Brain Sciences

23 pages, 993 KB

Open AccessReview

Multimodal Neuroprotection in Ischemic Stroke: Emerging Non-Pharmacological Interventions from Bench to Bedside

by Junzhao Cui, Jingyi Yang, Luji Liu, Xiaoyun Liu and Xunming Ji

Brain Sci. 2025, 15(10), 1111; https://doi.org/10.3390/brainsci15101111 - 15 Oct 2025

Currently, the effective therapeutic strategies for acute ischemic stroke (AIS) remain revascularization therapies, including intravenous thrombolysis and endovascular thrombectomy. However, the narrow time window and reperfusion injury associated with reperfusion therapy limit favorable outcomes in some patients. As adjuncts to revascularization, certain neuroprotective [...] Read more.

Currently, the effective therapeutic strategies for acute ischemic stroke (AIS) remain revascularization therapies, including intravenous thrombolysis and endovascular thrombectomy. However, the narrow time window and reperfusion injury associated with reperfusion therapy limit favorable outcomes in some patients. As adjuncts to revascularization, certain neuroprotective agents have demonstrated robust preclinical results, but only a few have achieved successful clinical translation due to challenges in dosing and safety concerns. In recent years, convenient and relatively safe non-pharmacological neuroprotective interventions—such as hypothermia, remote ischemic conditioning (RIC), and normobaric hyperoxia (NBO)—have gained increasing research attention. These approaches offer advantages including high safety profiles, excellent tolerability, low cost, and the potential to synergize with reperfusion therapy, underscoring their broad clinical applicability. Numerous clinical trials have validated their potential to improve neurological functional outcomes, and this review explores the mechanisms and clinical applications of non-pharmacological neuroprotective therapies in ischemic stroke. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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13 pages, 3708 KB

Open AccessArticle

Panax notoginseng Flower Extract Attenuates Pentylenetetrazole-Induced Epilepsy by Restoring Glutamate Homeostasis

by Yang Zhao, Feiya Zhu, Jiayu Xie, Yiting Wang, Motlalepula Matsabisa and Minke Tang

Brain Sci. 2025, 15(10), 1110; https://doi.org/10.3390/brainsci15101110 - 15 Oct 2025

Abstract

Objectives: One-third of patients experience inadequate seizure control with antiseizure medications. Therefore, safer and more effective therapeutic strategies remain urgently needed. Research evidence indicates that Panax notoginseng flower may exhibit potential antiepileptic properties. The study aimed to investigate the neuroprotective and antiepileptic effects [...] Read more.

Objectives: One-third of patients experience inadequate seizure control with antiseizure medications. Therefore, safer and more effective therapeutic strategies remain urgently needed. Research evidence indicates that Panax notoginseng flower may exhibit potential antiepileptic properties. The study aimed to investigate the neuroprotective and antiepileptic effects of Panax notoginseng flower (PNF) extract in a chronic pentylenetetrazole (PTZ)-kindled mouse model and explore its potential mechanisms, focusing on glutamate homeostasis. Methods: Chronic epilepsy was induced in ICR mice via repeated subconvulsive PTZ intraperitoneal injections. Following successful kindling, mice were orally treated with PNF (1.5 g/kg or 3 g/kg) for 30 days. Seizure behaviors were scored using Racines scale. Neuronal survival, systemic and cerebral cytokines, hippocampal glutamate levels (in vivo microdialysis with LC-MS/MS analysis), glutamate homeostasis related proteins glutamate transporter-2 (GLT-1), glutamate-aspartate transporter-1 (GLAST), and glutamine synthetase (GS) were investigated. Results: PNF treatment significantly reduced seizure severity and restored neuronal nuclei (NeuN+) cell neurons in the cortex and hippocampal CA1 region of PTZ kindled mice. PNF attenuated systemic and neuroinflammation by lowering interleukin-1ß (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-α) levels and increasing interleukin-10 (IL-10) in serum and brain of PTZ mice. PNF reduced hippocampal glutamate accumulation and upregulated GLT-1, GLAST, and GS expression, which were altered by PTZ stimulation. Conclusions: The PNF extract exhibits significant neuroprotective and antiepileptic effects in PTZ-kindled mice, likely through restoring glutamate homeostasis, and suppressing inflammation. These findings, with further clinical development, support the therapeutic potential of PNF as a complementary approach for epilepsy management. Full article

(This article belongs to the Collection Collection on Molecular and Cellular Neuroscience)

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16 pages, 462 KB

Open AccessArticle

Integration of Gestalt Therapy with Evidence-Based Interventions for Borderline Personality Disorder—Theoretical Framework and Clinical Model

by Enrico Moretto, Roberta Stanzione, Chiara Scognamiglio, Valeria Cioffi, Lucia Luciana Mosca, Francesco Marino, Ottavio Ragozzino, Enrica Tortora and Raffaele Sperandeo

Brain Sci. 2025, 15(10), 1109; https://doi.org/10.3390/brainsci15101109 - 15 Oct 2025

Abstract

Background/Objectives: Gestalt therapy traditionally opposes categorical diagnostic labelling due to its fundamental inconsistency with phenomenological and process-oriented ontology. However, this epistemological rigour can limit integration with structured evidence-based interventions for complex personality organizations such as Borderline Personality Disorder (BPD). Despite the evidence base [...] Read more.

Background/Objectives: Gestalt therapy traditionally opposes categorical diagnostic labelling due to its fundamental inconsistency with phenomenological and process-oriented ontology. However, this epistemological rigour can limit integration with structured evidence-based interventions for complex personality organizations such as Borderline Personality Disorder (BPD). Despite the evidence base for DBT and Schema Therapy in treating BPD, these approaches may inadvertently minimize the lived phenomenological experience and organismic wisdom central to recovery. Meanwhile, Gestalt therapy’s anti-diagnostic stance limits its integration with structured evidence-based protocols. This paper proposes a hybrid theoretical model that addresses this gap by integrating the clinical epistemology of Gestalt therapy with Linehan’s biosocial theory of Dialectical Behaviour Therapy (DBT) and schema-focused interventions, while preserving the core principles of Gestalt. Methods: we present a model of theoretical integration that draws on Gestalt contact theory, the four modules of DBT (mindfulness, distress tolerance, emotional regulation, interpersonal effectiveness) and the experiential techniques of Schema Therapy. The integration focuses on the dialectic of acceptance and change, which mirrors Gestalt’s paradoxical theory of change. The proposed framework preserves the non-protocol dimension of Gestalt therapy while incorporating the pragmatic utility of DBT and Schema Therapy. Results: key conceptual contributions we propose include: (1) theorizing the “Draft Self” as the object and subject of therapeutic work, (2) integrating mindfulness and grounding as embodied processes within live Gestalt experiments, (3) activation techniques to explore the identity fragmentation endemic to BPD. Conclusions:his integration offers a coherent, embodied, and process-oriented framework for understanding and treating BPD that validates patients’ lived experience, mobilizes evidence-based interventions, and opens up meaningful intertheoretical dialogue. Full article

(This article belongs to the Special Issue Beyond the Brain: Merging Embodied Mind and AI in the Clinical Neuroscience of Psychotherapy)

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11 pages, 851 KB

Open AccessArticle

Distinguishing Among Variants of Primary Progressive Aphasia with a Brief Multimodal Test of Nouns and Verbs

by Marco A. Lambert, Melissa D. Stockbridge, Lindsey Kelly, Isidora Diaz-Carr, Voss Neal and Argye E. Hillis

Brain Sci. 2025, 15(10), 1108; https://doi.org/10.3390/brainsci15101108 - 15 Oct 2025

Abstract

Background: Primary Progressive Aphasia (PPA) variants include the non-fluent agrammatic (nfvPPA), logopenic (lvPPA), and semantic (svPPA), which differ in their effects on speech production. However, their impact on modality (oral vs. written) and grammatical word class (nouns vs. verbs) remains controversial. A significant [...] Read more.

Background: Primary Progressive Aphasia (PPA) variants include the non-fluent agrammatic (nfvPPA), logopenic (lvPPA), and semantic (svPPA), which differ in their effects on speech production. However, their impact on modality (oral vs. written) and grammatical word class (nouns vs. verbs) remains controversial. A significant effect of these variables might assist in classification. Materials and Methods: This study used first-visit data from 300 participants with PPA who completed oral and written noun and verb naming (matched in surface word frequency across word class) to test the hypothesis that the three variants show differential impairment on word class or modality. Group differences were evaluated with rank-transformed repeated measures ANOVA. Within individual differences between nouns and verbs and between oral and written modalities were tested with Fisher’s exact tests. Results: A significant modality × variant interaction (p = 0.017) was observed. Participants with lvPPA and nfvPPA demonstrated greater oral than written naming, with nfvPPA also performing better on nouns than verbs. Those with svPPA showed no modality or word class effects but had an overall low accuracy. Three participants with svPPA (but no individuals with the other variants) demonstrated significantly (p = 0.003) more accurate verb than noun naming. Conclusions: Differing modality and word class patterns characterize PPA variants, with nfvPPA more accurate in nouns than verbs on average. Within individuals, only those with svPPA occasionally showed significantly more proficient verb than noun naming. Grammatical word class effects likely arise at distinct levels of cognitive processing underlying naming. Full article

(This article belongs to the Special Issue Primary Progressive Aphasia: What Happens to Speech and Language? What Can We Do to Help?)

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17 pages, 4020 KB

Open AccessArticle

Medication vs. Movement in ADHD: Interaction Between Medication and Physical Activity on Neurocognitive Functioning

by Beverly-Ann Hoy, Michelle Bi, Matthew Lam, Androu Abdalmalak and Barbara Fenesi

Brain Sci. 2025, 15(10), 1107; https://doi.org/10.3390/brainsci15101107 - 15 Oct 2025

Abstract

Background/Objectives: Movement during attention-demanding tasks may help compensate for cortical under-arousal in pediatric ADHD patients. However, the influence of medication during movement is unknown. This study assessed the impact of concurrent movement during executive functioning tasks on dorsolateral prefrontal cortex (DLPFC) activation [...] Read more.

Background/Objectives: Movement during attention-demanding tasks may help compensate for cortical under-arousal in pediatric ADHD patients. However, the influence of medication during movement is unknown. This study assessed the impact of concurrent movement during executive functioning tasks on dorsolateral prefrontal cortex (DLPFC) activation and inhibitory control, with a particular focus on the influence of medication status. Methods: Twenty-six children with ADHD (15 medicated; 11 unmedicated) and 24 children without ADHD performed a Stroop task under two conditions: while remaining seated (Stationary condition) and while pedalling on a desk cycle (Movement condition). Functional near-infrared spectroscopy (fNIRS) was used to measure changes in oxygenated and deoxygenated hemoglobin levels in the left DLPFC. Results: Sixty-four percent of unmedicated children with ADHD showed greater left DLPFC activity while desk-cycling compared to remaining stationary. Only 37% of medicated children with ADHD showed the same pattern, with 63% showing greater left DLPFC activation when remaining stationary during executive functioning. Children without ADHD had similar DLPFC patterns as unmedicated ADHD children, with 65% showing increased activation during movement. Unmedicated ADHD children who were able to desk-cycle during the Stroop task had higher overall and incongruent accuracy scores; no Stroop differences were found between conditions for children with ADHD who were medicated or for controls. Conclusions: Medicated ADHD children did not benefit from physical activity during tasks requiring executive control, yet unmedicated ADHD children showed significantly greater DLPFC activation and inhibitory control when engaging in movement. If medication is not suitable for children with ADHD due to adverse side effects, movement during executive functioning may help mimic the benefit of medications and similarly support attention. Full article

(This article belongs to the Section Cognitive, Social and Affective Neuroscience)

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32 pages, 5306 KB

Open AccessReview

Neuroimaging and Machine Learning in OCD: Advances in Diagnostic and Therapeutic Insights

by Norah A. Alturaiqi, Wijdan S. Aljebreen, Wedad Alawad, Shuaa S. Alharbi and Haifa F. Alhasson

Brain Sci. 2025, 15(10), 1106; https://doi.org/10.3390/brainsci15101106 - 14 Oct 2025

Abstract

Background/Objectives: Obsessive–Compulsive Disorder (OCD) is a chronic mental health condition characterized by intrusive thoughts and repetitive behaviors. Traditional diagnostic methods rely on subjective clinical assessments, delaying effective intervention. This review examines how advanced neuroimaging techniques, such as Magnetic Resonance Imaging (MRI) and Diffusion [...] Read more.

Background/Objectives: Obsessive–Compulsive Disorder (OCD) is a chronic mental health condition characterized by intrusive thoughts and repetitive behaviors. Traditional diagnostic methods rely on subjective clinical assessments, delaying effective intervention. This review examines how advanced neuroimaging techniques, such as Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI), integrated with machine learning (ML), can improve OCD diagnostics by identifying structural and functional brain abnormalities, particularly in the cortico-striato-thalamo-cortical (CSTC) circuit. Methods: Findings from studies using MRI and DTI to identify OCD-related neurobiological markers are synthesized. Machine learning algorithms like Convolutional Neural Networks (CNNs) and Support Vector Machines (SVMs) are evaluated for their ability to analyze neuroimaging data. The role of transfer learning in overcoming dataset limitations and heterogeneity is also explored. Results: ML algorithms have achieved diagnostic accuracies exceeding 80%, revealing subtle neurobiological markers linked to OCD. Abnormalities in the CSTC circuit are consistently identified. Transfer learning shows promise in enhancing predictive modeling and enabling personalized treatment strategies, especially in resource-constrained settings. Conclusions: The integration of neuroimaging and ML represents a transformative approach to OCD diagnostics, offering improved accuracy and biologically informed insights. Future research should focus on optimizing multimodal imaging techniques, increasing data generalizability, and addressing interpretability challenges to enhance clinical applicability. These innovations have the potential to advance precision diagnostics and support more targeted therapeutic interventions, ultimately improving outcomes for individuals with OCD. Full article

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

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30 pages, 2250 KB

Open AccessReview

The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential

by Toni Capó, Jaume Lillo, Joan Biel Rebassa, Pau Badia, Iu Raïch, Erik Cubeles-Juberias, Irene Reyes-Resina and Gemma Navarro

Brain Sci. 2025, 15(10), 1105; https://doi.org/10.3390/brainsci15101105 - 14 Oct 2025

Abstract

According to the World Drug Report, there are nearly 300 million drug users globally. Drug addiction is a chronic, relapsing brain disease that leads to medical, psychological, and social complications. This neuropsychiatric disorder is characterized by a compulsive drug-seeking behavior, continued use despite [...] Read more.

According to the World Drug Report, there are nearly 300 million drug users globally. Drug addiction is a chronic, relapsing brain disease that leads to medical, psychological, and social complications. This neuropsychiatric disorder is characterized by a compulsive drug-seeking behavior, continued use despite harmful consequence, and long-lasting changes in the brain. The reward system, which involves dopaminergic circuits, plays a key role in addiction. Dopamine levels have been described to fluctuate throughout the day, in a circadian fashion, and the effects of drugs have been shown to depend on the time when they are used. Hence, due to its important role in the control of circadian rhythms, the orexinergic system seems to have a role in the regulation of addiction. This system is composed by the orexin receptors 1 and 2 (OX₁R and OX₂R), the ligands orexin A (OXA) and orexin B (OXB) and their respective enzymes for degradation or synthesis. Here, we explore how orexin receptors and orexin peptides are involved in addiction. For instance, OX₁R has been shown to be strongly involved in specific behaviors such as drug-seeking for stimulants, alcohol and other addiction problems, whereas OX₂R appears to be linked with arousal and stress responses. We also investigate how the orexinergic system may regulate drug-seeking behavior by interaction with other brain systems such as the dopaminergic, cannabinoid or opioid systems. Finally, the potential of receptor complexes as new therapeutic targets to treat drug addiction is explored. Full article

(This article belongs to the Special Issue Editorial Board Collection Series: Innovative Research in Molecular and Cellular Neuroscience for Regulation of Cell Death Mechanisms for Functional Neuroprotection)

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17 pages, 976 KB

Open AccessReview

Current State-of-the-Art Animal Models of Pediatric Brain Tumors

by Tanusri Gudavalli, Fred C. Lam, Santosh Guru, Deyaldeen AbuReesh, Yusuke S. Hori, Susan Hiniker, David J. Park and Steven D. Chang

Brain Sci. 2025, 15(10), 1104; https://doi.org/10.3390/brainsci15101104 - 14 Oct 2025

Abstract

Brain tumors are unfortunately the most common types of solid tumors in the pediatric population, superseded only by leukemias, and largely bode a poor prognosis. Despite advances in our ability to diagnose and treat pediatric brain tumors, there remains a large unmet need [...] Read more.

Brain tumors are unfortunately the most common types of solid tumors in the pediatric population, superseded only by leukemias, and largely bode a poor prognosis. Despite advances in our ability to diagnose and treat pediatric brain tumors, there remains a large unmet need to develop novel therapies to improve patient outcomes. The recent understanding of the molecular drivers of oncogenesis for many of these tumors has led to the engineering of preclinical small animal models which serve as valuable tools for scientists to study the mechanisms of tumor biology, to understand interactions with the tumor microenvironment, and allow for translatable novel therapeutic discovery. This review focuses on the state-of-the art development of preclinical models of two difficult-to-treat pediatric brain tumors: (1) diffuse midline gliomas, the most lethal form of pediatric brain cancer; (2) medulloblastoma, the most common embryonal tumor of the central nervous system. We will then round off this review with a discussion on the emerging use of multi-omics and AI approaches to complement the testing of novel therapies using these in vivo animal models. Full article

(This article belongs to the Section Neuro-oncology)

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14 pages, 5156 KB

Open AccessArticle

Detection of EEG Activity in Response to the Surrounding Environment: A Neuro-Architecture Study

by Jesús S. García-Salinas, Anna Wróblewska and Michal T. Kucewicz

Brain Sci. 2025, 15(10), 1103; https://doi.org/10.3390/brainsci15101103 - 14 Oct 2025

Abstract

Background: The external environment continuously shapes human perception, often without conscious awareness. This influence can be objectively studied using non-invasive recordings of brain activity in controlled virtual reality (VR) settings. We hypothesized that brief presentations of natural features would elicit distinct neural [...] Read more.

Background: The external environment continuously shapes human perception, often without conscious awareness. This influence can be objectively studied using non-invasive recordings of brain activity in controlled virtual reality (VR) settings. We hypothesized that brief presentations of natural features would elicit distinct neural oscillatory patterns detectable through changes in the spectral power of resting-state electroencephalogram (EEG) activity in specific brain regions. Methods: To test this, participants passively viewed three minimalist VR environments—with and without biophilic elements—while their EEG was recorded. Results: Our results revealed consistent changes in spectral power, particularly suppression in the alpha band and an increase in the theta band in the occipital cortex. Conclusions: These findings support the use of resting-state EEGs in immersive VR as a promising and objective method for evaluating how specific design elements influence neural activity, offering valuable insights into the field of neuro-architecture. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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16 pages, 682 KB

Open AccessArticle

Confusion Assessment Protocol: Italian Cross-Cultural Adaptation and Validation

by Giulia Ferri, Anna Carannante, Manuela Iannetti, Sara Schiattone, Paola Ciurli, Fabiana Mogavero, Valentina Massimi, Marta Aloisi, Rita Formisano and Marco Giustini

Brain Sci. 2025, 15(10), 1102; https://doi.org/10.3390/brainsci15101102 - 13 Oct 2025

Abstract

Background: This study validated the Italian version of the Confusion Assessment Protocol (CAP), a tool designed to assess Post-Traumatic Confusional State (PTCS) in patients with severe acquired brain injury (sABI) who are not evaluable with standard neuropsychological evaluations. Objectives: The primary aim [...] Read more.

Background: This study validated the Italian version of the Confusion Assessment Protocol (CAP), a tool designed to assess Post-Traumatic Confusional State (PTCS) in patients with severe acquired brain injury (sABI) who are not evaluable with standard neuropsychological evaluations. Objectives: The primary aim of this study was to promote the CAP as a tool for assessing patients who are not still eligible for standard neuropsychological evaluation and to adapt it to Italian-speaking sABI patients by translating it into Italian and conducting a cross-cultural adaptation and evaluating its psychometric properties. The secondary objective was to correlate the CAP scores with broader functional scales, such as the Levels of Cognitive Functioning Assessment Scale (LCF) and Disability Rating Scale (DRS). Methods: A total of 42 sABI patients were enrolled at IRCCS Fondazione Santa Lucia. The CAP was translated and culturally adapted using international back-translation guidelines. Cross-cultural validity was assessed in 20 patients. The final version was administered by three trained raters over two days to evaluate inter- and intra-rater reliability. Results: The Italian version of the CAP demonstrated high internal consistency and substantial inter-rater reliability for key symptoms, including night-time sleep disturbances, decreased daytime arousal, and psychotic-type symptoms. Cognitive impairment showed moderate inter-rater agreement, likely due to symptom fluctuations typical of this recovery phase. The convergent validity of the CAP was confirmed through its correlations with the Levels of Cognitive Functioning (LCF) and the Disability Rating Scale (DRS), demonstrating its clinical utility in integrating cognitive and behavioral symptom assessments. Conclusions: The Italian version of the CAP is a reliable and valid tool for assessing PTCS in sABI. Future developments should address limitations related to symptom intensity, behavioral domains, and differential symptom weighting. Full article

(This article belongs to the Special Issue At the Frontiers of Neurorehabilitation: 3rd Edition)

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26 pages, 1071 KB

Open AccessReview

Therapeutic Advances in Targeting the Amyloid-β Pathway for Alzheimer’s Disease

by Beiyu Zhang, Yunan Li, Huan Li, Xinai Shen and Zheying Zhu

Brain Sci. 2025, 15(10), 1101; https://doi.org/10.3390/brainsci15101101 - 13 Oct 2025

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neuropathological hallmarks, including amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), and neurodegeneration. Since the amyloid cascade hypothesis was proposed, Aβ has remained a central therapeutic target, with interventions [...] Read more.

Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neuropathological hallmarks, including amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), and neurodegeneration. Since the amyloid cascade hypothesis was proposed, Aβ has remained a central therapeutic target, with interventions aiming to reduce Aβ production, aggregation, or downstream toxicity. This review first outlines the historical development of the Aβ hypothesis and the two major APP processing pathways (α-cleavage and β-cleavage), highlighting the role of biomarkers in early diagnosis, patient stratification, and regulatory approval. We then summarize the development and clinical outcomes of anti-Aβ small-molecule drugs, including β-secretase inhibitors, γ-secretase modulators, Aβ aggregation inhibitors, receptor/synapse modulators, and metabolic or antioxidant modalities. We further review the progression of biologic therapies, with a particular focus on monoclonal antibodies, vaccines, and emerging gene-silencing strategies, such as small interfering RNA (siRNA) and antisense oligonucleotides. Finally, we discuss future perspectives, including next-generation biologics, multi-target approaches, optimized delivery platforms, and early-prevention strategies. Collectively, these efforts underscore both the challenges and opportunities in translating anti-Aβ therapies into meaningful clinical benefits for patients with AD. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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12 pages, 556 KB

Open AccessArticle

Difficulty in Attention Switching and Its Neural Basis in Problematic Smartphone Use

by Nanase Kobayashi, Daisuke Jitoku, Toshitaka Hamamura, Masaru Honjo, Yusei Yamaguchi, Masaaki Shimizu, Shunsuke Takagi, Junya Fujino, Genichi Sugihara and Hidehiko Takahashi

Brain Sci. 2025, 15(10), 1100; https://doi.org/10.3390/brainsci15101100 - 13 Oct 2025

Abstract

Background: Problematic smartphone use (PSU) involves excessive smartphone engagement that disrupts daily functioning and is linked to attentional control deficits and altered reward processing. The nucleus accumbens (NAcc), a key structure in the reward system, may contribute to difficulty disengaging from rewarding [...] Read more.

Background: Problematic smartphone use (PSU) involves excessive smartphone engagement that disrupts daily functioning and is linked to attentional control deficits and altered reward processing. The nucleus accumbens (NAcc), a key structure in the reward system, may contribute to difficulty disengaging from rewarding digital content. This study examined relationships between NAcc volume, attentional switching, and objectively measured nighttime screen time in individuals with PSU. Methods: Fifty-three participants (aged ≥ 13 years) from an outpatient internet dependency clinic completed psychological assessments, brain MRI, and smartphone logging. PSU was diagnosed by two psychiatrists. Attentional switching was measured via the Autism Spectrum Quotient subscale. Nighttime screen time (00:00–06:00) was recorded via smartphone. MRI-derived NAcc volumes were normalized to total gray matter volume. Correlations, multiple regression (controlling for ASD and ADHD), and mediation analyses were conducted. Results: Difficulty in attention switching correlated with larger right NAcc volume (r = 0.45, p = 0.012) and increased nighttime screen time (r = 0.44, p = 0.014). Right NAcc volume also correlated with nighttime screen time (r = 0.46, p = 0.012). Regression showed right NAcc volume predicted nighttime screen time (β = 0.33, p = 0.022), whereas attentional switching was not significant. Mediation was unsupported. Sensitivity analyses confirmed associations. Conclusions: Larger right NAcc volume independently predicts prolonged nighttime smartphone use and is associated with impaired attentional switching in PSU. Structural variations in reward-related regions may underlie difficulty disengaging from digital content. Integrating neurobiological, cognitive, and behavioral measures offers a framework for understanding PSU. Full article

(This article belongs to the Special Issue The Latest Exploration of Gaming Disorders and Related Mental Health Issues)

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11 pages, 1875 KB

Open AccessArticle

When Time Equals Vision: The Neuro-Ophthalmic Outcomes of Patients with Fulminant Idiopathic Intracranial Hypertension Undergoing Emergent Cerebral Transverse Venous Stenting

by Assaf Kratz, Eyal Walter, Asaf Honig, Alexander Chorny, Gal Ben-Arie, Erez Tsumi, Tamir Regev and Anat Horev

Brain Sci. 2025, 15(10), 1099; https://doi.org/10.3390/brainsci15101099 - 13 Oct 2025

Abstract

Background: Fulminant idiopathic intracranial hypertension (IIH) is a rare and vision-threatening variant of IIH, characterized by rapid visual deterioration and a high risk of irreversible blindness. Urgent intervention is required to prevent permanent optic nerve damage. Cerebral transverse venous stenting (CTVS) has emerged [...] Read more.

Background: Fulminant idiopathic intracranial hypertension (IIH) is a rare and vision-threatening variant of IIH, characterized by rapid visual deterioration and a high risk of irreversible blindness. Urgent intervention is required to prevent permanent optic nerve damage. Cerebral transverse venous stenting (CTVS) has emerged as an effective treatment for medically refractory IIH, but data on its use in fulminant cases remain limited. Methods: A retrospective consecutive cohort study was conducted at a tertiary center and included all patients with fulminant IIH diagnosed by modified Dandy criteria, with bilateral transverse sinus stenosis > 50% and a trans-stenotic pressure gradient ≥ 8 mmHg on venography. Before stenting, patients received high-dose acetazolamide (up to 3000 mg/day) and IV methylprednisolone (1000 mg/day × 3). Neuro-ophthalmic assessment included BCVA, Ishihara color vision, pupillary exam, disc edema grading, Humphrey visual fields, and optical coherence tomography (OCT). Follow-up occurred at baseline (admission), 1 week, 1 month, 3 months, and 12 months. Results: Five young female patients underwent successful CTVS without peri- or post-procedural complications. Significant improvement in headache and stabilization or recovery of visual function were observed in all patients. OCT revealed early retinal nerve fiber layer thinning within one week, preceding clinical resolution of papilledema. Conclusions: Emergent CTVS appears to be a safe and effective vision-preserving procedure in fulminant IIH, offering rapid intracranial pressure reduction and early neuro-ophthalmologic improvement. OCT may serve as a useful early predictor of treatment success, supporting its role in post-procedural monitoring. Larger prospective studies are warranted. Full article

(This article belongs to the Special Issue The Eye as the Window to Brain Science: Fields of Neuroscience Created from Eye Research)

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1 pages, 129 KB

Open AccessCorrection

Correction: Marchant et al. Ankle Somatosensation and Lower-Limb Neuromuscular Function on a Lunar Gravity Analogue. Brain Sci. 2025, 15, 443

by Ashleigh Marchant, Nick Ball, Jeremy Witchalls, Sarah B. Wallwork and Gordon Waddington

Brain Sci. 2025, 15(10), 1098; https://doi.org/10.3390/brainsci15101098 - 13 Oct 2025

Abstract

This update pertains to the article previously published by Marchant et al [...] Full article

32 pages, 532 KB

Open AccessReview

by Elena Barbuti, Claudia Piervincenzi, Serena Ruggieri and Maria Petracca

Brain Sci. 2025, 15(10), 1097; https://doi.org/10.3390/brainsci15101097 - 11 Oct 2025

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that affects women more frequently than men. This sex gap has widened over the past century, and appears to be shaped by lifestyle factors more than biological factors. This narrative [...] Read more.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that affects women more frequently than men. This sex gap has widened over the past century, and appears to be shaped by lifestyle factors more than biological factors. This narrative review examines the evidence for sex-specific differences in lifestyle risk factors and their impact on both MS susceptibility and disease progression, with implications for diagnosis, monitoring, and treatment. Smoking, obesity, vitamin D deficiency, ultraviolet radiation exposure, and Epstein–Barr virus infection all interact with sex-related biological pathways to influence MS risk. Women appear to be more vulnerable to the pathogenic effects of smoking and obesity, both independently and in synergy with genetic risk alleles, while vitamin D and UV exposure confer stronger protective effects in females than in males. EBV infection also exhibits sex-dependent immune responses, shaped by hormonal regulation and host–virus genetic interactions. Sex-related lifestyle factors also modulate MS progression. Women experience more inflammatory activity and relapses, whereas men more often develop a progressive phenotype with greater neurodegeneration. Hormonal changes during female reproductive phases, such as pregnancy, breastfeeding, menopause, and hormone-based therapies, critically influence disease activity and progression in MS. Obesity, smoking, vitamin D status, diet, and gut microbiota further interact with sex hormones and genetic background, contributing to variable disease trajectories, also modulated by social determinants such as education level. These findings underscore the need to integrate into clinical practice the evaluation of lifestyle factors in a sex-specific way for diagnosis, monitoring, and treatment of MS. Full article

(This article belongs to the Special Issue Lifestyle and Risk Factors for Multiple Sclerosis)

20 pages, 3090 KB

Open AccessArticle

Regional Brain Volume Changes Across Adulthood: A Multi-Cohort Study Using MRI Data

by Jae Hyuk Shim, Hyeon-Man Baek and Jung Hoon

Brain Sci. 2025, 15(10), 1096; https://doi.org/10.3390/brainsci15101096 - 11 Oct 2025

Abstract

Background/Objectives: Age-related structural changes in the human brain provide essential insights into cognitive aging and the onset of neurodegenerative diseases. This study aimed to comprehensively characterize age-related volumetric changes across multiple brain regions in a large, diverse, cognitively healthy cohort spanning adulthood (ages [...] Read more.

Background/Objectives: Age-related structural changes in the human brain provide essential insights into cognitive aging and the onset of neurodegenerative diseases. This study aimed to comprehensively characterize age-related volumetric changes across multiple brain regions in a large, diverse, cognitively healthy cohort spanning adulthood (ages 21–90), integrating Korean, Information eXtraction from Images (IXI), and Alzheimer’s Disease Neuroimaging Initiative (ADNI) MRI datasets of cognitively healthy participants to characterize normative volumetric changes across adulthood using demographically diverse datasets. Methods: High resolution 3T T1-weighted MRI images from three distinct cohorts (totaling 1833 subjects) were processed through an optimized neuroimaging pipeline, combining advanced preprocessing with neural network-based segmentation. Volumetric data for 95 brain structures were segmented and analyzed across seven age bins (21–30 through 81–90). Pipeline reliability was validated against FreeSurfer using intraclass correlation coefficients (ICC) and coefficients of variation (CoV). Regression-based correction was used to correct for sex and cohort effects on brain region volume. Then, percentage change in each mean bilateral volumes of regions across the lifespan were computed to describe volumetric changes across life spans. Results: The segmentation pipeline demonstrated excellent agreement with FreeSurfer (mean ICC: 0.9965). Drastic volumetric expansions were observed in white matter hypointensities (122.6%), lateral ventricles (115.9%), and inferior lateral ventricles (116.8%). Moderate-to-notable shrinkage was found predominantly in the frontal lobe (pars triangularis: 21.5%), parietal lobe (inferior parietal: 20.4%), temporal lobe (transverse temporal: 21.6%), and cingulate cortex (caudal anterior cingulate: 16.1%). Minimal volume changes occurred in regions such as the insula (3.7%) and pallidum (2.6%). Conclusions: This study presents a comprehensive reference of normative regional brain volume changes across adulthood, highlighting substantial inter-regional variability. The findings can provide an essential foundation for differentiating normal aging patterns from early pathological alterations. Full article

(This article belongs to the Section Developmental Neuroscience)

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6 pages, 151 KB

Open AccessEditorial

Recent Advances in Assessment and Rehabilitation of Individuals with Communication and Language Disorders

by Dionysios Tafiadis, Angelos Papadopoulos, Louiza Voniati and Nafsika Ziavra

Brain Sci. 2025, 15(10), 1095; https://doi.org/10.3390/brainsci15101095 - 11 Oct 2025

Abstract

Currently, in the field of rehabilitation, there is a need for researchers and clinicians to stay updated on recent knowledge worldwide [...] Full article

(This article belongs to the Special Issue Recent Advances in Assessment and Rehabilitation of Individuals with Communication and Language Disorders)

23 pages, 961 KB

Open AccessSystematic Review

Driving Performance in Schizophrenia: The Role of Neurocognitive Correlates—A Systematic Review

by Georgia Karakitsiou, Spyridon Plakias, Aikaterini Arvaniti, Magdalini Katsikidou, Katerina Kedraka and Maria Samakouri

Brain Sci. 2025, 15(10), 1094; https://doi.org/10.3390/brainsci15101094 - 10 Oct 2025

Abstract

Background/Objectives: Schizophrenia is associated with cognitive deficits that may compromise everyday functioning, including driving. This review systematically examined recent original research (2015–2025) on driving performance in individuals with schizophrenia with a focus on neuropsychological factors, applying a narrative synthesis given the heterogeneity [...] Read more.

Background/Objectives: Schizophrenia is associated with cognitive deficits that may compromise everyday functioning, including driving. This review systematically examined recent original research (2015–2025) on driving performance in individuals with schizophrenia with a focus on neuropsychological factors, applying a narrative synthesis given the heterogeneity of designs and outcomes, while no quantitative meta-analysis was feasible. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a structured search of PubMed and Scopus was conducted on 4 May 2025. The inclusion criteria were original studies involving individuals diagnosed with schizophrenia, published between 2015 and 2025. Studies on animals, other psychiatric or neurological conditions, and healthy populations were also excluded. Critical appraisal was performed using the Joanna Briggs Institute (JBI) tools. Extracted data included sample demographics, cognitive deficits, neuropsychological assessments, brain imaging, and the main findings. A narrative synthesis was then performed. Results: Six high-quality studies met the inclusion criteria. Findings were grouped into three categories: (1) driving behavior: fitness to drive varied widely across individuals, (2) cognitive deficits and brain activity: poorer driving-related performance was consistently associated with specific impairments in cognition and brain structure, and (3) medication effects: individuals taking certain atypical antipsychotics demonstrated better driving performance compared to those on other types of medication, while extrapyramidal symptoms negatively influenced driving fitness. Conclusions: Driving in schizophrenia is shaped by cognitive, clinical, and pharmacological factors. These findings highlight the clinical relevance of individualized evaluations, integration into personalized care and targeted rehabilitation to promote driving autonomy and community inclusion. This area remains under-researched, as only six studies met the inclusion criteria, which restricts the robustness and generalizability of the conclusions. Funding: This review received no funding from any external sources. Registration: The review protocol was submitted to PROSPERO (International Prospective Register of Systematic Reviews) under registration number CRD420251060580. Full article

(This article belongs to the Special Issue Optimizing Driving Safety: Neurocognitive Insights, Health-Promoting Strategies, and Policy Innovation)

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20 pages, 321 KB

Open AccessArticle

Obsessive Beliefs, Metacognitive Beliefs, and Rumination in Parents of Adolescents with and Without Obsessive–Compulsive Disorder: A Linear Mixed-Effects Model

by Emre Mısır and Mutlu Muhammed Özbek

Brain Sci. 2025, 15(10), 1093; https://doi.org/10.3390/brainsci15101093 - 10 Oct 2025

Abstract

Background: Parental cognitive characteristics may represent environmental risk factors in obsessive–compulsive disorder (OCD). This study compared obsessive beliefs, metacognitions, and ruminative thinking in parents of adolescents with OCD and healthy controls (HCs), and examined links with clinical features in patients. Methods: Participants were [...] Read more.

Background: Parental cognitive characteristics may represent environmental risk factors in obsessive–compulsive disorder (OCD). This study compared obsessive beliefs, metacognitions, and ruminative thinking in parents of adolescents with OCD and healthy controls (HCs), and examined links with clinical features in patients. Methods: Participants were 45 adolescents with OCD, 45 HCs, and both their mothers and fathers. The Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) assessed symptom severity in adolescents. Parents completed the Obsessive Beliefs Questionnaire (OBQ), Ruminative Thought Style Questionnaire (RTSQ), 30-item Metacognitions Questionnaire (MCQ-30), and Patient Health Questionnaire-9 (PHQ-9). Data were analyzed using linear mixed-effects models, followed by correlation and regression analyses. Results: Parents of patients had higher scores on the importance/control of thoughts, the need to control thoughts, and cognitive self-consciousness (MCQ-CSC). Mothers of adolescents with OCD had the highest scores on inflated responsibility/threat estimation (OBQ-RTE), perfectionism/intolerance of uncertainty (OBQ-PIU), rumination, and cognitive confidence (MCQ-CC). Regression analyses showed that lower maternal MCQ-CC predicted earlier OCD onset, while higher rumination predicted later onset. Obsession severity in adolescents was linked to higher maternal MCQ-CSC, obsessive slowness to maternal OBQ-PIU, and pathological doubt to greater maternal rumination. Children’s indecisiveness correlated with paternal OBQ-RTE and OBQ-PIU. Conclusions: Our findings revealed elevated cognitive vulnerabilities for OCD in mothers of affected adolescents and identified specific associations between parental cognitive characteristics and their children’s symptom profiles. Future longitudinal studies using dyadic parental design with larger samples may further elucidate the role of parental cognitive patterns in the development and course of OCD. Full article

(This article belongs to the Section Neuropsychiatry)

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