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Volume 15
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Brain Sci., Volume 15, Issue 8 (August 2025) – 83 articles

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14 pages, 249 KiB  
Review
Balancing Risk and Reward: Dopamine’s Central Role in Economic Decision-Making
by Luca Aquili and Lee Wei Lim
Brain Sci. 2025, 15(8), 857; https://doi.org/10.3390/brainsci15080857 (registering DOI) - 12 Aug 2025
Abstract
Dopamine has been increasingly implicated in shaping economic and financial decision-making, yet much of the evidence remains fragmented across paradigms and mechanistic levels, and heavily based on preclinical or clinical populations. This review synthesises pharmacological, neuroimaging, and genetic findings from studies involving healthy [...] Read more.
Dopamine has been increasingly implicated in shaping economic and financial decision-making, yet much of the evidence remains fragmented across paradigms and mechanistic levels, and heavily based on preclinical or clinical populations. This review synthesises pharmacological, neuroimaging, and genetic findings from studies involving healthy human participants, highlighting dopamine’s role in risk-taking, delay discounting, social fairness, reward sensitivity, and feedback learning. It distinguishes between transient state-related effects and stable trait-level influences, and clarifies how dopaminergic tone, receptor subtype activity—particularly D2—and corticostriatal circuitry modulate economic choices. In doing so, the review advances a mechanism-focused framework for understanding adaptive and biased decision strategies. Full article
(This article belongs to the Special Issue Advances in Dopamine and Cognition)
5 pages, 148 KiB  
Editorial
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
Abstract
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  
Article
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  
Article
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  
Review
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  
Article
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  
Brief 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
Viewed by 80
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 (CMBven). 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 CMBven, though there was no difference between persons with AD and healthy controls (AD 6.6%, healthy controls 7.4%, p = 0.773). Persons with CMBven 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 CMBven. Discussion: CMBven 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  
Review
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
Viewed by 238
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  
Systematic 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
Viewed by 155
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  
Review
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
Viewed by 187
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  
Communication
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
Viewed by 165
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  
Article
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
Viewed by 208
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  
Brief 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
Viewed by 186
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  
Article
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
Viewed by 179
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 αvβ3, 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 αvβ3, 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 αvβ3 (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  
Article
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
Viewed by 329
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  
Article
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
Viewed by 243
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  
Article
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
Viewed by 222
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  
Article
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
Viewed by 268
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  
Review
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
Viewed by 298
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  
Correction
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
Viewed by 137
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)
16 pages, 2443 KiB  
Article
Contralateral Structure and Molecular Response to Severe Unilateral Brain Injury
by Xixian Liao, Xiaojian Xu, Ming Li, Runfa Tian, Yuan Zhuang and Guoyi Gao
Brain Sci. 2025, 15(8), 837; https://doi.org/10.3390/brainsci15080837 - 5 Aug 2025
Viewed by 375
Abstract
Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, [...] Read more.
Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, can help discover potential treatment strategies to promote recovery after severe brain trauma on one side. Methods: In our study, the right motor cortex was surgically removed to simulate severe unilateral brain injury, and changes in glial cells and synaptic structure in the contralateral cortex were subsequently assessed through immunohistological, morphological, and Western blot analyses. We conducted transcriptomic studies to explore changes in gene expression levels associated with the inflammatory response. Results: Seven days after corticotomy, levels of reactive astrocytes and hypertrophic microglia increased significantly in the experimental group, while synapsin-1 and PSD-95 levels in the contralateral motor cortex increased. These molecular changes are associated with structural changes, including destruction of dendritic structures and the encapsulation of astrocytes by synapses. Genome-wide transcriptome analysis showed a significant increase in gene pathways involved in inflammatory responses, synaptic activity, and nerve fiber regeneration in the contralateral cortex after corticorectomy. Key transcription factors such as NF-κB1, Rela, STAT3 and Jun were identified as potential regulators of these contralateral changes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the mRNA expression levels of Cacna1c, Tgfb1 and Slc2a1 genes related to STAT3, JUN, and NF-κB regulation significantly increased in the contralateral cortex of the experimental group. Conclusions: After unilateral brain damage occurs, changes in the contralateral cerebral hemisphere are closely related to processes involving inflammation and synaptic function. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms Regulating Neuronal Function, Homeostasis, and Disease)
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10 pages, 209 KiB  
Article
“Hangry” in Forensic Psychiatry? Analysis of the Relationship Between Eating Disorders and Aggressive Behavior in Patients with Substance Use Disorders
by Judith Streb, Tinatin Deisenhofer, Samira Schneider, Victoria Peters and Manuela Dudeck
Brain Sci. 2025, 15(8), 836; https://doi.org/10.3390/brainsci15080836 - 4 Aug 2025
Viewed by 339
Abstract
Background/Objectives: Substance use disorders and eating disorders frequently co-occur and are both associated with increased aggression. As a result, individuals with these conditions are overrepresented in prison populations. The present study investigated whether symptoms of eating disorders in male forensic psychiatric inpatients [...] Read more.
Background/Objectives: Substance use disorders and eating disorders frequently co-occur and are both associated with increased aggression. As a result, individuals with these conditions are overrepresented in prison populations. The present study investigated whether symptoms of eating disorders in male forensic psychiatric inpatients with substance use disorders are associated with heightened aggression. To this end, various forms of aggressive behavior—including spontaneous and reactive aggression, excitability, and violent offenses—were analyzed. Methods: Fifty-six male patients from two forensic psychiatric hospitals in Germany participated in the study. Symptoms of eating disorders were evaluated with the German version of the Eating Disorder Examination Questionnaire (EDE-Q), and aggression was measured with the Short Questionnaire for the Assessment of Aggression Factors (K-FAF) and by considering the violent index offense. Data were analyzed by generalized linear models, with age and body mass index (BMI) included as covariates. Results: Higher EDE-Q scores significantly predicted increased spontaneous aggression and excitability. However, no significant association was found between eating disorder symptoms and reactive aggression or the likelihood of a violent index offense. Age and BMI did not significantly influence any aggression subscales. Conclusions: The findings suggest that in patients with substance use disorder, eating disorder symptoms may be linked to heightened internalized forms of aggression. These results support the clinical relevance of screening for eating disorder symptoms in forensic psychiatric settings and integrating dietary interventions into therapeutic efforts to manage aggression. Full article
(This article belongs to the Special Issue Substance Abuse in the Psychiatric Population)
27 pages, 1766 KiB  
Article
A Novel Optimized Hybrid Deep Learning Framework for Mental Stress Detection Using Electroencephalography
by Maithili Shailesh Andhare, T. Vijayan, B. Karthik and Shabana Urooj
Brain Sci. 2025, 15(8), 835; https://doi.org/10.3390/brainsci15080835 - 4 Aug 2025
Viewed by 345
Abstract
Mental stress is a psychological or emotional strain that typically occurs because of threatening, challenging, and overwhelming conditions and affects human behavior. Various factors, such as professional, environmental, and personal pressures, often trigger it. In recent years, various deep learning (DL)-based schemes using [...] Read more.
Mental stress is a psychological or emotional strain that typically occurs because of threatening, challenging, and overwhelming conditions and affects human behavior. Various factors, such as professional, environmental, and personal pressures, often trigger it. In recent years, various deep learning (DL)-based schemes using electroencephalograms (EEGs) have been proposed. However, the effectiveness of DL-based schemes is challenging because of the intricate DL structure, class imbalance problems, poor feature representation, low-frequency resolution problems, and complexity of multi-channel signal processing. This paper presents a novel hybrid DL framework, BDDNet, which combines a deep convolutional neural network (DCNN), bidirectional long short-term memory (BiLSTM), and deep belief network (DBN). BDDNet provides superior spectral–temporal feature depiction and better long-term dependency on the local and global features of EEGs. BDDNet accepts multiple EEG features (MEFs) that provide the spectral and time-domain features of EEGs. A novel improved crow search algorithm (ICSA) was presented for channel selection to minimize the computational complexity of multichannel stress detection. Further, the novel employee optimization algorithm (EOA) is utilized for the hyper-parameter optimization of hybrid BDDNet to enhance the training performance. The outcomes of the novel BDDNet were assessed using a public DEAP dataset. The BDDNet-ICSA offers improved recall of 97.6%, precision of 97.6%, F1-score of 97.6%, selectivity of 96.9%, negative predictive value NPV of 96.9%, and accuracy of 97.3% to traditional techniques. Full article
(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)
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34 pages, 1876 KiB  
Article
The Interaction of Target and Masker Speech in Competing Speech Perception
by Sheyenne Fishero, Joan A. Sereno and Allard Jongman
Brain Sci. 2025, 15(8), 834; https://doi.org/10.3390/brainsci15080834 - 4 Aug 2025
Viewed by 282
Abstract
Background/Objectives: Speech perception typically takes place against a background of other speech or noise. The present study investigates the effectiveness of segregating speech streams within a competing speech signal, examining whether cues such as pitch, which typically denote a difference in talker, [...] Read more.
Background/Objectives: Speech perception typically takes place against a background of other speech or noise. The present study investigates the effectiveness of segregating speech streams within a competing speech signal, examining whether cues such as pitch, which typically denote a difference in talker, behave in the same way as cues such as speaking rate, which typically do not denote the presence of a new talker. Methods: Native English speakers listened to English target speech within English two-talker babble of a similar or different pitch and/or a similar or different speaking rate to identify whether mismatched properties between target speech and masker babble improve speech segregation. Additionally, Dutch and French masker babble was tested to identify whether an unknown language masker improves speech segregation capacity and whether the rhythm patterns of the unknown language modulate the improvement. Results: Results indicated that a difference in pitch or speaking rate between target and masker improved speech segregation, but when both pitch and speaking rate differed, only a difference in pitch improved speech segregation. Results also indicated improved speech segregation for an unknown language masker, with little to no role of rhythm pattern of the unknown language. Conclusions: This study increases the understanding of speech perception in a noisy ecologically valid context and suggests that there is a link between a cue’s potential to denote a new speaker and its ability to aid in speech segregation during competing speech perception. Full article
(This article belongs to the Special Issue Language Perception and Processing)
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20 pages, 681 KiB  
Review
Unraveling Glioblastoma Heterogeneity: Advancing Immunological Insights and Therapeutic Innovations
by Joshua H. Liu, Maksym Horiachok, Santosh Guru and Cecile L. Maire
Brain Sci. 2025, 15(8), 833; https://doi.org/10.3390/brainsci15080833 - 2 Aug 2025
Viewed by 555
Abstract
Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new [...] Read more.
Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article
(This article belongs to the Special Issue Recent Advances in Translational Neuro-Oncology)
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11 pages, 770 KiB  
Article
Acute Ischemic Stroke Treatment in Germany (2015–2023): Nationwide Trends in Thrombolysis and Thrombectomy by Age and Sex
by Sara Hirsch, Karel Kostev, Christian Tanislav and Ali Hammed
Brain Sci. 2025, 15(8), 832; https://doi.org/10.3390/brainsci15080832 - 2 Aug 2025
Viewed by 390
Abstract
Background: The implementation of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in acute ischemic stroke (AIS) has proven effective, offering significant benefits for patient outcomes. We therefore investigated trends in the implementation of IVT and MT in Germany between 2015 and 2023. Methods: [...] Read more.
Background: The implementation of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in acute ischemic stroke (AIS) has proven effective, offering significant benefits for patient outcomes. We therefore investigated trends in the implementation of IVT and MT in Germany between 2015 and 2023. Methods: We conducted a retrospective analysis using German Diagnosis-Related Group (DRG) statistics from 2015 to 2023. Treatment numbers were analyzed annually based on OPS codes. We examined the age and sex distribution of patients undergoing these treatments. Additionally, we analyzed all hospital cases coded with ICD-10 for acute ischemic stroke (AIS). Results: Between 2015 and 2023, the number of AIS cases in Germany slightly declined from 250,802 to 248,107 (−1.1%), with the largest annual decrease (−4.3%) occurring during the COVID-19 pandemic (2019–2020). Despite this, the use of IVT increased from 40,766 cases (16.25%) in 2015 to 48,378 (19.50%) in 2023. MT usage rose even more sharply, from 7840 cases (3.13%) to 22,445 (9.05%). Among MT recipients, the proportion of patients aged ≥80 years rose significantly, from 27.2% to 42.1%. In this age group, women consistently comprised the majority of MT patients—65.4% in 2015 and 65.5% in 2023. Conclusions: Despite a stable stroke incidence, the use of IVT—and particularly MT—continued to increase in Germany from 2015 to 2023, even during the COVID-19 pandemic. MT usage nearly tripled, especially among patients aged ≥80 years. These trends highlight a resilient stroke care system and underscore the need for future planning to meet the rising demand for endovascular treatment in an aging population. Full article
(This article belongs to the Special Issue Management of Acute Stroke)
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30 pages, 919 KiB  
Systematic Review
Advances in Research on Brain Structure and Activation Characteristics in Patients with Anterior Cruciate Ligament Reconstruction: A Systematic Review
by Jingyi Wang, Yaxiang Jia, Qiner Li, Longhui Li, Qiuyu Dong and Quan Fu
Brain Sci. 2025, 15(8), 831; https://doi.org/10.3390/brainsci15080831 - 1 Aug 2025
Viewed by 232
Abstract
Objectives: To synthesize evidence on structural and functional neuroplasticity in patients after anterior cruciate ligament reconstruction (ACLR) and its clinical implications. Methods: Adhering to the PRISMA guidelines for systematic reviews and meta-analyses, a literature search was conducted using PubMed, Embase, Web of [...] Read more.
Objectives: To synthesize evidence on structural and functional neuroplasticity in patients after anterior cruciate ligament reconstruction (ACLR) and its clinical implications. Methods: Adhering to the PRISMA guidelines for systematic reviews and meta-analyses, a literature search was conducted using PubMed, Embase, Web of Science, Scopus, and Cochrane CENTRAL (2018–2025) using specific keyword combinations, screening the results based on predetermined inclusion and exclusion criteria. Results: Among the 27 included studies were the following: (1) sensory cortex reorganization with compensatory visual dependence (5 EEG/fMRI studies); (2) reduced motor cortex efficiency evidenced by elevated AMT (TMS, 8 studies) and decreased γ-CMC (EEG, 3 studies); (3) progressive corticospinal tract degeneration (increased radial diffusivity correlating with postoperative duration); (4) enhanced sensory-visual integration correlated with functional recovery. Conclusions: This review provides a novel synthesis of evidence from transcranial magnetic stimulation (TMS), electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), diffusion tensor imaging (DTI), and functional magnetic resonance imaging (fMRI) studies. It delineates characteristic patterns of post-ACLR structural and functional neural reorganization. Targeting visual–cognitive integration and corticospinal facilitation may optimize rehabilitation. Full article
(This article belongs to the Special Issue Diagnosis, Therapy and Rehabilitation in Neuromuscular Diseases)
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15 pages, 1033 KiB  
Article
Transcranial Pulse Stimulation in Alzheimer’s: Long-Term Feasibility and a Multifocal Treatment Approach
by Celine Cont-Richter, Nathalie Stute, Anastasia Galli, Christina Schulte and Lars Wojtecki
Brain Sci. 2025, 15(8), 830; https://doi.org/10.3390/brainsci15080830 - 1 Aug 2025
Viewed by 378
Abstract
Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and [...] Read more.
Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and potential cognitive benefits of TPS over one year in patients with Alzheimer’s disease, focusing on domains such as memory, speech, orientation, visuo-construction, and depressive symptoms. Methods: We analyzed preliminary data from the first ten out of thirty-five patients enrolled in a prospective TPS study who completed one year of follow-up and were included in a dedicated long-term database. The protocol consisted of six initial TPS sessions over two weeks, followed by monthly booster sessions delivering 6000 pulses each for twelve months. Patients underwent regular neuropsychological assessments using the Alzheimer Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI-II). All adverse events (AEs) were documented and monitored throughout the study. Results: Adverse events occurred in less than 1% of stimulation sessions and mainly included mild focal pain or transient unpleasant sensations, as well as some systemic behavioral or vigilance changes, particularly in patients with underlying medical conditions, with some potentially related to the device’s stimulation as adverse device reactions (ADRs). Cognitive test results showed significant improvement after the initial stimulation cycle (ADAS total improved significantly after the first stimulation cycle (M_pre = 28.44, M_post = 18.56; p = 0.001, d = 0.80, 95% CI (0.36, 1.25)), with stable scores across all domains over one year. Improvements were most notable in memory, speech, and mood. Conclusions: TPS appears to be a generally safe and feasible add-on treatment for AD, although careful patient selection and monitoring are advised. While a considerable number of participants were lost to follow-up for various reasons, adverse events and lack of treatment effect were unlikely primary causes. A multifocal stimulation approach (F-TOP2) is proposed to enhance effects across more cognitive domains. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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29 pages, 3958 KiB  
Article
Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy
by Somaiyeh Azmoun, Freeman C. Lewis, Daniel Shoieb, Yan Jin, Elena Colicino, Isha Mhatre-Winters, Haiwei Gu, Hari Krishnamurthy, Jason R. Richardson, Donatella Placidi, Luca Lambertini and Roberto G. Lucchini
Brain Sci. 2025, 15(8), 829; https://doi.org/10.3390/brainsci15080829 - 31 Jul 2025
Viewed by 445
Abstract
Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on [...] Read more.
Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m3 (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article
(This article belongs to the Special Issue From Bench to Bedside: Motor–Cognitive Interactions—2nd Edition)
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18 pages, 778 KiB  
Article
The Effects of Handedness Consistency on the Identification of Own- and Cross-Race Faces
by Raymond P. Voss, Jr., Ryan Corser, Stephen Prunier and John D. Jasper
Brain Sci. 2025, 15(8), 828; https://doi.org/10.3390/brainsci15080828 - 31 Jul 2025
Viewed by 297
Abstract
Background/Objectives: People are better at recognizing the faces of racial in-group members than out-group members. This own-race bias relies on pattern recognition and memory processes, which rely on hemispheric specialization. We hypothesized that handedness, a proxy for hemispheric specialization, would moderate own-race [...] Read more.
Background/Objectives: People are better at recognizing the faces of racial in-group members than out-group members. This own-race bias relies on pattern recognition and memory processes, which rely on hemispheric specialization. We hypothesized that handedness, a proxy for hemispheric specialization, would moderate own-race bias. Specifically, consistently handed individuals perform better on tasks that require the hemispheres to work independently, while inconsistently handed individuals perform better on tasks that require integration. This led to the hypothesis that inconsistently handed individuals would show less own-race bias, driven by an increase in accuracy. Methods: 281 participants completed the study in exchange for course credit. Of those, the sample was isolated to Caucasian (174) and African American individuals (41). Participants were shown two target faces (one Caucasian and one African American), given several distractor tasks, and then asked to identify the target faces during two sequential line-ups, each terminating when participants made an identification judgment. Results: Continuous handedness score and the match between participant race and target face race were entered into a binary logistic regression predicting correct/incorrect identifications. The overall model was statistically significant, Χ2 (3, N = 430) = 11.036, p = 0.012, Nagelkerke R2 = 0.038, culminating in 76% correct classifications. Analyses of the parameter estimates showed that the racial match, b = 0.53, SE = 0.23, Wald Χ2 (1) = 5.217, p = 0.022, OR = 1.703 and the interaction between handedness and the racial match, b = 0.51, SE = 0.23, Wald test = 4.813, p = 0.028, OR = 1.671 significantly contributed to the model. The model indicated that the probability of identification was similar for own- or cross-race targets amongst inconsistently handed individuals. Consistently handed individuals, by contrast, showed an increase in accuracy for the own-race target and a decrease in accuracy for cross-race targets. Conclusions: Results partially supported the hypotheses. Inconsistently handed individuals did show less own-race bias. This finding, however, seemed to be driven by differences in accuracy amongst consistently handed individuals rather than a hypothesized increase in accuracy amongst inconsistently handed individuals. Underlying hemispheric specialization, as measured by proxy with handedness, may impact the own-race bias in facial recognition. Future research is required to investigate the mechanisms, however, as the directional differences were different than hypothesized. Full article
(This article belongs to the Special Issue Advances in Face Perception and How Disorders Affect Face Perception)
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