Brain Sciences

5 pages, 148 KiB

Open AccessEditorial

Editorial: The Application of EEG in Neurorehabilitation

by Ryouhei Ishii

Brain Sci. 2025, 15(8), 856; https://doi.org/10.3390/brainsci15080856 - 12 Aug 2025

The field of neurorehabilitation stands at a pivotal juncture, driven by a confluence of advancements in neuroscience, engineering, and data science [...] Full article

(This article belongs to the Special Issue The Application of EEG in Neurorehabilitation)

16 pages, 927 KiB

Open AccessArticle

Predicting State Anxiety Level Change Using EEG Parameters: A Pilot Study in Two Museum Settings

by Maria Elide Vanutelli, Annalisa Banzi, Maria Cicirello, Raffaella Folgieri and Claudio Lucchiari

Brain Sci. 2025, 15(8), 855; https://doi.org/10.3390/brainsci15080855 - 11 Aug 2025

Abstract

Background: Museums are increasingly being recognized not only as cultural institutions but also as potential resources for enhancing psychological well-being. Prior research has shown that museum visits can reduce stress and anxiety, yet there is a pressing need for evidence-based interventions supported by [...] Read more.

Background: Museums are increasingly being recognized not only as cultural institutions but also as potential resources for enhancing psychological well-being. Prior research has shown that museum visits can reduce stress and anxiety, yet there is a pressing need for evidence-based interventions supported by neurophysiological data. While neuroscientific studies suggest a combined role of emotional and cognitive mechanisms in aesthetic experiences, less is known about the neural predictors of individual responsiveness to such interventions. Methods: This study was conducted in two Milan-based museums and included an initial profiling phase (sociodemographic information, trait anxiety, perceived stress, museum experience), followed by pre- and post-visit assessments of state anxiety and mood. Electrocortical activity was recorded via a portable brain–computer interface (BCI), focusing on the theta/beta ratio (TBR) as a marker of cortical–subcortical integration. Results: Museum visits were associated with significant improvements in mood (M = 1.17; p < 0.001) and reductions in state anxiety (M = −6.36; p < 0.001) in both arts and science museums. The baseline TBR predicted the magnitude of state anxiety change, alongside individual differences in trait anxiety and perceived stress. Conclusions: These findings support the idea that aesthetic experiences in museums engage both emotional and cognitive systems, and that resting state neurophysiological markers can help forecast individual responsiveness to well-being interventions. Such insights not only contribute to existing knowledge about the cognitive and emotional processes during aesthetic fruition, but could also guide future applications of personalized interventions in museum settings, further integrating cultural participation with mental health promotion. Full article

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

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29 pages, 2939 KiB

Open AccessArticle

Automated Sleep Stage Classification Using PSO-Optimized LSTM on CAP EEG Sequences

by Manjur Kolhar, Manahil Mohammed Alfuraydan, Abdulaziz Alshammary, Khalid Alharoon, Abdullah Alghamdi, Ali Albader, Abdulmalik Alnawah and Aryam Alanazi

Brain Sci. 2025, 15(8), 854; https://doi.org/10.3390/brainsci15080854 - 11 Aug 2025

Abstract

The automatic classification of sleep stages and Cyclic Alternating Pattern (CAP) subtypes from electroencephalogram (EEG) recordings remains a significant challenge in computational sleep research because of the short duration of CAP events and the inherent class imbalance in clinical datasets. Background/Objectives: The research [...] Read more.

The automatic classification of sleep stages and Cyclic Alternating Pattern (CAP) subtypes from electroencephalogram (EEG) recordings remains a significant challenge in computational sleep research because of the short duration of CAP events and the inherent class imbalance in clinical datasets. Background/Objectives: The research introduces a domain-specific deep learning system that employs an LSTM network optimized through a PSO-Hyperband hybrid hyperparameter tuning method. Methods: The research enhances EEG-based sleep analysis through the implementation of hybrid optimization methods within an LSTM architecture that addresses CAP sequence classification requirements without requiring architectural changes. Results: The developed model demonstrates strong performance on the CAP Sleep Database by achieving 97% accuracy for REM and 96% accuracy for stage S0 and ROC AUC scores exceeding 0.92 across challenging CAP subtypes (A1–A3). The model transparency is improved through the application of SHAP-based interpretability techniques, which highlight the role of spectral and morphological EEG features in classification outcomes. Conclusions: The proposed framework demonstrates resistance to class imbalance and better discrimination between visually similar CAP subtypes. The results demonstrate how hybrid optimization methods improve the performance, generalizability, and interpretability of deep learning models for EEG-based sleep microstructure analysis. Full article

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22 pages, 1071 KiB

Open AccessReview

The Interplay of Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation in Autism Spectrum Disorder: Behavioral Implications and Therapeutic Strategies

by Ansab Akhtar and SK Batin Rahaman

Brain Sci. 2025, 15(8), 853; https://doi.org/10.3390/brainsci15080853 - 11 Aug 2025

Abstract

Autism spectrum disorder (ASD) deals with several symptoms, including language and speech impairment and developmental delays. The main brain regions affected could be the prefrontal cortex (PFC) or the temporal lobe. The detrimental features could include oxidative stress, mitochondrial dysfunction, and neuroinflammation. Most [...] Read more.

Autism spectrum disorder (ASD) deals with several symptoms, including language and speech impairment and developmental delays. The main brain regions affected could be the prefrontal cortex (PFC) or the temporal lobe. The detrimental features could include oxidative stress, mitochondrial dysfunction, and neuroinflammation. Most often, these phenomena are interrelated and can lead to one another, creating a vicious cycle. They also influence the regulation of certain genes involved in the pathogenesis of ASD or related behavior. In the brain regions prone to these detrimental features, a cascade of free radicals, inflammatory cytokines, and mitochondrial energy disruptions is initiated. These actions during the prenatal or developmental stage of the child potentially lead to ASD symptomatic features, such as social isolation, communication difficulty, speech and language impairment, cognitive dysfunction, and intellectual disability. The more recent theories, including genetics, epigenetics, and the gut–brain axis, have been demonstrated to play a greater role in ASD pathology, often being associated with the more common ones as mentioned above. We also introduced some of the neurological disorders possessing shared genetic and behavioral traits with ASD. Many genes playing a role in ASD-like features and their potential targeted drugs were explained briefly. However, there are limited therapeutic options, and molecular pathways related to this disorder are less explored. Currently, researchers and therapists are racing to uncover a concrete remedy. This review also provides a brief outline of potential antioxidant, mitochondrial, and anti-inflammatory therapies. We finally included some novel strategies to diagnose and manage autistic pathology and symptoms. Full article

(This article belongs to the Special Issue Role of Inflammation, Oxidative Stress, and Metabolic Dysfunction in Neurodevelopmental and Neurodegenerative Diseases: Pharmacological Targets and Therapeutic Interventions)

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16 pages, 1359 KiB

Open AccessArticle

Comparing Immersive and Non-Immersive VR: Effects on Spatial Learning and Aesthetic Experience in Museum Settings

by Laura Piccardi, Marcello Massidda, Laura Travaglini, Sofia Pescarin, Marco Giancola, Massimiliano Palmiero, Matteo Deflorian, Sabrina Apollaro, Roberta Lista and Raffaella Nori

Brain Sci. 2025, 15(8), 852; https://doi.org/10.3390/brainsci15080852 - 11 Aug 2025

Abstract

Background/Objectives: The use of virtual reality (VR) solutions in design has rapidly increased globally. However, it remains unclear to what extent these technologies enhance people’s cognitive abilities. Understanding the impact of such technologies is essential for assessing their validity and effectiveness. In this [...] Read more.

Background/Objectives: The use of virtual reality (VR) solutions in design has rapidly increased globally. However, it remains unclear to what extent these technologies enhance people’s cognitive abilities. Understanding the impact of such technologies is essential for assessing their validity and effectiveness. In this controlled study, we investigated how HMD and non-immersive VR museum environments affect the ability to learn about the environment and the perception of the experience. Methods: A total of 87 college students (46 females) were randomly assigned to either HMD or non-immersive VR museum environments. Subsequently, they had to answer questions related to the sense of immersion and pleasantness of the museum experience, as well as their willingness to repeat similar museum experiences. Results: The results indicated that the HMD setting was preferred for its greater sense of immersion, pleasantness, and intention to repeat a similar experience. Conclusions: The data are discussed in the context of fostering appreciation and promoting the preservation of cultural heritage. Full article

(This article belongs to the Section Behavioral Neuroscience)

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8 pages, 404 KiB

Open AccessBrief Report

Cerebral Microbleeds with a Venous Connection on 3 Tesla Susceptibility-Weighted Imaging in Persons with Alzheimer’s Disease and Healthy Aging Controls

by Ulf Jensen-Kondering, Veronique Kuhn, Hannes Schacht, Alexander Neumann, Georg Royl and Peter Schramm

Brain Sci. 2025, 15(8), 851; https://doi.org/10.3390/brainsci15080851 - 10 Aug 2025

Abstract

Introduction: It has been recently demonstrated that some cerebral microbleeds (CMBs) are connected to cerebral veins in patients with cerebral small vessel disease (CSVD) including cerebral amyloid angiopathy (CAA). We sought to demonstrate the presence of CMB at 3 Tesla using susceptibility-weighted [...] Read more.

Introduction: It has been recently demonstrated that some cerebral microbleeds (CMBs) are connected to cerebral veins in patients with cerebral small vessel disease (CSVD) including cerebral amyloid angiopathy (CAA). We sought to demonstrate the presence of CMB at 3 Tesla using susceptibility-weighted imaging and speculated that it was more prevalent in persons with Alzheimer’s disease (AD), another amyloid-related disease, than in healthy ageing controls. Material and Methods: We included persons from the publicly available OASIS3-database. Persons were included if they had a structural MRI including a susceptibility-weighted sequence (SWI) and relevant clinical data. Two raters assessed the presence and location of CMBs and CMBs with a venous connection (CMB_ven). Results: A total of 571 persons (AD, n = 140, healthy controls, n = 431) were included. In total, 367 CMBs were detected, encompassing 26/571 persons (4.5%) who had a total of 40/367 (10.9%) CMBs with a CMB_ven, though there was no difference between persons with AD and healthy controls (AD 6.6%, healthy controls 7.4%, p = 0.773). Persons with CMB_ven had a higher total CMB load, were more likely female, displayed an APOE ε2/2 genotype and had antithrombotic treatment more often. Logistic regression revealed a higher number of CMB (OR (95% CI) = 1.351 (1.161–1.688), p < 0.0014) and a lower MoCA score (OR (95% CI) = 0.862 (0.762–0.982), p = 0.018), indicating a statistically significant association with the presence of CMB_ven. Discussion: CMB_ven are not an uncommon finding in persons with AD and healthy ageing controls. Our results highlight the potential venous contribution to CSVD. Histopathological studies will be needed to assess these further. Full article

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

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15 pages, 950 KiB

Open AccessReview

Methylphenidate as a Novel Adjunct in Opioid-Taking Patients: Insights into Dopaminergic Neuroadaptation and Hypoactive Delirium

by Nikodem Świderski, Patryk Rodek and Krzysztof Kucia

Brain Sci. 2025, 15(8), 850; https://doi.org/10.3390/brainsci15080850 - 8 Aug 2025

Abstract

Background and aim of this review: The ongoing opioid epidemic underscores the urgent need for innovative pharmacological and behavioral interventions to mitigate the impact of opioid use disorder (OUD). This review aims to explore theoretical overlaps between the neurobiological mechanisms underlying OUD development [...] Read more.

Background and aim of this review: The ongoing opioid epidemic underscores the urgent need for innovative pharmacological and behavioral interventions to mitigate the impact of opioid use disorder (OUD). This review aims to explore theoretical overlaps between the neurobiological mechanisms underlying OUD development and the pharmacodynamic profile of methylphenidate (MPH). Particular attention is given to the potential shared molecular targets, safety considerations, and therapeutic implications of MPH use in this clinical context. Main finding: In the development of opioid dependence, the negative reinforcement of the dopaminergic transmission of the mesocorticolimbic pathway induced by the supraspinal action of opioid receptor agonists plays a major role. The induced state of hypodopaminergic and hyperadrenergic modulates the underlying disease process by affecting cognitive control, affective regulation, and motivational drive. MPH, acting as a dopamine reuptake inhibitor and modulator of vesicular monoamine transporter 2 (VMAT-2), increases extracellular dopamine availability and enhances dopaminergic signaling, suggesting potential utility in restoring dopaminergic tone in OUD. Additionally, MPH has shown efficacy in hypoactive delirium in patients with terminal cancer, improving both cognitive function and psychomotor drive. Conclusions and future perspectives: There appear to be converging neurobiological mechanisms between the action of MPH and the pathophysiology of OUD, particularly within the dopaminergic system. However, well-designed clinical trials are essential to identify the patient subgroups that may benefit from adjunctive MPH treatment, to evaluate its efficacy in this setting, and to assess the long-term safety and risk profile of stimulant use in individuals with OUD. Full article

(This article belongs to the Topic New Advances in Addiction Behavior)

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41 pages, 2785 KiB

Open AccessSystematic Review

A Systematic Review of Preclinical Studies Investigating the Effects of Pharmacological Agents on Learning and Memory in Prolonged Aluminum-Exposure-Induced Neurotoxicity

by Mahnoor Hayat, Noor Ul Huda Khola and Touqeer Ahmed

Brain Sci. 2025, 15(8), 849; https://doi.org/10.3390/brainsci15080849 - 8 Aug 2025

Abstract

Background: Aluminum accumulation in the brain causes cognitive deficits. No comprehensive synthesis of pharmacological treatments against aluminum neurotoxicity has been conducted, which led us to systematically review the effects of various pharmacological agents against aluminum-induced neurotoxicity, primarily addressing learning and memory after chronic [...] Read more.

Background: Aluminum accumulation in the brain causes cognitive deficits. No comprehensive synthesis of pharmacological treatments against aluminum neurotoxicity has been conducted, which led us to systematically review the effects of various pharmacological agents against aluminum-induced neurotoxicity, primarily addressing learning and memory after chronic aluminum exposure (≥2 months) in rodent models. Methods: A literature search was performed in PubMed, Google Scholar, Science Direct, and Scopus for studies published between 2000 and 2023. A total of 45 studies were selected according to the inclusion criteria. Primary outcomes focused on assessing learning and memory, with 39 different pharmacological agents evaluated explicitly for their effects against aluminum-induced neurotoxicity. Meta-analysis and subgroup analysis were performed to evaluate cognitive improvement in the Morris water maze (MWM) for learning and memory, and oxidative stress parameters were evaluated through superoxide dismutase (SOD) and catalase (CAT) in aluminum-induced neurotoxicity models. Results: According to the systematic analysis, most treatments significantly improve learning and memory, except for insulin and melatonin. According to the MWM analysis, Memantine, Hypericum perforatum extract, Bennincasa hespidia, and, based on the biochemical analysis, Chrysin showed better results. The meta-analysis (random effects) revealed reduced escape latency (SMD = 0.97, 95% CI: 0.74 to 1.19) and increased SOD (SMD = −0.54, 95% CI: −0.79 to −0.29) and CAT levels (SMD = −0.50, 95% CI: −0.73 to −0.27) in treated groups versus aluminum. Egger’s regression tests showed no strong evidence of publication bias. Conclusions: This study effectively synthesized preclinical evidence, identifying promising pharmacological agents for mitigating aluminum-induced cognitive deficits. These findings offer a scientific basis for future experimental studies and therapeutic development targeting aluminum neurotoxicity. Full article

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

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16 pages, 493 KiB

Open AccessReview

Educational Discrimination and Challenges of Inclusion During the Pandemic: The Case of Students with Autism Spectrum Disorder (ASD) from an International Perspective

by José Jesús Sánchez Amate, Antonio Luque de la Rosa and Pedro Tadeu

Brain Sci. 2025, 15(8), 848; https://doi.org/10.3390/brainsci15080848 - 8 Aug 2025

Abstract

Background: The COVID-19 pandemic exposed the fragility of educational systems in ensuring inclusive schooling, especially for students with Autism Spectrum Disorder (ASD). Disruptions to daily routines, the shift to remote learning, and the suspension of specialized services intensified pre-existing inequalities and affected the [...] Read more.

Background: The COVID-19 pandemic exposed the fragility of educational systems in ensuring inclusive schooling, especially for students with Autism Spectrum Disorder (ASD). Disruptions to daily routines, the shift to remote learning, and the suspension of specialized services intensified pre-existing inequalities and affected the educational continuity and well-being of this group. Methods: This narrative review analyzes the educational discrimination experienced by students with ASD during the pandemic. A structured search was conducted across databases including Scopus, Web of Science, PubMed, ERIC, Dialnet, and Google Scholar. Sixteen empirical studies published between 2020 and 2024 were selected based on criteria such as open access, focus on compulsory education, and direct analysis of pandemic-related exclusion. Results: The findings reveal four key challenges: unequal access to digital resources, the interruption of support services, increased family burden, and limited institutional responses. These factors contributed to emotional distress, regression in skills, and reduced participation in educational and social settings. Conclusions: The review concludes that the pandemic acted as a magnifying glass for structural barriers already present in inclusive education. Moving forward, educational systems must develop flexible, sustainable, and equity-oriented frameworks to ensure that students with ASD are not left behind during future crises. Full article

(This article belongs to the Special Issue Advances in Educational Neuroscience: Current Status and Future Directions)

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9 pages, 588 KiB

Open AccessCommunication

Differential Neuroendocrine Responses and Dysregulation of the Hypothalamic–Pituitary–Adrenal Axis Following Repeated Mild Concussive Impacts and Blast Exposures in a Rat Model

by Rex Jeya Rajkumar Samdavid Thanapaul, Jishnu K. S. Krishnan, Manoj Y. Govindarajulu, Chetan Y. Pundkar, Gaurav Phuyal, Joseph B. Long and Peethambaran Arun

Brain Sci. 2025, 15(8), 847; https://doi.org/10.3390/brainsci15080847 - 8 Aug 2025

Abstract

Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term [...] Read more.

Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term neuroendocrine consequences of mild, repetitive brain trauma are poorly understood. In this study, we investigated the temporal dynamics of hypothalamic–pituitary–adrenal (HPA) axis dysregulation following repeated mild concussive head impacts and blast exposures using two clinically relevant rodent models. Male Sprague-Dawley rats were subjected to repeated mild concussive impacts using a modified weight drop model or repeated blast exposures using an advanced blast simulator. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were measured on days 1 and 30 post-injuries. Our findings revealed that repeated blast exposures induced elevation of plasma ACTH and corticosterone on days 1 and 30 post-blasts. After the repeated mild concussive impacts, increased plasma levels of corticosterone were observed on days 1 and 30, but ACTH levels were increased only on day 30. This study is among the first to directly compare neuroendocrine outcomes of repeated mild concussive impacts and blast exposures within a unified experimental framework. Our findings demonstrate distinct temporal trajectories of HPA axis dysregulation depending on injury type and highlight plasma levels of ACTH and corticosterone as potential biomarkers of subclinical brain trauma. These insights may inform early diagnostic approaches and therapeutic strategies aimed at mitigating long-term stress-related complications following mild traumatic brain injuries. Full article

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

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36 pages, 1926 KiB

Open AccessArticle

Emotional Brain Development: Neurobiological Indicators from Fetus Through Toddlerhood

by Gerry Leisman, Rahela Alfasi and Amedeo D’Angiulli

Brain Sci. 2025, 15(8), 846; https://doi.org/10.3390/brainsci15080846 - 8 Aug 2025

Abstract

The maturation of brain regions involved in emotion regulation—particularly the amygdala and prefrontal cortex—from fetal life to age two is a dynamic process shaped by genetic and environmental factors. Early experiences, especially responsive caregiving, promote the growth of neural circuits supporting emotional expression [...] Read more.

The maturation of brain regions involved in emotion regulation—particularly the amygdala and prefrontal cortex—from fetal life to age two is a dynamic process shaped by genetic and environmental factors. Early experiences, especially responsive caregiving, promote the growth of neural circuits supporting emotional expression and regulation. In contrast, early adversity such as neglect or chronic stress may disrupt these circuits and increase vulnerability to emotional difficulties. Elevated levels of placental CRH are linked to alterations in fetal brain development related to emotion. Neurodevelopmental processes like synaptic pruning and myelination, active during the first years, further shape emotional circuitry. These findings underscore the importance of early caregiving and timely interventions in fostering healthy emotional development. The present article proposes an integrative conceptual framework for early emotional and cognitive development, combining neurobiological models with contemporary theories in developmental psychology. Full article

(This article belongs to the Special Issue Emotional Brain Development in Children)

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11 pages, 1369 KiB

Open AccessBrief Report

Immunohistochemical Evaluation of Acetylcholinesterase-Positive Neurons in the Brain Cortex of Rats After Administration of Rebaudioside A

by Karol Rycerz, Krzysztof Balawender, Tommaso Cassano, Agnieszka Żuryń, Marcin B. Arciszewski, Jerzy Walocha and Agata Wawrzyniak

Brain Sci. 2025, 15(8), 845; https://doi.org/10.3390/brainsci15080845 - 8 Aug 2025

Abstract

Objectives: The aim of this study was to investigate the effect of Rebaudioside A (RebA) on acetylcholinesterase (AChE) immunoreactivity in cortical neurons of the rat brain. RebA is a steviol glycoside commonly used in the production of sweeteners. Beyond its application as a [...] Read more.

Objectives: The aim of this study was to investigate the effect of Rebaudioside A (RebA) on acetylcholinesterase (AChE) immunoreactivity in cortical neurons of the rat brain. RebA is a steviol glycoside commonly used in the production of sweeteners. Beyond its application as a food additive for diabetes management, steviol glycosides have been shown to influence memory and learning processes. Methods: RebA was administered to rats at two concentrations (1 mg/mL and 2 mg/mL of water) over both short-term (15 days) and long-term (45 days) periods. Indirect immunohistochemical peroxidase–antiperoxidase staining was performed on histological frontal sections of the brain cortex. Results: Acetylcholinesterase-positive neurons were analyzed both morphologically and morphometrically. The results of the experiment revealed no significant morphological changes in AChE-immunopositive neurons, indicating an absence of neurotoxic effects associated with the sweetener in these neurons. However, the analysis demonstrated a reduction in AChE immunoreactivity, particularly after 45 days of treatment. Conclusions: These preliminary findings demonstrates that RebA affects the immunoreactivity of neurons positive for AChE. Given the observed effects, further studies should be implemented to investigate the exact influence of this dietary supplement on the cholinergic nervous system. Full article

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16 pages, 1002 KiB

Open AccessArticle

A Targeted Radiotheranostic Agent for Glioblastoma: [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK)

by Alireza Mirzaei, Samia Ait-Mohand, Prenitha Mercy Ignatius Arokia Doss, Étienne Rousseau and Brigitte Guérin

Brain Sci. 2025, 15(8), 844; https://doi.org/10.3390/brainsci15080844 - 7 Aug 2025

Abstract

Glioblastoma multiforme (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with poor prognosis and limited therapeutic options. Background/Objectives: Integrin α_vβ₃, a cell surface receptor overexpressed in GBM, specifically binds to cyclic arginine-glycine-aspartate-D-phenylalanine-lysine (c(RGDfK)) motif, making [...] Read more.

Glioblastoma multiforme (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with poor prognosis and limited therapeutic options. Background/Objectives: Integrin α_vβ₃, a cell surface receptor overexpressed in GBM, specifically binds to cyclic arginine-glycine-aspartate-D-phenylalanine-lysine (c(RGDfK)) motif, making it a valuable target for tumor-specific delivery and PET imaging. This study explores a novel radiotheranostic agent, [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK), which combines the imaging and therapeutic capabilities of copper-64 (⁶⁴Cu) and the cytotoxic activity of a terpyridine-platinum (TP) complex, conjugated to c(RGDfK). Methods: A robust protocol was developed for the small-scale preparation of NOTA-TP-c(RGDfK). Comparative cellular studies were conducted using U87 MG glioblastoma (GBM) cells and SVG p12 human astrocytes to evaluate the performance of [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) relative to [⁶⁴Cu]Cu-NOTA-c(RGDfK), [⁶⁴Cu]Cu-NOTA-TP, ^natCu-NOTA-TP-c(RGDfK), cisplatin, and temozolomide. Results: ⁶⁴Cu-radiolabeling of NOTA-TP-c(RGDfK) was achieved with >99% radiochemical purity, and competition assays confirmed high binding affinity to integrin α_vβ₃ (IC₅₀ = 16 ± 8 nM). Cellular uptake, internalization, and retention studies demonstrated significantly higher accumulation of [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) in U87 MG cells compared to control compounds, with 38.8 ± 1.8% uptake and 28.0 ± 1.0% internalization at 24 h. Nuclear localization (6.0 ± 0.5%) and stable intracellular retention further support its therapeutic potential for inducing localized DNA damage. Importantly, [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) exhibited the highest cytotoxicity in U87 MG cells (IC₅₀ = 10 ± 2 nM at 48 h), while maintaining minimal toxicity in normal SVG p12 astrocytes. Conclusions: These results highlight [⁶⁴Cu]Cu-NOTA-TP-c(RGDfK) as a promising targeted radiotheranostic agent for GBM, warranting further preclinical development Full article

(This article belongs to the Special Issue New Advances in the Development of New Drugs and Treatment Targets for Brain Cancers (2nd Edition))

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19 pages, 427 KiB

Open AccessArticle

The Role of Fear of Negative Evaluation and Loneliness in Linking Insecure Attachment to Social Media Addiction: Evidence from Chinese University Students

by Di Xu and Ruoxi He

Brain Sci. 2025, 15(8), 843; https://doi.org/10.3390/brainsci15080843 - 7 Aug 2025

Abstract

Background and Objectives: With the widespread integration of digital media into daily life, social media addiction (SMA) has become a growing concern for university students’ mental health. Based on attachment theory, this study examined how attachment anxiety and avoidance influence SMA through fear [...] Read more.

Background and Objectives: With the widespread integration of digital media into daily life, social media addiction (SMA) has become a growing concern for university students’ mental health. Based on attachment theory, this study examined how attachment anxiety and avoidance influence SMA through fear of negative evaluation (FNE) and loneliness. Methods: A sample of 400 Chinese university students completed the 16-item short version of the Experiences in Close Relationships Scale (ECR), the 8-item Brief Fear of Negative Evaluation Scale (BFNE), the 6-item Revised UCLA Loneliness Scale–Short Form (RULS-6), and the 6-item Bergen Social Media Addiction Scale (BSMAS). Using the PROCESS macro (Model 6), a chained mediation model was tested. Results: Attachment anxiety positively predicts SMA (β = 0.42); the chained mediation pathway through FNE and loneliness accounts for ab = 0.06 of this effect, alongside additional single-mediator paths. In contrast, attachment avoidance shows a weaker total effect (β = −0.08) and a small negative chained mediation effect (ab = −0.02), offset by opposing single-mediator paths via FNE (negative) and loneliness (positive), resulting in a nonsignificant total indirect effect. Discussion: These findings suggest that in the Chinese cultural context, where social evaluation and belonging are emphasized, insecure attachment may heighten emotional reliance on social media. This study elucidates the socio-emotional mechanisms underlying SMA and extends the application of attachment theory to the digital media environment. Full article

(This article belongs to the Special Issue The Perils of Social Media Addiction)

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15 pages, 440 KiB

Open AccessArticle

Automated Detection of Epileptic Seizures in EEG Signals via Micro-Capsule Networks

by Baozeng Wang, Jiayue Zhou, Hualiang Zhang, Jin Zhou and Changyong Wang

Brain Sci. 2025, 15(8), 842; https://doi.org/10.3390/brainsci15080842 - 7 Aug 2025

Abstract

Background: Epilepsy is a chronic neurological disorder that affects individuals across all age groups. Early detection and intervention are crucial for minimizing both physical and psychological distress. However, the unpredictable nature of seizures presents considerable challenges for timely detection and accurate diagnosis. Method: [...] Read more.

Background: Epilepsy is a chronic neurological disorder that affects individuals across all age groups. Early detection and intervention are crucial for minimizing both physical and psychological distress. However, the unpredictable nature of seizures presents considerable challenges for timely detection and accurate diagnosis. Method: To address the challenge of low recognition accuracy in small-sample, single-channel epileptic electroencephalogram (EEG) signals, this study proposes an automated seizure detection method using a micro-capsule network. First, we propose a dimensionality-increasing transformation technique for single-channel EEG signals to meet the network’s input requirements. Second, a streamlined micro-capsule network is designed by optimizing and simplifying the framework’s architecture. Finally, EEG features are encoded as feature vectors to better represent spatial hierarchical relationships between seizure patterns, enhancing the framework’s adaptability and improving detection accuracy. Result: Compared to existing EEG-based detection methods, our approach achieves higher accuracy on small-sample datasets while maintaining a reduction in computational complexity. Conclusions: By leveraging its micro-capsule network architecture, the framework demonstrates superior classification accuracy when analyzing single-channel epileptiform EEG signals, significantly outperforming both convolutional neural network-based implementations and established machine learning methodologies. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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14 pages, 288 KiB

Open AccessArticle

Emotional Status in Relation to Metacognitive Self-Awareness and Level of Functional Disability Following Acquired Brain Injury

by Valentina Bandiera, Dolores Villalobos, Alberto Costa, Gaia Galluzzi, Alessia Quinzi, Arianna D’Aprile and Umberto Bivona

Brain Sci. 2025, 15(8), 841; https://doi.org/10.3390/brainsci15080841 - 6 Aug 2025

Abstract

Background/Objectives: Impairment in self-awareness (ISA) is one of the common consequences of an acquired brain injury (ABI) and is associated with anosodiaphoria. Collectively, these co-occurring neuropsychological disorders pose significant obstacles in the neurorehabilitation of moderate-to-severe ABI patients. Individuals who recover from ISA [...] Read more.

Background/Objectives: Impairment in self-awareness (ISA) is one of the common consequences of an acquired brain injury (ABI) and is associated with anosodiaphoria. Collectively, these co-occurring neuropsychological disorders pose significant obstacles in the neurorehabilitation of moderate-to-severe ABI patients. Individuals who recover from ISA may present with anxiety and/or depression as adaptive reactions to the ABI, along with related functional disabilities. The present study investigated whether the level of metacognitive self-awareness (SA) is associated with the presence of anxiety and depression, apathy, or anosodiaphoria in patients with moderate-to-severe ABI. It aimed also at investigating the possible relationship between the severity of disability and both psycho-emotional diseases and the presence of PTSD symptoms in patients with high metacognitive SA. Methods: Sixty patients with moderate-to-severe ABI and different levels of metacognitive SA completed a series of questionnaires, which assessed their self-reported metacognitive SA, anosodiaphoria, anxiety and depression, apathy, and PTSD symptoms. Results: Low-metacognitive-SA patients showed lower levels of anxiety and depression and higher anosodiaphoria than high-metacognitive-SA patients. Patients with high metacognitive SA and high levels of disability showed significant higher states of anxiety and PTSD symptoms than patients with high metacognitive SA and low levels of disability. Conclusions: The neurorehabilitation of individuals with moderate to severe ABI should address, in particular, the complex interaction between ISA and anxiety and depression in patients during the rehabilitation process. Full article

(This article belongs to the Special Issue Anosognosia and the Determinants of Self-Awareness)

11 pages, 576 KiB

Open AccessArticle

Phasic REM: Across Night Behavior and Transitions to Wake

by Giuseppe Barbato and Thomas A. Wehr

Brain Sci. 2025, 15(8), 840; https://doi.org/10.3390/brainsci15080840 - 6 Aug 2025

Abstract

Background/Objectives: Rapid eye movements (REMs) during sleep were initially associated with dreaming, suggesting a relationship between REMs and dream content; however, this hypothesis was questioned by their differences with the REMs during wakefulness and the evidence that REMs are also present in blind [...] Read more.

Background/Objectives: Rapid eye movements (REMs) during sleep were initially associated with dreaming, suggesting a relationship between REMs and dream content; however, this hypothesis was questioned by their differences with the REMs during wakefulness and the evidence that REMs are also present in blind individuals with no visual dreaming. Successive studies have focused on the phenomenology and physiological significance of REMs during sleep. REMs are categorized as expressions of the phasic REM component, which is characterized by bursts of eye movements, whereas the tonic REM component is characterized by quiescent periods without eye movements. Methods: The study is a retrospective analysis of 105 sleep records from 15 subjects. We analyzed the two components, tonic and phasic REM, across the sleep period, the REM activity in the first 5 min and in the last 5 min of each REM period were also assessed. Results: Phasic epochs were more represented than tonic epochs across the whole night period. REM activity in the first and last five minutes of an REM period presented different, although non-significant, patterns across the night. REM activity in the first 5 min showed a curvilinear profile, whereas REM activity in the last 5 min showed a linear increasing trend. A significant correlation was found between the REM activity in the first 5 min of the REM period and the total duration of the REM period. Conclusions: According to our results, the analysis of REM activity and the focus on segments of an REM period could provide more information both on the temporal evolution of REM activity within an REM period and on the possible role of REMs in REM sleep regulation and its significance in psychiatric and neurological disorders. Full article

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

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34 pages, 1136 KiB

Open AccessReview

Efficacy of Transcranial Magnetic Stimulation and Transcranial Direct-Current Stimulation in Primary Progressive Aphasia Treatment: A Review

by Elena Gobbi, Ilaria Pagnoni, Elena Campana, Rosa Manenti and Maria Cotelli

Brain Sci. 2025, 15(8), 839; https://doi.org/10.3390/brainsci15080839 - 5 Aug 2025

Abstract

Background: In recent years, there has been increasing interest in the application of repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct-Current Stimulation (tDCS) to enhance and rehabilitate the language abilities in individuals with neurodegenerative diseases. Objective: The aim of this narrative [...] Read more.

Background: In recent years, there has been increasing interest in the application of repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct-Current Stimulation (tDCS) to enhance and rehabilitate the language abilities in individuals with neurodegenerative diseases. Objective: The aim of this narrative literature review is to investigate the usefulness of rTMS and tDCS to improve language abilities in people with Primary Progressive Aphasia (PPA). Methods: This narrative literature review was conducted through a search of the PubMed online database to identify studies investigating the effects of multiple sessions of rTMS or tDCS on language abilities in PPA patients, applied either as stand-alone interventions or in combination with language treatment. Results: Thirty-three studies fulfilled the inclusion criteria; five studies employed rTMS without language treatment; two studies applied tDCS as stand-alone intervention; twenty-two studies combined tDCS with language treatment; and four studies assessed the effects of tDCS during verbal task without language treatment. Conclusions: rTMS and tDCS applied with or without concomitant language treatment appear to be promising interventions for enhancing language abilities in PPA, with sustained effects reported over time. Further research is necessary to optimise stimulation protocols and to improve our understanding of their long-term effects. Moreover, randomised controlled trials (RCTs) with larger sample sizes are critically needed to clarify the true impact of brain stimulation in PPA, with a focus on changes in cognitive and functional performance, neural activity, and potential molecular correlates. Full article

(This article belongs to the Special Issue Latest Research on the Treatments of Speech and Language Disorders)

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3 pages, 148 KiB

Open AccessCorrection

Correction: Zarate-Calderon et al. Risk of Cerebrovascular Events in Deep Brain Stimulation for Parkinson’s Disease Focused on STN and GPi: Systematic Review and Meta-Analysis. Brain Sci. 2025, 15, 413

by Cristofer Zarate-Calderon, Carlos Castillo-Rangel, Iraís Viveros-Martínez, Estefanía Castro-Castro, Luis I. García and Gerardo Marín

Brain Sci. 2025, 15(8), 838; https://doi.org/10.3390/brainsci15080838 - 5 Aug 2025

Abstract

In the original publication, there was a mistake in the legend for Table 1 [...] Full article

(This article belongs to the Section Neurodegenerative Diseases)

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