Brain Sciences

18 pages, 989 KiB

Open AccessReview

Neurological Manifestations of Hemolytic Uremic Syndrome: A Comprehensive Review

by Una Tonkovic, Marko Bogicevic, Aarish Manzar, Nikola Andrejic, Aleksandar Sic, Marko Atanaskovic, Selena Gajić, Ana Bontić, Sara Helena Ksiazek, Ana Mijušković, Nikola M. Stojanović and Marko Baralić

Brain Sci. 2025, 15(7), 717; https://doi.org/10.3390/brainsci15070717 (registering DOI) - 4 Jul 2025

Abstract

Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga [...] Read more.

Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga toxin-producing Escherichia coli (STEC)-associated HUS (typical (tHUS)). This review explores the clinical spectrum, pathophysiology, diagnostic workup, and age-specific outcomes of neurologic involvement in both typical (tHUS) and atypical (aHUS). Neurologic complications occur in up to 11% of pediatric and over 40% of adult STEC-HUS cases in outbreak settings. Presentations include seizures, encephalopathy, focal deficits, movement disorders, and posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) commonly reveals basal ganglia or parieto-occipital lesions, though subtle or delayed findings may occur. Laboratory workup typically confirms microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and kidney damage, with additional markers of inflammation or metabolic dysregulation. Eculizumab is the first-line treatment for aHUS with CNS involvement, while its utility in STEC-HUS remains uncertain. Although many children recover fully, those with early CNS involvement are at greater risk of developing epilepsy, cognitive delays, or fine motor deficits. Adults may experience lingering neurocognitive symptoms despite apparent clinical recovery. Differences in presentation and imaging findings between age groups emphasize the need for tailored diagnostic and therapeutic strategies. Comprehensive neurorehabilitation and long-term follow-up are crucial for identifying residual deficits. Continued research into predictive biomarkers, neuroprotective interventions, and standardized treatment protocols is needed for improving outcomes in HUS patients with neurological complications. Full article

(This article belongs to the Special Issue New Advances in Neuroimmunology and Neuroinflammation)

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27 pages, 6187 KiB

Open AccessReview

Looking into Abnormal Co-Expressions of Tau and TDP-43 in the Realm of Mixed Dementia Types: A Double-Punch Scenario

by Hossam Youssef, Carina Weissmann, Gokhan Uruk and Rodolfo Gabriel Gatto

Brain Sci. 2025, 15(7), 716; https://doi.org/10.3390/brainsci15070716 - 3 Jul 2025

Abstract

Transactive response DNA-binding protein of 43 kDa (TDP-43) and tau proteins play critical roles in neurodegenerative diseases, particularly frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). The co-occurrence of TDP-43 and tau pathologies raises questions about their role in disease progression. This review [...] Read more.

Transactive response DNA-binding protein of 43 kDa (TDP-43) and tau proteins play critical roles in neurodegenerative diseases, particularly frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). The co-occurrence of TDP-43 and tau pathologies raises questions about their role in disease progression. This review explores the simultaneous presence of tau and TDP-43 co-pathologies, emphasizing their molecular interactions and the resultant neuropathological implications. Additionally, we provide representative examples of their clinical presentations, neuroimaging, and neuropathological findings associated with FTLD-TDP and FTLD-tau, emphasizing the need for a comprehensive understanding of these intertwined pathologies. We analyze various clinical scenarios, including argyrophilic grain disease (AGD), primary age-related tauopathy (PART), and limbic predominant age-related TDP-43 encephalopathy (LATE), to elucidate the complex relationship between these proteinopathies. From the literature, the co-occurrence of tau and TDP-43 is linked to more severe and poorer clinical outcomes compared to isolated pathologies. This review underscores the necessity of considering co-pathologies in the context of FTLD, as they may act as accelerators of cognitive decline. This highlights the importance of integrated approaches in diagnosing and treating neurodegenerative conditions characterized by tau and TDP-43 misfolding. Understanding the interplay between these molecular markers is vital for advancing therapeutic strategies for such disorders. Full article

(This article belongs to the Special Issue Molecular and Neuroimaging Biomarkers in Alzheimer’s Disease and Frontotemporal Lobar Degeneration)

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17 pages, 6488 KiB

Open AccessSystematic Review

Magnetic Resonance Neuroimaging in Amyotrophic Lateral Sclerosis: A Comprehensive Umbrella Review of 18 Studies

by Sadegh Ghaderi, Sana Mohammadi and Farzad Fatehi

Brain Sci. 2025, 15(7), 715; https://doi.org/10.3390/brainsci15070715 - 3 Jul 2025

Abstract

Background/Objectives: Despite extensive research, the underlying causes of amyotrophic lateral sclerosis (ALS) remain unclear. This umbrella review aims to synthesize a vast body of evidence from advanced magnetic resonance imaging (MRI) studies of ALS, encompassing a wide range of neuroimaging techniques and patient [...] Read more.

Background/Objectives: Despite extensive research, the underlying causes of amyotrophic lateral sclerosis (ALS) remain unclear. This umbrella review aims to synthesize a vast body of evidence from advanced magnetic resonance imaging (MRI) studies of ALS, encompassing a wide range of neuroimaging techniques and patient cohorts. Methods: Following the PRISMA guidelines, we conducted an extensive search of four databases (PubMed, Scopus, Web of Science, and Embase) for articles published until 3 December 2024. Data extraction and quality assessment were independently performed using the AMSTAR2 tool. Results: This review included 18 studies that incorporated data from over 29,000 ALS patients. Structural MRI consistently showed gray matter atrophy in the motor and extra-motor regions, with significant white matter (WM) atrophy in the corticospinal tract and corpus callosum. Magnetic resonance spectroscopy revealed metabolic disruptions, including reduced N-acetylaspartate and elevated choline levels. Functional MRI studies have demonstrated altered brain activation patterns and functional connectivity, reflecting compensatory mechanisms and neurodegeneration. fMRI also demonstrated disrupted motor network connectivity and alterations in the default mode network. Diffusion MRI highlighted microstructural changes, particularly reduced fractional anisotropy in the WM tracts. Susceptibility-weighted imaging and quantitative susceptibility mapping revealed iron accumulation in the motor cortex and non-motor regions. Perfusion MRI indicated hypoperfusion in regions associated with cognitive impairment. Conclusions: Multiparametric MRI consistently highlights widespread structural, functional, and metabolic changes in ALS, reflecting neurodegeneration and compensatory mechanisms. Full article

(This article belongs to the Special Issue Biomarkers in Neurodegenerative Diseases: Advancements and Future Directions)

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24 pages, 24510 KiB

Open AccessArticle

Application of Graph-Theoretic Methods Using ERP Components and Wavelet Coherence on Emotional and Cognitive EEG Data

by Sencer Melih Deniz, Ahmet Ademoglu, Adil Deniz Duru and Tamer Demiralp

Brain Sci. 2025, 15(7), 714; https://doi.org/10.3390/brainsci15070714 - 2 Jul 2025

Abstract

Background/Objectives: Emotion and cognition, two essential components of human mental processes, have traditionally been studied independently. The exploration of emotion and cognition is fundamental for gaining an understanding of human mental functioning. Despite the availability of various methods to measure and evaluate emotional [...] Read more.

Background/Objectives: Emotion and cognition, two essential components of human mental processes, have traditionally been studied independently. The exploration of emotion and cognition is fundamental for gaining an understanding of human mental functioning. Despite the availability of various methods to measure and evaluate emotional states and cognitive processes, physiological measurements are considered to be one of the most reliable methods due to their objective approach. In particular, electroencephalography (EEG) provides unique insight into emotional and cognitive activity through the analysis of event-related potentials (ERPs). In this study, we discriminated pleasant/unpleasant emotional moods and low/high cognitive states using graph-theoretic features extracted from spatio-temporal components. Methods: Emotional data were collected at the Physiology Department of Istanbul Medical Faculty at Istanbul University, whereas cognitive data were obtained from the DepositOnce repository of Technische Universität Berlin. Wavelet coherence values for the N100, N200, and P300 single-trial ERP components in the delta, theta, alpha, and beta frequency bands were investigated individually. Then, graph-theoretic analyses were performed using wavelet coherence-based connectivity maps. Global and local graph metrics such as energy efficiency, strength, transitivity, characteristic path length, and clustering coefficient were used as features for classification using support vector machines (SVMs), k-nearest neighbor(K-NN), and linear discriminant analysis (LDA). Results: The results show that both pleasant/unpleasant emotional moods and low/high cognitive states can be discriminated, with average accuracies of up to 92% and 89%, respectively. Conclusions: Graph-theoretic metrics based on wavelet coherence of ERP components in the delta band with the SVM algorithm allow for the discrimination of emotional and cognitive states with high accuracy. Full article

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

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12 pages, 794 KiB

Open AccessArticle

Biomolecular Predictors of Recurrence Patterns and Survival in IDH-Wild-Type Glioblastoma: A Retrospective Analysis of Patients Treated with Radiotherapy and Temozolomide

by Paolo Tini, Flavio Donnini, Francesco Marampon, Marta Vannini, Tommaso Carfagno, Pierpaolo Pastina, Giovanni Rubino, Salvatore Chibbaro, Alfonso Cerase, Giulio Bagnacci, Armando Perrella, Maria Antonietta Mazzei, Alessandra Pascucci, Vincenzo D’Alonzo, Anna Maria Di Giacomo and Giuseppe Minniti

Brain Sci. 2025, 15(7), 713; https://doi.org/10.3390/brainsci15070713 - 2 Jul 2025

Abstract

Background and Aim: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with poor prognosis despite maximal surgical resection, radiotherapy (RT), and temozolomide (TMZ) per the Stupp protocol. IDH-wild-type GBM, the predominant molecular subtype, frequently harbors EGFR amplification and is resistant [...] Read more.

Background and Aim: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with poor prognosis despite maximal surgical resection, radiotherapy (RT), and temozolomide (TMZ) per the Stupp protocol. IDH-wild-type GBM, the predominant molecular subtype, frequently harbors EGFR amplification and is resistant to therapy, while MGMT promoter methylation predicts improved TMZ response. This study aimed to assess the prognostic impact of EGFR and MGMT status on survival and recurrence patterns in IDH-wild-type GBM. Materials and Methods: We retrospectively analyzed 218 patients with IDH-wild-type GBM treated at the Azienda Ospedaliero-Universitaria Senese (2016–2024). All patients underwent maximal safe surgical resection whenever feasible. The cohort includes patients who received gross total resection (GTR), subtotal resection (STR), or biopsy only, depending on tumor location and clinical condition, followed by intensity-modulated RT (59.4–60 Gy) with concurrent and adjuvant TMZ. EGFR amplification was assessed via FISH/NGS and immunohistochemistry; MGMT promoter methylation was determined using methylation-specific PCR. Progression-free survival (PFS), overall survival (OS), and recurrence patterns (in-field, marginal, out-field) were evaluated using Kaplan–Meier, Cox regression, and logistic regression analyses. Results: Among patients (64.7% male; mean age 61.8), 58.7% had EGFR amplification and 49.1% showed MGMT methylation. Median OS and PFS were 14 and 8 months, respectively. EGFR non-amplified/MGMT methylated tumors had the best outcomes (OS: 22.0 months, PFS: 10.5 months), while EGFR-amplified/MGMT unmethylated tumors fared worst (OS: 10.0 months, PFS: 5.0 months; p < 0.001). MGMT methylation was an independent positive prognostic factor (HR: 0.48, p < 0.001), while EGFR amplification predicted worse survival (HR: 1.57, p = 0.02) and higher marginal recurrence (OR: 2.42, p = 0.01). Conclusions: EGFR amplification and MGMT methylation significantly influence survival and recurrence dynamics in IDH-wild-type GBM. Incorporating these biomarkers into treatment planning may enable tailored therapeutic strategies, potentially improving outcomes in this challenging disease. Prospective studies are needed to validate biomolecularly guided management approaches. Full article

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

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2 pages, 133 KiB

Open AccessEditorial

Advances in Assessment and Training of Perceptual-Motor Performance

by Gary B. Wilkerson

Brain Sci. 2025, 15(7), 712; https://doi.org/10.3390/brainsci15070712 - 2 Jul 2025

Abstract

Historically, efforts to optimize human health and performance have focused on the assessment and training of physical capabilities, such as muscle strength, flexibility, power, endurance, and speed [...] Full article

(This article belongs to the Special Issue Advances in Assessment and Training of Perceptual-Motor Performance)

13 pages, 785 KiB

Open AccessArticle

A Community Study on Sleep Characteristics and Anxiety Symptoms in Children with Dyslexia

by Katrin Jeffcock and Dagmara Dimitriou

Brain Sci. 2025, 15(7), 711; https://doi.org/10.3390/brainsci15070711 - 1 Jul 2025

Abstract

Objectives: Sleep serves a crucial role in the optimal development of cognitive, emotional, and physical domains. Sleep disturbances and disorders have been reported to frequently occur in many neurodevelopmental conditions, including ADHD and Autism Spectrum Disorder. The connection between dyslexia and sleep, however, [...] Read more.

Objectives: Sleep serves a crucial role in the optimal development of cognitive, emotional, and physical domains. Sleep disturbances and disorders have been reported to frequently occur in many neurodevelopmental conditions, including ADHD and Autism Spectrum Disorder. The connection between dyslexia and sleep, however, is sparsely explored. This community study aimed to enhance knowledge about sleep disturbances in children with dyslexia and explore the potential impact of anxiety. Method: The parents of 160 children aged 7–13 years old with a primary diagnosis of dyslexia completed the Children’s Sleep Habits Questionnaire (CSHQ) and the Spence Children’s Anxiety Scale (SCAS). Results: Sixty-six percent of the children showed pathological levels of sleep disturbances, with clinical scores observed in the subscales of Sleep Onset Delay, Sleep Anxiety, and Daytime Sleepiness. Overall, sleep and anxiety were correlated, but anxiety levels were not elevated and not correlated with Sleep Onset Delay. Conclusions: The current results suggest that the majority of children with dyslexia suffer from sleep disturbances, such as delayed sleep onset and shorter sleep durations, irrespective of the scores given on the anxiety scale. Given the importance of sleep for optimal development, there is an alarming need for more studies to be carried out to explore additional factors that interact with healthy sleep to develop sleep interventions. Full article

(This article belongs to the Section Sleep and Circadian Neuroscience)

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22 pages, 2274 KiB

Open AccessArticle

Quercetin and Tranylcypromine Improve Memory, Behavioral Performance, and Cholinergic Function in Male Rats Subjected to Chronic Restraint Stress

by Vitor Bastianello Mostardeiro, Charles Elias Assmann, Adriel Antonio Schirmann, Marcylene Vieira da Silveira, Bianca Vedoin Copês Rambo, Mairin Schott, Aline da Silva Pereira, Vanessa Valéria Miron, Heloiza Winck Soares, Larissa Varotto Dambrós, Sabrina Fontana Belinazo, Thamires Gelatti Vidal, Margarete Dulce Bagatini, Maria Rosa Chitolina Schetinger and Vera Maria Melchiors Morsch

Brain Sci. 2025, 15(7), 709; https://doi.org/10.3390/brainsci15070709 - 1 Jul 2025

Abstract

Background/Objectives: Major depressive disorder (MDD) is a debilitating illness, and chronic stress is a contributing factor for depressive symptoms. However, despite intense research, the mechanisms of MDD remain substantially unidentified. Quercetin is a powerful flavonoid and could be used as a possible [...] Read more.

Background/Objectives: Major depressive disorder (MDD) is a debilitating illness, and chronic stress is a contributing factor for depressive symptoms. However, despite intense research, the mechanisms of MDD remain substantially unidentified. Quercetin is a powerful flavonoid and could be used as a possible therapeutic strategy for depression. Acknowledging the potential benefits of quercetin, this study investigated its effect alone or in association with the standard drug tranylcypromine (TCP) in a rodent model of chronic restraint stress (CRS). Methods: Adult male rats were subjected to a CRS model consisting of an immobilization session of 4 h daily during 14 consecutive days. Quercetin (50 mg/kg, gavage) was administered for 45 days. TCP (10 mg/kg, gavage) was administered for 14 days. Behavioral tasks were conducted to assess locomotor functions, memory, anhedonia, depression-like behaviors, and anxiety-like behaviors. The activity, gene expression, and protein density of acetylcholinesterase (AChE) were investigated. Results: Behavioral tasks showed that the CRS model effectively induced stable behavioral changes. CRS did not alter locomotor function assessed by the open field test (OFT) or anhedonia behavior assessed by the sucrose preference test (SPT). CRS increased total fecal count, which was prevented by quercetin administration in rats. TCP and the association of quercetin and TCP increased the recognition index in comparison with the CRS group in the novel object recognition (NOR) test and improved the swimming and immobility times in comparison to stressed animals in the forced swim test (FST). All treatments were able to decrease the anxiety index assessed by the elevated plus maze (EPM) test. The activity, gene expression, and protein density of AChE were increased in the CRS model compared to control males. Overall, quercetin and TCP proved to reverse CRS-induced alterations in these parameters. Conclusions: Quercetin mitigated cognitive deficits, behavioral impairments, and neurochemical alterations induced by the CRS model, especially in association with TCP, supporting its potential as a promising therapeutic agent for depression. Full article

(This article belongs to the Special Issue Mental Health: From a Neurobiology Perspective)

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9 pages, 527 KiB

Open AccessBrief Report

Correlation of Different Non-Invasive Neuromonitoring Tools Assessing Intracranial Hemodynamics

by Rossella Zangari, Luca D’Amelio, Elisa Gouvea Bogossian and Fabio Silvio Taccone

Brain Sci. 2025, 15(7), 710; https://doi.org/10.3390/brainsci15070710 - 30 Jun 2025

Abstract

Background: Intracranial pressure (ICP) monitoring is crucial in managing acute brain injury (ABI) to prevent secondary brain injury. While invasive techniques remain the gold standard, they can carry notable risks, such as infection and hemorrhage. Non-invasive techniques are increasingly used, but their inter-modality [...] Read more.

Background: Intracranial pressure (ICP) monitoring is crucial in managing acute brain injury (ABI) to prevent secondary brain injury. While invasive techniques remain the gold standard, they can carry notable risks, such as infection and hemorrhage. Non-invasive techniques are increasingly used, but their inter-modality correlation and concordance have not been systematically evaluated. This study aimed to assess the correlation and concordance among four commonly used non-invasive neuromonitoring tools in patients with ABI undergoing invasive ICP monitoring. Methods: This was a secondary analysis of prospectively collected data from 100 adult patients admitted to the intensive care unit with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH) who underwent invasive ICP monitoring. Simultaneous assessments using optic nerve sheath diameter (ONSD), transcranial Doppler-derived pulsatility index (PI), estimated ICP (eICP), and the neurological pupil index (NPi) were performed. Correlation between modalities was assessed using Spearman’s correlation coefficient (ρ), and concordance was evaluated with Cohen’s kappa coefficient (k). Results: We found weak correlations between ONSD and PI (ρ = 0.29), ONSD and NPi (ρ = −0.33), and PI and NPi (ρ = −0.33); moderate correlations between ONSD and eICP (ρ = 0.54) and PI and eICP (ρ = 0.48); and a strong inverse correlation between eICP and NPi (ρ = −0.71; all p < 0.05). Concordance was generally low, with the highest agreement between PI and eICP (k = 0.69). Most other tool pairings showed poor-to-fair concordance (k ≤ 0.30). Conclusions: Non-invasive neuromonitoring tools show variable correlation and limited agreement, suggesting they are not interchangeable. Each modality captures different aspects of cerebral physiology, supporting the use of a multimodal approach to improve accuracy in ICP estimation. Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

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19 pages, 668 KiB

Open AccessReview

The Promise of Intranasal Oxytocin in Treating Borderline Personality Disorder: A Narrative Review

by Eleni Giannoulis, Christos Nousis, Lydia-Angeliki Eytaxia, Olga Kaimakami and Ioannis Malogiannis

Brain Sci. 2025, 15(7), 708; https://doi.org/10.3390/brainsci15070708 - 30 Jun 2025

Abstract

Background/Objectives: Borderline personality disorder (BPD) is a complex psychiatric condition marked by emotional dysregulation, interpersonal instability, and impulsivity. Despite the advances in psychotherapy and pharmacotherapy, many patients show a partial or unstable response. Recent research suggests that oxytocin, a neuropeptide involved in social [...] Read more.

Background/Objectives: Borderline personality disorder (BPD) is a complex psychiatric condition marked by emotional dysregulation, interpersonal instability, and impulsivity. Despite the advances in psychotherapy and pharmacotherapy, many patients show a partial or unstable response. Recent research suggests that oxytocin, a neuropeptide involved in social cognition and emotional regulation, may offer novel therapeutic avenues. Methods: We systematically synthesize evidence from PubMed, PsycINFO, Web of Science, and Google Scholar on oxytocin’s role in BPD, prioritizing studies on neurobiology, emotion regulation, clinical interventions, and adjunctive therapy models. Thirty studies were included and critically appraised using PRISMA and Cochrane’s tools. Due to methodological heterogeneity, no meta-analysis was conducted; instead, the findings were integrated through a narrative synthesis approach. Results: Evidence supports oxytocin’s modulatory effects on amygdala reactivity, prefrontal–limbic connectivity, and hypothalamic–pituitary–adrenal axis function. Intranasal oxytocin appears beneficial for emotional regulation and interpersonal sensitivity, particularly in individuals with early trauma. The reported effect sizes ranged from small (Cohen’s d ≈ 0.40) to large (d ≈ 0.83), though some trials reported null or adverse effects, such as increased hypermentalization. Heterogeneous responses were influenced by factors such as sex, trauma history, and OXTR gene variants. Conclusions: Although intranasal oxytocin shows promise in modulating core neurobiological systems implicated in BPD and enhancing emotion regulation and social cognition, its clinical effects remain variable and context-dependent. The evidence supports cautious exploration of oxytocin as an adjunct to psychotherapeutic interventions rather than as a standalone treatment. Future research should focus on biomarker-informed, stratified trials that account for trauma history, genetic variation, and sex differences to clarify its therapeutic potential. Full article

(This article belongs to the Special Issue Advanced Technologies and Approaches for Understanding and Treating Psychological Disorders)

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16 pages, 2095 KiB

Open AccessArticle

Multimodal Knowledge Distillation for Emotion Recognition

by Zhenxuan Zhang and Guanyu Lu

Brain Sci. 2025, 15(7), 707; https://doi.org/10.3390/brainsci15070707 - 30 Jun 2025

Abstract

Multimodal emotion recognition has emerged as a prominent field in affective computing, offering superior performance compared to single-modality methods. Among various physiological signals, EEG signals and EOG data are highly valued for their complementary strengths in emotion recognition. However, the practical application of [...] Read more.

Multimodal emotion recognition has emerged as a prominent field in affective computing, offering superior performance compared to single-modality methods. Among various physiological signals, EEG signals and EOG data are highly valued for their complementary strengths in emotion recognition. However, the practical application of EEG-based approaches is often hindered by high costs and operational complexity, making EOG a more feasible alternative in real-world scenarios. To address this limitation, this study introduces a novel framework for multimodal knowledge distillation, designed to improve the practicality of emotion decoding while maintaining high accuracy, with the framework including a multimodal fusion module to extract and integrate interactive and heterogeneous features, and a unimodal student model structurally aligned with the multimodal teacher model for better knowledge alignment. The framework combines EEG and EOG signals into a unified model and distills the fused multimodal features into a simplified EOG-only model. To facilitate efficient knowledge transfer, the approach incorporates a dynamic feedback mechanism that adjusts the guidance provided by the multimodal model to the unimodal model during the distillation process based on performance metrics. The proposed method was comprehensively evaluated on two datasets based on EEG and EOG signals. The accuracy of the valence and arousal of the proposed model in the DEAP dataset are 70.38% and 60.41%, respectively. The accuracy of valence and arousal in the BJTU-Emotion dataset are 61.31% and 60.31%, respectively. The proposed method achieves state-of-the-art classification performance compared to the baseline method, with statistically significant improvements confirmed by paired t-tests (p < 0.05), and the framework effectively transfers knowledge from multimodal models to unimodal EOG models, enhancing the practicality of emotion recognition while maintaining high accuracy, thus expanding the applicability of emotion recognition in real-world scenarios. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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11 pages, 389 KiB

Open AccessArticle

Metabolic Syndrome and Parkinson’s Disease: Two Villains Join Forces

by Lucas Udovin, Sofía Bordet, Hanny Barbar, Matilde Otero-Losada, Santiago Pérez-Lloret and Francisco Capani

Brain Sci. 2025, 15(7), 706; https://doi.org/10.3390/brainsci15070706 - 30 Jun 2025

Abstract

Background: Metabolic syndrome and Parkinson’s disease have common pathophysiological denominators. This study aimed to investigate how metabolic syndrome contributes to Parkinson’s disease progression, as well as the genetic traits shared by PD and MetS. Methods: Four hundred and twenty-three newly diagnosed drug-naïve PD [...] Read more.

Background: Metabolic syndrome and Parkinson’s disease have common pathophysiological denominators. This study aimed to investigate how metabolic syndrome contributes to Parkinson’s disease progression, as well as the genetic traits shared by PD and MetS. Methods: Four hundred and twenty-three newly diagnosed drug-naïve PD patients were analyzed from the Parkinson’s Progression Markers Initiative (PPMI) database. We compared longitudinal changes in the total and subscale scores of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) between PD patients with and without metabolic syndrome over a five-year follow-up. We assessed the frequency of PD-associated genetic variants in both groups. Results: At baseline, Parkinson’s patients with MetS were typically men (p < 0.01) and older (p = 0.04), with a higher Hoehn and Yahr score (p = 0.01) compared with their counterparts without MetS. They showed higher Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total scores at baseline and in follow-up years 2, 3, 4, and 5 (all p-values < 0.05) as analyzed by the Generalized Estimating Equation model. These differences were primarily driven by elevated motor scores (MDS-UPDRS Part III) (p < 0.01). MetS was associated with a higher frequency of the ZNF646.KAT8.BCKDK_rs14235 variant and a lower frequency of the NUCKS1_rs823118 and CTSB_rs1293298 variants. Conclusions: PD patients with MetS had worse motor symptomatology. Both conditions appear to share genetic susceptibility, involving genes related to lipid metabolism (BCKDK), autophagy and inflammation (CTSB), and chromatin regulation (NUCKS1). Full article

(This article belongs to the Special Issue Clinical Research on Parkinson’s Disease: Opportunities and Challenges (2nd Edition))

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14 pages, 1037 KiB

Open AccessReview

Spinoplastic Surgery: A Review of Techniques, Indications, and Optimal Patient Selection

by Daniel Vernik, Camryn Payne, Krishna Sinha, Casey Martinez, Walter Nicholas Jungbauer, Jonathan L. Jeger, Michael Bohl, Alexander E. Ropper, Sebastian Winocour and Edward Reece

Brain Sci. 2025, 15(7), 705; https://doi.org/10.3390/brainsci15070705 - 30 Jun 2025

Abstract

Background/Objectives: Spinoplastic surgery is an emerging multidisciplinary field developed to address and reduce the complication of pseudoarthrosis following complex spinal reconstructions. While the number of spinal fusion procedures continues to rise every year, fusion failure rates remain as high as 40%. Although pseudoarthrosis [...] Read more.

Background/Objectives: Spinoplastic surgery is an emerging multidisciplinary field developed to address and reduce the complication of pseudoarthrosis following complex spinal reconstructions. While the number of spinal fusion procedures continues to rise every year, fusion failure rates remain as high as 40%. Although pseudoarthrosis may not always manifest clinically, it remains a leading cause of persistent pain and need for subsequent revision surgeries. The multidisciplinary collaboration between spine and plastic surgeons in spinoplastic surgery has therefore emerged as a proactive strategy aimed at preventing complications, particularly in patients identified as high-risk for pseudoarthrosis. As the patient population expands and spinoplastic surgery continues to evolve, refining patient selection criteria becomes essential for achieving optimal surgical outcomes. This review aims to provide a comprehensive overview of recent advancements in spinoplastic surgery, highlighting current indications, surgical techniques, recent case reports, and strategies for identifying suitable candidates. Methods: We performed a narrative review of English language literature through April 2025. Spinoplastic case reports and case series published within the last 20 years were included in the review. Results: Indications for use of a spinoplastic approach clustered into prior fusion failure, extensive oncologic resection, severe spinal deformity, procedures requiring extensive spinal involvement, and/or patients at risk for impaired bone healing. Succesful radiographic union and improvement of symptoms were widely reported across all 9 case reports/series. Conclusions: Although evidence is presently limited, spinoplastic surgery appears to achieve high bone graft fusion rates with acceptable morbidity and functional improvement in a carefully selected group of high-risk spinal reconstruction patients. Still, larger prospective studies are warranted to refine patient selection and validate functional benefit. Full article

(This article belongs to the Special Issue Contemporary Spinal Surgery: Surgical Optimization and Technological Innovation)

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13 pages, 535 KiB

Open AccessArticle

Relationship Between Nutritional Indexes and Clinical Outcomes in Stroke Patients Undergoing Mechanical Thrombectomy

by Özgür Zülfükar Ertuğrul, Fırat Karaaslan, Reşit Yılmaz and Mehmet Cudi Tuncer

Brain Sci. 2025, 15(7), 704; https://doi.org/10.3390/brainsci15070704 - 30 Jun 2025

Abstract

Background/objectives: Nutritional status is increasingly acknowledged as a pivotal determinant of clinical course and recovery in patients with acute ischemic stroke (AIS). Malnutrition can compromise immune competence, delay neurological recovery, and exacerbate adverse outcomes, particularly in those undergoing intensive interventions such as mechanical [...] Read more.

Background/objectives: Nutritional status is increasingly acknowledged as a pivotal determinant of clinical course and recovery in patients with acute ischemic stroke (AIS). Malnutrition can compromise immune competence, delay neurological recovery, and exacerbate adverse outcomes, particularly in those undergoing intensive interventions such as mechanical thrombectomy (MT). To objectively assess nutritional status, indices such as the Prognostic Nutritional Index (PNI) and the Controlling Nutritional Status (CONUT) score have been utilized in various clinical populations. These indices incorporate routinely available laboratory parameters, reflecting both nutritional and inflammatory states. This study explores whether PNI and CONUT scores are associated with 90-day clinical outcomes in AIS patients treated with MT, aiming to evaluate their potential utility as prognostic biomarkers in acute stroke care. Methods: A total of 404 patients with AIS who underwent MT between 2023 and 2024 were retrospectively evaluated. Demographic, clinical, and laboratory data were collected, and nutritional status was assessed using PNI and CONUT scores. Clinical outcomes were stratified as favorable (modified Rankin Scale [mRS] 0–2) or unfavorable (mRS 3–6) at 90 days post-stroke. Results: Among the 404 patients included in the study, 50.5% had favorable and 49.5% had unfavorable clinical outcomes. Patients with favorable outcomes were younger (71 vs. 78 years, p = 0.001), had lower National Institutes of Health Stroke Scale (NIHSS) scores, and higher Alberta Stroke Program Early CT Scores (ASPECTS) (p = 0.001). The puncture-to-recanalization time was significantly longer in the unfavorable outcome group (47.5 min vs. 30.0 min, p = 0.003). Laboratory findings revealed higher glucose levels (p = 0.029), and lower serum albumin (p = 0.003) and lymphocyte levels (p = 0.001) in the unfavorable outcome group. Among nutritional indices, the CONUT score was significantly higher in the unfavorable outcome group (p = 0.001), whereas the PNI score was higher in the favorable outcome group (p = 0.001). ROC analysis showed that the CONUT score had significant prognostic performance (AUC = 0.721, p < 0.001), while the PNI had poor discriminatory power (AUC = 0.274, p < 0.001). Multivariate logistic regression identified age, baseline NIHSS, ASPECT score, and CONUT score as independent predictors of clinical outcome (p < 0.05). Conclusions: Among the two nutritional indices evaluated, the CONUT score demonstrated significant prognostic value in predicting 90-day clinical outcomes after MT. In contrast, the PNI showed limited discriminatory power, highlighting the superiority of CONUT as a reliable biomarker in acute stroke care. Full article

(This article belongs to the Section Neurorehabilitation)

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21 pages, 584 KiB

Open AccessSystematic Review

The Effect of Physical Activity on Executive Functions in the Elderly Population: A Systematic Review of Randomized Controlled Trials

by Carmela Matrisciano, Roberta Minino, Anna Maria Mariani and Cristiana D’Anna

Brain Sci. 2025, 15(7), 703; https://doi.org/10.3390/brainsci15070703 - 30 Jun 2025

Abstract

Background/Objectives: In recent years, there has been increasing interest in the scientific, educational, and health sectors in investigating aspects upon which to design physical-activity interventions to prevent cognitive decline, a phenomenon that affects levels of autonomy and quality of life in older [...] Read more.

Background/Objectives: In recent years, there has been increasing interest in the scientific, educational, and health sectors in investigating aspects upon which to design physical-activity interventions to prevent cognitive decline, a phenomenon that affects levels of autonomy and quality of life in older adulthood. Physical activity (PA) has been shown to be an effective strategy that can be used to preserve executive functions (EFs) by improving brain flexibility and efficiency. This systematic review aims to identify the most effective strategies used to maintain EF, prevent decline, and promote independence in the elderly. Methods: A systematic literature review was conducted according to PRISMA guidelines. The search was conducted in the following databases: Google Scholar, PubMed, Scopus, and Web of Science; the search used keywords such as “cognitive decline”; “cognitive flexibility”; “elderly”; “executive functions”; “inhibition”; “physical activity”; and “working memory”. Experimental studies published between 2019 and 2025 examining the effects of PA on EFs in adults over 60 were selected. After considering the inclusion and exclusion criteria, nine studies were included. The methodological quality of the included studies ranged from moderate to high according to the PEDro scale. Results: The analyzed studies show that short-term interventions positively affect one or two components of EFs, while medium- and long-term interventions produce benefits for all components (working memory, inhibition, and cognitive flexibility). Interventions combined with cognitive stimulation show a greater impact than PA alone. Conclusions: PA is an effective strategy for preserving EFs in the elderly, but the lack of standardized protocols makes it difficult to identify optimal interventions. Further research is needed to more precisely define the most effective intervention approaches. Full article

(This article belongs to the Special Issue Unraveling the Role of Physical Activity in Brain, Cognition, and Mental Health)

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17 pages, 387 KiB

Open AccessReview

Glucagon-like Peptide-1 Receptor Agonists: A New Frontier in Treating Alcohol Use Disorder

by Tyler S. Oesterle and Ming-Fen Ho

Brain Sci. 2025, 15(7), 702; https://doi.org/10.3390/brainsci15070702 - 29 Jun 2025

Abstract

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with [...] Read more.

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with the multifaceted nature of addiction by targeting both peripheral metabolic and central reward pathways. This review focused on the current clinical trials and real-world evidence regarding the effects of GLP-1RAs as novel therapeutics for AUD. We also discussed early but encouraging results from clinical trials in AUD, observational and real-world evidence, safety profiles, psychiatric considerations, and future directions leading beyond GLP-1RAs. Methods: A comprehensive English-language literature search was conducted per PRISMA guidelines across PubMed, Medline, Google Scholar, Web of Science, and trial registries. Using targeted keywords, we identified relevant clinical and observational studies on GLP-1RAs for alcohol use disorder, excluding off-topic or non-English works and assessing all studies for eligibility. Results: Out of 1080 records identified, seven studies met the inclusion criteria. The findings from recent clinical trials, large-scale observational studies, and real-world evidence suggest that GLP-1RAs may significantly reduce alcohol consumption, cravings, and alcohol-related hospitalizations. Their central effect on reward processing, coupled with a generally favorable safety profile, supports their potential therapeutic role beyond metabolic disorders. Conclusions: Emerging evidence positions GLP-1RAs as a promising new pharmacologic approach for managing AUD. Ongoing and future research should prioritize larger, longer-duration randomized controlled trials that include diverse populations, with specific attention to treatment motivation, co-occurring psychiatric conditions, and long-term outcomes. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Biomarkers of Substance Use Disorders)

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17 pages, 5686 KiB

Open AccessArticle

Transcranial Magneto-Acoustic Stimulation Enhances Cognitive and Working Memory in AD Rats by Regulating Theta-Gamma Oscillation Coupling and Synergistic Activity in the Hippocampal CA3 Region

by Jinrui Mi, Shuai Zhang, Xiaochao Lu and Yihao Xu

Brain Sci. 2025, 15(7), 701; https://doi.org/10.3390/brainsci15070701 - 29 Jun 2025

Abstract

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction and working memory impairment, with early hippocampal damage being a prominent feature. Transcranial magneto-acoustic stimulation (TMAS) has been shown to target specific brain regions for neuroregulation. Methods: This study investigated [...] Read more.

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction and working memory impairment, with early hippocampal damage being a prominent feature. Transcranial magneto-acoustic stimulation (TMAS) has been shown to target specific brain regions for neuroregulation. Methods: This study investigated the effects of TMAS on cognitive function, working memory, and hippocampal CA3 neural rhythms in AD rats by specifically stimulating the hippocampal region. Results: The novel object recognition test and T-maze test were employed to assess behavioral performance, while time-frequency analyses were conducted to evaluate memory-related activity, neural synchronization, and cross-frequency phase-amplitude coupling. TMAS significantly improved cognitive and working memory deficits in AD rats, enhancing long-term memory performance. Additionally, the abnormal energy levels observed in the θ and γ rhythm power spectra of the CA3 region were markedly restored, suggesting the recovery of normal neural function. This improvement was accompanied by a partial resurgence of neural activity, indicating enhanced inter-neuronal communication. Furthermore, the previously damaged coupling between the θ-fast γ and θ-slow γ rhythms was successfully improved, resulting in a notable enhancement of synchronized activity. Conclusions: These findings suggest that TMAS effectively alleviates cognitive and working memory impairments in AD rats and may provide experimental support for developing new treatments for AD. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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11 pages, 439 KiB

Open AccessArticle

Are Changes in Corticomotor Excitability Associated with Improved Arm Functional Performance Following a Tailored Strength Training Intervention in Chronic Stroke Survivors?

by Stephania Palimeris, Yekta Ansari, Anthony Remaud, François Tremblay, Hélène Corriveau, Marie-Hélène Boudrias and Marie-Hélène Milot

Brain Sci. 2025, 15(7), 700; https://doi.org/10.3390/brainsci15070700 - 29 Jun 2025

Abstract

Background/Objectives: We showed that a tailored strengthening intervention based on the size of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in the affected hemisphere resulted in an improved affected arm function, regardless of stroke severity. Also, adding anodal transcranial direct [...] Read more.

Background/Objectives: We showed that a tailored strengthening intervention based on the size of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in the affected hemisphere resulted in an improved affected arm function, regardless of stroke severity. Also, adding anodal transcranial direct stimulation (atDCS) during training did not alter the results as participants receiving real or sham stimulation showed similar gains. The goal of this study was to report on the changes in basic measures of corticomotor excitability in response to the intervention and to determine whether these changes were influenced by tDCS and correlated with those measured in arm function. Methods: The TMS measures consisted of the resting motor threshold (rMT), MEP amplitude at rest, and the silent period (SP) duration. Clinical outcomes included the Box and Block test (BBT) and grip strength (GS). Results: Post-intervention, regardless of atDCS (p > 0.62), no significant change in corticomotor excitability was noted (p > 0.15), as well as no association between the changes in TMS measures and arm function gains (p > 0.06). Conclusions: As observed for clinical measures, atDCS did not influence corticomotor excitability. The absence of an increase in the excitability of the affected hemisphere and important associations between changes in corticomotor excitability and clinical gains suggest that factors other than brain plasticity could mediate gains in arm function. Further investigations are required regarding the role of tDCS in stroke rehabilitation. Full article

(This article belongs to the Section Neurorehabilitation)

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12 pages, 675 KiB

Open AccessArticle

Cannabis Use in Opioid Maintenance Therapy: Prevalence, Clinical Correlates and Reasons for Use

by Markus Backmund, Greta G. Zámbó, Susanne Schöfl and Michael Soyka

Brain Sci. 2025, 15(7), 699; https://doi.org/10.3390/brainsci15070699 - 29 Jun 2025

Abstract

Background and aims: Opioid maintenance therapy (OMT) is the first-line treatment for opioid use disorder (OUD), reducing opioid use and mortality while improving physical and mental health. However, concomitant substance use remains common, with cannabis being the most frequently used substance. This study [...] Read more.

Background and aims: Opioid maintenance therapy (OMT) is the first-line treatment for opioid use disorder (OUD), reducing opioid use and mortality while improving physical and mental health. However, concomitant substance use remains common, with cannabis being the most frequently used substance. This study assessed the prevalence and clinical correlates of cannabis use in OMT patients, as well as individual motivations. Methods: In this cross-sectional, single-center study, 128 OUD patients (96 male, 32 female) receiving OMT were assessed using standardized questionnaires: the Marijuana Smoking History Questionnaire (MSHQ), Cannabis Problems Questionnaire (CPQ) and the Severity of Dependence Scale (SDS). Cannabis users and non-users were compared regarding type (methadone vs. buprenorphine) and dosage of maintenance medication. Results: Cannabis use was reported by 41% of patients, 73% met criteria for cannabis dependence, 30% of the full sample. Of the patients, 85% reported cannabis-related legal issues. Common reasons for use included recreational motives (mood change, enhancement) and reduction in cravings for other substances. Cannabis dependence was significantly more common in patients receiving buprenorphine than methadone. Higher methadone doses were also associated with increased cannabis use. These results suggest a clinically relevant pattern. Conclusions: Cannabis use is highly prevalent and appears to be influenced by type and dosage of substitution medication. These findings highlight a complex interaction between opioid treatment and cannabis use, possibly involving behavioral coping or regulatory processes. Further longitudinal and placebo-controlled trials are needed to investigate the clinical and pharmacological interactions between cannabis and OMT, including effects on craving, withdrawal, and overall treatment outcomes. Full article

(This article belongs to the Special Issue Brain Development—Shedding Light on Opioid Exposure and Health Disparities)

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