eating disorders (EDs) frequently co-occur with trauma-related symptoms and elevated autistic traits (ATs), both of which contribute to clinical complexity. Social camouflaging, strategies used to mask or compensate for ATs, has been increasingly described in ED populations, yet its relationship with trauma-related symptoms remains poorly understood. This study aimed to examine the association between social camouflaging and post-traumatic stress symptoms in individuals with EDs and to evaluate whether trauma-related symptomatology is associated with camouflaging behaviors. Methods: A total of 67 ED patients were assessed using the Adult Autism Subthreshold Spectrum, the Trauma and Loss Spectrum—Self Report (TALS-SR), the Camouflaging Autistic Traits questionnaire (CAT-Q), and the Eating Disorder Inventory (EDI-2). Participants were divided into high-trauma-symptoms (HTS) (N = 36, 53.7%) and low-trauma-symptoms (LTS) (N = 31; 46.3%) groups based on TALS-SR criteria. Results: The sample was predominantly female (92.5%), and gender distribution differed between groups, which may represent a potential confounding factor and limits the generalizability of the findings. The HTS group reported significantly higher TALS-SR, EDI-2, CAT-Q, and AdAS Spectrum scores, although for the latter the p-value was barely significant (p = 0.046). No differences emerged in the distribution of ED diagnoses between groups. CAT-Q scores were significantly positively correlated with TALS-SR total scores and with domains related to reaction to losses, maladaptive coping, avoidance/numbing, and personal vulnerability. Regression analyses showed that overall trauma-related symptoms were significantly associated with greater camouflaging; however, the proportion of explained variance was modest, suggesting that trauma-related symptoms represent only one of multiple factors linked to camouflaging. Conclusions: Among individuals with EDs, higher trauma-related symptomatology is linked to greater use of social camouflaging strategies. These findings suggest that camouflaging may represent a transdiagnostic correlate connecting neurodevelopmental vulnerability and trauma responses within ED populations, underscoring the importance of integrated assessment and trauma-informed care.

Brain Sciences doi: 10.3390/brainsci16030302

Authors: Rosa Ayuso-Moreno Ana Rubio-Morales Rubén Llanos-Muñoz Tomás García-Calvo Inmaculada González-Ponce

Background/Objectives: Adolescence is a critical period for executive function (EF) maturation. While sleep and physical activity (PA) are key lifestyle factors, their longitudinal impact on EF in ecologically valid settings is insufficiently characterised. This study examined the associations between objectively measured sleep duration, daily steps, and EF performance across one academic year (~9 months). Methods: A longitudinal study was conducted with 168 Spanish adolescents (13–16 years). Sleep duration and daily steps were monitored using Fitbit Charge 6 wearables for 7-day periods at baseline (M1; September 2024) and follow-up (M2; June 2025). EFs were assessed using three validated tasks: Stroop (inhibitory control), Psychomotor Vigilance Task-Brief (PVT-B; sustained attention), and Paced Auditory Serial Addition Test (PASAT; working memory). Linear Mixed Models (LMM) were employed to analyse the effects of the fixed factors (i.e., Group and Time), and their interactions. Results: PA, but not sleep duration, significantly predicted executive performance. The High_PA group demonstrated faster reaction times in inhibitory control (p = 0.007) and significantly fewer attentional lapses in sustained attention (p = 0.014). In contrast, sleep duration showed no significant main effects on EF domains (p > 0.05). Regression analyses confirmed that higher daily steps predicted faster reaction times in inhibitory control in the total sample (r = −0.173, p = 0.002), although an unexpected positive association was observed in the Low_PA group for inhibitory control, warranting cautious interpretation. Conclusions: These findings suggest that habitual PA is associated with better EF performance in adolescents, whereas sleep duration alone (without considering timing or variability) showed no significant associations with cognitive outcomes. Sensitivity analyses using clinically informed thresholds and continuous standardised predictors confirmed the robustness of these findings.

Brain Sciences doi: 10.3390/brainsci16030301

Authors: Hesam Akbari Sara Bagherzadeh Javid Farhadi Sedehi Rab Nawaz Reza Rostami Reza Kazemi Sadiq Muhammad Haihua Chen Mutlu Mete

Background/Objectives: Predicting individual response to depression therapy prior to treatment initiation remains a critical clinical challenge, as the response rate to both selective serotonin reuptake inhibitors (SSRIs) and repetitive transcranial magnetic stimulation (rTMS) is approximately 50%, leaving treatment selection largely trial-based. This study presents a computer-aided decision (CAD) framework that predicts depression therapy outcomes from pre-treatment electroencephalogram (EEG) signals using advanced time-frequency representations and pretrained convolutional neural networks (CNNs). Methods: EEG signals from 30 SSRI patients and 46 rTMS patients are transformed into time-frequency images using Continuous Wavelet Transform (CWT), Variational Mode Decomposition (VMD), and their pixel-level fusion. Four pretrained CNN architectures, including ResNet-18, MobileNet-V3, EfficientNet-B0, and TinyViT-Hybrid, are fine-tuned and evaluated under both image-independent and subject-independent 6-fold cross-validation (CV). Results: Results reveal a clear therapy-specific pattern: CWT-based representations yield superior discrimination for SSRI outcome prediction, with ResNet-18 achieving 99.43% image-level accuracy, while VMD-based representations are statistically superior for rTMS outcome prediction, with ResNet-18 reaching 98.77%. Pixel-level fusion of CWT and VMD does not consistently improve performance over the best individual representation in either therapy context. Pairwise Wilcoxon signed-rank tests confirm a two-tier architectural hierarchy in which ResNet-18 and TinyViT-Hybrid significantly outperform MobileNet-V3 and EfficientNet-B0 across all conditions, while remaining statistically indistinguishable from each other. At the subject level, the framework achieves 82.50% and 83.53% accuracy for SSRI and rTMS, respectively, under strict subject-independent evaluation. Per-channel analysis reveals occipital dominance for SSRI under CWT and frontotemporal dominance for rTMS under VMD, consistent with known neurophysiological mechanisms. Conclusions: These findings demonstrate that the choice of time-frequency representation is therapy-specific and at least as important as architectural complexity, and that competitive performance can be achieved without recurrent or attention layers by combining well-designed spectral images with a simple pretrained residual network.