Brain Sciences

52 pages, 38034 KB

Open AccessArticle

An Augmented Reality and AI-Based System for Contextual Appliance Guidance: Implications for Cognitive Accessibility and Assistive Interaction

by Kimia Hafezi, Atra Hossein Tafreshi, Christian Napoli, Cristian Randieri and Samuele Russo

Brain Sci. 2026, 16(8), 783; https://doi.org/10.3390/brainsci16080783 (registering DOI) - 24 Jul 2026

Abstract

Background: Modern household appliances often present complex interfaces that can be difficult to use, especially for older adults, people with visual impairments, and users with mild cognitive difficulties. In such cases, interacting with appliances may require sustained attention, visuospatial search, working memory, and [...] Read more.

Background: Modern household appliances often present complex interfaces that can be difficult to use, especially for older adults, people with visual impairments, and users with mild cognitive difficulties. In such cases, interacting with appliances may require sustained attention, visuospatial search, working memory, and sequential action planning, while traditional user manuals often provide limited contextual support. Methods: To address this issue, this study presents a proof-of-concept augmented reality (AR) and artificial intelligence (AI)-based system for contextual appliance guidance. The proposed architecture integrates visual sensing, deep learning, and large language models to detect appliance controls, interpret user queries, retrieve relevant information from user manuals, and provide step-by-step guidance directly on the real interface. A YOLOv8 model trained on a custom dataset was used for button detection, YOLO-Seg was employed to enhance visual highlighting through segmentation, and BoT-SORT was used to maintain detection consistency across frames. A Unity-based mobile application displayed real-time AR overlays with customizable visual settings for accessibility needs, such as low vision and color blindness that may be relevant for future accessibility-oriented applications. In addition to its technical pipeline, the system is conceptually relevant as a potential form of external cognitive support because it transforms static manual instructions into situated, sequential, and visually grounded guidance.Results: Experimental results showed promising technical performance for button detection and segmentation, while a preliminary user evaluation in a non-clinical sample suggested good usability, clarity, and acceptability of the interface. Conclusions: These findings support the technical feasibility and preliminary usability of the approach, while cognitive workload, confidence, functional autonomy, and clinical benefit were not directly measured. Targeted validation in older adults, people with visual impairments, and clinical populations is therefore still needed. Future developments will include multimodal feedback, read-aloud guidance, and more specific evaluation of workload, confidence, and functional autonomy. Full article

(This article belongs to the Section Neural Engineering, Neuroergonomics and Neurorobotics)

34 pages, 1330 KB

Open AccessArticle

The Effects of In-Phase Bilateral Upper-Limb Exercises on Corticospinal Plasticity in People with Progressive Multiple Sclerosis: A Pilot Randomized Single-Case Concurrent Multiple-Baseline Design

by Marinos Chatzikonstantinou, Kyriaki Michailidou, Marios Pantzaris, Gavriella Alexandrou, Charalambos C. Charalambous and Dimitris Sokratous

Brain Sci. 2026, 16(8), 782; https://doi.org/10.3390/brainsci16080782 - 24 Jul 2026

Abstract

Background: Corticospinal plasticity is impaired in MS. In-phase bilateral upper-limb exercises have been shown to improve corticospinal excitability in people with relapsing-remitting multiple sclerosis, but there is limited literature that supports the same conclusion for progressive multiple sclerosis. Therefore, our aim was to [...] Read more.

Background: Corticospinal plasticity is impaired in MS. In-phase bilateral upper-limb exercises have been shown to improve corticospinal excitability in people with relapsing-remitting multiple sclerosis, but there is limited literature that supports the same conclusion for progressive multiple sclerosis. Therefore, our aim was to investigate whether a 12-week in-phase bilateral upper-limb exercise protocol could enhance corticospinal plasticity and improve clinical outcomes in people with progressive multiple sclerosis. Methods: Five participants (two females; age = 61 ± 12.04 years) with secondary or primary progressive multiple sclerosis were randomized and recruited in a single-case concurrent multiple-baseline design study. The exercise protocol lasted for 12 consecutive weeks (30–60 min/session × 3 sessions/week) and incorporated adapted sport-specific activities, functional training and proprioceptive neuromuscular facilitation exercises. To define the functional relationship between the intervention and the results, a visual analysis was conducted. A statistical analysis was performed when a potential sizeable effect was observed. Results: Statistically significant reductions in active motor threshold (primary outcome) were observed in two of the five participants for the left upper limb and in one of the five participants for the right upper limb. Statistically significant improvements were partially observed in muscle strength, pinch strength and cognitive processing speed. Conclusions: Based on the preliminary findings of the current study, in-phase bilateral upper-limb exercises may modulate corticospinal plasticity and improve clinical outcomes in people with progressive multiple sclerosis. However, larger studies are needed to reproduce these results and to establish the effects of in-phase bilateral exercise on both corticospinal plasticity and related clinical outcomes. Full article

(This article belongs to the Section Neurorehabilitation)

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18 pages, 5539 KB

Open AccessArticle

A Comparison of Machine Learning Models for Classification of Parkinson’s Disease During a Working Memory and Sustained Attention Task

by Mercedes A. Terry, Samuel A. Birkholz, Jeffrey S. Johnson, Jau-Shin Lou, Asenath X. A. Huether, Jessica Keller and Enrique Alvarez-Vazquez

Brain Sci. 2026, 16(8), 781; https://doi.org/10.3390/brainsci16080781 - 24 Jul 2026

Abstract

Background and Objectives: Individuals with Parkinson’s disease (PD) experience deficits in working memory (WM) and sustained attention (ATTN), but diagnosing and monitoring these deficits remains challenging. This study compares machine learning (ML) classification models trained on EEG and pupillometry data from WM and [...] Read more.

Background and Objectives: Individuals with Parkinson’s disease (PD) experience deficits in working memory (WM) and sustained attention (ATTN), but diagnosing and monitoring these deficits remains challenging. This study compares machine learning (ML) classification models trained on EEG and pupillometry data from WM and ATTN tasks to identify task-specific and shared cognitive biomarkers of PD. Methods: EEG and pupillometry were recorded from PD patients and healthy controls (HC) during a visual change detection WM task and a continuous performance ATTN task. A standardized toolbox extracted 108 features, reduced via PCA and recursive elimination (RE) and classified using an SVM-RBF within a nested, 5-fold cross-validated pipeline, with class balancing (SMOTE) and feature selection performed strictly within training folds to prevent leakage. Results: On internal test folds, WM achieved 71% accuracy (F1 = 0.701) and ATTN achieved 73% (F1 = 0.699); on an independent hold-out set, WM achieved 63% accuracy (F1 = 0.626) and ATTN achieved 70% (F1 = 0.623). ATTN showed higher accuracy and precision, WM showed higher recall, and univariate analyses independently supported several top-ranked features (e.g., theta/beta and alpha/theta ratios); PAI and FAA, though top features in both tasks, reached univariate significance only in ATTN. These results indicate WM and ATTN yield complementary, task-linked neurophysiological signatures relevant to PD classification. Conclusion: At its current stage, this pipeline functions as a research tool for biomarker discovery rather than a clinical diagnostic, though larger, externally validated samples could support future screening and monitoring applications. Full article

(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)

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22 pages, 2979 KB

Open AccessCase Report

Transcranial Magnetic Stimulation (TMS) Plus Modified Constraint-Induced Aphasia Therapy (mCIAT): A Pilot Feasibility Study with Sham and Real cTBS in Two Cases of Chronic Anomia–Protocol Deliverability and Greek Adaptation of mCIAT

by Anastasios M. Georgiou, Panagiota Papaioannou and Maria Kambanaros

Brain Sci. 2026, 16(8), 780; https://doi.org/10.3390/brainsci16080780 - 24 Jul 2026

Abstract

Background/Objectives: Stroke-related aphasia significantly impairs communication and quality of life (QoL). Constraint-induced aphasia therapy (CIAT) and repetitive transcranial magnetic stimulation (rTMS) are evidence-based approaches targeting language recovery. No combined protocol exists for Greek, a morphologically complex language. The present study was designed as [...] Read more.

Background/Objectives: Stroke-related aphasia significantly impairs communication and quality of life (QoL). Constraint-induced aphasia therapy (CIAT) and repetitive transcranial magnetic stimulation (rTMS) are evidence-based approaches targeting language recovery. No combined protocol exists for Greek, a morphologically complex language. The present study was designed as a feasibility pilot, with the primary objective of determining if a modified CIAT (mCIAT) protocol, with or without continuous theta burst stimulation (cTBS), could be delivered safely and acceptably in a Cypriot clinical context, while also reporting the first mCIAT protocol adapted for Greek. Methods: A single-subject experimental design (SSED) was employed. Two participants (PAs) with chronic anomic aphasia underwent a 10-day treatment protocol. PA1 received sham cTBS plus mCIAT-GR; PA2 received real cTBS (to the right inferior frontal gyrus) plus mCIAT. Multiple language, cognitive, and QoL measures were administered across three baselines and two follow-up time points. Results: Both PAs completed the full protocol with 100% session adherence and no adverse effects, establishing the feasibility of delivery. Neither participant showed improvements in standardized expressive language measures following mCIAT with or without cTBS; Standard Error of Measurement (SEM) analysis confirmed that observed score fluctuations on most measures fell within expected measurement noise. PA2 showed improvement in QoL (SAQOL-39g) domains at the two-year follow-up, though this finding requires cautious interpretation given the follow-up interval and regression-to-mean considerations. Conclusions: The Greek mCIAT protocol is feasible and safe to deliver in a Cypriot clinical setting. The absence of clear language improvements may reflect several factors, including ceiling effects, limited assessment sensitivity, insufficient treatment dosage, or limited intervention effects. These findings should be interpreted cautiously and require confirmation in larger, adequately powered studies. Full article

(This article belongs to the Special Issue Recent Advances in Assessment and Rehabilitation of Communication and Language Disorders: Enhancing Innovations, Neuromodulation and AI)

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29 pages, 1565 KB

Open AccessReview

Toward a Predictive Coding Account of Hypnotic Hypoalgesia: Integrating EEG Oscillations and Somatosensory Evoked Responses

by Vilfredo De Pascalis

Brain Sci. 2026, 16(8), 779; https://doi.org/10.3390/brainsci16080779 - 23 Jul 2026

Abstract

Hypnotic hypoalgesia effectively reduces various types of pain, but its neurophysiological mechanisms remain unclear. EEG and somatosensory event-related potentials (SERPs) can help elucidate how hypnotic suggestions influence pain processing across sensory, emotional, and cognitive domains. This review synthesizes evidence on EEG oscillatory activity [...] Read more.

Hypnotic hypoalgesia effectively reduces various types of pain, but its neurophysiological mechanisms remain unclear. EEG and somatosensory event-related potentials (SERPs) can help elucidate how hypnotic suggestions influence pain processing across sensory, emotional, and cognitive domains. This review synthesizes evidence on EEG oscillatory activity and SERP correlates in hypnotic pain modulation and interprets the findings through predictive coding and active inference frameworks. The review integrated relevant studies on EEG frequency-band oscillations, SERPs, and the modulation of pain by hypnosis, focusing on a convergent neurophysiological account of hypnotic pain modulation rather than on individual studies. Research indicates that hypnotic hypoalgesia is associated with concerted changes across multiple EEG frequency bands. Theta activity is linked to focused internal attention and the maintenance of suggestion-consistent representations, while increased alpha activity may indicate inhibitory sensory gating and reduced nociceptive gain. Beta oscillations enhance pain relief in cognitive and motor functions, while decreased gamma activity indicates reduced significance of pain signals. SERP findings show that hypnotic suggestions primarily affect late evaluative components (e.g., P200/P250, P300) rather than early sensory elements, suggesting changes in salience assignment and affective-cognitive appraisal rather than uniform suppression of nociceptive input. Predictive coding and active inference explain how hypnotic suggestions change pain-related expectations and bodily perceptions. This insight is key to enhancing personalized pain management and guiding future neuroscience research. Full article

(This article belongs to the Special Issue Hypnotherapy: From Basic Research to Clinical Practice)

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22 pages, 45396 KB

Open AccessCase Report

Magnetoencephalography (MEG) Augments Semiology in Stereotactic Electroencephalography (SEEG) Evaluations

by Andrew J. Zillgitt, Garnett C. Smith, David E. Burdette, Cesar A. Serrano Almeida, Anant Krishnan, Michael D. Staudt and Paul Ferrari

Brain Sci. 2026, 16(8), 778; https://doi.org/10.3390/brainsci16080778 - 23 Jul 2026

Abstract

The foundation of a successful stereotactic electroencephalography (SEEG) evaluation has remained relatively unchanged since the first SEEG implantation in 1957 and is predicated on a robust semiology-driven hypothesis. Although epilepsy presurgical evaluation has expanded since the 1950s with the introduction of new technology, [...] Read more.

The foundation of a successful stereotactic electroencephalography (SEEG) evaluation has remained relatively unchanged since the first SEEG implantation in 1957 and is predicated on a robust semiology-driven hypothesis. Although epilepsy presurgical evaluation has expanded since the 1950s with the introduction of new technology, e.g., brain magnetic resonance imaging (MRI), few, if any, noninvasive diagnostic studies provide significant complementary information to the epilepsy presurgical evaluation as magnetoencephalography (MEG). As SEEG becomes increasingly ubiquitous as the intracranial EEG modality of choice for more comprehensive epilepsy centers, the importance of MEG in the epilepsy presurgical evaluation also increases. In this review, the use of MEG in addition to seizure semiology in the development of an SEEG implantation strategy will be reviewed and illustrated with two representative cases. Finally, within this review, epilepsy surgical outcomes from presurgical evaluations that incorporated MEG will be discussed. Full article

(This article belongs to the Special Issue Application of Neurophysiological Studies in the Treatment of Epilepsy)

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21 pages, 3792 KB

Open AccessArticle

Dapsone and N-Acetylcysteine Exert a Synergistic Antinociceptive Effect Associated with Oxidative Stress After Traumatic Spinal Cord Injury: An Isobolographic Study

by Héctor Alonso Romero-Sánchez, Camilo Ríos, María de los Ángeles Martínez-Cárdenas, Luz Navarro, Luis Alfonso Moreno-Rocha, Alfonso Mata-Bermudez and Araceli Díaz-Ruiz

Brain Sci. 2026, 16(8), 777; https://doi.org/10.3390/brainsci16080777 - 23 Jul 2026

Abstract

Background/Objectives: Neuropathic pain (NP) after traumatic spinal cord injury (SCI) is highly prevalent, markedly impairs quality of life, and remains difficult to treat because available therapies show limited efficacy and may cause relevant adverse effects. Because oxidative stress and glutamate-mediated excitotoxicity contribute [...] Read more.

Background/Objectives: Neuropathic pain (NP) after traumatic spinal cord injury (SCI) is highly prevalent, markedly impairs quality of life, and remains difficult to treat because available therapies show limited efficacy and may cause relevant adverse effects. Because oxidative stress and glutamate-mediated excitotoxicity contribute to central sensitization after SCI, this study evaluated the antinociceptive and antioxidant effects of dapsone (DDS), N-acetylcysteine (NAC), and their combination in rats with SCI. An isobolographic analysis was also performed to determine the pharmacodynamic interaction between the two drugs. Methods: Female Wistar rats with SCI that developed stimulus-dependent hypersensitivity from day 15 after injury were treated once daily for 7 days with DDS (1.5–12.5 mg/kg, i.p.), NAC (9.3–75 mg/kg, i.p.), or 1:1 fixed-ratio combinations. Mechanical allodynia and hyperalgesia were assessed with Von Frey filaments, whereas lipid peroxidation (LP) and reduced glutathione (GSH) were quantified in injured spinal cord tissue. Results: DDS and NAC produced dose-dependent antinociceptive effects, with DDS being more potent than NAC in both endpoints. The individual ED₅₀ values were 4.92 and 33.47 mg/kg for allodynia, and 4.06 and 27.74 mg/kg for hyperalgesia, for DDS and NAC, respectively. The DDS/NAC combination showed synergistic interactions in allodynia (ED₅₀ = 7.45 mg/kg vs. Zadd = 19.19 mg/kg; γ = 0.388) and hyperalgesia (ED₅₀ = 4.21 mg/kg vs. Zadd = 15.90 mg/kg; γ = 0.265), with stronger synergism in hyperalgesia. Combined treatment also improved LP and GSH levels. Conclusions: These findings indicate that DDS and NAC exert complementary actions and that their combination produces a synergistic antinociceptive effect associated with diminished oxidative stress after SCI. Full article

(This article belongs to the Special Issue Inflammation and Its Treatment in Spinal Cord Injury and Neurodegenerative Diseases)

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19 pages, 1760 KB

Open AccessArticle

Peripheral Hematological and Immune-Endocrine Markers in Children with Specific Learning Disorder: An Exploratory Retrospective Case–Control Study

by Dilek Altun Varmış, Cumali Yüksekkaya, Hülya Binokay, Serkan Güneş, Nazmiye İnce, Elif Koçak, Elif Gözde Yüce Antepüzümü, Kübra Şahin and Esra Erol Tanrıkulu

Brain Sci. 2026, 16(8), 776; https://doi.org/10.3390/brainsci16080776 - 23 Jul 2026

Abstract

Background: Specific learning disorder (SLD), termed “specific learning disability” in the Human Phenotype Ontology (HP:0001328), is a heterogeneous neurodevelopmental disorder, and the association between peripheral biological changes and cognitive function remains not well understood. Peripheral hematological and immune-endocrine biomarkers and their relationships with [...] Read more.

Background: Specific learning disorder (SLD), termed “specific learning disability” in the Human Phenotype Ontology (HP:0001328), is a heterogeneous neurodevelopmental disorder, and the association between peripheral biological changes and cognitive function remains not well understood. Peripheral hematological and immune-endocrine biomarkers and their relationships with neuropsychological evaluations were evaluated in children with SLD. Methods: In this retrospective case–control study, we evaluated the peripheral biomarkers of a complete blood count and biochemical panel in 103 children with SLD and 102 well-child outpatient controls. Within the SLD group, we examined the association of systemic inflammatory indices with cognitive domains as assessed by the Wechsler Intelligence Scale for Children—Revised. Results: Group comparisons revealed modest peripheral changes, including reduced mean platelet volume (MPV) and increased eosinophil counts, that persisted after false discovery rate correction. Both differences remained significant after adjustment for age and sex. Inflammatory indices from complete blood count showed poor discriminative validity and were not strongly related to the global intelligence quotient. Exploratory analyses revealed only nominal, domain-specific associations between systemic inflammation indices and particular Wechsler subtests for verbal abstraction and visuospatial organization that did not survive multiple-comparison correction. Conclusions: The findings indicate a selective peripheral hematological pattern in SLD rather than evidence of generalized systemic inflammation. The evaluated indices showed limited discriminative utility and were not independently associated with global cognitive performance after multiple-testing correction. They should not be considered screening or diagnostic biomarkers for SLD. The selective pattern of lower MPV and higher eosinophil count observed in children with SLD appears to be novel but should be considered preliminary and requires independent confirmation in larger, prospectively recruited groups. Full article

(This article belongs to the Section Developmental Neuroscience)

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37 pages, 4196 KB

Open AccessReview

Stem Cells in Post-Stroke Regenerative Therapy: Current Role of Wharton’s Jelly Mesenchymal Stem Cells in the Orchestrum

by Anastassiya Ganina, Naizabek Yerzhigit, Oleg Lookin, Aliya Orassay, Galiya Shaimardanova, Elmira Chuvakova, Manarbek Askarov and Abay Baigenzhin

Brain Sci. 2026, 16(8), 775; https://doi.org/10.3390/brainsci16080775 - 23 Jul 2026

Abstract

Background/Objectives: Modern approaches for post-stroke rehabilitation cover mechanistically different ways—from physiotherapy to digital technologies. Among these approaches, stem cell-based therapy represents probably the most complex but promising strategy. Methods: We discuss the current state-of-the-art of using mesenchymal stem cells (MSCs) in post-stroke regenerative [...] Read more.

Background/Objectives: Modern approaches for post-stroke rehabilitation cover mechanistically different ways—from physiotherapy to digital technologies. Among these approaches, stem cell-based therapy represents probably the most complex but promising strategy. Methods: We discuss the current state-of-the-art of using mesenchymal stem cells (MSCs) in post-stroke regenerative therapy. Despite relatively wide use of bone marrow and adipose tissue MSCs, these cells represent a more mature (“adult”) state, which limits their proliferative and regenerative potentials. Compared to the “adult” MSCs, less “mature” MSCs obtained from umbilical cord, specifically Wharton’s jelly MSCs (WJ-MSCs), demonstrate unique functional capabilities and are free from certain technical and ethical issues. Results: The molecular and cellular mechanisms of action of WJ-MSCs are thoroughly discussed in comparison with abundantly used “adult” types of MSCs. We also comparatively evaluate their preclinical and clinical application for treating post-stroke patients. Recent findings indicate that not only MSCs but also their secretome/exosomes (cell-free product) represent a therapeutically beneficial cellular drug in post-stroke recovery. Specially designed and carefully evaluated protocols, which preserve the bioactivity of the cell-free product intact, are mentioned. Neuroprotective and neuroreparative properties of cell-free products—secretome and exosomes—derived from Wharton’s jelly MSCs are summarized. Conclusions: Cell-free products obtained from WJ-MSCs are an innovative adjunct therapy for post-stroke disorders, despite certain challenges and limitations of this type of therapy still present. By further investigation of the molecular composition and biological mechanisms of the WJ-MSC secretome and exosomes, their clinical applicability in neuroinflammatory and neurodegenerative pathologies will be promoted. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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19 pages, 4954 KB

Open AccessArticle

Association of Altered V1-M2 Neuronal Activation with Balance and Coordination Deficits in a Corneal Alkali Burn Mouse Model of Visual Impairment

by Yunan Zhou, Xiaoming Shi, Ruilan Dai, Mingxuan Gao, Yingfang Ao, Guogang Xing, Jin Cheng and Mingxin Ao

Brain Sci. 2026, 16(8), 774; https://doi.org/10.3390/brainsci16080774 - 23 Jul 2026

Abstract

Background: Visual impairment frequently impairs balance and motor coordination, yet the underlying neural circuit mechanisms remain poorly understood and require further investigation. In this study, we established a mouse model of visual impairment to assess the effects of defective vision on balance and [...] Read more.

Background: Visual impairment frequently impairs balance and motor coordination, yet the underlying neural circuit mechanisms remain poorly understood and require further investigation. In this study, we established a mouse model of visual impairment to assess the effects of defective vision on balance and coordination and further elucidated the functional role of the V1-M2 neural circuit in this process. Methods: A mouse model of corneal alkali burn was generated. Corneal morphology was observed, visual function was detected, and balance as well as motor coordination were evaluated. Neuronal activation in the V1 and M2 brain regions was quantified via c-Fos immunostaining. Viral tracing was performed to map the V1-M2 neural pathway, and chemogenetic manipulation was applied to modulate the V1-M2 circuit. Results: Mice subjected to corneal alkali burn exhibited abnormal corneal morphology and impaired visual function, accompanied by significant deficits in balance and motor coordination. The number of c-Fos⁺ neurons was markedly reduced in both the V1 and M2 regions. The direct V1-M2 neural circuit was anatomically verified. Chemogenetic activation of the V1-M2 circuit elevated c-Fos expression in M2 and rescued impaired motor performance. Conclusions: Visual impairment disrupts balance and motor coordination in mice. The V1 and M2 cortical areas mediate this behavioral dysfunction, likely due to attenuated activation of the V1-M2 neural circuit. These findings identify a promising neural circuit for dissecting the fundamental mechanisms underlying visuomotor integration. Full article

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24 pages, 8056 KB

Open AccessArticle

AMPAR Subunit Gene Expression Marks a Synaptic Transcriptional State in Lower-Grade Glioma

by Bruno Rodrigues, Matheus Dalmolin, Henrique Ritter Dal-Pizzol, Osvaldo Malafaia, Marcelo A. C. Fernandes, Karina Munhoz de Paula Alves Coelho, Rafael Roesler and Gustavo R. Isolan

Brain Sci. 2026, 16(8), 773; https://doi.org/10.3390/brainsci16080773 - 23 Jul 2026

Abstract

Background: Glutamatergic neuron-to-glioma signaling mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) has emerged as an important mechanism in glioma progression. Objectives/Methods: We analyzed the expression of the AMPAR subunit genes GRIA1, GRIA2, GRIA3, and GRIA4 in lower-grade glioma (LGG). Results: Expression [...] Read more.

Background: Glutamatergic neuron-to-glioma signaling mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) has emerged as an important mechanism in glioma progression. Objectives/Methods: We analyzed the expression of the AMPAR subunit genes GRIA1, GRIA2, GRIA3, and GRIA4 in lower-grade glioma (LGG). Results: Expression of GRIA1–GRIA4 was highest in IDH-mutant/1p19q-codeleted tumors and lowest in IDH-wildtype tumors across both The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts. High expression of each GRIA gene was associated with longer overall survival (OS). Transcriptome-wide analyses identified positive correlations between an AMPAR score and genes involved in synaptic organization, neuronal connectivity, and neurotransmission. Co-expression analyses demonstrated coordinated expression between GRIA1–GRIA4 and genes encoding AMPAR auxiliary proteins. Gene Ontology (GO) enrichment revealed overrepresentation of synaptic signaling, trans-synaptic communication, and synapse organization. Although the AMPAR score was associated with favorable survival in univariate analyses, it did not retain independent prognostic significance after adjustment for key clinicomolecular variables. Elevated expression of AMPAR subunit genes in LGG was associated with favorable molecular subtypes and a synaptic transcriptional program. Conclusions: These findings suggest that GRIA1–GRIA4 expression is associated with a synaptically enriched transcriptional program in LGG, although its cellular origin remains uncertain. Full article

(This article belongs to the Special Issue Brain Tumors: From Molecular Basis to Therapy: 2nd Edition)

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16 pages, 3485 KB

Open AccessArticle

Relative Device-Output Music Intensity and Virtual-Reality-Based Postural Control in Trained Athletes

by Hanifi Korkmaz, İpek Balıkçı Çiçek, Özgür Eken and Monira I. Aldhahi

Brain Sci. 2026, 16(8), 772; https://doi.org/10.3390/brainsci16080772 - 23 Jul 2026

Abstract

Background/Objectives: Postural control depends on the integration and reweighting of visual, somatosensory, vestibular, and contextual sensory information. Stable auditory cues may support balance, whereas complex musical stimulation may impose additional sensory-cognitive demand during multisensory conflict. This study examined the acute effects of relative [...] Read more.

Background/Objectives: Postural control depends on the integration and reweighting of visual, somatosensory, vestibular, and contextual sensory information. Stable auditory cues may support balance, whereas complex musical stimulation may impose additional sensory-cognitive demand during multisensory conflict. This study examined the acute effects of relative device-output music intensity on virtual-reality-based postural control in trained athletes and explored whether responses differed by sport background. Methods: Forty-eight athletes from tennis, combat sports, swimming, football, and volleyball completed the Clinical Test of Sensory Interaction in Balance delivered through virtual reality (CTSIB-VR) and Limits of Stability (LOS) assessments under four auditory conditions: routine/no sound and low (+10 dB), moderate (+20 dB), and high (+30 dB) relative device-output increments. Linear mixed-effects models included sport, auditory condition, and their interaction as fixed effects and participant-specific random intercepts and random linear condition slopes. Model-based estimated marginal means, Bonferroni-adjusted contrasts, 1.5×IQR sensitivity analyses, and robust generalized estimating equations were calculated. Results: Auditory condition affected all five CTSIB-VR outcomes (Wald χ²(3) = 16.773–94.404, all p < 0.001). The routine condition exceeded the high-intensity condition for composite score (adjusted mean difference = 6.05, 95% CI 3.99–8.10; Bonferroni-adjusted p < 0.001) and somatosensory score (8.62, 95% CI 6.78–10.46; adjusted p < 0.001). Sport × condition interactions were significant for all CTSIB-VR outcomes (χ²(12) = 54.869–98.953, all p < 0.001), but sport-stratified findings were exploratory. For LOS, auditory-condition effects were detected for endpoint excursion (p = 0.004), maximum excursion (p < 0.001), and directional control (p = 0.002), whereas reaction time (p = 0.648) and movement velocity (p = 0.056) did not show clear main effects. Sensitivity analyses supported the endpoint-excursion, maximum-excursion, and directional-control findings; movement-velocity inference was method-sensitive. Conclusions: Relative device-output music intensity was associated with consistent changes in CTSIB-VR sensory-organization measures and outcome-specific changes in LOS performance. Sport-related patterns require confirmation in adequately powered, balanced samples. Full article

(This article belongs to the Special Issue New Insights into Movement Generation: Sensorimotor Processes—2nd Edition)

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28 pages, 7850 KB

Open AccessArticle

Writing Increases Precision-Weighted Inference of Conceptual Organization: A Bayesian-Brain Active-Inference Model of the Writing-over-Speaking Advantage in Analytic Thinking

by Angelica Maria Silva, Renata Melanie Truelove, Anthony Millán De Lange and Roberto Limongi

Brain Sci. 2026, 16(8), 771; https://doi.org/10.3390/brainsci16080771 - 23 Jul 2026

Abstract

Background: The analytic thinking score (ATS) has been interpreted as a linguistic marker of organized thought. Written language typically shows a higher ATS than spoken language. From the perspective of active inference under the free-energy principle, we proposed a preliminary neurocomputational model of [...] Read more.

Background: The analytic thinking score (ATS) has been interpreted as a linguistic marker of organized thought. Written language typically shows a higher ATS than spoken language. From the perspective of active inference under the free-energy principle, we proposed a preliminary neurocomputational model of this writing-over-speaking advantage. We propose that ATS is an externally computed linguistic measure reflecting analytic-thinking active states that arise from precision-weighted inference over internal conceptual-organization (CO) states. We hypothesize that written production shows a higher ATS when the active-inference agent increases posterior confidence in high-CO states. Methods: ATSs were extracted from written and spoken samples produced by university students who described thematic apperception test images. Participants were modeled as active-inference agents using a two-timestep Markov decision process (MDP) in which speaking and writing sensory cues updated beliefs about internal CO states which then drove analytic thinking active states. Belief updating was formalized through marginal message-passing and theoretically interpreted in terms of prediction-error signaling and precision-weighted neuronal synaptic gain. An attention-related parameter (AP) controlled the precision of the CO-sensory state mapping. Bayesian model selection was used to assess the model’s preliminary construct validity. Results: Written responses showed higher ATSs than spoken responses. The AP estimate indicated that writing cues supported posterior inference toward high-CO states stronger than speaking cues. Bayesian model selection favored the active-inference MDP over a Variational Laplace linear model. Conclusions: The current preliminary evidence speaks to a candidate active-inference model in which writing ascribes higher precision-weighted inference of CO, reflected in higher ATSs. Full article

(This article belongs to the Special Issue Writing on the Brain: Current Trends, Challenges and Future Venues)

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19 pages, 336 KB

Open AccessArticle

HbA1c and Cognitive Functioning Across Bipolar Disorder, Recurrent Major Depressive Disorder, and Schizophrenia: Findings from a Non-Diabetic Sample

by Ece Buyuksandalyaci Tunc, Serhat Tunc, Murat Ilhan Atagun and Samet Kose

Brain Sci. 2026, 16(7), 770; https://doi.org/10.3390/brainsci16070770 - 22 Jul 2026

Abstract

Objective: This study examined the association between glycemic status, indexed by HbA1c, and cognitive functioning in individuals with bipolar disorder (BD), recurrent major depressive disorder (rMDD), schizophrenia (SZ), and healthy controls (HCs). Methods: In this cross-sectional study, 215 participants (45 HCs, 64 BD, [...] Read more.

Objective: This study examined the association between glycemic status, indexed by HbA1c, and cognitive functioning in individuals with bipolar disorder (BD), recurrent major depressive disorder (rMDD), schizophrenia (SZ), and healthy controls (HCs). Methods: In this cross-sectional study, 215 participants (45 HCs, 64 BD, 62 rMDD, 44 SZ) were assessed. Cognitive performance was evaluated using a comprehensive neuropsychological battery measuring attention, processing speed, memory, executive functions, and social cognition. Sociodemographic characteristics, chlorpromazine-equivalent antipsychotic doses (CEDA), and metabolic variables (body mass index, waist circumference, lipid profile, fasting glucose, and HbA1c) were collected. Group differences, correlation analyses, and multiple regression models were performed. Results: All patient groups showed significantly poorer cognitive performance compared with HCs. HbA1c levels were highest in the SZ group; however, associations between HbA1c and cognitive performance were strongest in the BD group and less consistent in rMDD. In regression analyses, HbA1c was associated with cognitive performance in BD and HCs, with weaker effects in rMDD. CEDA was associated with HbA1c levels and partially attenuated the relationship between HbA1c and cognitive outcomes. Conclusions: HbA1c levels were associated with cognitive performance in non-diabetic individuals, particularly in BD and rMDD. These findings suggest that subclinical variation in glycemic regulation may be relevant to cognitive functioning in psychiatric disorders. Further longitudinal studies are needed to clarify the influence of metabolic factors and psychotropic medication on cognitive outcomes. Full article

(This article belongs to the Section Neuropsychiatry)

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20 pages, 3137 KB

Open AccessArticle

EEG Markers as a Tool for the Individualization of Education and Optimization of Social Interventions for Children from Alcohol-Affected Families

by Małgorzata Chojak and Marta Czechowska-Bieluga

Brain Sci. 2026, 16(7), 769; https://doi.org/10.3390/brainsci16070769 - 22 Jul 2026

Abstract

Background: Children growing up in alcohol-affected families are exposed to chronic stress, adverse childhood experiences (ACEs), emotional insecurity, and environmental instability, all of which may influence neurodevelopmental processes. Numerous EEG markers have been proposed as indicators of attentional regulation, emotional functioning, and [...] Read more.

Background: Children growing up in alcohol-affected families are exposed to chronic stress, adverse childhood experiences (ACEs), emotional insecurity, and environmental instability, all of which may influence neurodevelopmental processes. Numerous EEG markers have been proposed as indicators of attentional regulation, emotional functioning, and stress responsivity; however, their relative diagnostic and practical value remains unclear. The aim of the present study was to verify whether commonly reported EEG markers remain valid indicators of neurofunctional difficulties in children from alcohol-affected families, to establish their hierarchy of importance, and to determine how identified neurofunctional profiles may inform the sequencing of educational interventions and the development of individualized support plans used by educators and social workers. Methods: The study included children aged 6–10 years from alcohol-affected families (n = 20) and a control group from non-dysfunctional family environments (n = 25). Resting-state EEG recordings were conducted under eyes-open and eyes-closed conditions, with analyses focused on the eyes-open condition. Quantitative EEG (qEEG) indices included global, frontal, prefrontal, and midline Theta–Beta Ratio (TBR), frontal alpha asymmetry (FAA), temporal beta stress and parietal beta2 tension. EEG preprocessing was performed using EEGLAB and included artifact rejection, filtering, epoch segmentation, and spectral power analysis. Group differences were analyzed using Welch’s t-tests with Benjamini–Hochberg correction for multiple comparisons. Results: The analyzed EEG markers differed in their ability to distinguish children from alcohol-affected families and controls. The strongest effects were observed for Theta–Beta Ratio (TBR) measures, particularly in frontal and prefrontal regions, indicating impairments in attention regulation, executive functioning, and self-control. Elevated temporal beta stress and parietal beta2 tension reflected increased physiological arousal and chronic stress. In contrast, frontal alpha asymmetry (FAA), commonly associated with depressive emotional processing, was not significant after correction for multiple comparisons. The obtained findings enabled the establishment of a hierarchy of neurofunctional markers, with attentional and executive-function indicators demonstrating greater importance than markers related to depressive symptomatology. Conclusions: The EEG profile of children from alcohol-affected families is characterized primarily by chronic stress, heightened physiological activation, and impaired attention regulation rather than by neurophysiological patterns associated with depression. The results suggest that educational difficulties in this group may stem mainly from deficits in attention control, inhibitory processes, and cognitive flexibility. Consequently, educational interventions should prioritize learning strategies, attentional training, and self-regulated learning skills. The identified hierarchy of EEG markers may also support the development of individualized educational plans and social-support programs, including participation in structured extracurricular activities and interventions aimed at strengthening executive and learning-related competencies. However, given the pilot nature of the present study and the relatively small sample size, these findings should be considered preliminary. Replication in larger, more diverse, and independent cohorts is necessary to confirm the stability, reliability, and generalizability of the identified neurofunctional profile and the proposed hierarchy of qEEG markers before they can be recommended for broader educational and social applications. Full article

(This article belongs to the Special Issue Neuroeducation: Bridging Cognitive Science and Classroom Practice)

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18 pages, 2723 KB

Open AccessArticle

Herpesvirus-Associated Visual Impairment: Clinical Features, Etiological Spectrum, and Treatment Outcomes in Consecutive Patients from a Tertiary Neurological Clinic

by Lei Liu, Jingxiao Zhang, Qiuying Ma and Jiawei Wang

Brain Sci. 2026, 16(7), 768; https://doi.org/10.3390/brainsci16070768 - 22 Jul 2026

Abstract

[Background] Herpesvirus infections can induce diverse visual impairments with permanent sequelae, yet systematic data on their clinical spectrum and outcomes remain scarce. [Methods] We conducted a single-center retrospective cohort study at the Department of Neurology, Beijing Tongren Hospital, Capital Medical University. Thirteen consecutive [...] Read more.

[Background] Herpesvirus infections can induce diverse visual impairments with permanent sequelae, yet systematic data on their clinical spectrum and outcomes remain scarce. [Methods] We conducted a single-center retrospective cohort study at the Department of Neurology, Beijing Tongren Hospital, Capital Medical University. Thirteen consecutive patients (19 affected eyes) with herpesvirus-related visual impairment admitted between January 2016 and January 2025 were enrolled. Demographic data, clinical manifestations, etiological tests (polymerase chain reaction [PCR], metagenomic next-generation sequencing [mNGS], serology), neuroimaging, treatment regimens, and visual outcomes were analyzed. [Results] The cohort had a mean age of 50.4 years (range 31–66), with male predominance (84.6%, 11/13). Varicella zoster virus (VZV) was the leading pathogen (76.9%, 10/13), followed by herpes simplex virus type 1 (HSV-1), Epstein–Barr virus (EBV), and pseudorabies virus (PRV). Eight patients (61.5%) developed optic neuritis (ON) secondary to VZV infection, and five patients (38.5%) suffered from acute retinal necrosis (ARN), which was caused by VZV (n = 2), HSV-1 (n = 2), and PRV (n = 1). Bilateral involvement occurred in 46.2% (6/13) of patients. ARN was associated with the most severe visual loss. At the disease nadir, 46.2% of patients (6/13) presented with no light perception (NLP). Notably, five of these six NLP cases were diagnosed with ARN. Etiological confirmation was achieved in only 38.5% (5/13) of cases. mNGS of cerebrospinal and vitreous fluid, alongside aqueous humor PCR, are pivotal for diagnosing HSV-1/EBV mixed infections and rare PRV infection. All patients received antiviral therapy, 11 of whom (84.6%) were treated with intravenous antiviral agents. Glucocorticoids were administered as combination therapy to all patients. However, only one of eight VZV–ON eyes showed genuine visual improvement. In VZV–ARN, the initially involved eyes stayed NLP at final follow-up, while the fellow eyes recovered vision. Still, all non-VZV ARN patients had persistent bilateral NLP during follow-up. [Conclusions] Herpesvirus-associated visual impairment is dominated by VZV, manifests as ON or ARN, and carries a high risk of severe permanent vision loss—particularly in ARN. The emergence of zoonotic PRV underscores the need for heightened clinical vigilance. Diagnostic delays and insufficient interdisciplinary collaboration contribute substantially to poor outcomes. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

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16 pages, 1581 KB

Open AccessCase Report

Long-Lasting Changes of Repeated Anodal Transcranial Direct Current Stimulation in Decreasing Chronic Pain in Patients with Multiple Sclerosis: A Case Series

by Renming Liu, Shapour Jaberzadeh, Mona Malekahmad, Murray Taverner, Jamie Young and Maryam Zoghi

Brain Sci. 2026, 16(7), 767; https://doi.org/10.3390/brainsci16070767 - 22 Jul 2026

Abstract

Background: Pain affects 50–75% of individuals with multiple sclerosis (MS) and is more common than in the general population. Chronic pain is difficult to manage and may involve motor cortical and sensorimotor network alterations. Anodal transcranial direct current stimulation (tDCS) over the primary [...] Read more.

Background: Pain affects 50–75% of individuals with multiple sclerosis (MS) and is more common than in the general population. Chronic pain is difficult to manage and may involve motor cortical and sensorimotor network alterations. Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been explored as a neuromodulatory approach, although its effects and mechanisms remain unclear. Objective: This case series describes longitudinal changes in pain and anxiety following repeated anodal tDCS over left M1 in six individuals with MS-related chronic pain and descriptively reports concurrent changes in transcranial magnetic stimulation (TMS)-derived neurophysiological measures. Methods: Six adults with MS and chronic pain (≥4/10) received 1 mA anodal tDCS over M1 (10 min stimulation, 25 min interval, 10 min stimulation) in two 5-day blocks separated by 2 weeks (10 sessions total), with usual care maintained. Pain and anxiety (0–10) were assessed before and after sessions and at follow-up. TMS assessed corticospinal excitability and intracortical inhibition and facilitation at baseline, post blocks, and at follow-up. Results: Marked inter-individual variability was observed in clinical and neurophysiological trajectories following repeated anodal tDCS. Response patterns included immediate improvement after stimulation blocks, delayed improvement after the second block, and transient rebound during the inter-block interval. TMS-derived measures showed heterogeneous changes, with no consistent correspondence with clinical outcomes. Conclusions: This case series describes variable changes in pain, anxiety, and neurophysiological measures following repeated anodal tDCS over M1 in MS-related chronic pain. The findings are observational and highlight inter-individual variability, supporting further controlled studies. Full article

(This article belongs to the Special Issue Non-Invasive Brain Stimulation in Neurological Diseases and Neurorehabilitation)

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16 pages, 282 KB

Open AccessReview

Autism and Neurodegeneration: Distinct Disorders or a Shared Biological Continuum?

by Jorge Manzo and María Elena Hernández-Aguilar

Brain Sci. 2026, 16(7), 766; https://doi.org/10.3390/brainsci16070766 - 21 Jul 2026

Abstract

Background/Objectives: Autism spectrum disorder (ASD) is traditionally classified as a neurodevelopmental condition, whereas neurodegenerative diseases are defined by progressive neuronal decline in later life. This separation has shaped research and clinical practice, yet emerging evidence suggests potential biological overlap. This review aims to [...] Read more.

Background/Objectives: Autism spectrum disorder (ASD) is traditionally classified as a neurodevelopmental condition, whereas neurodegenerative diseases are defined by progressive neuronal decline in later life. This separation has shaped research and clinical practice, yet emerging evidence suggests potential biological overlap. This review aims to evaluate whether ASD and neurodegenerative disorders represent distinct entities or are linked through shared mechanisms operating across the lifespan. Methods: This narrative review synthesizes findings from genetic, molecular, cellular, circuit-level, and epidemiological studies examining ASD and major neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis. Emphasis is placed on identifying convergent pathways and evaluating evidence within a lifespan-oriented framework. Results: Across multiple levels of analysis, ASD and neurodegenerative diseases share partially overlapping biological mechanisms, including mitochondrial dysfunction, impaired proteostasis, neuroimmune alterations, and network-level instability. Genetic and molecular data reveal pleiotropic pathways influencing both early neurodevelopment and later neuronal resilience. Circuit-level studies highlight shared principles of network vulnerability, including cerebellar involvement and excitation–inhibition imbalance. Epidemiological data further indicate increased risk of dementia and parkinsonian features in autistic adults. These convergences suggest that early neurodevelopmental alterations may establish latent vulnerabilities that, under specific conditions, intersect with neurodegenerative processes later in life. Conclusions: ASD and neurodegenerative diseases are best understood as distinct clinical conditions that share partially overlapping biological substrates. Rather than implying a deterministic progression, the evidence supports a model of lifespan convergence in which timing, context, and individual susceptibility shape outcomes. This framework highlights the need for integrated research and clinical approaches that consider brain health as a continuous process from development through aging. Full article

(This article belongs to the Special Issue Autism Spectrum Disorder: Current Concepts and Emerging Directions in Research and Clinical Care)

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38 pages, 2643 KB

Open AccessReview

Cognitive Impairment Associated with Chemotherapy: Neuroimmunological Interactions, Gut–Brain Axis, and Therapeutic Approaches

by Beatriz Alejandra Llanes-Cervantes, José Alfonso Cruz-Ramos, María Esthela Barón-Cárdenas, Paola Montserrat Zepeda-Olmos, Sandra López-Verdín, Jennifer Mariana Vargas-López and Emmanuel de la Mora-Jiménez

Brain Sci. 2026, 16(7), 765; https://doi.org/10.3390/brainsci16070765 - 21 Jul 2026

Abstract

Chemotherapy is a treatment designed to contain or eradicate neoplastic cells; however, patients may experience various treatment-related adverse effects. Chemotherapy-related cognitive impairment (CRCI), clinically referred to as “chemobrain,” is a frequent complication with a duration ranging from months to years, affecting between 17% [...] Read more.

Chemotherapy is a treatment designed to contain or eradicate neoplastic cells; however, patients may experience various treatment-related adverse effects. Chemotherapy-related cognitive impairment (CRCI), clinically referred to as “chemobrain,” is a frequent complication with a duration ranging from months to years, affecting between 17% and 70% of cancer patients. These cognitive deficits not only impair social, educational, and occupational functioning but may also impact survival outcomes, possibly by interfering with medication adherence and health-related behaviors. Emerging evidence has converged on an integrative cascade in which chemotherapy-induced systemic inflammation, intestinal dysbiosis, blood–brain barrier disruption, microglial/astroglial activation, and impaired hippocampal neurogenesis act in sequence rather than as independent pathways. Underlying pathophysiological mechanisms include neuroinflammation, reduced neurogenesis, loss of dendritic spines, oxidative stress, hormonal changes, epigenetic modifications, and mitochondrial dysfunction. In contrast, repair mechanisms involve complex glial responses, particularly those of astrocytes and microglia. Emerging studies suggest a link between changes in the microbiome and cognitive decline, demonstrating the importance of bidirectional communication in the gut–brain axis. Current research seeks to determine appropriate tests to identify chemobrain. Therefore, several biomarkers, such as GFAP, S100β, and isoprostanes, have been proposed to assess chemobrain, alongside screening tools such as MoCA, MMSE, and CAB-CF, to evaluate cognitive impairment and enable early detection. Pharmacological candidates—including lithium, fluoxetine, methylphenidate, modafinil, metformin, agomelatine, and melatonin—as well as nutritional and lifestyle interventions such as physical exercise, omega-3 fatty acids, curcumin, probiotics, and traditional Chinese medicine formulations—have been investigated, predominantly in animal models. These remain candidate, not validated, therapies; clinical evidence in CRCI populations is limited, heterogeneous, or absent, and well-powered randomized controlled trials are required before any recommendation can be issued. However, optimal strategies for symptom improvement remain unclear, as various approaches have yielded mixed outcomes. This review provides a comprehensive overview of chemobrain, focusing on its molecular mechanisms, interactions with the gut–brain axis, and potential therapeutic targets to improve the quality of life for cancer survivors. Full article

(This article belongs to the Special Issue Current Basic and Clinical Approaches in Neurodegenerative Diseases: Diagnostics and Therapeutics)

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