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Brain Sci., Volume 15, Issue 7 (July 2025) – 93 articles

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21 pages, 1875 KiB  
Review
Translating Exosomal microRNAs from Bench to Bedside in Parkinson’s Disease
by Oscar Arias-Carrión, María Paulina Reyes-Mata, Joaquín Zúñiga and Daniel Ortuño-Sahagún
Brain Sci. 2025, 15(7), 756; https://doi.org/10.3390/brainsci15070756 - 16 Jul 2025
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and therapeutic intervention. Exosomes facilitate intercellular communication, cross the blood–brain barrier, and protect miRNAs from degradation, rendering them suitable for non-invasive diagnostics and targeted delivery. Specific exosomal miRNAs modulate neuroinflammatory cascades, oxidative stress, and synaptic dysfunction, and their altered expression in cerebrospinal fluid and plasma correlates with disease onset, severity, and progression. Despite their translational promise, challenges persist, including methodological variability in exosome isolation, miRNA profiling, and delivery strategies. This review integrates findings from preclinical models, patient-derived samples, and systems biology to delineate the functional impact of exosomal miRNAs in PD. We propose mechanistic hypotheses linking miRNA dysregulation to molecular pathogenesis and present an interactome model highlighting therapeutic nodes. Advancing exosomal miRNA research may transform the clinical management of PD by enabling earlier diagnosis, molecular stratification, and the development of disease-modifying therapies. Full article
(This article belongs to the Special Issue Molecular Insights in Neurodegeneration)
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17 pages, 554 KiB  
Review
Post-Concussion Syndrome and Functional Neurological Disorder: Diagnostic Interfaces, Risk Mechanisms, and the Functional Overlay Model
by Ioannis Mavroudis, Foivos Petridis, Eleni Karantali, Alin Ciobica, Sotirios Papagiannopoulos and Dimitrios Kazis
Brain Sci. 2025, 15(7), 755; https://doi.org/10.3390/brainsci15070755 - 16 Jul 2025
Abstract
Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, [...] Read more.
Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article
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26 pages, 2058 KiB  
Review
Neuromodulation Interventions for Language Deficits in Alzheimer’s Disease: Update on Current Practice and Future Developments
by Fei Chen, Yuyan Nie and Chen Kuang
Brain Sci. 2025, 15(7), 754; https://doi.org/10.3390/brainsci15070754 - 16 Jul 2025
Abstract
Alzheimer’s disease (AD) is a leading cause of dementia, characterized by progressive cognitive and language impairments that significantly impact communication and quality of life. Neuromodulation techniques, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS), have [...] Read more.
Alzheimer’s disease (AD) is a leading cause of dementia, characterized by progressive cognitive and language impairments that significantly impact communication and quality of life. Neuromodulation techniques, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS), have emerged as promising interventions. This study employs bibliometric analysis to evaluate global research trends in neuromodulation treatments for AD-related language impairments. A total of 88 publications from the Web of Science Core Collection (2006–2024) were analyzed using bibliometric methods. Key indicators such as publication trends, citation patterns, collaboration networks, and research themes were examined to map the intellectual landscape of this field. The analysis identified 580 authors across 65 journals, with an average of 34.82 citations per article. Nearly half of the publications were produced after 2021, indicating rapid recent growth. The findings highlight a predominant focus on non-invasive neuromodulation methods, particularly rTMS and tDCS, within neurosciences and neurology. While research activity is increasing, significant challenges persist, including ethical concerns, operational constraints, and the translational gap between research and clinical applications. This study provides insights into the current research landscape and future directions for neuromodulation in AD-related language impairments. The results emphasize the need for novel neuromodulation techniques and interdisciplinary collaboration to enhance therapeutic efficacy and clinical integration. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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30 pages, 891 KiB  
Review
Communication Abilities, Assessment Procedures, and Intervention Approaches in Rett Syndrome: A Narrative Review
by Louiza Voniati, Angelos Papadopoulos, Nafsika Ziavra and Dionysios Tafiadis
Brain Sci. 2025, 15(7), 753; https://doi.org/10.3390/brainsci15070753 - 15 Jul 2025
Abstract
Background/Objectives: Rett syndrome (RTT) is a rare neurodevelopmental disorder that affects movement and communication skills primarily in females. This study aimed to synthesize the research from the last two decades regarding the verbal and nonverbal communication abilities, assessment procedures, and intervention approaches for [...] Read more.
Background/Objectives: Rett syndrome (RTT) is a rare neurodevelopmental disorder that affects movement and communication skills primarily in females. This study aimed to synthesize the research from the last two decades regarding the verbal and nonverbal communication abilities, assessment procedures, and intervention approaches for individuals with RTT. Methods: A structured literature search was conducted using the Embase, Scopus, and PubMed databases. Fifty-seven studies were selected and analyzed based on inclusion criteria. The data were categorized into four domains (verbal communication skills, nonverbal communication skills, assessment procedures, and intervention approaches). Results: The findings indicated a wide variety of communicative behaviors across the RTT population, including prelinguistic signals, regression in verbal output, and preserved nonverbal communicative intent. Moreover, the results highlighted the importance of tailored assessments (Inventory of Potential Communicative Acts, eye tracking tools, and Augmentative and Alternative Communication) to facilitate functional communication. The individualized intervention approaches were found to be the most effective in improving communicative participation. Conclusions: The current review provides an overview of the current evidence with an emphasis on the need for personalized and evidence-based clinical practices. Additionally, it provided guidance for professionals, clinicians, and researchers seeking to improve the quality of life for individuals with RTT. Full article
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19 pages, 1521 KiB  
Article
SAGEFusionNet: An Auxiliary Supervised Graph Neural Network for Brain Age Prediction as a Neurodegenerative Biomarker
by Suraj Kumar, Suman Hazarika and Cota Navin Gupta
Brain Sci. 2025, 15(7), 752; https://doi.org/10.3390/brainsci15070752 - 15 Jul 2025
Abstract
Background: The ability of Graph Neural Networks (GNNs) to analyse brain structural patterns in various kinds of neurodegenerative diseases, including Parkinson’s disease (PD), has drawn a lot of interest recently. One emerging technique in this field is brain age prediction, which estimates biological [...] Read more.
Background: The ability of Graph Neural Networks (GNNs) to analyse brain structural patterns in various kinds of neurodegenerative diseases, including Parkinson’s disease (PD), has drawn a lot of interest recently. One emerging technique in this field is brain age prediction, which estimates biological age to identify ageing patterns that may serve as biomarkers for such disorders. However, a significant problem with most of the GNNs is their depth, which can lead to issues like oversmoothing and diminishing gradients. Methods: In this study, we propose SAGEFusionNet, a GNN architecture specifically designed to enhance brain age prediction and assess PD-related brain ageing patterns using T1-weighted structural MRI (sMRI). SAGEFusionNet learns important ROIs for brain age prediction by incorporating ROI-aware pooling at every layer to overcome the above challenges. Additionally, it incorporates multi-layer feature fusion to capture multi-scale structural information across the network hierarchy and auxiliary supervision to enhance gradient flow and feature learning at multiple depths. The dataset utilised in this study was sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. It included a total of 580 T1-weighted sMRI scans from healthy individuals. The brain sMRI scans were parcellated into 56 regions of interest (ROIs) using the LPBA40 brain atlas in CAT12. The anatomical graph was constructed based on grey matter (GM) volume features. This graph served as input to the GNN models, along with GM and white matter (WM) volume as node features. All models were trained using 5-fold cross-validation to predict brain age and subsequently tested for performance evaluation. Results: The proposed framework achieved a mean absolute error (MAE) of 4.24±0.38 years and a mean Pearson’s Correlation Coefficient (PCC) of 0.72±0.03 during cross-validation. We also used 215 PD patient scans from the Parkinson’s Progression Markers Initiative (PPMI) database to assess the model’s performance and validate it. The initial findings revealed that out of 215 individuals with Parkinson’s disease, 213 showed higher and 2 showed lower predicted brain ages than their actual ages, with a mean MAE of 13.36 years (95% confidence interval: 12.51–14.28). Conclusions: These results suggest that brain age prediction using the proposed method may provide important insights into neurodegenerative diseases. Full article
(This article belongs to the Section Neurorehabilitation)
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13 pages, 590 KiB  
Article
Subtyping Early Parkinson’s Disease by Mapping Cognitive Profiles to Brain Atrophy with Visual MRI Ratings
by Tania Álvarez-Avellón, Carmen Solares, Juan Álvarez-Carriles and Manuel Menéndez-González
Brain Sci. 2025, 15(7), 751; https://doi.org/10.3390/brainsci15070751 - 15 Jul 2025
Abstract
Background: Cognitive heterogeneity in Parkinson’s disease (PD) remains a diagnostic and prognostic challenge, particularly in early stages. In this cross-sectional study, we aimed to identify clinically relevant cognitive subtypes in early PD by integrating neuropsychological profiles with regional brain atrophy assessed via visual [...] Read more.
Background: Cognitive heterogeneity in Parkinson’s disease (PD) remains a diagnostic and prognostic challenge, particularly in early stages. In this cross-sectional study, we aimed to identify clinically relevant cognitive subtypes in early PD by integrating neuropsychological profiles with regional brain atrophy assessed via visual MRI scales. Methods: Eighty-one de novo PD patients (≤36 months from diagnosis) and twenty healthy controls underwent 3T MRI with visual atrophy ratings and completed an extensive neuropsychological battery. Results: Using a mixed a priori–a posteriori approach, we defined eight anatomocognitive subtypes reflecting distinct patterns of regional vulnerability: frontosubcortical, posterior cortical, left/right hippocampal, global, and preserved cognition. Specific MRI markers correlated with cognitive deficits in executive, visuospatial, memory, and language domains. Cluster analyses supported subtype validity (AUC range: 0.68–0.95). Conclusions: These results support a practical classification model linking cognitive performance to brain structural changes in early PD. This scalable approach may improve early patient stratification and guide personalized management strategies. Longitudinal studies are needed to assess progression patterns and therapeutic implications. Full article
(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease)
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14 pages, 2907 KiB  
Article
Neural Dynamics of Strategic Early Predictive Saccade Behavior in Target Arrival Estimation
by Ryo Koshizawa, Kazuma Oki and Masaki Takayose
Brain Sci. 2025, 15(7), 750; https://doi.org/10.3390/brainsci15070750 - 15 Jul 2025
Abstract
Background/Objectives: Accurately predicting the arrival position of a moving target is essential in sports and daily life. While predictive saccades are known to enhance performance, the neural mechanisms underlying the timing of these strategies remain unclear. This study investigated how the timing [...] Read more.
Background/Objectives: Accurately predicting the arrival position of a moving target is essential in sports and daily life. While predictive saccades are known to enhance performance, the neural mechanisms underlying the timing of these strategies remain unclear. This study investigated how the timing of saccadic strategies—executed early versus late—affects cortical activity patterns, as measured by electroencephalography (EEG). Methods: Sixteen participants performed a task requiring them to predict the arrival position and timing of a parabolically moving target that became occluded midway through its trajectory. Based on eye movement behavior, participants were classified into an Early Saccade Strategy Group (SSG) or a Late SSG. EEG signals were analyzed in the low beta band (13–15 Hz) using the Hilbert transform. Group differences in eye movements and EEG activity were statistically assessed. Results: No significant group differences were observed in final position or response timing errors. However, time-series analysis showed that the Early SSG achieved earlier and more accurate eye positioning. EEG results revealed greater low beta activity in the Early SSG at electrode sites FC6 and P8, corresponding to the frontal eye field (FEF) and middle temporal (MT) visual area, respectively. Conclusions: Early execution of predictive saccades was associated with enhanced cortical activity in visuomotor and motion-sensitive regions. These findings suggest that early engagement of saccadic strategies supports more efficient visuospatial processing, with potential applications in dynamic physical tasks and digitally mediated performance domains such as eSports. Full article
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16 pages, 2725 KiB  
Article
Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study
by Yong-Won Shin and Sang Bin Hong
Brain Sci. 2025, 15(7), 749; https://doi.org/10.3390/brainsci15070749 - 14 Jul 2025
Viewed by 128
Abstract
Background/Objectives: Epilepsy and sleep disturbances frequently co-occur, yet the causal nature of this relationship remains uncertain, particularly in relation to epilepsy subtypes and status epilepticus. We investigated potential bidirectional causal associations between sleep-related traits and epilepsy, including subtypes and status epilepticus, using [...] Read more.
Background/Objectives: Epilepsy and sleep disturbances frequently co-occur, yet the causal nature of this relationship remains uncertain, particularly in relation to epilepsy subtypes and status epilepticus. We investigated potential bidirectional causal associations between sleep-related traits and epilepsy, including subtypes and status epilepticus, using Mendelian randomization (MR). Methods: We conducted two-sample MR using genome-wide association study (GWAS) summary statistics from European ancestry cohorts. Epilepsy, its subtypes, and status epilepticus were analyzed using data from the International League Against Epilepsy Consortium on Complex Epilepsies (ILAE) and the FinnGen study. Nine self-reported sleep-related traits were derived from the UK Biobank-based GWAS. Causal estimates were primarily obtained using inverse variance weighted models with additional MR analysis methods. Pleiotropy and heterogeneity were assessed to enhance the robustness of the finding. Results: Several subtype-specific associations were identified, with direction and statistical significance varying across cohorts and subtypes. After correction for multiple testing and filtering for tests with ≥10 instrumental variables to ensure robust and reliable MR estimates, several consistent and potentially mutually reinforcing associations emerged. In the ILAE cohort, focal epilepsy with hippocampal sclerosis was associated with an increased risk of insomnia, and juvenile myoclonic epilepsy with reduced sleep duration. In the FinnGen cohort, overall epilepsy was associated with increased risk of both insomnia and daytime sleepiness. In reverse MR, daytime sleepiness and napping were associated with increased risk of epilepsy, while daytime napping and frequent insomnia symptoms were linked to elevated risk of status epilepticus. Conclusions: Our findings reveal subtype-specific and bidirectional causal links between epilepsy and sleep-related traits. These results highlight the biological interplay between epileptic networks and sleep regulation and underscore the need for further clinical and mechanistic studies. Full article
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2 pages, 165 KiB  
Correction
Correction: Macchini et al. Intra-Arrest Therapeutic Hypothermia and Neurologic Outcome in Patients Admitted After Out-of-Hospital Cardiac Arrest: A Post Hoc Analysis of the Princess Trial. Brain Sci. 2022, 12, 1374
by Elisabetta MACCHINI, Emelie DILLENBECK, Martin JONSSON, Filippo ANNONI, Sune FORSBERG, Jacob HOLLENBERG, Anatolij TRUHLAR, Leif SVENSSON, Per NORDBERG and Fabio Silvio TACCONE
Brain Sci. 2025, 15(7), 748; https://doi.org/10.3390/brainsci15070748 - 14 Jul 2025
Viewed by 43
Abstract
In the original publication [...] Full article
3 pages, 141 KiB  
Comment
Redefining Clinical Perspectives on MCS: Toward an Evidence-Based, Multisystem Model. Comment on Jacques, L. Multiple Chemical Sensitivity: A Clinical Perspective. Brain Sci. 2024, 14, 1261
by Elaine Psaradellis
Brain Sci. 2025, 15(7), 747; https://doi.org/10.3390/brainsci15070747 - 14 Jul 2025
Viewed by 68
Abstract
The article “Multiple Chemical Sensitivity: A Clinical Perspective”, published in Brain Sciences, suggests that multiple chemical sensitivity (MCS) is primarily a psychogenic disorder, rooted in unresolved emotional trauma and stress responses [...] Full article
16 pages, 823 KiB  
Review
GABAergic Influences on Medulloblastoma
by Viviane Aline Buffon, Jurandir M. Ribas Filho, Osvaldo Malafaia, Isadora D. Tassinari, Rafael Roesler and Gustavo R. Isolan
Brain Sci. 2025, 15(7), 746; https://doi.org/10.3390/brainsci15070746 - 11 Jul 2025
Viewed by 161
Abstract
Medulloblastoma (MB) is the most common malignant brain tumor in children and typically arises in the cerebellum, likely due to disruptions in neuronal precursor development. The primary inhibitory neurotransmitter in the central nervous system (CNS), γ-aminobutyric acid (GABA), exerts its effects through GABA [...] Read more.
Medulloblastoma (MB) is the most common malignant brain tumor in children and typically arises in the cerebellum, likely due to disruptions in neuronal precursor development. The primary inhibitory neurotransmitter in the central nervous system (CNS), γ-aminobutyric acid (GABA), exerts its effects through GABAA, GABAB, and GABAC receptors. GABA receptor activity regulates the development and function of cerebellar neurons, including glutamatergic cerebellar granule cells (CGCs). Beyond the nervous system, GABA is also a common metabolite in non-neuronal cell types. An increasing body of evidence indicates that GABA can influence cell proliferation, differentiation, and migration in several types of adult solid tumors, including brain cancers. GABA and GABAA receptor agonists can impair the viability and survival of MB cells, primarily acting on GABAA receptors containing the α5 subunit. A marked expression of the gene encoding the α5 subunit is found across all MB tumor molecular subgroups, particularly Group 3 MB, which has a poor prognosis. Importantly, high levels of the γ-aminobutyric acid type A receptor subunit α5 (GABRA5) gene are associated with shorter patient overall survival in Group 3 and Group 4 MB. In contrast, high γ-aminobutyric acid type A receptor subunit β1 (GABRB1) gene expression is related to longer survival in all MB subgroups. The GABAergic system may, therefore, regulate MB cell function and tumor progression and influence patient prognosis, and is worthy of further investigation as a biomarker and therapeutic target in MB. Full article
(This article belongs to the Special Issue Editorial Board Collection Series: Advances in Neuro-Oncology)
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12 pages, 674 KiB  
Article
Quality of Life in Multiple Sclerosis Compared to Amyotrophic Lateral Sclerosis: Fatigue and Fast Disease Progression Interferes with the Ability to Psychosocially Adjust
by Luisa T. Balz, Ingo Uttner, Jochen Weishaupt, Albert C. Ludolph, Daniela Taranu, Ioannis Vardakas, Stefanie Jung, Tanja Fangerau, Deborah K. Erhart, Makbule Senel, Hayrettin Tumani and Dorothée E. Lulé
Brain Sci. 2025, 15(7), 745; https://doi.org/10.3390/brainsci15070745 - 11 Jul 2025
Viewed by 213
Abstract
Background/Objectives: Multiple sclerosis (MS) is a complex neurological disease that is associated with a broad spectrum of physical and psychological symptoms. Psychosocial adjustment (PSA) refers to the ability to cope with these challenges, which influence quality of life (QoL) and depressiveness in [...] Read more.
Background/Objectives: Multiple sclerosis (MS) is a complex neurological disease that is associated with a broad spectrum of physical and psychological symptoms. Psychosocial adjustment (PSA) refers to the ability to cope with these challenges, which influence quality of life (QoL) and depressiveness in ways not yet fully understood. This study explores the relationship of PSA and disease-specific symptoms in MS, including fatigue, a prominent MS symptom. Additionally, PSA was compared to Amyotrophic Lateral Sclerosis (ALS) to disentangle the impact of disease trajectory on PSA. Methods: We interviewed 77 MS patients using patient-reported outcome measures on QoL and depression and compared them to 30 ALS patients. Confirmatory factor analysis and regression analysis were used to identify PSA indicators and predictors in MS, while t-tests assessed PSA differences across diseases. Results: Key PSA indicators in MS included physical (PQoL), mental (MQoL), and subjective (SQoL) quality of life, as well as depressiveness, with cognitive and motor fatigue emerging as significant predictors. MS patients had higher PQoL and SQoL and lower levels of depression compared to ALS patients, while both groups were comparable with regard to MQoL. Conclusions: PSA in MS is supported by high QoL and low depression levels, with fatigue being a significant predictor. Despite different disease trajectories, patients with MS and ALS showed comparable MQoL, indicating that both diseases similarly impact mental QoL, reflecting a partial overlap in psychosocial adjustment. Overall, psychosocial adjustment was more favorable in MS, likely due to its slower disease progression compared to ALS. Full article
(This article belongs to the Special Issue Neuropsychological Impact and Quality of Life in Chronic Illness)
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18 pages, 1399 KiB  
Article
Single-Stage Endovascular Management of Concurrent Intracranial Aneurysms and Arterial Stenoses: Clinical Outcomes, Procedural Strategies, and Predictive Factors
by Marat Sarshayev, Shayakhmet Makhanbetkhan, Aiman Maidan, Roger Barranco Pons, Dimash Davletov, Abzal Zhumabekov and Mynzhylky Berdikhojayev
Brain Sci. 2025, 15(7), 744; https://doi.org/10.3390/brainsci15070744 - 11 Jul 2025
Viewed by 227
Abstract
Background: The coexistence of extracranial arterial stenoses and intracranial aneurysms presents a unique clinical dilemma. While staged interventions are traditionally preferred to reduce procedural risks, recent advances have enabled single-stage endovascular treatment. This study evaluates the clinical outcomes, procedural strategies, and predictive factors [...] Read more.
Background: The coexistence of extracranial arterial stenoses and intracranial aneurysms presents a unique clinical dilemma. While staged interventions are traditionally preferred to reduce procedural risks, recent advances have enabled single-stage endovascular treatment. This study evaluates the clinical outcomes, procedural strategies, and predictive factors associated with such combined interventions. Methods: This retrospective study included 47 patients treated with single-stage endovascular procedures for concurrent extracranial stenosis and intracranial aneurysm between 2016 and 2024. Clinical, angiographic, and procedural data were collected. Outcomes were assessed using the mmodified Rankin Scale (mRS), and statistical analyses were performed to identify associations between clinical variables and functional outcomes. Results: Of the 47 patients, 85.1% achieved favorable outcomes (mRS 0–2) at ≥6-month follow-up. The most commonly treated arteries were the internal carotid artery (70.2%) and the middle cerebral artery (34%). Stent-assisted coiling or flow diversion was performed in 93.6% of aneurysm cases, while 91.5% underwent carotid or vertebral stenting. Lesion laterality (left-sided aneurysms, p = 0.019) and stenosis length (p = 0.0469) were significantly associated with outcomes. Smoking was linked to multiple stenoses (p = 0.0191). Two patients experienced major complications: one aneurysmal rebleed after stenting, and one intraoperative rupture. Conclusions: Single-stage endovascular treatment for patients with concurrent extracranial stenosis and intracranial aneurysm is technically feasible and clinically effective in selected cases. Lesion configuration, anatomical considerations, and individualized planning are critical in optimizing outcomes. Full article
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9 pages, 199 KiB  
Review
Glial Diversity and Evolution: Insights from Teleost Fish
by Carla Lucini and Claudia Gatta
Brain Sci. 2025, 15(7), 743; https://doi.org/10.3390/brainsci15070743 - 11 Jul 2025
Viewed by 263
Abstract
Glial cells, once considered mere support for neurons, have emerged as key players in brain function across vertebrates. The historical study of glia dates to the 19th century with the identification of ependymal cells and astrocytes, followed by the discovery of oligodendrocytes and [...] Read more.
Glial cells, once considered mere support for neurons, have emerged as key players in brain function across vertebrates. The historical study of glia dates to the 19th century with the identification of ependymal cells and astrocytes, followed by the discovery of oligodendrocytes and microglia. While neurocentric perspectives overlooked glial functions, recent research highlights their essential roles in neurodevelopment, synapse regulation, brain homeostasis, and neuroimmune responses. In teleost fish, a group comprising over 32,000 species, glial cells exhibit unique properties compared to their mammalian counterparts. Thus, the aim of this review is synthesizing the current literature on fish glial cells, emphasizing their evolutionary significance, diversity, and potential as models for understanding vertebrate neurobiology. Microglia originate from both yolk sac cells and hematopoietic stem cells, forming distinct populations with specialized functions in the adult brain. Neural stem cells, including radial glial cells (RGCs) and neuroepithelial cells, remain active throughout life, supporting continuous neuro- and gliogenesis, a phenomenon far more extensive than in mammals. Ependymocytes line brain ventricles and show structural variability, with some resembling quiescent progenitor cells. Astrocytes are largely absent in most fish species. However, zebrafish exhibit astrocyte-like glial cells which show some structural and functional features in common with mammalian astrocytes. Oligodendrocytes share conserved mechanisms with mammals in myelination and axon insulation. Full article
(This article belongs to the Section Neuroglia)
18 pages, 638 KiB  
Case Report
Feasibility of Home-Based Transcranial Direct Current Stimulation with Telerehabilitation in Primary Progressive Aphasia—A Case Series
by Anna Uta Rysop, Tanja Grewe, Caterina Breitenstein, Ferdinand Binkofski, Mandy Roheger, Nina Unger, Agnes Flöel and Marcus Meinzer
Brain Sci. 2025, 15(7), 742; https://doi.org/10.3390/brainsci15070742 - 10 Jul 2025
Viewed by 222
Abstract
Background: Primary progressive aphasia (PPA) is a neurodegenerative disease characterised by progressive impairment of speech and language abilities. Intensive speech and language teletherapy combined with remotely supervised, self-administered transcranial direct current stimulation (tDCS) may be suited to remove barriers to accessing potentially effective [...] Read more.
Background: Primary progressive aphasia (PPA) is a neurodegenerative disease characterised by progressive impairment of speech and language abilities. Intensive speech and language teletherapy combined with remotely supervised, self-administered transcranial direct current stimulation (tDCS) may be suited to remove barriers to accessing potentially effective treatments, but there is only limited evidence on the feasibility of this combined approach. Methods: This pilot case series investigated the feasibility, tolerability and preliminary efficacy of a novel telerehabilitation programme combined with home-based, self-administered tDCS for people with primary progressive aphasia (pwPPA). The intervention programme was co-developed with pwPPA and their caregivers, to reflect their priorities regarding treatment content and outcomes (i.e., naming, functional communication). Results: Two pwPPA successfully completed the telerehabilitation intervention with daily naming training and communicative-pragmatic therapy paired with tDCS, over 10 consecutive workdays. Caregivers assisted in the setup of equipment required for teletherapy and home-based tDCS. Participants successfully completed the programme with a 95% completion rate. Home-based tDCS was well tolerated. Both participants showed improvements in naming and communication, suggesting preliminary efficacy of the intervention. Conclusions: Overall, this study demonstrates the feasibility and potential benefit of a novel, easily accessible and patient-relevant telerehabilitation intervention for pwPPA, which requires confirmation in a future larger-scale exploratory trial. Full article
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27 pages, 344 KiB  
Article
Biopsychosocial Profile of Chronic Alcohol Users: Insights from a Cross-Sectional Study
by Luciana Angela Ignat, Raluca Oana Tipa, Alina Roxana Cehan and Vladimir Constantin Bacârea
Brain Sci. 2025, 15(7), 741; https://doi.org/10.3390/brainsci15070741 - 10 Jul 2025
Viewed by 265
Abstract
Introduction: Chronic alcohol use is a complex condition influenced by psychological, behavioral, and socio-demographic factors. This study aimed to develop a comprehensive psychosocial profile of individuals with alcohol use disorder (AUD) by examining associations between psychometric variables and relapse risk including repeated psychiatric [...] Read more.
Introduction: Chronic alcohol use is a complex condition influenced by psychological, behavioral, and socio-demographic factors. This study aimed to develop a comprehensive psychosocial profile of individuals with alcohol use disorder (AUD) by examining associations between psychometric variables and relapse risk including repeated psychiatric hospitalizations. Methodology: A cross-sectional observational analytical study was conducted on a sample of 104 patients admitted for alcohol withdrawal management at the “Prof. Dr. Al. Obregia” Psychiatric Clinical Hospital in Bucharest between March 2023 and September 2024. Participants completed a set of validated psychometric tools: the Drinker Inventory of Consequences—Lifetime Version (DrInC), Readiness to Change Questionnaire—Treatment Version (RTCQ), Drinking Expectancy Questionnaire (DEQ), and Drinking Refusal Self-Efficacy Questionnaire (DRSEQ). Additional data were collected on the socio-demographic (education level, socio-professional category), genetic (family history of alcohol use), and behavioral factors (length of abstinence, tobacco use, co-occurring substance use disorders). Results: Higher alcohol-related consequence scores (DrInC) were significantly associated with lower education (p < 0.001, η2 = 0.483), disadvantaged socio-professional status (p < 0.001, η2 = 0.514), and family history of alcohol use (p < 0.001, η2 = 0.226). Self-efficacy (DRSEQ) was significantly lower among individuals with co-occurring substance use (p < 0.001) and nicotine dependence (p < 0.001). Logistic regression showed that the DrInC scores significantly predicted readmission within three months (OR = 1.09, p = 0.001). Conclusions: Psychometric tools are effective in identifying individuals at high risk. Personalized, evidence-based interventions tailored to both psychological and socio-professional profiles, combined with structured post-discharge support, are essential for improving long-term recovery and reducing the readmission rates. Full article
(This article belongs to the Section Neuropathology)
12 pages, 211 KiB  
Case Report
Acute Medical Events in Adults with Profound Autism: A Review and Illustrative Case Series
by Heli Patel, Anamika L. Shrimali, Christopher J. McDougle and Hannah M. Carroll
Brain Sci. 2025, 15(7), 740; https://doi.org/10.3390/brainsci15070740 - 10 Jul 2025
Viewed by 212
Abstract
Background: Autism spectrum disorder (ASD) is associated with social-communication challenges that can hinder timely diagnosis and treatment during acute medical events (AMEs). The purpose of this report is to review the literature on medical comorbidities and AMEs in adults with profound ASD [...] Read more.
Background: Autism spectrum disorder (ASD) is associated with social-communication challenges that can hinder timely diagnosis and treatment during acute medical events (AMEs). The purpose of this report is to review the literature on medical comorbidities and AMEs in adults with profound ASD and highlight how healthcare teams can better understand atypical presentations of acute pain and discomfort in adults with profound ASD to reduce delayed diagnoses, delays in treatment, and ultimately improve health outcomes. Methods: The literature on medical comorbidities and AMEs in adults with profound ASD was reviewed using the following databases: PubMed, PsycINFO, and Google Scholar. The histories of three adults with profound ASD who experienced AMEs—specifically, appendicitis, nephrolithiasis, and eosinophilic esophagitis (EoE)—are described. The clinical cases were selected to illustrate the challenges inherent in diagnosing and treating AMEs in adults with profound ASD in the context of the review. Results: In Case 1, a 31-year-old male with autism was diagnosed with perforated appendicitis after his family noticed behavioral changes. In Case 2, a 36-year-old male with autism experienced intermittent pain from nephrolithiasis and communicated his discomfort through irritability and pointing. In Case 3, a 34-year-old male with autism exhibited atypical behavior due to pain from undiagnosed EoE, identified after years of untreated pain and multiple unsuccessful clinical procedures. Conclusions: This review and the illustrative cases demonstrate the significant role that communication barriers play in delayed medical diagnoses for adults with profound ASD during AMEs. Integrating caregiver insights and recognizing atypical pain expressions are essential for improving the accuracy and timeliness of diagnosis and treatment in this population. Full article
19 pages, 1039 KiB  
Article
Prediction of Parkinson Disease Using Long-Term, Short-Term Acoustic Features Based on Machine Learning
by Mehdi Rashidi, Serena Arima, Andrea Claudio Stetco, Chiara Coppola, Debora Musarò, Marco Greco, Marina Damato, Filomena My, Angela Lupo, Marta Lorenzo, Antonio Danieli, Giuseppe Maruccio, Alberto Argentiero, Andrea Buccoliero, Marcello Dorian Donzella and Michele Maffia
Brain Sci. 2025, 15(7), 739; https://doi.org/10.3390/brainsci15070739 - 10 Jul 2025
Viewed by 267
Abstract
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting countless individuals worldwide. PD is characterized by the onset of a marked motor symptomatology in association with several non-motor manifestations. The clinical phase of the disease is usually [...] Read more.
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting countless individuals worldwide. PD is characterized by the onset of a marked motor symptomatology in association with several non-motor manifestations. The clinical phase of the disease is usually preceded by a long prodromal phase, devoid of overt motor symptomatology but often showing some conditions such as sleep disturbance, constipation, anosmia, and phonatory changes. To date, speech analysis appears to be a promising digital biomarker to anticipate even 10 years before the onset of clinical PD, as well serving as a useful prognostic tool for patient follow-up. That is why, the voice can be nominated as the non-invasive method to detect PD from healthy subjects (HS). Methods: Our study was based on cross-sectional study to analysis voice impairment. A dataset comprising 81 voice samples (41 from healthy individuals and 40 from PD patients) was utilized to train and evaluate common machine learning (ML) models using various types of features, including long-term (jitter, shimmer, and cepstral peak prominence (CPP)), short-term features (Mel-frequency cepstral coefficient (MFCC)), and non-standard measurements (pitch period entropy (PPE) and recurrence period density entropy (RPDE)). The study adopted multiple machine learning (ML) algorithms, including random forest (RF), K-nearest neighbors (KNN), decision tree (DT), naïve Bayes (NB), support vector machines (SVM), and logistic regression (LR). Cross-validation technique was applied to ensure the reliability of performance metrics on train and test subsets. These metrics (accuracy, recall, and precision), help determine the most effective models for distinguishing PD from healthy subjects. Result: Among all the algorithms used in this research, random forest (RF) was the best-performing model, achieving an accuracy of 82.72% with a ROC-AUC score of 89.65%. Although other models, such as support vector machine (SVM), could be considered with an accuracy of 75.29% and a ROC-AUC score of 82.63%, RF was by far the best one when evaluated across all metrics. The K-nearest neighbor (KNN) and decision tree (DT) performed the worst. Notably, by combining a comprehensive set of long-term, short-term, and non-standard acoustic features, unlike previous studies that typically focused on only a subset, our study achieved higher predictive performance, offering a more robust model for early PD detection. Conclusions: This study highlights the potential of combining advanced acoustic analysis with ML algorithms to develop non-invasive and reliable tools for early PD detection, offering substantial benefits for the healthcare sector. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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6 pages, 352 KiB  
Article
A Single-Incision Method for the Removal of Vagus Nerve Stimulators: A Single-Institution Retrospective Review
by Michael Baumgartner, Matthew Diehl and James E. Baumgartner
Brain Sci. 2025, 15(7), 738; https://doi.org/10.3390/brainsci15070738 - 10 Jul 2025
Viewed by 208
Abstract
Vagal nerve stimulators (VNSs) improve seizure control in up to half of the patients who have them implanted. In non-responding patients, VNS removal may be necessary. Removal is traditionally accomplished through two incisions. We present our experience removing VNSs through a single incision. [...] Read more.
Vagal nerve stimulators (VNSs) improve seizure control in up to half of the patients who have them implanted. In non-responding patients, VNS removal may be necessary. Removal is traditionally accomplished through two incisions. We present our experience removing VNSs through a single incision. Background/Objectives: To determine if VNS removal can be safely performed through a single incision. Methods: The medical records of 73 consecutive patients who underwent VNS removal at our institution from 2012 to 2024 were reviewed. Patients were divided into single-incision and two-incision treatment groups. Operative time and surgical complications were compared between groups. Results: A total of 73 patients underwent VNS removal during the study timeframe. Forty-eight VNS removals were accomplished via a single incision, while 25 required both incisions. Time in the operating room was roughly half as long for single-incision removal vs. two-incision removal (29.4 min, range 11–84 vs. 74.2 min, range 33–203); however, single incision was initially attempted in all cases. In two of the incision cases, the neck dissection resulted in an injury to the internal jugular (IJ) vein. In one case, the IJ was repaired and the lead wire removed. In a second case, the IJ could not be repaired, and a segment of lead wire was retained. In a third case, a short length of lead wire was discovered after a single-incision removal and a second procedure was necessary for removal. There were no significant differences in the rates of transient vocal cord weakness, cough, and/or dysphagia between both treatment groups (p = 0.7368), and there were no cases of permanent nerve palsy. Conclusions: VNS removal can be safely accomplished via a single incision in most cases. Successful single-incision procedures may be shorter than the two-incision approach. Attempted VNS removal via a single incision may result in increased incidence of transient hoarseness, dysphagia, and/or cough, but may result in reduced rates of permanent injury or IJ injury. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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15 pages, 295 KiB  
Article
Validity Evidence of the TRIACOG-Online Administered In-Person to Adults Post Stroke
by Luana Comito Muner, Guilherme Domingos Martins, Ana Beatriz Santos Honda, Natália Becker and Jaqueline de Carvalho Rodrigues
Brain Sci. 2025, 15(7), 737; https://doi.org/10.3390/brainsci15070737 - 10 Jul 2025
Viewed by 246
Abstract
Background/Objectives: Neuropsychological assessment tools adapted for digital formats are crucial to expanding access and improving cognitive evaluation in post-stroke patients. This study aimed to examine the reliability, convergent validity, and criterion-related validity (concurrent and known-groups) of TRIACOG-Online, a computerized cognitive screening tool [...] Read more.
Background/Objectives: Neuropsychological assessment tools adapted for digital formats are crucial to expanding access and improving cognitive evaluation in post-stroke patients. This study aimed to examine the reliability, convergent validity, and criterion-related validity (concurrent and known-groups) of TRIACOG-Online, a computerized cognitive screening tool designed to assess multiple domains in post-stroke adults in person or remotely. Methods: 98 participants (47 neurologically healthy adults and 51 post-stroke patients) completed a sociodemographic questionnaire, the Mini-Mental State Examination—MMSE, G-38—Nonverbal Intelligence Test, and the TRIACOG-Online assessment. Evaluations were conducted in person, computer mediated. Results: TRIACOG-Online demonstrated high internal consistency (Cronbach’s α = 0.872; McDonald’s ω = 0.923). Statistically significant differences were found between groups in episodic memory, attention, executive functions, and numerical processing, with healthy individuals outperforming post-stroke participants. Effect sizes were medium to large in several domains, especially for visual memory. Validity evidence based on the relationship with external variables was supported by negative correlations with age and positive correlations with education and reading and writing habits, particularly in the clinical group. Educational level showed stronger associations with verbal memory and language, suggesting a protective role in post-stroke cognitive performance. TRIACOG-Online scores demonstrated evidence of convergent validity with MMSE and G-38. Conclusions: TRIACOG-Online shows strong psychometric properties for the cognitive assessment of post-stroke adults. Its computerized format represents a promising tool for clinical and research use in neuropsychology, especially for bedside applications. Full article
(This article belongs to the Special Issue Advances in Cognitive and Psychometric Evaluation)
14 pages, 1117 KiB  
Article
Factors Influencing Virtual Art Therapy in Patients with Stroke
by Marco Iosa, Roberto De Giorgi, Federico Gentili, Alberto Ciotti, Cristiano Rubeca, Silvia Casolani, Claudia Salera and Gaetano Tieri
Brain Sci. 2025, 15(7), 736; https://doi.org/10.3390/brainsci15070736 - 9 Jul 2025
Viewed by 262
Abstract
Background: Art therapy was recently administered to stroke patients using immersive virtual reality technology, chosen to provide the illusion of being able to replicate an artistic masterpiece. This approach was effective in improving rehabilitative outcomes due to the so-called Michelangelo effect: patients’ [...] Read more.
Background: Art therapy was recently administered to stroke patients using immersive virtual reality technology, chosen to provide the illusion of being able to replicate an artistic masterpiece. This approach was effective in improving rehabilitative outcomes due to the so-called Michelangelo effect: patients’ interaction with artistic stimuli reduced perceived fatigue and improved performance. The aim of the present study was to investigate which factors may influence those outcomes (e.g., type of artwork, esthetic valence, perceived fatigue, clinical conditions). Methods: An observational study was conducted on 25 patients with stroke who performed the protocol of virtual art therapy (VAT). In each trial, patients were asked to rate the esthetic valence of the artworks and their perceived fatigue, whereas therapists assessed patients’ participation in the therapy (Pittsburgh Rehabilitation Participation Scale, PRPS). Moreover, before and after treatment, patients’ independence in daily living activities (Barthel Index, BI), and their upper limb functioning (Manual Muscle Test, MMT) and spasticity (Ashworth Scale, AS) were measured. Results: The after-treatment BI scores depended on the before-treatment BI score (p < 0.001) and on the PRPS score (p = 0.006), which, in turn, was increased by the subjective esthetic valence (p = 0.044). Perceived fatigue is a complex factor that may have influenced the outcomes (p = 0.049). Conclusions: There was a general effect of art in reducing fatigue and improving participation of patients during therapy. The variability observed among patients mainly depended on their clinical conditions, but also on the esthetic valence given to each artwork, that could also be intertwined with the difficulty of the task. Art therapy has a high potential to improve rehabilitation outcomes, especially if combined with new technologies, but psychometric investigation of the effects of each factor is needed to design the most effective protocols. Full article
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21 pages, 1842 KiB  
Article
Acute Stroke Severity Assessment: The Impact of Lesion Size and Functional Connectivity
by Karolin Weigel, Christian Gaser, Stefan Brodoehl, Franziska Wagner, Elisabeth Jochmann, Daniel Güllmar, Thomas E. Mayer and Carsten M. Klingner
Brain Sci. 2025, 15(7), 735; https://doi.org/10.3390/brainsci15070735 - 9 Jul 2025
Viewed by 307
Abstract
Background/Objectives: Early and accurate prediction of stroke severity is crucial for optimizing guided therapeutic decisions and improving outcomes. This study investigates the predictive value of lesion size and functional connectivity for neurological deficits, assessed by the National Institutes of Health Stroke Scale (NIHSS [...] Read more.
Background/Objectives: Early and accurate prediction of stroke severity is crucial for optimizing guided therapeutic decisions and improving outcomes. This study investigates the predictive value of lesion size and functional connectivity for neurological deficits, assessed by the National Institutes of Health Stroke Scale (NIHSS score), in patients with acute or subacute subcortical ischemic stroke. Methods: Forty-four patients (mean age: 68.11 years, 23 male, and admission NIHSS score 4.30 points) underwent high-resolution anatomical and resting-state functional Magnetic Resonance Imaging (rs-fMRI) within seven days of stroke onset. Lesion size was volumetrically quantified, while functional connectivity within the motor, default mode, and frontoparietal networks was analyzed using seed-based correlation methods. Multiple linear regression and cross-validation were applied to develop predictive models for stroke severity. Results: Our results showed that lesion size explained 48% of the variance in NIHSS scores (R2 = 0.48, cross-validated R2 = 0.49). Functional connectivity metrics alone were less predictive but enhanced model performance when combined with lesion size (achieving an R2 = 0.71, cross-validated R2 = 0.73). Additionally, left hemisphere connectivity features were particularly informative, as models based on left-hemispheric connectivity outperformed those using right-hemispheric or bilateral predictors. This suggests that the inclusion of contralateral hemisphere data did not enhance, and in some configurations, slightly reduced, model performance—potentially due to lateralized functional organization and lesion distribution in our cohort. Conclusions: The findings highlight lesion size as a reliable early marker of stroke severity and underscore the complementary value of functional connectivity analysis. Integrating rs-fMRI into clinical stroke imaging protocols offers a potential approach for refining prognostic models. Future research efforts should prioritize establishing this approach in larger cohorts and analyzing additional biomarkers to improve predictive models, advancing personalized therapeutic strategies for stroke management. Full article
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45 pages, 6622 KiB  
Review
Evolutionary Trajectories of Consciousness: From Biological Foundations to Technological Horizons
by Evgenii Gusev, Alexey Sarapultsev and Maria Komelkova
Brain Sci. 2025, 15(7), 734; https://doi.org/10.3390/brainsci15070734 - 9 Jul 2025
Viewed by 538
Abstract
Consciousness remains one of the most critical yet least understood functions of the brain, not only in humans but also in certain highly organized animal species. In this review, we propose treating consciousness as an emergent, goal-directed informational system organized by the subjective [...] Read more.
Consciousness remains one of the most critical yet least understood functions of the brain, not only in humans but also in certain highly organized animal species. In this review, we propose treating consciousness as an emergent, goal-directed informational system organized by the subjective “self” as an active system-forming factor. We present an integrative theoretical–systems framework in which subjectivity functions as system-forming factor of consciousness (SFF) throughout biological evolution. Beginning with proto-conscious invertebrates, we trace progressive elaborations of working and long-term memory, the refinement of behavioral programs, and the emergence of an internal arbiter capable of resolving competing drives. In endothermic vertebrates, subjectivity acquires distinct functional features—sensory filtering, causal reasoning, and adaptive arbitration—underpinned by increasingly complex neural architectures. This evolutionary trajectory culminates in humans, where subjectivity attains its highest level of organization through culturally mediated networks. Although the framework does not assume any specific neural substrate, it provides a testable roadmap linking evolutionary biology, information theory, and quantitative modeling. By clarifying why consciousness arose and how subjectivity shapes complex networks, this perspective also lays the groundwork for exploring possible nonbiological extensions of subjectivity. Full article
(This article belongs to the Special Issue Understanding the Functioning of Brain Networks in Health and Disease)
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16 pages, 283 KiB  
Review
The Brain in the Age of Smartphones and the Internet: The Possible Protective Role of Sport
by Laura Coco, Jonida Balla, Leonardo Noto, Valentina Perciavalle, Andrea Buscemi, Donatella Di Corrado and Marinella Coco
Brain Sci. 2025, 15(7), 733; https://doi.org/10.3390/brainsci15070733 - 9 Jul 2025
Viewed by 386
Abstract
Background: The widespread use of smartphones and the internet has transformed communication, but excessive use has raised concerns about smartphone and internet addiction, which can lead to psychological, physical, and social issues. The objective of this literature review is to explore the relationship [...] Read more.
Background: The widespread use of smartphones and the internet has transformed communication, but excessive use has raised concerns about smartphone and internet addiction, which can lead to psychological, physical, and social issues. The objective of this literature review is to explore the relationship between smartphone and internet addiction and physical activity, particularly focusing on whether physical exercise, especially sports, can serve as a protective factor against addiction. The review aims to examine how physical activity can reduce the negative impacts of addiction and improve overall mental health. Methods: This review synthesizes empirical research on smartphone and internet addiction and its connection to physical activity. It examines studies exploring how addiction leads to physical inactivity and how participation in physical activities, especially sports, can counteract this effect. The review also evaluates research on psychological mechanisms, such as self-esteem, self-control, and emotional resilience, that mediate the relationship between physical activity and addiction. Additionally, it discusses how sociodemographic and contextual factors influence this relationship. Conclusions: The findings consistently show an inverse relationship between smartphone and internet use and physical activity, with physical activity acting as a protective factor against addiction. Sports and other physical activities have been linked to reduced addictive behaviors, enhanced psychological well-being, and improved emotional resilience. Promoting physical activity, particularly sports, along with psychological interventions, appears to be an effective strategy for preventing and treating smartphone and internet addiction. Future research should focus on developing tailored interventions and studying diverse populations to optimize addiction prevention. Full article
15 pages, 559 KiB  
Article
Exploring Fixation Times During Emotional Decoding in Intimate Partner Violence Perpetrators: An Eye-Tracking Pilot Study
by Carolina Sarrate-Costa, Marisol Lila, Luis Moya-Albiol and Ángel Romero-Martínez
Brain Sci. 2025, 15(7), 732; https://doi.org/10.3390/brainsci15070732 - 8 Jul 2025
Viewed by 199
Abstract
Background/Objectives: Deficits in emotion recognition abilities have been described as risk factors for intimate partner violence (IPV) perpetration. However, much of this research is based on self-reports or instruments that present limited psychometric properties. While current scientific literature supports the use of eye [...] Read more.
Background/Objectives: Deficits in emotion recognition abilities have been described as risk factors for intimate partner violence (IPV) perpetration. However, much of this research is based on self-reports or instruments that present limited psychometric properties. While current scientific literature supports the use of eye tracking to assess cognitive and emotional processes, including emotional decoding abilities, there is a gap in the scientific literature when it comes to measuring these processes in IPV perpetrators using eye tracking in an emotional decoding task. Hence, the aim of this study was to examine the association between fixation times via eye tracking and emotional decoding abilities in IPV perpetrators, controlling for potential confounding variables. Methods: To this end, an emotion recognition task was created using an eye tracker in a group of 52 IPV perpetrators. This task consisted of 20 images with people expressing different emotions. For each picture, the facial region was selected as an area of interest (AOI). The fixation times were added to obtain a total gaze fixation time score. Additionally, an ad hoc emotional decoding multiple-choice test about each picture was developed. These instruments were complemented with other self-reports previously designed to measure emotion decoding abilities. Results: The results showed that the longer the total fixation times on the AOI, the better the emotional decoding abilities in IPV perpetrators. Specifically, fixation times explained 20% of the variance in emotional decoding test scores. Additionally, our ad hoc emotional decoding test was significantly correlated with previously designed emotion recognition tools and showed similar reliability to the eyes test. Conclusions: Overall, this pilot study highlights the importance of including eye movement signals to explore attentional processes involved in emotion recognition abilities in IPV perpetrators. This would allow us to adequately specify the therapeutic needs of IPV perpetrators to improve current interventions. Full article
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17 pages, 1326 KiB  
Review
State-Dependent Transcranial Magnetic Stimulation Synchronized with Electroencephalography: Mechanisms, Applications, and Future Directions
by He Chen, Tao Liu, Yinglu Song, Zhaohuan Ding and Xiaoli Li
Brain Sci. 2025, 15(7), 731; https://doi.org/10.3390/brainsci15070731 - 8 Jul 2025
Viewed by 333
Abstract
Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) has emerged as a transformative tool for probing cortical dynamics with millisecond precision. This review examines the state-dependent nature of TMS-EEG, a critical yet underexplored dimension influencing measurement reliability and clinical applicability. By integrating TMS’s neuromodulatory [...] Read more.
Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) has emerged as a transformative tool for probing cortical dynamics with millisecond precision. This review examines the state-dependent nature of TMS-EEG, a critical yet underexplored dimension influencing measurement reliability and clinical applicability. By integrating TMS’s neuromodulatory capacity with EEG’s temporal resolution, this synergy enables real-time analysis of brain network dynamics under varying neural states. We delineate foundational mechanisms of TMS-evoked potentials (TEPs), discuss challenges posed by temporal and inter-individual variability, and evaluate advanced paradigms such as closed-loop and task-embedded TMS-EEG. The former leverages real-time EEG feedback to synchronize stimulation with oscillatory phases, while the latter aligns TMS pulses with task-specific cognitive phases to map transient network activations. Current limitations—including hardware constraints, signal artifacts, and inconsistent preprocessing pipelines—are critically analyzed. Future directions emphasize adaptive algorithms for neural state prediction, phase-specific stimulation protocols, and standardized methodologies to enhance reproducibility. By bridging mechanistic insights with personalized neuromodulation strategies, state-dependent TMS-EEG holds promise for advancing both basic neuroscience and precision medicine, particularly in psychiatric and neurological disorders characterized by dynamic neural dysregulation. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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28 pages, 2586 KiB  
Review
Diagnostic, Therapeutic, and Prognostic Applications of Artificial Intelligence (AI) in the Clinical Management of Brain Metastases (BMs)
by Kyriacos Evangelou, Panagiotis Zemperligkos, Anastasios Politis, Evgenia Lani, Enrique Gutierrez-Valencia, Ioannis Kotsantis, Georgios Velonakis, Efstathios Boviatsis, Lampis C. Stavrinou and Aristotelis Kalyvas
Brain Sci. 2025, 15(7), 730; https://doi.org/10.3390/brainsci15070730 - 8 Jul 2025
Viewed by 400
Abstract
Brain metastases (BMs) are the most common intracranial tumors in adults. Their heterogeneity, potential multifocality, and complex biomolecular behavior pose significant diagnostic and therapeutic challenges. Artificial intelligence (AI) has the potential to revolutionize BM diagnosis by facilitating early lesion detection, precise imaging segmentation, [...] Read more.
Brain metastases (BMs) are the most common intracranial tumors in adults. Their heterogeneity, potential multifocality, and complex biomolecular behavior pose significant diagnostic and therapeutic challenges. Artificial intelligence (AI) has the potential to revolutionize BM diagnosis by facilitating early lesion detection, precise imaging segmentation, and non-invasive molecular characterization. Machine learning (ML) and deep learning (DL) models have shown promising results in differentiating BMs from other intracranial tumors with similar imaging characteristics—such as gliomas and primary central nervous system lymphomas (PCNSLs)—and predicting tumor features (e.g., genetic mutations) that can guide individualized and targeted therapies. Intraoperatively, AI-driven systems can enable optimal tumor resection by integrating functional brain maps into preoperative imaging, thus facilitating the identification and safeguarding of eloquent brain regions through augmented reality (AR)-assisted neuronavigation. Even postoperatively, AI can be instrumental for radiotherapy planning personalization through the optimization of dose distribution, maximizing disease control while minimizing adjacent healthy tissue damage. Applications in systemic chemo- and immunotherapy include predictive insights into treatment responses; AI can analyze genomic and radiomic features to facilitate the selection of the most suitable, patient-specific treatment regimen, especially for those whose disease demonstrates specific genetic profiles such as epidermal growth factor receptor mutations (e.g., EGFR, HER2). Moreover, AI-based prognostic models can significantly ameliorate survival and recurrence risk prediction, further contributing to follow-up strategy personalization. Despite these advancements and the promising landscape, multiple challenges—including data availability and variability, decision-making interpretability, and ethical, legal, and regulatory concerns—limit the broader implementation of AI into the everyday clinical management of BMs. Future endeavors should thus prioritize the development of generalized AI models, the combination of large and diverse datasets, and the integration of clinical and molecular data into imaging, in an effort to maximally enhance the clinical application of AI in BM care and optimize patient outcomes. Full article
(This article belongs to the Section Neuro-oncology)
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20 pages, 600 KiB  
Review
Neurological Disorders and Clinical Progression in Boxers from the 20th Century: A Narrative Review
by Rudolph J. Castellani, Nicolas Kostelecky, Jared T. Ahrendsen, Malik Nassan, Pouya Jamshidi and Grant L. Iverson
Brain Sci. 2025, 15(7), 729; https://doi.org/10.3390/brainsci15070729 - 8 Jul 2025
Viewed by 258
Abstract
Introduction: There are no validated clinical diagnostic criteria for chronic traumatic encephalopathy or traumatic encephalopathy syndrome (TES). To understand the historical clinical condition, its applicability to modern day athletes, and the pathogenesis of clinical problems, we examined the literature describing boxers from [...] Read more.
Introduction: There are no validated clinical diagnostic criteria for chronic traumatic encephalopathy or traumatic encephalopathy syndrome (TES). To understand the historical clinical condition, its applicability to modern day athletes, and the pathogenesis of clinical problems, we examined the literature describing boxers from the 20th century, with specific attention paid to neurological findings and characteristics of clinical disease progression. Methods: Data were extracted for 243 boxers included in 45 articles published between 1928 and 1999, including cases from articles originally published in German. The presence or absence of 22 neurological signs and features were extracted. Results: The most common neurological problems were slurring dysarthria (49%), gait disturbances (44%), and memory loss (36%), with several other problems that were less frequent, including hyperreflexia (25%), ataxia (22%), increased tone (19%), and extensor Babinski sign (16%). Frank dementia appeared in some cases (17%). There were significantly fewer neurological deficits reported in boxers who fought in the latter part of the 20th century compared to boxers who fought earlier in the century. For more than half of the cases, there were no comments about whether the neurological problems were progressive (145, 60%). A progressive condition was described in 71 cases (29%) and a stationary or improving condition was described in 27 cases (11%). Canonical neurodegenerative disease-like progression was described in 15 cases (6%). Discussion: Neurological problems associated with boxing-related neurotrauma during the 20th century are the foundation for present-day TES. However, the clinical signs and features in the 20th century differ in most ways from the modern criteria for TES. Full article
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18 pages, 959 KiB  
Article
Response to Training in Emotion Recognition Function for Mild TBI/PTSD Survivors: Pilot Study
by J. Kay Waid-Ebbs, Kristen Lewandowski, Yi Zhang, Samantha Graham and Janis J. Daly
Brain Sci. 2025, 15(7), 728; https://doi.org/10.3390/brainsci15070728 - 8 Jul 2025
Viewed by 539
Abstract
Background/Objectives: For those with comorbid mild traumatic brain injury/post-traumatic stress disorder (mTBI/PTSD), deficits are common with regard to recognition of emotion expression in others. These deficits can cause isolation and suicidal ideation. For mTBI/PTSD, there is a dearth of information regarding effective treatment. [...] Read more.
Background/Objectives: For those with comorbid mild traumatic brain injury/post-traumatic stress disorder (mTBI/PTSD), deficits are common with regard to recognition of emotion expression in others. These deficits can cause isolation and suicidal ideation. For mTBI/PTSD, there is a dearth of information regarding effective treatment. In pilot work, we developed and tested an innovative treatment to improve recognition of both affect (facial expression of emotion) and prosody (spoken expression of emotion). Methods: We enrolled eight Veterans with mTBI/PTSD and administered eight treatment sessions. Measures included the following: Florida Affect Battery (FAB), a test of emotion recognition of facial affect and spoken prosody; Attention Index of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); and Emotion Recognition Test (ERT), a speed test of facial emotion recognition. Results: There was a significant treatment response according to the FAB (p = 0.01, effect size = 1.2); RBANS attention index (p = 0.04, effect size = 0.99); and trending toward significance for the ERT (0.17, effect size 0.75). Participants were able to engage actively in all eight sessions and provided qualitative evidence supporting generalization of the training to interpersonal relationships. Conclusions: Our data show promising clinical potential and warrant future research, given the importance of developing novel interventions to train and restore recognition of emotion in Veterans with mTBI/PTSD. Full article
(This article belongs to the Special Issue At the Frontiers of Neurorehabilitation: 3rd Edition)
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17 pages, 932 KiB  
Review
Retinal Neurochemistry
by Dominic Man-Kit Lam and George Ayoub
Brain Sci. 2025, 15(7), 727; https://doi.org/10.3390/brainsci15070727 - 8 Jul 2025
Viewed by 164
Abstract
The vertebrate retina is a complex neural tissue composed of a repeating array of distinct cell types that communicate through specialized synaptic connections. The neurochemistry underlying these connections reveals the synaptic chemistry, including the neurotransmitters involved and their corresponding receptors. The basic pattern [...] Read more.
The vertebrate retina is a complex neural tissue composed of a repeating array of distinct cell types that communicate through specialized synaptic connections. The neurochemistry underlying these connections reveals the synaptic chemistry, including the neurotransmitters involved and their corresponding receptors. The basic pattern of communication is that the pathway from photoreceptors to bipolar cells to ganglion cells typically uses glutamate as the signaling transmitter, with three ionotropic and one metabotropic receptor types. In contrast, much of the lateral feedback, performed by horizontal cells and amacrine cells, uses the inhibitory neurotransmitter GABA, while other amacrine cells use glycine or dopamine. This review examines all of these neurotransmitter systems for each retinal cell type, along with how these systems process the visual signals transmitted to the lateral geniculate nucleus and the visual cortex. Full article
(This article belongs to the Special Issue Retinal Neurochemistry and Development)
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