Brain Sciences

14 pages, 945 KB

Open AccessArticle

Understanding the Impact of Multiple Sclerosis on Quality of Life: An Italian Pilot Study

by Elsa Vitale, Roberto Lupo, Ludovica Panzanaro, Rebecca Visconti, Maria Rosaria Tumolo, Paolo Caldararo, Federico Cucci, Donato Cascio, Giorgio De Nunzio, Stefano Botti, Ivan Rubbi and Luana Conte

Brain Sci. 2025, 15(9), 960; https://doi.org/10.3390/brainsci15090960 (registering DOI) - 3 Sep 2025

Abstract

Backgorund. Multiple sclerosis (MS) profoundly affects the lives of patients and their families. The experience of the disease is shaped not only by its progression and specific characteristics but also by the quality of medical and caregiving support received. The diagnosis of MS [...] Read more.

Backgorund. Multiple sclerosis (MS) profoundly affects the lives of patients and their families. The experience of the disease is shaped not only by its progression and specific characteristics but also by the quality of medical and caregiving support received. The diagnosis of MS represents a transformative event that may lead to job loss, the need for continuous care, and a significant reorganization of family roles. In Italy, more than 140,000 people are affected by MS (AISM data, 2024). The impact of the disease is multifaceted and complex, involving various aspects of the patient’s life. Dependence on external assistance often becomes an unavoidable necessity, highlighting the importance of exploring the quality of life of people with MS in the Italian context. The main objective is to assess the quality of life of individuals affected by MS, both before diagnosis and during the course of the disease. A secondary aim is to identify related psycho-physical consequences, including care-related needs. Methods: An online survey was conducted through various associations operating across Italy, involving a sample of 99 individuals diagnosed with MS. Results: The results show a predominance of female participants, with a mean age of 41 years. The disease was reported to be at an early stage in 66.7% of cases and advanced in 33.3%, with none of the respondents being in a terminal phase. The most frequent clinical form was relapsing–remitting MS (RRMS), which accounted for 78.8% of the cases. In terms of employment and daily activities, more than half of the participants reported underperforming (59.6%) or limiting specific tasks (51.5%) due to disability caused by the disease. Emotional distress had even more pronounced effects, with 63.6% reporting a decline in performance and 62.6% experiencing concentration difficulties. Quality of life was significantly affected, particularly in the physical and emotional domains. Vitality, physical pain, perceived health, and psychological well-being emerged as compromised dimensions, pointing to the need for a multidimensional care model that integrates therapeutic, rehabilitative, and psychosocial interventions. Individuals in the early stages of MS tended to maintain better work relationships and demonstrated higher levels of professional engagement. Conclusions: The findings underscore the importance of a continuous and personalized care approach, addressing not only clinical treatment but also psychological and social support. These aspects are crucial for monitoring patients’ needs, promoting quality of life, facilitating disease acceptance, and mitigating psychological distress. Full article

(This article belongs to the Special Issue Palliative Care for Patients with Severe Neurological Impairment)

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6 pages, 176 KB

Open AccessCommentary

Neuropsychiatric Symptoms in Cerebral Amyloid Angiopathy: A Significant but Overlooked Association

by Polona Rus Prelog, Matija Zupan and Senta Frol

Brain Sci. 2025, 15(9), 959; https://doi.org/10.3390/brainsci15090959 - 3 Sep 2025

Abstract

Cerebral amyloid angiopathy (CAA) is an increasingly recognized cause of cognitive decline and lobar intracerebral hemorrhage in older adults. Recent research highlights that neuropsychiatric symptoms (NPSs)—including depression, anxiety, apathy, and irritability—are highly prevalent in CAA, often emerging prior to overt cognitive impairment or [...] Read more.

Cerebral amyloid angiopathy (CAA) is an increasingly recognized cause of cognitive decline and lobar intracerebral hemorrhage in older adults. Recent research highlights that neuropsychiatric symptoms (NPSs)—including depression, anxiety, apathy, and irritability—are highly prevalent in CAA, often emerging prior to overt cognitive impairment or major vascular events. Compared to other cerebrovascular diseases, CAA presents a distinctive and multifaceted NPS profile, with symptoms closely linked to disease severity and neuroimaging biomarkers such as white matter hyperintensities and microbleeds. Critically, NPSs in CAA can complicate cognitive assessment and predict worse functional outcomes, yet remain underappreciated in clinical and research contexts. Management is complicated by pharmacologic risks—including heightened bleeding risk associated with SSRIs and novel anti-amyloid therapies—underscoring the need for individualized and multidisciplinary approaches. We highlight the urgent need for standardized NPS assessment, targeted research into mechanisms and treatment, and greater integration of neuropsychiatric evaluation into CAA care. We suggest that recognizing NPSs as core clinical features—not secondary complications—of CAA is essential to improving both patient outcomes and scientific understanding. Future studies should focus on longitudinal analyses, the development of tailored interventions, and robust comparative research to clarify the pathophysiology, clinical trajectory, and optimal management of NPSs in CAA. Full article

(This article belongs to the Special Issue Cerebral Amyloid Angiopathy: Advances in the Field)

11 pages, 246 KB

Open AccessProtocol

A Multidisciplinary Occupational Medicine-Based Intervention Protocol for Conflict Prevention and Crisis Management in High-Stress Professional Environments

by Martina Corsi, Dorotea Stefanini, Isabella Biagioni, Chiara Bertini, Matteo Accardo, Mirko Bottari, Claudia Antunes, Laura Lazzarini, Ilaria Pertici, Chiara Ciarfella, Giovanni Tritto, Salvio Perretta, Poupak Fallahi and Rudy Foddis

Brain Sci. 2025, 15(9), 958; https://doi.org/10.3390/brainsci15090958 (registering DOI) - 2 Sep 2025

Abstract

Background/Objectives: Workplace conflict and aggression pose significant psychosocial risks across diverse professional sectors. This protocol outlines a novel, university-based educational intervention. Developed by a multidisciplinary team from the University Hospital of Pisa, Italy, including occupational physicians and a psychiatrist specializing in work and [...] Read more.

Background/Objectives: Workplace conflict and aggression pose significant psychosocial risks across diverse professional sectors. This protocol outlines a novel, university-based educational intervention. Developed by a multidisciplinary team from the University Hospital of Pisa, Italy, including occupational physicians and a psychiatrist specializing in work and organizational psychology, its primary purpose is to enhance conflict prevention and crisis management skills. While initially developed and tested within the veterinary sector due to its identified vulnerabilities, the intervention is inherently generalizable to any high-stress professional environment characterized by intense client, customer, or public interactions. Methods: The intervention integrates didactic instruction with active, immersive learning through tailored role-playing scenarios simulating real-world challenging encounters. This study protocol details the structured methodology for evaluating the immediate effectiveness of this training. We are using a specifically developed efficacy scale to assess outcomes. Results: The results demonstrate a significant improvement in all assessed skills from the pre-training to the post-training evaluation. For every item on the scale, the median scores increased, indicating a positive shift in overall group performance. The p-value for each item was <0.001, confirming that the observed improvements were statistically significant. These results demonstrate enhanced conflict resolution skills, improved communication, and an increased sense of self-efficacy among participants. Conclusions: This protocol offers a comprehensive and generalizable approach to addressing workplace psychosocial risks through an innovative educational intervention. A key future goal involves advancing this training methodology by integrating virtual reality (VR) environments with AI-driven avatars for role-playing, aiming to achieve a more realistic and impactful learning experience and sustained behavioral change. Full article

(This article belongs to the Special Issue Burnout, Adjustment Disorder and Post-Traumatic Stress Disorder: Risk Factors, Impact, Preventive Strategies and Treatment Options)

11 pages, 257 KB

Open AccessReview

Gamma and Psychological Resilience: Where to Now?

by Damian L. Rocks, Christopher F. Sharpley, Vicki Bitsika, Kirstan A. Vessey, G. Lorenzo Odierna and Christopher B. Watson

Brain Sci. 2025, 15(9), 957; https://doi.org/10.3390/brainsci15090957 - 2 Sep 2025

Abstract

Because of their potential to enhance pathways for diagnosis and treatment, a great deal of research has been conducted to identify brain biomarkers of mental illnesses such as depression and anxiety. Similarly, the investigation of the biomarkers of those protective factors that help [...] Read more.

Because of their potential to enhance pathways for diagnosis and treatment, a great deal of research has been conducted to identify brain biomarkers of mental illnesses such as depression and anxiety. Similarly, the investigation of the biomarkers of those protective factors that help individuals resist, or recover from, these mental illnesses is also directly relevant to clinical practice. One such protective factor is Psychological Resilience (PR) but relatively little is known about its neurobiological underpinnings. A literature search was conducted of electroencephalographic data and PR, revealing seven studies that reported brain electrical activity categorised into bands of specified frequencies. Several studies reported significant associations between PR and alpha band activity, and somewhat less on beta band activity, principally via their roles in emotion regulation and problem solving. However, despite having a major role in many aspects of cognition and brain function, and being implicated in depression, only two studies examined gamma band activity specifically, and their results were equivocal. Several possible reasons for these apparently null results of the association between gamma band activity and PR are discussed, leading to a brief description of gamma, and suggestions for future research into its association with PR. Full article

(This article belongs to the Special Issue Anxiety, Depression and Stress)

13 pages, 2387 KB

Open AccessArticle

Action Video Gaming Enhances Brain Structure: Increased Cortical Thickness and White Matter Integrity in Occipital and Parietal Regions

by Chandrama Mukherjee, Kyle Cahill and Mukesh Dhamala

Brain Sci. 2025, 15(9), 956; https://doi.org/10.3390/brainsci15090956 - 2 Sep 2025

Abstract

Background: Action video games—particularly first-person-shooter (FPS), real-time-strategy (RTS), multiplayer-online-battle-arena (MOBA), and battle-royale (BR) titles—have been linked to enhanced visuospatial skills, yet their impact on brain structure remains unclear. Purpose: To examine, using a cross-sectional design, whether long-term exposure to high-speed genres is associated [...] Read more.

Background: Action video games—particularly first-person-shooter (FPS), real-time-strategy (RTS), multiplayer-online-battle-arena (MOBA), and battle-royale (BR) titles—have been linked to enhanced visuospatial skills, yet their impact on brain structure remains unclear. Purpose: To examine, using a cross-sectional design, whether long-term exposure to high-speed genres is associated with variations in cortical thickness and white matter microstructure. Methods: Structural and diffusion MRI were acquired from 27 video-game players (VGPs) and 19 non-video-game players (NVGPs). FreeSurfer-derived cortical thickness and DSI-Studio quantitative anisotropy (QA) were compared between groups, co-varying for intracranial volume. All p-values were Holm–Bonferroni- and FDR-corrected; bootstrap 95% CIs are reported. Results: VGPs showed greater cortical thickness in right inferior and superior parietal, supramarginal, and precuneus cortices (η_p² = 0.12–0.21) and higher QA along right SOG–SPL and left SOG–IPL tracts. Conclusions: Frequent action gaming is associated with greater cortical thickness in the dorsal stream and enhanced occipito-parietal connectivity. However, causal inference is precluded; longitudinal work is warranted. Full article

(This article belongs to the Special Issue Brain Network Connectivity Analysis in Neuroscience)

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34 pages, 1456 KB

Open AccessReview

The High-Risk Model of Threat Perception Modulates Learning of Placebo and Nocebo Effects and Functional Somatic Disorders

by Ian Wickramasekera

Brain Sci. 2025, 15(9), 955; https://doi.org/10.3390/brainsci15090955 - 2 Sep 2025

Abstract

Threat activation or deactivation in the brain–body is associated with learned nocebo or placebo somatic effects induced by fake invasive medical–surgical procedures. Some functional somatic disorders (FSDs) originate as acute nocebo somatic effects and can become 30–50% of chronic somatic presentations to primary [...] Read more.

Threat activation or deactivation in the brain–body is associated with learned nocebo or placebo somatic effects induced by fake invasive medical–surgical procedures. Some functional somatic disorders (FSDs) originate as acute nocebo somatic effects and can become 30–50% of chronic somatic presentations to primary care physicians. Patients with FSD overutilize medical–surgical services, despite the lack of identified pathophysiology, and are at risk for morbidity from unintentional iatrogenic injury. The Conditioned Response Model (CRM) of learning postulates three innate mechanisms, modulated by trait hypnotizability, which drive placebo and nocebo somatic effects and FSD. The High Risk Model of Threat Perception (HRMTP) postulates 10 psychosocial risk factors that modulate threat perception, driving placebo and nocebo somatic effectsandbiologically embedded FSD. Psychosocial factors and the trait of high and low hypnotizability modulate threat and are postulated to reduce heart rate variability(HRV), inducing autonomic nervous system(ANS)dysregulation. Reduced HRV was found in a large (N = 6,891) sample of patients with FSD. A total of 50% of patients with FSD with chronic pain (n = 224) without identified pathophysiology had a Paradoxical Increase in hand Temperature (PTI) during experimental threat induction. The HRMTP predicts that PTI associated with ANS dysregulation is associated with the risk factor Adverse Childhood Experiences (ACEs). This ACE prediction was independently confirmed. Learning predicts that threat activation by unconscious neutral stimuli (CS) can amplify nocebo and FSD and can negate placebo effects in clinician–patient relationships. Identifying psychosocial risk factors that modulate threat perception enables the diagnosis of FSD by inclusion and not simply by excluding pathophysiology. Full article

(This article belongs to the Special Issue Traumatic Stress and Dissociative Disorder)

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24 pages, 2419 KB

Open AccessArticle

Interpretable Disorder Signatures: Probing Neural Latent Spaces for Schizophrenia, Alzheimer’s, and Autism Stratification

by Zafar Iqbal, Md. Mahfuzur Rahman, Qasim Zia, Pavel Popov, Zening Fu, Vince D. Calhoun and Sergey Plis

Brain Sci. 2025, 15(9), 954; https://doi.org/10.3390/brainsci15090954 - 1 Sep 2025

Abstract

Objective: This study aims to develop and validate an interpretable deep learning framework that leverages self-supervised time reversal (TR) pretraining to identify consistent, biologically plausible functional network biomarkers across multiple neurological and psychiatric disorders. Methods: We pretrained a hierarchical LSTM model using a [...] Read more.

Objective: This study aims to develop and validate an interpretable deep learning framework that leverages self-supervised time reversal (TR) pretraining to identify consistent, biologically plausible functional network biomarkers across multiple neurological and psychiatric disorders. Methods: We pretrained a hierarchical LSTM model using a TR pretext task on the Human Connectome Project (HCP) dataset. The pretrained weights were transferred to downstream classification tasks on five clinical datasets (FBIRN, BSNIP, ADNI, OASIS, and ABIDE) spanning schizophrenia, Alzheimer’s disease, and autism spectrum disorder. After fine-tuning, we extracted latent features and employed a logistic regression probing analysis to decode class-specific functional network contributions. Models trained from scratch without pretraining served as a baseline. Statistical tests (one-sample and two-sample t-tests) were performed on the latent features to assess their discriminative power and consistency. Results: TR pretraining consistently improved classification performance in four out of five datasets, with AUC gains of up to 5.3%, particularly in data-scarce settings. Probing analyses revealed biologically meaningful and consistent patterns: schizophrenia was associated with reduced auditory network activity, Alzheimer’s with disrupted default mode and cerebellar networks, and autism with sensorimotor anomalies. TR-pretrained models produced more statistically significant latent features and demonstrated higher consistency across datasets (e.g., Pearson correlation = 0.9003 for schizophrenia probing vs. −0.67 for non-pretrained). In contrast, non-pretrained models showed unstable performance and inconsistent feature importance. Conclusions: Time Reversal pretraining enhances both the performance and interpretability of deep learning models for fMRI classification. By enabling more stable and biologically plausible representations, TR pretraining supports clinically relevant insights into disorder-specific network disruptions. This study demonstrates the utility of interpretable self-supervised models in neuroimaging, offering a promising step toward transparent and trustworthy AI applications in psychiatry. Full article

(This article belongs to the Special Issue Deep into the Brain: Artificial Intelligence in Brain Diseases—2nd Edition)

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20 pages, 2498 KB

Open AccessArticle

Gray and White Matter Networks Predict Mindfulness and Mind Wandering Traits: A Data Fusion Machine Learning Approach

by Minah Chang, Sara Sorella, Cristiano Crescentini and Alessandro Grecucci

Brain Sci. 2025, 15(9), 953; https://doi.org/10.3390/brainsci15090953 - 1 Sep 2025

Abstract

Background: Mindfulness and mind wandering are cognitive traits central to attentional control and psychological well-being, yet their neural underpinnings are yet to be elucidated. This study aimed to identify structural brain networks comprising gray matter (GM) and white matter (WM) that predict individual [...] Read more.

Background: Mindfulness and mind wandering are cognitive traits central to attentional control and psychological well-being, yet their neural underpinnings are yet to be elucidated. This study aimed to identify structural brain networks comprising gray matter (GM) and white matter (WM) that predict individual differences in mindfulness and distinct mind wandering tendencies (deliberate and spontaneous). Methods: Using structural MRI data and self-report measures from 76 participants, we applied an unsupervised data-fusion machine learning technique (parallel independent component analysis) to identify GM and WM networks associated with mindfulness and mind wandering traits. Results: Our analysis revealed several distinct brain networks linked to these cognitive constructs. Specifically, one GM network involving subcortical regions, including the caudate and thalamus, positively predicted mindfulness and deliberate mind wandering, while negatively influencing spontaneous mind wandering through the mediating role of the mindfulness facet “acting with awareness.” In addition, two separate WM networks, predominantly involving frontoparietal and temporal regions, were directly associated with reduced spontaneous mind wandering. Conclusions: These findings advance our current knowledge by demonstrating that specific GM and WM structures are involved in mindfulness and different forms of mind wandering. Our results also show that the “acting with awareness” facet has a mediating effect on spontaneous mind wandering, which provides supporting evidence for attentional and executive control models. These new insights into the neuroanatomical correlates of mindfulness and mind wandering have implications for ongoing research in the growing topic of mindfulness and mind wandering, mindfulness-based interventions, and other clinical applications. Full article

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

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15 pages, 2651 KB

Open AccessArticle

Cellular Abnormalities Induced by High Glucose in Mixed Glial Cultures Are Maintained, Although Glucose Returns to Normal Levels

by Brandon Isai Herrera Solis, Frida Guerrero-Padilla, Elvia Mera Jiménez, Juan Manuel Vega López, María de Jesús Perea-Flores, Octavio Rodríguez-Cortés, Martha Edith Macías Pérez and Maricarmen Hernández-Rodríguez

Brain Sci. 2025, 15(9), 952; https://doi.org/10.3390/brainsci15090952 - 1 Sep 2025

Abstract

Background: Metabolic memory refers to the long-term adverse effects of short-term disturbances in glucose metabolism. Recent evidence indicates that hyperglycemia-induced metabolic memory contributes to sustained cellular damage even after glycemic control, driven by increased production of reactive oxygen species (ROS), activation of inflammatory [...] Read more.

Background: Metabolic memory refers to the long-term adverse effects of short-term disturbances in glucose metabolism. Recent evidence indicates that hyperglycemia-induced metabolic memory contributes to sustained cellular damage even after glycemic control, driven by increased production of reactive oxygen species (ROS), activation of inflammatory pathways, and accumulation of advanced glycation end products (AGEs). Although well characterized in endothelial and smooth muscle cells, this phenomenon may also occur in other cell types, including glial cells. Objective: This study aimed to evaluate the persistence of high-glucose (HG)-induced alterations after returning to normal glucose (NG) conditions in primary mixed glial cell (MGC) cultures. Methods: Primary MGCs were obtained from neonatal Wistar rat pups and cultured under three conditions for 21 days: NG (5.5 mM glucose), HG (25 mM glucose), and HG-NG (14 days in HG followed by 7 days in NG). Cell proliferation, apoptosis, ROS production, lipid peroxidation, mitochondrial activity, TNF-α, IL-6, and AGE formation were assessed. Results: MGCs cultured under HG and HG-NG conditions exhibited reduced proliferation without increased apoptosis. Both HG and HG-NG conditions promoted ROS overproduction accompanied by reduced mitochondrial activity, whereas only HG increased lipid peroxidation. Notably, TNF-α and AGE levels were elevated in both HG and HG-NG conditions, while IL-6 production decreased exclusively in HG-NG. Conclusions: These findings demonstrate the persistence of deleterious effects induced by HG in MGCs, even after restoration to NG conditions. Full article

(This article belongs to the Special Issue The Role of Glia in Inflammatory Processes)

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19 pages, 2665 KB

Open AccessArticle

Entropy and Complexity in QEEG Reveal Visual Processing Signatures in Autism: A Neurofeedback-Oriented and Clinical Differentiation Study

by Aleksandar Tenev, Silvana Markovska-Simoska, Andreas Müller and Igor Mishkovski

Brain Sci. 2025, 15(9), 951; https://doi.org/10.3390/brainsci15090951 - 1 Sep 2025

Abstract

(1) Background: Quantitative EEG (QEEG) offers potential for identifying objective neurophysiological biomarkers in psychiatric disorders and guiding neurofeedback interventions. This study examined whether three nonlinear QEEG metrics—Lempel–Ziv Complexity, Tsallis Entropy, and Renyi Entropy—can distinguish children with autism spectrum disorder (ASD) from typically developing [...] Read more.

(1) Background: Quantitative EEG (QEEG) offers potential for identifying objective neurophysiological biomarkers in psychiatric disorders and guiding neurofeedback interventions. This study examined whether three nonlinear QEEG metrics—Lempel–Ziv Complexity, Tsallis Entropy, and Renyi Entropy—can distinguish children with autism spectrum disorder (ASD) from typically developing (TD) peers, and assessed their relevance for neurofeedback targeting. (2) Methods: EEG recordings from 19 scalp channels were analyzed in children with ASD and TD. The three nonlinear metrics were computed for each channel. Group differences were evaluated statistically, while machine learning classifiers assessed discriminative performance. Dimensionality reduction with t-distributed Stochastic Neighbor Embedding (t-SNE) was applied to visualize clustering. (3) Results: All metrics showed significant group differences across multiple channels. Machine learning classifiers achieved >90% accuracy, demonstrating robust discriminative power. t-SNE revealed distinct ASD and TD clustering, with nonlinear separability in specific channels. Visual processing–related channels were prominent contributors to both classifier predictions and t-SNE cluster boundaries. (4) Conclusions: Nonlinear QEEG metrics, particularly from visual processing regions, differentiate ASD from TD with high accuracy and may serve as objective biomarkers for neurofeedback. Combining complexity and entropy measures with machine learning and visualization techniques offers a relevant framework for ASD diagnosis and personalized intervention planning. Full article

(This article belongs to the Special Issue Advances in Neurofeedback Research)

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15 pages, 1891 KB

Open AccessArticle

Investigating PRDM8 DNA Methylation in Peripheral Tissues in Borderline Personality Disorder: Association with Symptom Severity but Not Adverse Childhood Experiences

by Annika Bender, Laila Bertele, Mirac Nur Musaoglu, Sarah Pasche, Susanne Edelmann and Vanessa Nieratschker

Brain Sci. 2025, 15(9), 950; https://doi.org/10.3390/brainsci15090950 - 30 Aug 2025

Abstract

Background: Borderline Personality Disorder (BPD) is a complex psychiatric condition with multifactorial origins, with a high proportion of patients reporting early trauma. Stressors such as adverse childhood experiences (ACEs) can shape the epigenetic landscape including DNA methylation (DNAm) and act on gene expression. [...] Read more.

Background: Borderline Personality Disorder (BPD) is a complex psychiatric condition with multifactorial origins, with a high proportion of patients reporting early trauma. Stressors such as adverse childhood experiences (ACEs) can shape the epigenetic landscape including DNA methylation (DNAm) and act on gene expression. DNAm is increasingly being investigated as a molecular link between environmental exposures such as ACE and psychiatric outcomes. Differential DNAm of the gene PR domain zinc finger protein 8 (PRDM8), a histone methyltransferase, has recently been reported to be sensitive to early life trauma. Its role in BPD, especially in the context of ACE, remains to be elucidated. Methods: This study investigated DNAm patterns of PRDM8 in peripheral blood and saliva obtained from BPD patients undergoing Dialectic Behavioral Therapy (DBT) compared to healthy control (HC) participants. Associations with ACE and BPD symptom severity were assessed, and therapy-related changes in DNAm were examined. Results: At baseline, BPD patients demonstrated significant hypomethylation of PRDM8 in blood relative to the HC group. Following DBT, a nominally significant increase in DNAm was observed, aligning with inversely correlated symptom severity. No significant differences in saliva were detected. ACE was not associated with PRDM8 DNAm. Conclusions: Our findings suggest that PRDM8 DNAm might be associated with BPD and therapeutic intervention but not with ACE. Together with prior research, the results underscore the importance of future investigation of gene–environment interactions and the functional significance of PRDM8 regulation in the pathophysiology of BPD. Full article

(This article belongs to the Section Neuropsychiatry)

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11 pages, 814 KB

Open AccessArticle

Conducting Performance-Assisted Resections in the Right Temporo-Insular Cortex: A Real-Time Neuropsychological Testing (RTNT) Protocol

by Barbara Tomasino, Ilaria Guarracino, Tamara Ius and Miran Skrap

Brain Sci. 2025, 15(9), 949; https://doi.org/10.3390/brainsci15090949 - 30 Aug 2025

Abstract

Background/Objectives: There is increasing interest within cognitive neuro-surgery in preserving domains not traditionally assessed during awake surgery. The study aims at proposing a specific protocol to assist surgical resection in right temporal areas. Patients were not evaluated during direct cortical stimulation; instead, assessments [...] Read more.

Background/Objectives: There is increasing interest within cognitive neuro-surgery in preserving domains not traditionally assessed during awake surgery. The study aims at proposing a specific protocol to assist surgical resection in right temporal areas. Patients were not evaluated during direct cortical stimulation; instead, assessments occurred during the resection itself. The real-time neuropsychological testing (RTNT) protocol employed tasks evaluating visuospatial and social cognition, administered repeatedly throughout the resection using varied items. Methods: A consecutive series of 24 patients (median age 44) performed RTNT. The aim of RTNT is to maintain high accuracy through resection. Lesions in the right temporal cortex and the subcortical white matter beneath can cause deficits; accordingly, not all of our patients had pre-surgery performance within the normal range. In this case, the aim of RTNT is to maintain the not perfect pre-surgery level. Results: We found a statistically significant between-tasks difference in the patients’ median values (across RTNT runs), in their minimum score reached during resection, and in the delta between performance at the last vs. the first RTNT run. The tasks that varied belonged to visual–spatial attention (landmark task), face processing (recognition of famous faces), and social cognition (theory of mind). The outcome was measured by pre- vs. post-surgery neuropsychological score comparison. The number of patients scoring below the normal range did not significantly differ between post- vs. pre-intervention. Conclusions: Results demonstrated the feasibility of implementing a continuous monitoring protocol during the resection phase, and the potential of the selected tasks to assess visuospatial and social functions associated with the non-dominant (right) hemisphere. Full article

(This article belongs to the Special Issue Editorial Board Collection Series: Advances in Neuro-Oncology)

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9 pages, 480 KB

Open AccessArticle

Exploring the Feasibility of a Telematic Version of Parkinson’s Disease—Cognitive Rating Scale (PD-CRS)

by Elisa Pini, Fulvio Pepe, Michelle Ingiardi, Veronica Laini, Nicoletta Ciccarelli and Eugenio Magni

Brain Sci. 2025, 15(9), 948; https://doi.org/10.3390/brainsci15090948 - 30 Aug 2025

Abstract

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder frequently associated with cognitive impairment. In the context of increasing interest in remote healthcare solutions, particularly after the COVID-19 pandemic, this preliminary study aimed to evaluate the feasibility of an online version of the [...] Read more.

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder frequently associated with cognitive impairment. In the context of increasing interest in remote healthcare solutions, particularly after the COVID-19 pandemic, this preliminary study aimed to evaluate the feasibility of an online version of the Parkinson’s Disease—Cognitive Rating Scale (PD-CRS), a first-level neuropsychological screening tool for mild cognitive impairment (MCI) in individuals with PD. Methods: Seventy-nine patients with idiopathic PD were recruited between October 2020 and February 2024. A telematic version of the PD-CRS was administered via video call using adapted materials (e.g., slide-based instructions and webcam-mediated tasks). Both patients and examiners completed a Visual Analogue Scale (VAS) to rate perceived difficulty. Descriptive statistics and non-parametric tests were used to analyze data. Results: Difficulty ratings were low for both patients (mean VAS = 1.60, SD = 0.88) and the examiner (mean VAS = 1.43, SD = 0.61), with no significant difference (p = 0.176). No demographic or clinical variable predicted difficulty. Conclusions: These findings support the feasibility and usability of an online version of PD-CRS. This approach may facilitate wider access to cognitive screening for PD patients, particularly those with mobility limitations or living in underserved areas. Full article

(This article belongs to the Special Issue New Challenges in the Study of Cognitive Impairment in Parkinson’s Disease)

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18 pages, 2255 KB

Open AccessArticle

Putamen Stiffness Declines with Age and Is Associated with Implicit Sequence Learning Outcomes

by Hyeon Jung Heselton, Aaron T. Anderson, Curtis L. Johnson, Neal J. Cohen, Bradley P. Sutton and Hillary Schwarb

Brain Sci. 2025, 15(9), 947; https://doi.org/10.3390/brainsci15090947 - 29 Aug 2025

Abstract

Background/Objectives: Sequence learning, the ability to pick up on regularities in our environment to facilitate behavior, is critically dependent on striatal structures in the brain, with the putamen emerging as a critical hub for implicit sequence learning. As the putamen is known to [...] Read more.

Background/Objectives: Sequence learning, the ability to pick up on regularities in our environment to facilitate behavior, is critically dependent on striatal structures in the brain, with the putamen emerging as a critical hub for implicit sequence learning. As the putamen is known to shrink with age, and age-related declines in sequence learning abilities are common, it has been hypothesized that the structural integrity of the putamen is likely related to sequence learning outcomes. However, the structural literature is sparse. One reason may be that traditional structural imaging measures, like volume, are not sufficiently sensitive to measure changes that are related to performance outcomes. We propose that magnetic resonance elastography (MRE), an emerging neuroimaging tool that provides quantitative measures of microstructural integrity, may fill this gap. Methods: In this study, both sequence learning abilities and the structural integrity of the putamen were assessed in 61 cognitively healthy middle-aged and older adults (range: 45–78 years old). Sequence learning was measured via performance on the Serial Reaction Time Task. Putamen integrity was assessed in two ways: first, via standard structural volume assessments, and second, via MRE measures of tissue integrity. Results: Age significantly correlated with both putamen volume and stiffness but not sequence learning scores. While sequence learning scores did not correlate with volume, MRE-derived measures of putamen stiffness were significantly correlated with learning outcomes such that individuals with stiffer putamen showed higher learning scores. A series of control analyses were performed to highlight the specificity and sensitivity of this putamen stiffness–sequence learning relationship. Conclusions: Together these data indicate that microstructural changes that occur in the putamen as we age may contribute to changes in sequence learning outcomes. Full article

(This article belongs to the Special Issue Heterogeneity in Cognitive Aging: From Healthy Aging to Neurodegenerative Disease)

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18 pages, 533 KB

Open AccessArticle

General Sense of Perceived Self-Efficacy and Loneliness Among Polish Adolescents: Communication with Peers as Mediator

by Małgorzata Szcześniak, Agata Hiacynta Świątek, Aniela Szczerba, Karolina Szpunar and Adam Falewicz

Brain Sci. 2025, 15(9), 946; https://doi.org/10.3390/brainsci15090946 - 29 Aug 2025

Abstract

Background: Adolescence is a particularly vulnerable period for experiencing loneliness. According to the latest statistics, there are worldwide increases in adolescents’ social isolation caused by different psychosocial challenges. A number of different studies have linked a strong belief in being successful at [...] Read more.

Background: Adolescence is a particularly vulnerable period for experiencing loneliness. According to the latest statistics, there are worldwide increases in adolescents’ social isolation caused by different psychosocial challenges. A number of different studies have linked a strong belief in being successful at doing something to lower levels of feeling lonely. Objectives: Because we know less about the potential mediators of this relationship, the aim of the current study was to assess: (1) the association between self-efficacy and loneliness; (2) the mediatory role of peer communication. Methods: A total of 191 primary and high school students (M_age = 16.22; SD = 1.44) completed the General Self-Efficacy Scale, the De Jong Gierveld Loneliness Scale, and the Scale of Communication of Adolescents with Peers. Results: The results of the correlation analyses revealed that self-efficacy was negatively associated with loneliness and difficulty in adolescents’ communication with peers. Conversely, self-efficacy was positively associated with openness in adolescents’ communication with peers. Moreover, the outcomes of the PROCESS macro for SPSS (model number 4; Hayes, 2013) showed that openness in adolescents’ communication with peers and difficulty in this communication were mediators in this relationship. Conclusions: Young people who strongly believe in their abilities to achieve success may be more willing to share ideas and personal experiences with others and have less difficulty in communicating with peers, which may lead to a reduced sense of loneliness. Full article

(This article belongs to the Special Issue Focus on Mental Health and Mental Illness in Adolescents)

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15 pages, 408 KB

Open AccessStudy Protocol

HIITing Anxiety and Depression in Parkinson’s Disease and Multiple Sclerosis—A Study Protocol of a Transdiagnostic Randomized Controlled Trial (HersenFIT)

by Arianne S. Gravesteijn, Marc B. Rietberg, Vincent de Groot, Mark A. Hirsch, Tim Vanbellingen, Richard T. Jaspers, Chris Vriend, Wilma D. J. van de Berg, Odile A. van den Heuvel, Erwin E. H. van Wegen and on behalf of the HersenFIT Consortium

Brain Sci. 2025, 15(9), 945; https://doi.org/10.3390/brainsci15090945 - 29 Aug 2025

Abstract

Background/Objectives: Parkinson’s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. [...] Read more.

Background/Objectives: Parkinson’s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. Exercise therapy—particularly aerobic training—has shown promise in alleviating non-motor symptoms, potentially through neuroplastic adaptations. However, traditional aerobic exercise is often time-consuming and monotonous, limiting long-term adherence. High-intensity interval training (HIIT) offers a time-efficient and potentially more engaging alternative, though its effects on non-motor symptoms in PD and MS remain understudied. Methods: This transdiagnostic randomized controlled trial will enroll 48 participants (24 PD, 24 MS) with clinically significant affective symptoms (hospital anxiety and depression scale [HADS] ≥ 8). The participants will be randomly assigned to one of three 8-week interventions: (1) HIIT, 5–6 intervals of 45 s of high-intensity cycling; (2) continuous aerobic training (CAT), 50 min of low-intensity cycling; (3) movement advice (MA), step goals, and physical education. The primary (affective symptoms) and secondary outcomes (cognition, fatigue, sleep, motor function) will be assessed at four time points: 4 and 1 weeks pre intervention, and 1 and 4 weeks post intervention. Weekly blood samples and pre/post brain imaging will be collected to study biofluid and MRI measures for potential neuroplasticity. Linear mixed models will analyze the time and group effects. Discussion: This trial will assess whether HIIT can more effectively improve non-motor and motor symptoms in PD and MS than CAT or MA. A multimodal approach will explore both the clinical outcomes and underlying mechanisms, informing scalable and engaging rehabilitation strategies. Full article

(This article belongs to the Section Neuropsychiatry)

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19 pages, 570 KB

Open AccessReview

Imaging of Cerebral Iron as an Emerging Marker for Brain Aging, Neurodegeneration, and Cerebrovascular Diseases

by Chi-Heng Zhou and Yi-Cheng Zhu

Brain Sci. 2025, 15(9), 944; https://doi.org/10.3390/brainsci15090944 - 29 Aug 2025

Abstract

Iron is critical for brain development, metabolism, and function; however, dysregulated iron disposition contributes to neurological diseases. Many neuroimaging techniques have enabled detection of iron susceptibility, and quantitative susceptibility mapping (QSM) offers a sensitive magnetic resonance imaging (MRI) technique for quantifying brain iron. [...] Read more.

Iron is critical for brain development, metabolism, and function; however, dysregulated iron disposition contributes to neurological diseases. Many neuroimaging techniques have enabled detection of iron susceptibility, and quantitative susceptibility mapping (QSM) offers a sensitive magnetic resonance imaging (MRI) technique for quantifying brain iron. To elucidate the functional role of cerebral iron and clarify the utility of QSM in establishing iron as a potential biomarker, this review synthesizes cellular and regional behaviours of iron from physiological aging to disease conditions, with a focus on neurodegeneration such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), as well as cerebral small vessel disease (CSVD) as cerebrovascular manifestation. Distinct patterns of iron distribution in deep gray matter and selective cortical regions are associated with motor and cognitive impairment, while the interaction between iron, vascular integrity, and glial function further stresses its pathological relevance. QSM of iron may, thereby, serve as a marker to monitor iron-related disease progression and facilitate intervention. Temporal dynamics of iron in brain pathology remain underexplored, and we emphasized the need for longitudinal mapping and multi-modality biomarker integration. Establishing iron as a clinically relevant imaging biomarker requires continued investigation into its topographical, molecular, and functional correlates across aging and disease trajectories. Full article

(This article belongs to the Special Issue Using Neuroimaging to Explore Neurodegenerative Diseases)

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11 pages, 598 KB

Open AccessPerspective

Systems of Care for Treating Severe Acquired Brain Injury: Comparing the United States to Italy

by Nicholas J Cioe, Rita Formisano, Gregory O’Shanick, Juliet Haarbauer-Krupa, Valentina Bandiera, Elisa Berardi, Vincenzo Vinicola and Umberto Bivona

Brain Sci. 2025, 15(9), 943; https://doi.org/10.3390/brainsci15090943 (registering DOI) - 29 Aug 2025

Abstract

Acquired Brain Injury (ABI) is now widely regarded as a chronic condition but this change in conceptualization has not yet been realized in the way rehabilitation and care are offered and funded in the United States. Similarly, it is widely accepted that an [...] Read more.

Acquired Brain Injury (ABI) is now widely regarded as a chronic condition but this change in conceptualization has not yet been realized in the way rehabilitation and care are offered and funded in the United States. Similarly, it is widely accepted that an optimized ABI system includes integration across the phases of care and recovery that considers the bio-psycho-socio-ecological (BPSE) dimensions beyond the injury itself. Despite the importance of BPSE factors informing care, typical post-injury care and management remain focused on acute presentation and the biological nature of the injury and there still exists relevant inter-country differences for disorders of consciousness (DoC) neurorehabilitation after severe ABI. This collaboration with Italian colleagues explores and compares the types and locations of rehabilitative services offered in a Post-Coma Unit of neurorehabilitation center in Italy (namely, Santa Lucia Foundation IRCCS in Rome) and in the United States following a “severe” ABI (sABI). This narrative seeks to describe the degree to which both systems utilize a BPSE informed approach to care. Full article

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

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22 pages, 734 KB

Open AccessReview

Brain Nuclei in the Regulation of Sexual Behavior, Peripheral Nerves Related to Reproduction, and Their Alterations in Neurodegenerative Diseases: A Brief Review

by María de la Paz Palacios-Arellano, Jessica Natalia Landa-García, Edson David García-Martínez, Jorge Manzo-Denes, Gonzalo Emiliano Aranda-Abreu, Fausto Rojas-Durán, Deissy Herrera-Covarrubias, María Rebeca Toledo-Cárdenas, Genaro Alfonso Coria-Ávila, Jorge Manuel Suárez-Medellín, César Antonio Pérez-Estudillo and María Elena Hernández-Aguilar

Brain Sci. 2025, 15(9), 942; https://doi.org/10.3390/brainsci15090942 - 29 Aug 2025

Abstract

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. [...] Read more.

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. This process culminates with ejaculation and the deposition of semen into the uterine tract with the aim of achieving fertilization. The brain plays a fundamental role in both generating motivation and executing male sexual behavior. Meanwhile, the spinal cord, through the autonomic nervous system and the pelvic ganglion, transmits information to the reproductive organs, including the testes. Currently, there is extensive evidence demonstrating the involvement of various brain structures in the regulation of sexual behavior, as well as specific regions of the spinal cord involved in the control of ejaculation. For instance, the medial preoptic area (MPOA) has been shown to regulate the secretion of pituitary hormones, which in turn modulate the function of reproductive organs. Among these, testosterone production is particularly notable, as this hormone not only directly affects reproductive organs but also exerts a modulatory role on brain nuclei responsible for sexual behavior. Although there is a reciprocal regulation between the nervous and endocrine systems, it is important to note that the execution of sexual behavior also impacts peripheral structures, such as the major pelvic ganglion (MPG) and the testis, preparing the organism for reproduction. The purpose of this mini-review is to provide an overview of the main brain nuclei involved in the regulation of sexual behavior, as well as the spinal cord regions implicated in reproduction. Finally, we discuss how these structures may alter their function in the context of neurodegenerative diseases, aiming to introduce readers to this field of study. Full article

(This article belongs to the Special Issue From Brain Circuits to Behavior: A Neuroendocrine Perspective)

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