Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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18 pages, 711 KB  
Review
Exploring Imagined Movement for Brain–Computer Interface Control: An fNIRS and EEG Review
by Robert Finnis, Adeel Mehmood, Henning Holle and Jamshed Iqbal
Brain Sci. 2025, 15(9), 1013; https://doi.org/10.3390/brainsci15091013 - 19 Sep 2025
Cited by 6 | Viewed by 4033
Abstract
Brain–Computer Interfaces (BCIs) offer a non-invasive pathway for restoring motor function, particularly for individuals with limb loss. This review explored the effectiveness of Electroencephalography (EEG) and function Near-Infrared Spectroscopy (fNIRS) in decoding Motor Imagery (MI) movements for both offline and online BCI systems. [...] Read more.
Brain–Computer Interfaces (BCIs) offer a non-invasive pathway for restoring motor function, particularly for individuals with limb loss. This review explored the effectiveness of Electroencephalography (EEG) and function Near-Infrared Spectroscopy (fNIRS) in decoding Motor Imagery (MI) movements for both offline and online BCI systems. EEG has been the dominant non-invasive neuroimaging modality due to its high temporal resolution and accessibility; however, it is limited by high susceptibility to electrical noise and motion artifacts, particularly in real-world settings. fNIRS offers improved robustness to electrical and motion noise, making it increasingly viable in prosthetic control tasks; however, it has an inherent physiological delay. The review categorizes experimental approaches based on modality, paradigm, and study type, highlighting the methods used for signal acquisition, feature extraction, and classification. Results show that while offline studies achieve higher classification accuracy due to fewer time constraints and richer data processing, recent advancements in machine learning—particularly deep learning—have improved the feasibility of online MI decoding. Hybrid EEG–fNIRS systems further enhance performance by combining the temporal precision of EEG with the spatial specificity of fNIRS. Overall, the review finds that predicting online imagined movement is feasible, though still less reliable than motor execution, and continued improvements in neuroimaging integration and classification methods are essential for real-world BCI applications. Broader dissemination of recent advancements in MI-based BCI research is expected to stimulate further interdisciplinary collaboration among roboticists, neuroscientists, and clinicians, accelerating progress toward practical and transformative neuroprosthetic technologies. Full article
(This article belongs to the Special Issue Exploring the Neurobiology of the Sensory-Motor System)
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33 pages, 1073 KB  
Review
Sleep Disorders in Children with Autism Spectrum Disorder: Developmental Impact and Intervention Strategies
by Maria Ludovica Albertini, Giulia Spoto, Graziana Ceraolo, Maria Flavia Fichera, Carla Consoli, Antonio Gennaro Nicotera and Gabriella Di Rosa
Brain Sci. 2025, 15(9), 983; https://doi.org/10.3390/brainsci15090983 - 13 Sep 2025
Cited by 6 | Viewed by 8942
Abstract
Sleep disorders are highly prevalent in children with Autism Spectrum Disorder (ASD), profoundly impacting their neurodevelopment and daily functioning. Alterations in sleep architecture and regulatory mechanisms contribute to difficulties with sleep onset, maintenance, and overall sleep quality. Sensory processing differences, commonly observed in [...] Read more.
Sleep disorders are highly prevalent in children with Autism Spectrum Disorder (ASD), profoundly impacting their neurodevelopment and daily functioning. Alterations in sleep architecture and regulatory mechanisms contribute to difficulties with sleep onset, maintenance, and overall sleep quality. Sensory processing differences, commonly observed in ASD, may further exacerbate these disturbances by affecting arousal regulation and environmental responsiveness during sleep. Given the fundamental role of sleep in brain maturation, its disruption negatively impacts synaptic plasticity and neurological development, particularly during critical periods. These sleep-related alterations can influence cognitive and behavioral outcomes and may serve as early indicators of ASD, highlighting their potential value in early diagnosis and intervention. Understanding the neurobiological mechanisms linking sleep and ASD is essential for developing targeted therapeutic strategies. Ongoing research increasingly focuses on pharmacological, nutraceutical, and behavioral interventions aimed at mitigating sleep disorders and their cascading effects on neurodevelopment. Optimizing these therapeutic approaches through a multidisciplinary lens is crucial for enhancing clinical outcomes and improving overall quality of life in children with ASD. Full article
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27 pages, 6187 KB  
Review
Looking into Abnormal Co-Expressions of Tau and TDP-43 in the Realm of Mixed Dementia Types: A Double-Punch Scenario
by Hossam Youssef, Carina Weissmann, Gokhan Uruk and Rodolfo Gabriel Gatto
Brain Sci. 2025, 15(7), 716; https://doi.org/10.3390/brainsci15070716 - 3 Jul 2025
Cited by 8 | Viewed by 4194
Abstract
Transactive response DNA-binding protein of 43 kDa (TDP-43) and tau proteins play critical roles in neurodegenerative diseases, particularly frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). The co-occurrence of TDP-43 and tau pathologies raises questions about their role in disease progression. This review [...] Read more.
Transactive response DNA-binding protein of 43 kDa (TDP-43) and tau proteins play critical roles in neurodegenerative diseases, particularly frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). The co-occurrence of TDP-43 and tau pathologies raises questions about their role in disease progression. This review explores the simultaneous presence of tau and TDP-43 co-pathologies, emphasizing their molecular interactions and the resultant neuropathological implications. Additionally, we provide representative examples of their clinical presentations, neuroimaging, and neuropathological findings associated with FTLD-TDP and FTLD-tau, emphasizing the need for a comprehensive understanding of these intertwined pathologies. We analyze various clinical scenarios, including argyrophilic grain disease (AGD), primary age-related tauopathy (PART), and limbic predominant age-related TDP-43 encephalopathy (LATE), to elucidate the complex relationship between these proteinopathies. From the literature, the co-occurrence of tau and TDP-43 is linked to more severe and poorer clinical outcomes compared to isolated pathologies. This review underscores the necessity of considering co-pathologies in the context of FTLD, as they may act as accelerators of cognitive decline. This highlights the importance of integrated approaches in diagnosing and treating neurodegenerative conditions characterized by tau and TDP-43 misfolding. Understanding the interplay between these molecular markers is vital for advancing therapeutic strategies for such disorders. Full article
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30 pages, 1333 KB  
Review
The APOE–Microglia Axis in Alzheimer’s Disease: Functional Divergence and Therapeutic Perspectives—A Narrative Review
by Aiwei Liu, Tingxu Wang, Liu Yang and Yu Zhou
Brain Sci. 2025, 15(7), 675; https://doi.org/10.3390/brainsci15070675 - 23 Jun 2025
Cited by 7 | Viewed by 6705
Abstract
Apolipoprotein E (APOE) alleles play distinct roles in the pathogenesis of Alzheimer’s disease (AD), with APOEε4 being the strongest genetic risk factor for late-onset AD, while APOEε2 appears protective. Despite extensive research, the precise mechanisms by which APOE alleles contribute to [...] Read more.
Apolipoprotein E (APOE) alleles play distinct roles in the pathogenesis of Alzheimer’s disease (AD), with APOEε4 being the strongest genetic risk factor for late-onset AD, while APOEε2 appears protective. Despite extensive research, the precise mechanisms by which APOE alleles contribute to AD pathology remain incompletely understood. Recent advances in multi-omics technologies and single-cell analyses have revealed that APOE alleles shape microglial phenotypes, thereby affecting amyloid clearance, inflammatory responses, tau pathology, and lipid metabolism. In this review, we provide a detailed overview of how APOE alleles differentially regulate microglial activation, inflammatory signaling, phagocytic activity, and lipid metabolism in the context of AD, with a particular focus on the APOEε4-mediated disruption of microglial homeostasis via pathways such as TREM2 signaling, NF-κB/NLRP3 activation, ACSL1 upregulation, and HIF-1α induction. These insights not only advance our understanding of APOE allele-specific contributions to AD pathology, but also highlight novel therapeutic strategies targeting the APOE–microglia axis. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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62 pages, 1422 KB  
Review
The Neural Correlates of Chewing Gum—A Neuroimaging Review of Its Effects on Brain Activity
by James Chmiel and Agnieszka Malinowska
Brain Sci. 2025, 15(6), 657; https://doi.org/10.3390/brainsci15060657 - 18 Jun 2025
Cited by 5 | Viewed by 20148
Abstract
Introduction: Chewing gum is a widespread, seemingly mundane behaviour that has been linked to diverse benefits such as improved cognitive performance, reduced stress, and enhanced alertness. While animal and human research indicate that mastication engages extensive sensorimotor networks and may also modulate higher-order [...] Read more.
Introduction: Chewing gum is a widespread, seemingly mundane behaviour that has been linked to diverse benefits such as improved cognitive performance, reduced stress, and enhanced alertness. While animal and human research indicate that mastication engages extensive sensorimotor networks and may also modulate higher-order cognitive and emotional processes, questions remain about the specific neural mechanisms involved. This review combines findings from neuroimaging studies—including fMRI, fNIRS, and EEG—that investigate how chewing gum alters brain activity in humans. Methods: Using a targeted search strategy, we screened the major databases (PubMed/Medline, Scopus, ResearchGate, Google Scholar, and Cochrane) from January 1980 to March 2025 for clinical studies published in English. Eligible studies explicitly measured brain activity during gum chewing using EEG, fNIRS, or fMRI. Results: After a title/abstract screening and a full-text review, thirty-two studies met the inclusion criteria for this review: 15 utilising fMRI, 10 using fNIRS, 2 using both fNIRS and EEG, and 5 employing EEG. Overall, the fMRI investigations consistently reported strong activation in bilateral motor and somatosensory cortices, the supplementary motor area, the insula, the cerebellum, and the thalamus, during gum chewing, with several studies also noting involvement of higher-order prefrontal and cingulate regions, particularly under stress conditions or when participants chewed flavoured gum. The fNIRS findings indicated that chewing gum increased oxygenated haemoglobin in the prefrontal cortex, reflecting heightened cortical blood flow; these effects were often amplified when the gum was flavoured or when participants were exposed to stressful stimuli, suggesting that both sensory and emotional variables can influence chewing-related cortical responses. Finally, the EEG studies documented transient increases in alpha and beta wave power during gum chewing, particularly when flavoured gum was used, and reported short-lived enhancements in vigilance or alertness, which tended to subside soon after participants ceased chewing. Conclusions: Neuroimaging data indicate that chewing gum reliably engages broad sensorimotor circuits while also influencing regions tied to attention, stress regulation, and possibly memory. Although these effects are often short-lived, the range of outcomes—from changes in cortical oxygenation to shifts in EEG power—underscores chewing gum’s capacity to modulate brain function beyond simple oral motor control. However, at this time, the neural changes associated with gum chewing cannot be directly linked to the positive behavioural and functional outcomes observed in studies that measure these effects without the use of neuroimaging techniques. Future research should address longer-term impacts, refine methods to isolate flavour or stress variables, and explore potential therapeutic applications for mastication-based interventions. Full article
(This article belongs to the Special Issue Brain Network Connectivity Analysis in Neuroscience)
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38 pages, 1158 KB  
Review
An Updated and Comprehensive Review Exploring the Gut–Brain Axis in Neurodegenerative Disorders and Neurotraumas: Implications for Therapeutic Strategies
by Ahmed Hasan, Sarah Adriana Scuderi, Anna Paola Capra, Domenico Giosa, Andrea Bonomo, Alessio Ardizzone and Emanuela Esposito
Brain Sci. 2025, 15(6), 654; https://doi.org/10.3390/brainsci15060654 - 18 Jun 2025
Cited by 11 | Viewed by 7899
Abstract
The gut–brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance [...] Read more.
The gut–brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance of this bidirectional pathway depends on the composition of the gut microbiome and its metabolites. While the causes of neurodegenerative diseases (NDDs) vary, the gut microbiome plays a crucial role in their development and prognosis. NDDs are often associated with an inflammation-related gut microbiome. However, restoring balance to the gut microbiome and reducing inflammation may have therapeutic benefits. In particular, introducing short-chain fatty acid-producing bacteria, key metabolites that support gut homeostasis, can help counteract the inflammatory microbiome. This strong pathological link between the gut and NDDs underscores the gut–brain axis (GBA) as a promising target for therapeutic intervention. This review, by scrutinizing the more recent original research articles published in PubMed (MEDLINE) database, emphasizes the emerging notion that GBA is an equally important pathological marker for neurological movement disorders, particularly in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease and neurotraumatic disorders such as traumatic brain injury and spinal cord injury. Additionally, the GBA presents a promising therapeutic target for managing these diseases. Full article
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16 pages, 4024 KB  
Systematic Review
Epileptic Seizure Detection Using Machine Learning: A Systematic Review and Meta-Analysis
by Lin Bai, Gerhard Litscher and Xiaoning Li
Brain Sci. 2025, 15(6), 634; https://doi.org/10.3390/brainsci15060634 - 12 Jun 2025
Cited by 12 | Viewed by 4212
Abstract
Background/Objectives: Epileptic seizures significantly impact patients’ lives due to their unpredictability, making early and accurate detection crucial for effective treatment. Machine learning (ML) models based on electroencephalogram (EEG) signals have been explored for automated seizure detection. This meta-analysis reviews the performance of ML [...] Read more.
Background/Objectives: Epileptic seizures significantly impact patients’ lives due to their unpredictability, making early and accurate detection crucial for effective treatment. Machine learning (ML) models based on electroencephalogram (EEG) signals have been explored for automated seizure detection. This meta-analysis reviews the performance of ML models in seizure detection and analyzes factors such as the model type (deep learning vs. traditional ML), data preprocessing methods, and dataset types. Aim: This study aims to provide an evidence-based foundation for the future development of intelligent tools by evaluating the performance of ML models in detecting epileptic seizures through a meta-analysis. Methods: A systematic search of multiple databases up to April 2025 identified 60 studies and 93 datasets. The pooled sensitivity, specificity, and area under the curve (AUC) were calculated using Stata 17.0. Subgroup analyses were performed to identify sources of heterogeneity. Publication bias was assessed using Deek’s test and funnel plots. Results: The pooled sensitivity, specificity, and AUC were 0.96 (95% CI 0.95–0.97), 0.97 (95% CI 0.96–0.98), and 0.99 (95% CI 0.98–1.00), respectively, indicating a good performance of ML in seizure detection. Subgroup analyses revealed that the model type, data preprocessing methods, and dataset type contributed to heterogeneity. Conclusions: ML shows a strong potential for EEG-based seizure detection. Imaging devices integrating ML may serve as effective tools for early epilepsy diagnosis. However, larger, multicenter clinical studies are needed to validate these algorithms and enhance their interpretability, safety, and applicability in real-world clinical settings. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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73 pages, 4141 KB  
Systematic Review
Neurotechnological Approaches to Cognitive Rehabilitation in Mild Cognitive Impairment: A Systematic Review of Neuromodulation, EEG, Virtual Reality, and Emerging AI Applications
by Evgenia Gkintoni, Stephanos P. Vassilopoulos, Georgios Nikolaou and Apostolos Vantarakis
Brain Sci. 2025, 15(6), 582; https://doi.org/10.3390/brainsci15060582 - 28 May 2025
Cited by 13 | Viewed by 8538
Abstract
Background/Objectives: Mild Cognitive Impairment (MCI) represents a clinical syndrome characterized by cognitive decline greater than expected for an individual’s age and education level but not severe enough to significantly interfere with daily activities, with variable trajectories that may remain stable, progress to dementia, [...] Read more.
Background/Objectives: Mild Cognitive Impairment (MCI) represents a clinical syndrome characterized by cognitive decline greater than expected for an individual’s age and education level but not severe enough to significantly interfere with daily activities, with variable trajectories that may remain stable, progress to dementia, or occasionally revert to normal cognition. This systematic review examines neurotechnological approaches to cognitive rehabilitation in MCI populations, including neuromodulation, electroencephalography (EEG), virtual reality (VR), cognitive training, physical exercise, and artificial intelligence (AI) applications. Methods: A systematic review following PRISMA guidelines was conducted on 34 empirical studies published between 2014 and 2024. Studies were identified through comprehensive database searches and included if they employed neurotechnological interventions targeting cognitive outcomes in individuals with MCI. Results: Evidence indicates promising outcomes across multiple intervention types. Neuromodulation techniques showed beneficial effects on memory and executive function. EEG analyses identified characteristic neurophysiological markers of MCI with potential for early detection and monitoring. Virtual reality enhanced assessment sensitivity and rehabilitation engagement through ecologically valid environments. Cognitive training demonstrated the most excellent efficacy with multi-domain, adaptive approaches. Physical exercise interventions yielded improvements through multiple neurobiological pathways. Emerging AI applications showed potential for personalized assessment and intervention through predictive modeling and adaptive algorithms. Conclusions: Neurotechnological approaches offer promising avenues for MCI rehabilitation, with the most substantial evidence for integrated interventions targeting multiple mechanisms. Neurophysiological monitoring provides valuable biomarkers for diagnosis and treatment response. Future research should focus on more extensive clinical trials, standardized protocols, and accessible implementation models to translate these technological advances into clinical practice. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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12 pages, 232 KB  
Review
The Impact of Chronic Pain on Cognitive Function
by Milan Patel, Jamal Hasoon, Rodrigo Diez Tafur, Giuliano Lo Bianco and Alaa Abd-Elsayed
Brain Sci. 2025, 15(6), 559; https://doi.org/10.3390/brainsci15060559 - 24 May 2025
Cited by 13 | Viewed by 6388
Abstract
Background: Chronic pain affects a significant proportion of the population in the United States and poses a significant public health concern. Beyond physical discomfort, chronic pain has been increasingly linked to cognitive dysfunction, including impairments in memory, attention, executive function, and decision-making. [...] Read more.
Background: Chronic pain affects a significant proportion of the population in the United States and poses a significant public health concern. Beyond physical discomfort, chronic pain has been increasingly linked to cognitive dysfunction, including impairments in memory, attention, executive function, and decision-making. The relationship is particularly pronounced in older adults and may contribute to the onset or progression of neurodegenerative diseases. Objective: This comprehensive review explores the relationship between chronic pain and cognitive function, emphasizing the underlying neurobiological mechanisms, structural brain changes, and associated comorbidities. Methods: A review was conducted using peer-reviewed studies that began with the earliest pain and cognition mechanisms, followed by further investigation of cognitive effects of chronic pain, neuroimaging findings, and comorbid neuropsychiatric and neurodegenerative conditions. Sources included large-scale cohort studies, functional MRI analyses, and neurobiological investigations focusing on prefrontal cortex activity, default mode network alterations, and gray matter atrophy. Results: Chronic pain is associated with cognitive deficits through multiple converging pathways. It contributes to measurable impairments in cognitive function and is linked to structural and functional brain alterations. Regions of interest include the dorsolateral prefrontal cortex, medial prefrontal cortex, and default mode network, which can be connected to the neural resource hypothesis because of their cognitive domain impairments. A better understanding of these mechanisms highlights the importance of early recognition and multidisciplinary management strategies, including neuromodulation and cognitive rehabilitation. Future research should prioritize longitudinal studies and integrated interventions targeting both pain and cognitive health. Full article
(This article belongs to the Special Issue Aging-Related Changes in Memory and Cognition)
28 pages, 566 KB  
Perspective
Cognitive Behavioural Therapy (CBT) for Managing Tinnitus, Hyperacusis, and Misophonia: The 2025 Tonndorf Lecture
by Hashir Aazh
Brain Sci. 2025, 15(5), 526; https://doi.org/10.3390/brainsci15050526 - 19 May 2025
Cited by 6 | Viewed by 11804
Abstract
Cognitive behavioural therapy (CBT) is an evidence-based intervention for managing distress associated with tinnitus, hyperacusis, and misophonia. This paper summarises key points from the 2025 Tonndorf Lecture presented at the third World Tinnitus Congress and the 14th International Tinnitus Seminar in Poland. The [...] Read more.
Cognitive behavioural therapy (CBT) is an evidence-based intervention for managing distress associated with tinnitus, hyperacusis, and misophonia. This paper summarises key points from the 2025 Tonndorf Lecture presented at the third World Tinnitus Congress and the 14th International Tinnitus Seminar in Poland. The lecture addressed (1) the theoretical foundations of CBT for these conditions, (2) clinical evidence on CBT delivered by psychologists, audiologists, and digital self-help, and (3) the proportion of patients who may benefit from CBT. Research demonstrates that CBT can effectively reduce distress related to tinnitus, hyperacusis, and misophonia. Both psychologist- and audiologist-delivered CBT approaches have demonstrated significant improvements in reducing the impact of tinnitus, hyperacusis, and misophonia on patients’ quality of life, while guided internet-based CBT also demonstrates positive outcomes. Unguided internet-based CBT is also effective, though it faces challenges such as higher dropout rates. Despite these promising results, not all patients experience the same level of benefit. Some continue to experience distress even after completing CBT, highlighting the need for alternative or complementary interventions and ongoing support. This paper estimates that approximately 1 in 52 individuals with tinnitus require CBT, indicating that while tinnitus is relatively common, the need for intensive therapy is comparatively small. To enhance treatment outcomes, future research should compare the effectiveness of psychologist- and audiologist-delivered CBT, explore hybrid models that combine face-to-face and digital interventions, and address challenges with internet-based CBT, particularly for hyperacusis and misophonia. Furthermore, incorporating neuroimaging and physiological measures in future randomised controlled trials could provide objective insights into the neural mechanisms underlying symptom improvement, ultimately helping to refine CBT interventions. Identifying characteristics of non-responders to CBT may also guide the development of more tailored therapeutic approaches. Full article
(This article belongs to the Section Behavioral Neuroscience)
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16 pages, 496 KB  
Review
Anti-NMDA Receptor Encephalitis: A Narrative Review
by Vlad Pădureanu, Dalia Dop, Rodica Pădureanu, Denisa Floriana Vasilica Pîrșcoveanu, Gabriela Olaru, Ioana Streata and Ana Maria Bugă
Brain Sci. 2025, 15(5), 518; https://doi.org/10.3390/brainsci15050518 - 18 May 2025
Cited by 7 | Viewed by 12926
Abstract
Antibodies against the NR1 or NR2 subunits of the NMDA receptor are linked to anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, a type of encephalitis that mainly affects women. Clinicians who treat patients of all ages should be aware of this type of encephalitis since it [...] Read more.
Antibodies against the NR1 or NR2 subunits of the NMDA receptor are linked to anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, a type of encephalitis that mainly affects women. Clinicians who treat patients of all ages should be aware of this type of encephalitis since it may be a treatable differential for symptoms and indicators observed in neurology and psychiatric clinics. Auditory and visual hallucinations, delusions, altered behavior (often accompanied by agitation), reduced consciousness, motor disruption (from dyskinesia to catatonia), seizures, and autonomic dysfunction are typical clinical characteristics. In recent years, the incidence of autoimmune encephalitis diagnoses has markedly risen among adults, children, and adolescents. This fact is unequivocally connected to the dynamic evolution of novel diagnostic techniques and the advancement of medical knowledge. A specific variant of this illness is anti-NMDA receptor encephalitis. Psychiatrists frequently serve as the initial specialists to treat patients with this diagnosis, owing to the manifestation of psychiatric symptoms associated with the condition. The differential diagnosis is quite challenging and predominantly relies on the patient’s history and the manifestation of characteristic clinical signs. Given its high prevalence, anti-NMDA receptor encephalitis should be included in the differential diagnosis in routine psychiatric treatment. We provide an overview of the research on the condition, covering its prognosis, management, epidemiology, differential diagnosis, and clinical presentation. Full article
(This article belongs to the Special Issue Novel Insights into Neuroinflammation and Brain Disease)
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27 pages, 997 KB  
Review
The Role of Selected Flavonoids in Modulating Neuroinflammation in Alzheimer’s Disease: Mechanisms and Therapeutic Potential
by Joanna Kruszka, Jakub Martyński, Karolina Szewczyk-Golec, Alina Woźniak and Jarosław Nuszkiewicz
Brain Sci. 2025, 15(5), 485; https://doi.org/10.3390/brainsci15050485 - 5 May 2025
Cited by 12 | Viewed by 3959
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-β (Aβ) deposition, tau hyperphosphorylation, oxidative stress, and chronic neuroinflammation. Growing evidence highlights neuroinflammation—driven by microglial activation and pro-inflammatory cytokine release—as a key contributor to AD pathogenesis and progression. In the [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-β (Aβ) deposition, tau hyperphosphorylation, oxidative stress, and chronic neuroinflammation. Growing evidence highlights neuroinflammation—driven by microglial activation and pro-inflammatory cytokine release—as a key contributor to AD pathogenesis and progression. In the absence of effective disease-modifying therapies, attention has turned to natural compounds with multi-target potential. Flavonoids, a diverse class of plant-derived polyphenols, have demonstrated neuroprotective properties through antioxidant activity, modulation of neuroinflammatory pathways, and interference with both Aβ aggregation and tau pathology. This narrative review provides an integrative overview of current findings on the mechanisms of action of key flavonoids—such as quercetin, luteolin, and apigenin—in both preclinical and clinical models. Emphasis is placed on their effects on microglial polarization, oxidative stress reduction, mitochondrial support, and synaptic function enhancement. Moreover, flavonoids show synergistic potential when combined with standard pharmacotherapies, such as acetylcholinesterase inhibitors, and may offer broader cognitive benefits in patients with mild cognitive impairment (MCI). Despite these promising findings, significant challenges persist, including poor bioavailability, inter-individual variability, and limited long-term clinical data. This review identifies critical gaps in knowledge and outlines future directions, including targeted drug delivery systems, biomarker-guided personalization, and long-duration trials. Flavonoids thus emerge not only as promising neuroprotective agents but also as complementary candidates in the development of future multi-modal strategies for AD treatment. Full article
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18 pages, 6031 KB  
Article
Semaglutide and High-Intensity Interval Exercise Attenuate Cognitive Impairment in Type 2 Diabetic Mice via BDNF Modulation
by Sijie Lai, Zhenghong Kang, Jianting Sun, Ziyu Wang, Yanzi Xu, Sisi Xing, Mengying Feng, Yiyi Wang and Hua Liu
Brain Sci. 2025, 15(5), 480; https://doi.org/10.3390/brainsci15050480 - 1 May 2025
Cited by 6 | Viewed by 3187
Abstract
Background/Objectives: Diabetes frequently leads to cognitive impairment, encompassing issues with memory and executive function, as well as depression and anxiety. This study examines the impact of high-intensity interval exercise (HIIE) alongside glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide on cognitive dysfunction associated [...] Read more.
Background/Objectives: Diabetes frequently leads to cognitive impairment, encompassing issues with memory and executive function, as well as depression and anxiety. This study examines the impact of high-intensity interval exercise (HIIE) alongside glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide on cognitive dysfunction associated with diabetes. Methods: Db/db mice were divided into a control group, semaglutide group, HIIE group, and semaglutide combined with HIIE group to study metabolic and neurobehavioral effects. Cognitive and behavioral tests, hippocampal morphology, and molecular analyses (APP, BDNF, Aβ, p-Tau, PKA, AMPK) were performed. HT22 cells under high glucose were treated with semaglutide, L-lactate, PKA inhibitor H89, and AMPK inhibitor Compound C to validate mechanisms. Results: Over 8 weeks, both HIIE and semaglutide improved neuronal morphology and cognitive performance while reducing depression in db/db mice. However, the current study observed no synergistic effects. Both therapies decreased Aβ and p-Tau protein levels and increased BDNF levels in the hippocampus, likely through the AMPK and PKA signaling pathways, respectively. In vitro, HT22 cells under high glucose conditions exhibited elevated APP and p-Tau expression and reduced BDNF levels, which could be altered by L-lactate and semaglutide. The AMPK inhibitor Compound C and the PKA inhibitor H89 attenuated the increase in BDNF levels induced by L-lactate and semaglutide, but their combination mitigated this inhibitory effect. This study suggests that while HIIE and semaglutide improve cognitive function and reduce depression via BDNF, their combined use did not show the anticipated synergistic benefits due to potential antagonism between the AMPK and PKA pathways. Conclusions: This has important implications for designing exercise prescriptions for cognitive impairment in diabetics. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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40 pages, 5811 KB  
Review
Metabolic Dysfunction and Dietary Interventions in Migraine Management: The Role of Insulin Resistance and Neuroinflammation—A Narrative and Scoping Review
by Cinzia Cavestro
Brain Sci. 2025, 15(5), 474; https://doi.org/10.3390/brainsci15050474 - 29 Apr 2025
Cited by 10 | Viewed by 6711
Abstract
Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, [...] Read more.
Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, it has been known that certain foods can trigger migraine attacks, which led for many years to the recommendation of elimination diets—now understood to primarily target histamine-rich foods. Over the past two decades, attention has shifted toward underlying metabolic disturbances, leading to the development of dietary approaches specifically aimed at addressing these dysfunctions. Methods: A scoping literature review was conducted using PubMed and Embase to evaluate the relationships among migraine, insulin-related mechanisms, neurogenic inflammation, and dietary interventions. Initial searches focused on “MIGRAINE AND (neurogenic inflammation)” (2019–15 April 2025), followed by expanded searches from 1950 onward using terms such as “MIGRAINE AND (insulin, insulin resistance, hyperinsulinism)”, and “MIGRAINE AND (diet, dietary, nutrition, nutritional)”. A specific search also targeted “(INSULIN OR insulin resistance OR hyperinsulinism) AND (neurogenic inflammation)”. Abstracts were screened, full texts were retrieved, and duplicates or irrelevant publications were excluded. No filters were applied by article type or language. Systematic reviews and meta-analyses were prioritized when available. Results: Migraine pathogenesis involves trigeminovascular system activation, neurogenic inflammation mediated by CGRP and PACAP, immune dysregulation, mast cell activation, and cortical spreading depression (CSD). Emerging evidence highlights significant associations between migraine, insulin resistance, and hyperinsulinism. Hyperinsulinism contributes to migraine through TRPV1 sensitization, increased CGRP release, oxidative stress, mitochondrial dysfunction, and systemic inflammation. Metabolic dysfunction, including obesity and insulin resistance, exacerbates migraine severity and frequency. Dietary interventions, particularly anti-inflammatory, Mediterranean, and ketogenic diets, show promise in reducing migraine frequency and severity through mechanisms involving reduced inflammation, oxidative stress, improved mitochondrial function, and glucose metabolism stabilization. Conclusions: The interplay between insulin resistance, metabolic dysfunction, and neuroinflammation is crucial in migraine pathophysiology. Targeted dietary interventions, including ketogenic and Mediterranean diets, demonstrate significant potential in managing migraines, emphasizing the need for personalized nutritional strategies to optimize therapeutic outcomes. Full article
(This article belongs to the Special Issue Advances in Neuroinflammation and Pain Medicine)
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26 pages, 1003 KB  
Systematic Review
From Gaze to Game: A Systematic Review of Eye-Tracking Applications in Basketball
by Michela Alemanno, Ilaria Di Pompeo, Martina Marcaccio, Daniele Canini, Giuseppe Curcio and Simone Migliore
Brain Sci. 2025, 15(4), 421; https://doi.org/10.3390/brainsci15040421 - 20 Apr 2025
Cited by 8 | Viewed by 3829
Abstract
Background/Objectives: Eye-tracking technology has gained increasing attention in sports science, as it provides valuable insights into visual attention, decision-making, and motor planning. This systematic review examines the application of eye-tracking technology in basketball, highlighting its role in analyzing cognitive and perceptual strategies in [...] Read more.
Background/Objectives: Eye-tracking technology has gained increasing attention in sports science, as it provides valuable insights into visual attention, decision-making, and motor planning. This systematic review examines the application of eye-tracking technology in basketball, highlighting its role in analyzing cognitive and perceptual strategies in players, referees, and coaches. Methods: A systematic search was conducted following PRISMA guidelines. Studies published up until December 2024 were retrieved from PubMed and Web of Science using keywords related to basketball, eye tracking, and visual search. The inclusion criteria focused on studies using eye-tracking technology to assess athletes, referees, and coaches. A total of 1706 articles were screened, of which 19 met the eligibility criteria. Results: Eye-tracking studies have shown that expert basketball players exhibit longer quiet eye (QE) durations and more efficient gaze behaviors compared to novices. In high-pressure situations, skilled players maintain more stable QE characteristics, leading to better shot accuracy. Referees rely on efficient gaze strategies to make split-second decisions, although less experienced referees tend to neglect key visual cues. In coaching, eye-tracking studies suggest that guided gaze techniques improve tactical understanding in novice players but have limited effects on experienced athletes. Conclusions: Eye tracking is a powerful tool for studying cognitive and behavioral functioning in basketball, offering valuable insights for performance enhancement and training strategies. Future research should explore real-game settings using mobile eye trackers and integrate artificial intelligence to further refine gaze-based training methods. Full article
(This article belongs to the Section Neuropsychology)
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21 pages, 1040 KB  
Review
Neuroplasticity and Nervous System Recovery: Cellular Mechanisms, Therapeutic Advances, and Future Prospects
by Ligia Gabriela Tataranu and Radu Eugen Rizea
Brain Sci. 2025, 15(4), 400; https://doi.org/10.3390/brainsci15040400 - 15 Apr 2025
Cited by 14 | Viewed by 16810
Abstract
Neuroplasticity, the ability of the nervous system to adapt structurally and functionally in response to environmental interactions and injuries, is a cornerstone of recovery in the central (CNS) and peripheral nervous systems (PNS). This review explores the mechanisms underlying neuroplasticity, focusing on the [...] Read more.
Neuroplasticity, the ability of the nervous system to adapt structurally and functionally in response to environmental interactions and injuries, is a cornerstone of recovery in the central (CNS) and peripheral nervous systems (PNS). This review explores the mechanisms underlying neuroplasticity, focusing on the dynamic roles of cellular and molecular processes in recovery from nervous system injuries. Key cellular players, including Schwann cells, oligodendrocytes, and neural stem cells, are highlighted for their contributions to nerve repair, myelination, and regeneration. Advances in therapeutic interventions, such as electrical stimulation, bioluminescent optogenetics, and innovative nerve grafting techniques, are discussed alongside their potential to enhance recovery and functional outcomes. The molecular underpinnings of plasticity, involving synaptic remodeling, homeostatic mechanisms, and activity-dependent regulation of gene expression, are elucidated to illustrate their role in learning, memory, and injury repair. Integrating emerging technologies and therapeutic approaches with a foundational understanding of neuroplasticity offers a pathway toward more effective strategies for restoring nervous system functionality after injury. Full article
(This article belongs to the Special Issue How to Rewire the Brain—Neuroplasticity)
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41 pages, 4809 KB  
Review
Neurocomputational Mechanisms of Sense of Agency: Literature Review for Integrating Predictive Coding and Adaptive Control in Human–Machine Interfaces
by Anirban Dutta
Brain Sci. 2025, 15(4), 396; https://doi.org/10.3390/brainsci15040396 - 14 Apr 2025
Cited by 6 | Viewed by 8782
Abstract
Background: The sense of agency (SoA)—the subjective experience of controlling one’s own actions and their consequences—is a fundamental aspect of human cognition, volition, and motor control. Understanding how the SoA arises and is disrupted in neuropsychiatric disorders has significant implications for human–machine interface [...] Read more.
Background: The sense of agency (SoA)—the subjective experience of controlling one’s own actions and their consequences—is a fundamental aspect of human cognition, volition, and motor control. Understanding how the SoA arises and is disrupted in neuropsychiatric disorders has significant implications for human–machine interface (HMI) design for neurorehabilitation. Traditional cognitive models of agency often fail to capture its full complexity, especially in dynamic and uncertain environments. Objective: This review synthesizes computational models—particularly predictive coding, Bayesian inference, and optimal control theories—to provide a unified framework for understanding the SoA in both healthy and dysfunctional brains. It aims to demonstrate how these models can inform the design of adaptive HMIs and therapeutic tools by aligning with the brain’s own inference and control mechanisms. Methods: I reviewed the foundational and contemporary literature on predictive coding, Kalman filtering, the Linear–Quadratic–Gaussian (LQG) control framework, and active inference. I explored their integration with neurophysiological mechanisms, focusing on the somato-cognitive action network (SCAN) and its role in sensorimotor integration, intention encoding, and the judgment of agency. Case studies, simulations, and XR-based rehabilitation paradigms using robotic haptics were used to illustrate theoretical concepts. Results: The SoA emerges from hierarchical inference processes that combine top–down motor intentions with bottom–up sensory feedback. Predictive coding frameworks, especially when implemented via Kalman filters and LQG control, provide a mechanistic basis for modeling motor learning, error correction, and adaptive control. Disruptions in these inference processes underlie symptoms in disorders such as functional movement disorder. XR-based interventions using robotic interfaces can restore the SoA by modulating sensory precision and motor predictions through adaptive feedback and suggestion. Computer simulations demonstrate how internal models, and hypnotic suggestions influence state estimation, motor execution, and the recovery of agency. Conclusions: Predictive coding and active inference offer a powerful computational framework for understanding and enhancing the SoA in health and disease. The SCAN system serves as a neural hub for integrating motor plans with cognitive and affective processes. Future work should explore the real-time modulation of agency via biofeedback, simulation, and SCAN-targeted non-invasive brain stimulation. Full article
(This article belongs to the Special Issue New Insights into Movement Generation: Sensorimotor Processes)
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24 pages, 2133 KB  
Article
Sex-Specific Behavioral Features of the Prenatal Valproic Acid Rat Model of Autism Spectrum Disorder
by Patience Mulalo Mamali, Christine Dignon, Ayanda Ngwenya and Busisiwe Constance Maseko
Brain Sci. 2025, 15(4), 388; https://doi.org/10.3390/brainsci15040388 - 9 Apr 2025
Cited by 3 | Viewed by 16741
Abstract
Background/Objectives: Autism is a complex neurodevelopmental disorder characterized by restricted behaviors and impaired social and communication skills. The exact cause of autism remains unknown. One promising animal model for studying autism is the valproic acid rat model. Due to a 1 to 4 [...] Read more.
Background/Objectives: Autism is a complex neurodevelopmental disorder characterized by restricted behaviors and impaired social and communication skills. The exact cause of autism remains unknown. One promising animal model for studying autism is the valproic acid rat model. Due to a 1 to 4 bias for males in autism occurrence, most animal model studies investigate only males and neglect females. However, female autism often appears different from that observed in males. Females are said to be less regularly diagnosed because they can “mask” their symptoms. Female autism is as necessary to investigate as male autism. Methods: Fertile adult female Sprague-Dawley rats were impregnated and injected with valproic acid on gestational day 13. Male and female offspring were subjected to behavioral tests to investigate autistic symptoms. Tests included novel object recognition, balance-beam, Y-maze, hole-board, three-chamber, marble burying, olfactory, light/dark and hot plate tests. Results: The tests revealed that VPA-exposed rats had increased anxiety-like behaviors, hyperactivity, and impaired non-verbal communication. However, they did not display repetitive behaviors or cognitive impairments. Notably, male and female rats showed different autism-like traits, with both showing hyperactivity, and males (but not females) additionally showing impaired sociability and increased anxiety. Conclusions: The findings suggest that prenatal exposure to VPA induces autism-like behaviors in both male and female Sprague-Dawley rat offspring. However, males appear more impacted by VPA exposure as evinced by their display of more autism-like symptoms relative to females. This study provides support for including both sexes in all studies modelling autism, as outcomes are seemingly impacted by the sex being observed. Full article
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28 pages, 2293 KB  
Article
Self-Supervised Learning with Adaptive Frequency-Time Attention Transformer for Seizure Prediction and Classification
by Yajin Huang, Yuncan Chen, Shimin Xu, Dongyan Wu and Xunyi Wu
Brain Sci. 2025, 15(4), 382; https://doi.org/10.3390/brainsci15040382 - 7 Apr 2025
Cited by 10 | Viewed by 5789
Abstract
Background: In deep learning-based epilepsy prediction and classification, enhancing the extraction of electroencephalogram (EEG) features is crucial for improving model accuracy. Traditional supervised learning methods rely on large, detailed annotated datasets, limiting the feasibility of large-scale training. Recently, self-supervised learning approaches using masking-and-reconstruction [...] Read more.
Background: In deep learning-based epilepsy prediction and classification, enhancing the extraction of electroencephalogram (EEG) features is crucial for improving model accuracy. Traditional supervised learning methods rely on large, detailed annotated datasets, limiting the feasibility of large-scale training. Recently, self-supervised learning approaches using masking-and-reconstruction strategies have emerged, reducing dependence on labeled data. However, these methods are vulnerable to inherent noise and signal degradation in EEG data, which diminishes feature extraction robustness and overall model performance. Methods: In this study, we proposed a self-supervised learning Transformer network enhanced with Adaptive Frequency-Time Attention (AFTA) for learning robust EEG feature representations from unlabeled data, utilizing a masking-and-reconstruction framework. Specifically, we pretrained the Transformer network using a self-supervised learning approach, and subsequently fine-tuned the pretrained model for downstream tasks like seizure prediction and classification. To mitigate the impact of inherent noise in EEG signals and enhance feature extraction capabilities, we incorporated AFTA into the Transformer architecture. AFTA incorporates an Adaptive Frequency Filtering Module (AFFM) to perform adaptive global and local filtering in the frequency domain. This module was then integrated with temporal attention mechanisms, enhancing the model’s self-supervised learning capabilities. Result: Our method achieved exceptional performance in EEG analysis tasks. Our method consistently outperformed state-of-the-art approaches across TUSZ, TUAB, and TUEV datasets, achieving the highest AUROC (0.891), balanced accuracy (0.8002), weighted F1-score (0.8038), and Cohen’s kappa (0.6089). These results validate its robustness, generalization, and effectiveness in seizure detection and classification tasks on diverse EEG datasets. Full article
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20 pages, 1075 KB  
Review
Eye Tracking in Parkinson’s Disease: A Review of Oculomotor Markers and Clinical Applications
by Pierluigi Diotaiuti, Giulio Marotta, Francesco Di Siena, Salvatore Vitiello, Francesco Di Prinzio, Angelo Rodio, Tommaso Di Libero, Lavinia Falese and Stefania Mancone
Brain Sci. 2025, 15(4), 362; https://doi.org/10.3390/brainsci15040362 - 31 Mar 2025
Cited by 13 | Viewed by 4964
Abstract
(1) Background. Eye movement abnormalities are increasingly recognized as early biomarkers of Parkinson’s disease (PD), reflecting both motor and cognitive dysfunction. Advances in eye-tracking technology provide objective, quantifiable measures of saccadic impairments, fixation instability, smooth pursuit deficits, and pupillary changes. These advances offer [...] Read more.
(1) Background. Eye movement abnormalities are increasingly recognized as early biomarkers of Parkinson’s disease (PD), reflecting both motor and cognitive dysfunction. Advances in eye-tracking technology provide objective, quantifiable measures of saccadic impairments, fixation instability, smooth pursuit deficits, and pupillary changes. These advances offer new opportunities for early diagnosis, disease monitoring, and neurorehabilitation. (2) Objective. This narrative review explores the relationship between oculomotor dysfunction and PD pathophysiology, highlighting the potential applications of eye tracking in clinical and research settings. (3) Methods. A comprehensive literature review was conducted, focusing on peer-reviewed studies examining eye movement dysfunction in PD. Relevant publications were identified through PubMed, Scopus, and Web of Science, using key terms, such as “eye movements in Parkinson’s disease”, “saccadic control and neurodegeneration”, “fixation instability in PD”, and “eye-tracking for cognitive assessment”. Studies integrating machine learning (ML) models and VR-based interventions were also included. (4) Results. Patients with PD exhibit distinct saccadic abnormalities, including hypometric saccades, prolonged saccadic latency, and increased anti-saccade errors. These impairments correlate with executive dysfunction and disease progression. Fixation instability and altered pupillary responses further support the role of oculomotor metrics as non-invasive biomarkers. Emerging AI-driven eye-tracking models show promise for automated PD diagnosis and progression tracking. (5) Conclusions. Eye tracking provides a reliable, cost-effective tool for early PD detection, cognitive assessment, and rehabilitation. Future research should focus on standardizing clinical protocols, validating predictive AI models, and integrating eye tracking into multimodal treatment strategies. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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15 pages, 2597 KB  
Article
Specialized Large Language Model Outperforms Neurologists at Complex Diagnosis in Blinded Case-Based Evaluation
by Sami Barrit, Nathan Torcida, Aurelien Mazeraud, Sebastien Boulogne, Jeanne Benoit, Timothée Carette, Thibault Carron, Bertil Delsaut, Eva Diab, Hugo Kermorvant, Adil Maarouf, Sofia Maldonado Slootjes, Sylvain Redon, Alexis Robin, Sofiene Hadidane, Vincent Harlay, Vito Tota, Tanguy Madec, Alexandre Niset, Mejdeddine Al Barajraji, Joseph R. Madsen, Salim El Hadwe, Nicolas Massager, Stanislas Lagarde and Romain Carronadd Show full author list remove Hide full author list
Brain Sci. 2025, 15(4), 347; https://doi.org/10.3390/brainsci15040347 - 27 Mar 2025
Cited by 12 | Viewed by 3281
Abstract
Background/Objectives: Artificial intelligence (AI), particularly large language models (LLMs), has demonstrated versatility in various applications but faces challenges in specialized domains like neurology. This study evaluates a specialized LLM’s capability and trustworthiness in complex neurological diagnosis, comparing its performance to neurologists in [...] Read more.
Background/Objectives: Artificial intelligence (AI), particularly large language models (LLMs), has demonstrated versatility in various applications but faces challenges in specialized domains like neurology. This study evaluates a specialized LLM’s capability and trustworthiness in complex neurological diagnosis, comparing its performance to neurologists in simulated clinical settings. Methods: We deployed GPT-4 Turbo (OpenAI, San Francisco, CA, US) through Neura (Sciense, New York, NY, US), an AI infrastructure with a dual-database architecture integrating “long-term memory” and “short-term memory” components on a curated neurological corpus. Five representative clinical scenarios were presented to 13 neurologists and the AI system. Participants formulated differential diagnoses based on initial presentations, followed by definitive diagnoses after receiving conclusive clinical information. Two senior academic neurologists blindly evaluated all responses, while an independent investigator assessed the verifiability of AI-generated information. Results: AI achieved a significantly higher normalized score (86.17%) compared to neurologists (55.11%, p < 0.001). For differential diagnosis questions, AI scored 85% versus 46.15% for neurologists, and for final diagnosis, 88.24% versus 70.93%. AI obtained 15 maximum scores in its 20 evaluations and responded in under 30 s compared to neurologists’ average of 9 min. All AI-provided references were classified as relevant with no hallucinatory content detected. Conclusions: A specialized LLM demonstrated superior diagnostic performance compared to practicing neurologists across complex clinical challenges. This indicates that appropriately harnessed LLMs with curated knowledge bases can achieve domain-specific relevance in complex clinical disciplines, suggesting potential for AI as a time-efficient asset in clinical practice. Full article
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11 pages, 981 KB  
Perspective
Advancing Rehabilitation Medicine with the Metaverse: Opportunities and Challenges
by Rocco Salvatore Calabrò and Giovanni Morone
Brain Sci. 2025, 15(3), 321; https://doi.org/10.3390/brainsci15030321 - 19 Mar 2025
Cited by 5 | Viewed by 1609
Abstract
The metaverse, an immersive virtual environment, is emerging as a transformative tool in rehabilitation, offering innovative modalities for motor and cognitive treatments. Virtual reality and augmented reality within the metaverse facilitate interactive exercises, allowing patients to perform rehabilitative tasks in a gamified context, [...] Read more.
The metaverse, an immersive virtual environment, is emerging as a transformative tool in rehabilitation, offering innovative modalities for motor and cognitive treatments. Virtual reality and augmented reality within the metaverse facilitate interactive exercises, allowing patients to perform rehabilitative tasks in a gamified context, which can improve motivation and adherence. Furthermore, the metaverse supports treatments that are not easy to carry out during conventional therapy, such as the rehabilitation of social participation, and creates a real individuals-based platform of continuum of care thanks to its interoperability. However, challenges such as technological accessibility, user adaptability, and the need for comprehensive clinical guidelines remain. Future research should focus on long-term efficacy, integration into traditional rehabilitation frameworks, and addressing ethical considerations, ultimately positioning the metaverse as a valuable adjunct in rehabilitative practices. Full article
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19 pages, 675 KB  
Review
Vocal Feature Changes for Monitoring Parkinson’s Disease Progression—A Systematic Review
by Helen Wright and Vered Aharonson
Brain Sci. 2025, 15(3), 320; https://doi.org/10.3390/brainsci15030320 - 19 Mar 2025
Cited by 7 | Viewed by 3565
Abstract
Background: Parkinson’s disease has a significant impact on vocal characteristics and speech patterns, making them potential biomarkers for monitoring disease progression. To effectively utilise these biomarkers, it is essential to understand how they evolve over time as this degenerative disease progresses. Objectives: This [...] Read more.
Background: Parkinson’s disease has a significant impact on vocal characteristics and speech patterns, making them potential biomarkers for monitoring disease progression. To effectively utilise these biomarkers, it is essential to understand how they evolve over time as this degenerative disease progresses. Objectives: This review aims to identify the most used vocal features in Parkinson’s disease monitoring and to track the temporal changes observed in each feature. Methods: An online database search was conducted to identify studies on voice and speech changes associated with Parkinson’s disease progression. The analysis examined the features and their temporal changes to identify potential feature classes and trends. Results: Eighteen features were identified and categorised into three main aspects of speech: articulation, phonation and prosody. While twelve of these features exhibited measurable variations in Parkinsonian voices compared to those of healthy individuals, insights into long-term changes were limited. Conclusions: Vocal features can effectively discriminate Parkinsonian voices and may be used to monitor changes through disease progression. These changes remain underexplored and necessitate more evidence from long-term studies. The additional evidence could provide clinical insights into the disease and enhance the effectiveness of automated voice-based monitoring. Full article
(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease)
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20 pages, 1357 KB  
Review
Current Applications of Single-Cell RNA Sequencing in Glioblastoma: A Scoping Review
by Edgar G. Ordóñez-Rubiano, Nicolás Rincón-Arias, William J. Shelton, Andres F. Salazar, María Alejandra Sierra, Raphael Bertani, Diego F. Gómez-Amarillo, Fernando Hakim, Matías Baldoncini, César Payán-Gómez, Alba Lucia Cómbita, Sandra C. Ordonez-Rubiano and Rafael Parra-Medina
Brain Sci. 2025, 15(3), 309; https://doi.org/10.3390/brainsci15030309 - 14 Mar 2025
Cited by 6 | Viewed by 6891
Abstract
Background and Objective: The discovery of novel molecular biomarkers via next-generation sequencing technologies has revolutionized how glioblastomas (GBMs) are classified nowadays. This has resulted in more precise diagnostic, prognostic, and therapeutic approaches to address this malignancy. The present work examines the applications of [...] Read more.
Background and Objective: The discovery of novel molecular biomarkers via next-generation sequencing technologies has revolutionized how glioblastomas (GBMs) are classified nowadays. This has resulted in more precise diagnostic, prognostic, and therapeutic approaches to address this malignancy. The present work examines the applications of single-cell RNA sequencing (scRNA-seq) in GBM, focusing on its potential to address tumor complexity and therapeutic resistance and improve patient outcomes. Methods: A scoping review of original studies published between 2009 and 2024 was conducted using the PUBMED and EMBASE databases. Studies in English or Spanish related to single-cell analysis and GBM were included. Key Findings: The database search yielded 453 publications. Themes related to scRNA-seq applied for the diagnosis, prognosis, treatment, and understanding of the cancer biology of GBM were used as criteria for article selection. Of the 24 studies that were included in the review, 11 focused on the tumor microenvironment and cell subpopulations in GBM samples, 5 investigated the use of sequencing to elucidate the GBM cancer biology, 3 examined disease prognosis using sequencing models, 3 applied translational research through scRNA-seq, and 2 addressed treatment-related problems in GBM elucidated by scRNA-seq. Conclusions: This scoping review explored the various clinical applications of scRNA-seq technologies in approaching GBM. The findings highlight the utility of this technology in unraveling the complex cellular and immune landscapes of GBM, paving the way for improved diagnosis and personalized treatments. This cutting-edge approach might strengthen treatment strategies against tumor progression and recurrence, setting the stage for multi-targeted interventions that could significantly improve outcomes for patients with aggressive, treatment-resistant GBMs. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
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19 pages, 2229 KB  
Review
Neurobiological Relationships Between Neurodevelopmental Disorders and Mood Disorders
by Amanda Gollo Bertollo, Camila Ferreira Puntel, Brunna Varela da Silva, Marcio Martins, Margarete Dulce Bagatini and Zuleide Maria Ignácio
Brain Sci. 2025, 15(3), 307; https://doi.org/10.3390/brainsci15030307 - 14 Mar 2025
Cited by 10 | Viewed by 6892
Abstract
According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), neurodevelopmental disorders (NDDs) are a group of conditions that arise early in development and are characterized by deficits in personal, social, academic, or occupational functioning. These disorders frequently co-occur and include conditions [...] Read more.
According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), neurodevelopmental disorders (NDDs) are a group of conditions that arise early in development and are characterized by deficits in personal, social, academic, or occupational functioning. These disorders frequently co-occur and include conditions such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Mood disorders (MDs), such as major depressive disorder and bipolar disorder, also pose significant global health challenges due to their high prevalence and substantial impact on quality of life. Emerging evidence highlights overlapping neurobiological mechanisms between NDDs and MDs, including shared genetic susceptibilities, neurotransmitter dysregulation (e.g., dopaminergic and serotonergic pathways), neuroinflammation, and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Environmental factors such as early-life adversity further exacerbate these vulnerabilities, contributing to the complexity of their clinical presentation and comorbidity. Functional neuroimaging studies reveal altered connectivity in brain regions critical for emotional regulation and executive function, such as the prefrontal cortex and amygdala, across these disorders. Despite these advances, integrative diagnostic frameworks and targeted therapeutic strategies remain underexplored, limiting effective intervention. This review synthesizes current knowledge on the shared neurobiological underpinnings of NDDs and MDs, emphasizing the need for multidisciplinary research, including genetic, pharmacological, and psychological approaches, for unified diagnosis and treatment. Addressing these intersections can improve clinical outcomes and enhance the quality of life for individuals affected by these disorders. Full article
(This article belongs to the Special Issue Mental Health: From a Neurobiology Perspective)
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14 pages, 1080 KB  
Review
Global Perspectives on Sleep Health: Definitions, Disparities, and Implications for Public Health
by Lourdes M. DelRosso
Brain Sci. 2025, 15(3), 304; https://doi.org/10.3390/brainsci15030304 - 13 Mar 2025
Cited by 14 | Viewed by 13369
Abstract
Sleep health is a multidimensional construct encompassing sleep quality, duration, efficiency, regularity, and alignment with circadian rhythms, playing a crucial role in overall well-being. Sleep health remains inconsistently defined across research and clinical settings despite its importance, limiting the ability to standardize assessments [...] Read more.
Sleep health is a multidimensional construct encompassing sleep quality, duration, efficiency, regularity, and alignment with circadian rhythms, playing a crucial role in overall well-being. Sleep health remains inconsistently defined across research and clinical settings despite its importance, limiting the ability to standardize assessments and interventions. Recent studies have emphasized the significance of defining sleep health beyond the absence of sleep disorders, integrating subjective and objective measures to assess its impact on physical and mental health outcomes. Disparities in sleep health exist across gender, socioeconomic status, and geographic regions, particularly in low- and middle-income countries where inconsistent work schedules, economic stress, and healthcare access influence sleep patterns. Poor sleep health is associated with increased risks of cardiovascular disease, obesity, metabolic dysfunction, and mental health disorders, reinforcing its role as a modifiable risk factor in public health. Lifestyle factors such as caffeine consumption, physical activity, and irregular eating patterns also contribute to sleep disturbances, highlighting the need for behavioral interventions. This narrative review aims to synthesize the current knowledge on sleep health, focusing on its definitions, measurement tools, global disparities, and associations. Full article
(This article belongs to the Special Issue Advances in Global Sleep and Circadian Health)
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16 pages, 2059 KB  
Review
Demystifying the New Dilemma of Brain Rot in the Digital Era: A Review
by Ahmed Mohamed Fahmy Yousef, Alsaeed Alshamy, Ahmed Tlili and Ahmed Hosny Saleh Metwally
Brain Sci. 2025, 15(3), 283; https://doi.org/10.3390/brainsci15030283 - 7 Mar 2025
Cited by 28 | Viewed by 65114
Abstract
Background/Objectives: The widespread phenomenon of “brain rot”, named the Oxford Word of the Year 2024, refers to the cognitive decline and mental exhaustion experienced by individuals, particularly adolescents and young adults, due to excessive exposure to low-quality online materials, especially on social [...] Read more.
Background/Objectives: The widespread phenomenon of “brain rot”, named the Oxford Word of the Year 2024, refers to the cognitive decline and mental exhaustion experienced by individuals, particularly adolescents and young adults, due to excessive exposure to low-quality online materials, especially on social media. The present study is exploratory and interpretative in nature, aiming to investigate the phenomenon of “brain rot”, with a focus on its key pillars, psychological factors, digital behaviors, and the cognitive impact resulting from the overconsumption of low-quality digital content. Methods: This study employs a rapid review approach, examining research published between 2023 and 2024 across PubMed, Google Scholar, PsycINFO, Scopus, and Web of Science. It explores the causes and effects of brain rot, focusing on the overuse of social media, video games, and other digital platforms. Results: The findings reveal that brain rot leads to emotional desensitization, cognitive overload, and a negative self-concept. It is associated with negative behaviors, such as doomscrolling, zombie scrolling, and social media addiction, all linked to psychological distress, anxiety, and depression. These factors impair executive functioning skills, including memory, planning, and decision-making. The pervasive nature of digital media, driven by dopamine-driven feedback loops, exacerbates these effects. Conclusions: The study concludes by offering strategies to prevent brain rot, such as controlling screen time, curating digital content, and engaging in non-digital activities. Given the increasing prevalence of digital engagement, it is essential to explore a variety of strategies, including mindful technology use, to support cognitive health and emotional well-being. The results can guide various stakeholders—policymakers, practitioners, researchers, educators, and parents or caregivers—in addressing the pervasive impact of brain rot and promoting a balanced approach to technology use that fosters cognitive resilience among adolescents and young adults. Full article
(This article belongs to the Special Issue Focus on Mental Health and Mental Illness in Adolescents)
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33 pages, 474 KB  
Review
Current Trends in Pediatric Migraine: Clinical Insights and Therapeutic Strategies
by Adnan Khan, Sufang Liu and Feng Tao
Brain Sci. 2025, 15(3), 280; https://doi.org/10.3390/brainsci15030280 - 6 Mar 2025
Cited by 13 | Viewed by 11512
Abstract
Background/Objectives: Pediatric migraine is a prevalent neurological disorder that significantly impacts children’s quality of life, academic performance, and social interactions. Unlike migraines in adults, pediatric migraines often present differently and involve unique underlying mechanisms, making diagnosis and treatment more complex. Methods: This review [...] Read more.
Background/Objectives: Pediatric migraine is a prevalent neurological disorder that significantly impacts children’s quality of life, academic performance, and social interactions. Unlike migraines in adults, pediatric migraines often present differently and involve unique underlying mechanisms, making diagnosis and treatment more complex. Methods: This review discusses the clinical phases of pediatric migraine, key trigger factors, sex- and age-related differences, and the role of childhood maltreatment in migraine development. We also discuss episodic syndromes such as cyclic vomiting syndrome, abdominal migraine, benign paroxysmal vertigo, and benign paroxysmal torticollis, along with comorbidities such as psychiatric disorders, sleep disturbances, and epilepsy. Results: The underlying pathophysiological mechanisms for pediatric migraines, including genetic predispositions, neuroinflammation, and gut microbiota dysbiosis, are summarized. Current therapeutic strategies, including conventional and emerging pharmacological treatments, nutraceuticals, and non-pharmacological approaches, are evaluated. Non-pharmacological strategies, particularly evidence-based lifestyle interventions such as stress management, diet, hydration, sleep, exercise, screen time moderation, and cognitive behavioral therapy, are highlighted as key components of migraine prevention and management. The long-term prognosis and follow-up of pediatric migraine patients are reviewed, emphasizing the importance of early diagnosis, and tailored multidisciplinary care to prevent chronic progression. Conclusions: Future research should focus on novel therapeutic targets and integrating gut–brain axis modulation, with a need for longitudinal studies to better understand the long-term course of pediatric migraine. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
31 pages, 2670 KB  
Review
Molecular Motors in Blood–Brain Barrier Maintenance by Astrocytes
by Ana Filipa Sobral, Inês Costa, Vanessa Teixeira, Renata Silva and Daniel José Barbosa
Brain Sci. 2025, 15(3), 279; https://doi.org/10.3390/brainsci15030279 - 6 Mar 2025
Cited by 10 | Viewed by 5164
Abstract
The blood–brain barrier (BBB) comprises distinct cell types, including endothelial cells, pericytes, and astrocytes, and is essential for central nervous system (CNS) homeostasis by selectively regulating molecular transport and maintaining integrity. In particular, astrocytes are essential for BBB function, as they maintain BBB [...] Read more.
The blood–brain barrier (BBB) comprises distinct cell types, including endothelial cells, pericytes, and astrocytes, and is essential for central nervous system (CNS) homeostasis by selectively regulating molecular transport and maintaining integrity. In particular, astrocytes are essential for BBB function, as they maintain BBB integrity through their end-feet, which form a physical and biochemical interface that enhances endothelial cell function and barrier selectivity. Moreover, they secrete growth factors like vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β), which regulate tight junction (TJ) proteins (e.g., claudins and occludins) crucial for limiting paracellular permeability. Molecular motors like kinesins, dynein, and myosins are essential for these astrocyte functions. By facilitating vesicular trafficking and protein transport, they are essential for various functions, including trafficking of junctional proteins to support BBB integrity, the proper mitochondria localization within astrocyte processes for efficient energy supply, the polarized distribution of aquaporin (AQP)-4 at astrocyte end-feet for regulating water homeostasis across the BBB, and the modulation of neuroinflammatory responses. Moreover, myosin motors modulate actomyosin dynamics to regulate astrocyte process outgrowth, adhesion, migration, and morphology, facilitating their functional roles. Thus, motor protein dysregulation in astrocytes can compromise BBB function and integrity, increasing the risk of neurodegeneration. This review explores the complex interplay between astrocytes and molecular motors in regulating BBB homeostasis, which represents an attractive but poorly explored area of research. Full article
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51 pages, 838 KB  
Systematic Review
Quality of Assessment Tools for Aphasia: A Systematic Review
by Francescaroberta Panuccio, Giulia Rossi, Anita Di Nuzzo, Ilaria Ruotolo, Giada Cianfriglia, Rachele Simeon, Giovanni Sellitto, Anna Berardi and Giovanni Galeoto
Brain Sci. 2025, 15(3), 271; https://doi.org/10.3390/brainsci15030271 - 3 Mar 2025
Cited by 8 | Viewed by 9483
Abstract
Background/Objectives: Aphasia is a neurological condition affecting the ability to understand and/or express language fluently and accurately, and can occur following stroke, traumatic injuries, or other brain pathologies. The aim of the following study was to provide clinicians and researchers information regarding [...] Read more.
Background/Objectives: Aphasia is a neurological condition affecting the ability to understand and/or express language fluently and accurately, and can occur following stroke, traumatic injuries, or other brain pathologies. The aim of the following study was to provide clinicians and researchers information regarding the existing assessment tools to assess aphasia. Methods: For this Systematic Review, PubMed, CINAHL, Web of Science, and Scopus were searched for articles published up to August 2024. Authors independently identified eligible studies based on predefined inclusion criteria and extracted data. The study quality and risk of bias were assessed using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist. Results: Of the 1278 publications identified and screened, 238 studies fell within the inclusion criteria and were critically reviewed, and 164 assessment tools were found and divided into 8 main domains; the most used tools were the Language Screening Test (LAST), the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39), the Oxford Cognitive Screen (OCS), and the Token test. Conclusions: This review has emphasized the need for agreement among researchers as to which tool must be studied or adapted to other national contexts to develop universal norms and standards. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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27 pages, 3834 KB  
Article
Effect of Different Frequencies of Transcutaneous Electrical Acupoint Stimulation (TEAS) on EEG Source Localization in Healthy Volunteers: A Semi-Randomized, Placebo-Controlled, Crossover Study
by Rael Lopes Alves, Maxciel Zortea, David Mayor, Tim Watson and Tony Steffert
Brain Sci. 2025, 15(3), 270; https://doi.org/10.3390/brainsci15030270 - 3 Mar 2025
Cited by 2 | Viewed by 4231
Abstract
Background/Objectives: Transcutaneous electrical acupoint stimulation (TEAS), also known as transcutaneous electroacupuncture stimulation, delivers electrical pulses to the skin over acupuncture points (“acupoints”) via surface electrodes. Electroencephalography (EEG) is an important tool for assessing the changes in the central nervous system (CNS) that may [...] Read more.
Background/Objectives: Transcutaneous electrical acupoint stimulation (TEAS), also known as transcutaneous electroacupuncture stimulation, delivers electrical pulses to the skin over acupuncture points (“acupoints”) via surface electrodes. Electroencephalography (EEG) is an important tool for assessing the changes in the central nervous system (CNS) that may result from applying different TEAS frequencies peripherally—i.e., acting via the peripheral nervous system (PNS)—and determining how these influence cerebral activity and neural plasticity. Methods: A total of 48 healthy volunteers were allocated in a semi-randomized crossover study to receive four different TEAS frequencies: 2.5 pulses per second (pps); 10 pps; 80 pps; and sham (160 pps at a low, clinically ineffective amplitude). TEAS was applied for 20 min to each hand at the acupuncture point Hegu (LI4). The EEG was recorded during an initial 5 min baseline recording, then during TEAS application, and after stimulation for a further 15 min, separated into three periods of 5 min (initial, intermediate, and final) in order to assess post-stimulation changes. Source localization analysis was conducted for the traditional five EEG frequency bands: delta (0.1–3.9 Hz), theta (4–7.9 Hz), alpha (8–13 Hz), beta (14–30 Hz), and gamma (30.1–45 Hz). Results: Within-group source localization analyses of EEG data showed that during the initial 5 min post-stimulation, theta oscillations in the 2.5 pps TEAS group increased over the parahippocampal gyrus (t = 4.42, p < 0.01). The 10 pps TEAS group exhibited decreased alpha rhythms over the inferior parietal gyrus (t = −4.20, p < 0.05), whereas the sham (160 pps) TEAS group showed decreased delta rhythms over the postcentral gyrus (t = −3.97, p < 0.05). During the intermediate 5 min post-stimulation, the increased theta activity over the left parahippocampal gyrus (BA27) remained in the 2.5 pps TEAS group (t = 3.97, p < 0.05). However, diminished alpha rhythms were observed in the 10 pps TEAS group over the postcentral gyrus (t = −4.20, p < 0.01), as well as in the delta rhythms in the sham (160 pps) TEAS group in the same area (t = −4.35, p < 0.01). In the final 5 min post-stimulation, reduced alpha rhythms were exhibited over the insula in the 10 pps TEAS group (t = −4.07, p < 0.05). Interaction effects of condition by group demonstrate decreased alpha rhythms in the 10 pps TEAS group over the supramarginal gyrus during the initial 5 min post-stimulation (t = −4.31, p < 0.05), and decreased delta rhythms over the insula in the sham TEAS group during the final 5 min post-stimulation (t = −4.42, p < 0.01). Conclusions: This study revealed that low TEAS frequencies of 2.5 pps and 10 pps modulate theta and alpha oscillations over the brain areas related to emotional and attentional processes driven by external stimuli, as well as neural synchronization of delta rhythms in the sham group in brain areas related to stimulus expectation at baseline. It is hoped that these findings will stimulate further research in order to evaluate such TEAS modulation effects in clinical patients. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
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23 pages, 1484 KB  
Systematic Review
The Impact of Walking on BDNF as a Biomarker of Neuroplasticity: A Systematic Review
by Mohamed Hesham Khalil
Brain Sci. 2025, 15(3), 254; https://doi.org/10.3390/brainsci15030254 - 27 Feb 2025
Cited by 9 | Viewed by 12750
Abstract
Background/Objectives: The brain-derived neurotrophic factor (BDNF) is a critical exercise-induced modulator of various neuroplasticity processes, including adult hippocampal neurogenesis. Environmental affordance for physical activity is a novel theory that aims to increase the BDNF through walking or climbing stairs, stimulated by the urban [...] Read more.
Background/Objectives: The brain-derived neurotrophic factor (BDNF) is a critical exercise-induced modulator of various neuroplasticity processes, including adult hippocampal neurogenesis. Environmental affordance for physical activity is a novel theory that aims to increase the BDNF through walking or climbing stairs, stimulated by the urban and interior environment. In a systematic review, this paper explores the association between walking, as a structured or free-living form of physical activity, and changes in the BDNF in humans with healthy locomotion. Method: A systematic review with a registered protocol, INPLASY2024110093, and following the PRISMA guidelines, includes English-language original research articles on adult and older adult human subjects who are locomotor-healthy, studies on walking as a structured exercise or free-living physical activity that is presented in a non-combined intervention, and must report changes in the BDNF as a dependent variable. The search was conducted using three databases: PubMed, Web of Science, and Scopus, resulting in 21 eligible studies. Results: This systematic review finds that the impact of walking on the BDNF is evidenced, but subject to moderate to high intensities in single bouts. At the same time, the long-term effects are yet to be fully understood, potentially due to the uptake of the BDNF for functional brain improvements, neuroplasticity processes, or muscle repair, instead of an accumulation of the BDNF itself, yet still confirm the important role of the BDNF for neurosustainability. Age and environmental factors such as heat are also found to affect the increase in the BDNF. The narrative synthesis provides elaborate explanations for understanding those complex dynamics before reaching future conclusions on the impact of walking or environmental affordance for physical activity on the changes in the BDNF concentrations. Conclusions: This systematic review highlights the potential role played by moderate- and high-intensity walking as a lifestyle intervention that can be utilised through the built environment to promote adaptive brain changes, through the sustainable regulation of the BDNF. Full article
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28 pages, 1086 KB  
Review
Phytochemicals Targeting BDNF Signaling for Treating Neurological Disorders
by Alka Ashok Singh, Shweta Katiyar and Minseok Song
Brain Sci. 2025, 15(3), 252; https://doi.org/10.3390/brainsci15030252 - 27 Feb 2025
Cited by 18 | Viewed by 9561
Abstract
Neurological disorders are defined by a deterioration or disruption of the nervous system’s structure and function. These diseases, which include multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and schizophrenia, are caused by intricate pathological processes that include excitotoxicity, neuroinflammation, oxidative stress, genetic [...] Read more.
Neurological disorders are defined by a deterioration or disruption of the nervous system’s structure and function. These diseases, which include multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and schizophrenia, are caused by intricate pathological processes that include excitotoxicity, neuroinflammation, oxidative stress, genetic mutations, and compromised neurotrophic signaling. Although current pharmaceutical treatments relieve symptoms, their long-term efficacy is limited due to adverse side effects and weak neuroprotective properties. However, when combined with other neuroprotective drugs or adjunct therapy, they may offer additional benefits and improve treatment outcomes. Phytochemicals have emerged as attractive therapeutic agents due to their ability to regulate essential neurotrophic pathways, especially the brain-derived neurotrophic factor (BDNF) signaling cascade. BDNF is an important target for neurodegenerative disease (ND) treatment since it regulates neuronal survival, synaptic plasticity, neurogenesis, and neuroprotection. This review emphasizes the molecular pathways through which various phytochemicals—such as flavonoids, terpenoids, alkaloids, and phenolic compounds—stimulate BDNF expression and modulate its downstream signaling pathways, including GSK-3β, MAPK/ERK, PI3K/Akt/mTOR, CREB, and Wnt/β-catenin. This paper also highlights how phytochemical combinations may interact to enhance BDNF activity, offering new therapeutic options for ND treatment. Despite their potential for neuroprotection, phytochemicals face challenges related to pharmacokinetics, blood–brain barrier (BBB) permeability, and absorption, highlighting the need for further research into combination therapies and improved formulations. Clinical assessment and mechanistic understanding of BDNF-targeted phytotherapy should be the main goals of future studies. The therapeutic efficacy of natural compounds in regulating neurotrophic signaling is highlighted in this review, providing a viable approach to the prevention and treatment of NDs. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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19 pages, 1021 KB  
Review
Hypoxic Neuroinflammation in the Pathogenesis of Multiple Sclerosis
by Bethany Y. A. Hollingworth, Patrick N. Pallier, Stuart I. Jenkins and Ruoli Chen
Brain Sci. 2025, 15(3), 248; https://doi.org/10.3390/brainsci15030248 - 26 Feb 2025
Cited by 6 | Viewed by 3507
Abstract
Multiple sclerosis (MS) is an autoimmune disease that damages the myelin sheath around the central nervous system axons, leading to neurological dysfunction. Although the initial damage is driven by inflammation, hypoxia has been reported in several brain regions of MS patients, but the [...] Read more.
Multiple sclerosis (MS) is an autoimmune disease that damages the myelin sheath around the central nervous system axons, leading to neurological dysfunction. Although the initial damage is driven by inflammation, hypoxia has been reported in several brain regions of MS patients, but the significance of this for prognosis and treatment remains unclear. Neuroinflammation can induce hypoxia, and hypoxia can induce and exacerbate neuroinflammation, forming a vicious cycle. Within MS lesions, demyelination is often followed by remyelination, which may restore neurological function. However, demyelinated axons are vulnerable to damage, which leads to the accumulation of the permanent neurological dysfunction typical in MS, with this vulnerability heightened during hypoxia. Clinically approved therapies for MS are immunomodulatory, which can reduce relapse frequency/severity, but there is a lack of pro-regenerative therapies for MS, for example promoting remyelination. All tissues have protective responses to hypoxia, which may be relevant to MS lesions, especially during remyelinating episodes. When oxygen levels are reduced in the brain, constitutively expressed hypoxia-inducible factors (HIF) are stabilised, upregulating hundreds of genes, including neuroprotective factors. Furthermore, astrocytes upregulate heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) in the early stage of MS. HB-EGF promotes protective mechanisms and induces oligodendrocyte and neuron differentiation and survival. This review article outlines the neuroinflammation and hypoxia cycle in MS pathology and identifies potential therapeutic targets to limit neurodegeneration and/or promote regeneration. Both HIF and HB-EGF signalling pathways induce endogenous protection mechanisms in the CNS, promoting neuroprotection and remyelination directly, but also indirectly by modulating the immune response in MS. Promoting such endogenous protective signalling pathways could be an effective therapy for MS patients. Full article
(This article belongs to the Special Issue New Advances in Neuroimmunology and Neuroinflammation)
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14 pages, 2147 KB  
Article
Naringenin’s Neuroprotective Effect on Diazino-Induced Cerebellar Damage in Male Albino Rats, with Modulation of Acetylcholinesterase
by Abdullah A. Saati
Brain Sci. 2025, 15(3), 242; https://doi.org/10.3390/brainsci15030242 - 25 Feb 2025
Cited by 6 | Viewed by 1694
Abstract
Background: Diazinon, a well-known organophosphorus compound, is recognized for its neurotoxic effects, primarily through the inhibition of acetylcholinesterase (AChE) and induction of oxidative stress. Aim: This study evaluates the neuroprotective effects of naringenin, a citrus flavonoid, against diazinon-induced cerebellar damage in male albino [...] Read more.
Background: Diazinon, a well-known organophosphorus compound, is recognized for its neurotoxic effects, primarily through the inhibition of acetylcholinesterase (AChE) and induction of oxidative stress. Aim: This study evaluates the neuroprotective effects of naringenin, a citrus flavonoid, against diazinon-induced cerebellar damage in male albino rats. Materials and methods: Twenty-four rats were divided into four groups: control, naringenin, diazinon, and diazinon with naringenin. Results: Histological examination revealed altered structures of Purkinje cells in the cerebellum of the diazinon group. Naringenin co-treatment significantly improved cerebellar histology and modulated oxidative stress markers by decreasing malondialdehyde (MDA) and increasing glutathione (GSH) and glutathione peroxidase (GPx) levels. Additionally, naringenin exhibited anti-inflammatory effects by decreasing nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) levels, while increasing interleukin-10 (IL-10). It also reduced apoptotic markers, including p53, Bax, caspase-9, caspase-8, and caspase-3, while increasing the anti-apoptotic marker Bcl-2. Furthermore, naringenin modulated AChE activity, leading to decreased acetylcholine levels and reduced neurotoxicity. Conclusions: These findings suggest that naringenin’s antioxidant, anti-inflammatory, and anti-apoptotic properties contribute to its neuroprotective role against diazinon-induced cerebellar damage. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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15 pages, 1678 KB  
Article
The Brain That Understands Diversity: A Pilot Study Focusing on the Triple Network
by Taiko Otsuka, Keisuke Kokubun, Maya Okamoto and Yoshinori Yamakawa
Brain Sci. 2025, 15(3), 233; https://doi.org/10.3390/brainsci15030233 - 23 Feb 2025
Cited by 6 | Viewed by 2377
Abstract
Background/Objectives: Interest in diversity is growing worldwide. Today, an understanding and social acceptance of diverse people is becoming increasingly important. Therefore, in this study, we aimed to clarify the relationship between an individual’s gray matter volume (GMV), which is thought to reflect [...] Read more.
Background/Objectives: Interest in diversity is growing worldwide. Today, an understanding and social acceptance of diverse people is becoming increasingly important. Therefore, in this study, we aimed to clarify the relationship between an individual’s gray matter volume (GMV), which is thought to reflect brain health, and their understanding of diversity (gender, sexuality (LGBTQ), and origin). Methods: GMV was determined as the value of the Gray Matter Brain Healthcare Quotient (GM-BHQ) based on MRI image analysis. Meanwhile, participants’ understanding and acceptance of diversity was calculated based on their answers to the psychological questions included in the World Values Survey Wave 7 (WVS7). Results: Our analysis indicated that, in the group of participants with the highest understanding of diversity (PHUD. n = 11), not only the GMV at the whole brain level (t = 2.587, p = 0.027, Cohen’s d = 0.780) but also the GMV of the central executive network (CEN: t = 2.700, p= 0.022, Cohen’s d = 0.814) and saliency network (SN: t = 3.100, p = 0.011, Cohen’s d = 0.935) were shown to be significantly higher than the theoretical value estimated from sex, age, and BMI at the 5% level. In addition, the GMV of the default mode network (DMN: t = 2.063, p = 0.066, Cohen’s d = 0.622) was also higher than the theoretical value at the 10% level. Meanwhile, in the group of others (n = 10), there was no significant difference from the theoretical value. These differences between PHUD and others were also observed when comparing the two with and without controlling for educational and occupational covariates at the 5% or 10% levels. Conclusions: These results suggest that understanding diversity requires a healthy brain, centered on three networks that govern rational judgment, emotion regulation, other-awareness, self-awareness, and the valuing of actions. This is the first study to show that brain structure is related to an understanding and acceptance of the diversity of people. Full article
(This article belongs to the Section Behavioral Neuroscience)
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19 pages, 2306 KB  
Article
Cognitive Priming During Warmup Enhances Sport and Exercise Performance: A Goldilocks Effect
by Jesús Díaz-García, Ana Rubio-Morales, David Manzano-Rodríguez, Tomás García-Calvo and Christopher Ring
Brain Sci. 2025, 15(3), 235; https://doi.org/10.3390/brainsci15030235 - 23 Feb 2025
Cited by 6 | Viewed by 6449
Abstract
Background: Mental fatigue can impair sport, exercise and cognitive performance. Warmup activities can improve performance when the individual is rested. However, their effectiveness when the individual is fatigued has yet to be established. The research objectives were to evaluate the effects of physical [...] Read more.
Background: Mental fatigue can impair sport, exercise and cognitive performance. Warmup activities can improve performance when the individual is rested. However, their effectiveness when the individual is fatigued has yet to be established. The research objectives were to evaluate the effects of physical and combined physical plus cognitive warmup activities on subsequent sport, exercise, and cognitive performance when rested and fatigued by sleep restriction in athletes (Study 1) and older adults (Study 2). Methods: In Study 1, 31 padel players completed a padel performance test and Stroop task after physical and combined warmups when rested and fatigued by sleep deprivation. In Study 2, 32 older adults completed sit–stand, arm curl, walking, Stroop, and psychomotor vigilance tests after no warmup, physical warmup, and combined warmup when rested and fatigued by sleep deprivation. In both studies, combined warmups intermixed short-, medium-, or long-duration cognitive tasks between physical warmup activities. Mental fatigue was measured using visual analog scale ratings. Results: In both studies, sleep deprivation increased mental fatigue and impaired performance. In Study 1, relative to a physical warmup, padel and Stroop performance were improved by combined warmups (with short-to-medium cognitive tasks) when rested and fatigued. In Study 2, relative to no warmup, sit–stand, arm curl, walking, Stroop, and reaction time performance were improved by physical and combined warmups (with short-to-medium cognitive tasks) when rested and fatigued. Conclusions: The negative effects of sleep deprivation on sport, exercise, and cognitive performance were best mitigated by combined warmups with short-to-medium cognitive tasks. Combined warmups are effective countermeasures against the deleterious effects of mental fatigue on performance. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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15 pages, 431 KB  
Review
A Song for the Mind: A Literature Review on Singing and Cognitive Health in Aging Populations
by Panagiota Tragantzopoulou and Vaitsa Giannouli
Brain Sci. 2025, 15(3), 227; https://doi.org/10.3390/brainsci15030227 - 21 Feb 2025
Cited by 8 | Viewed by 48398
Abstract
Background/Objectives: As the global population ages, the need for effective nonpharmacological interventions to support cognitive health has become increasingly urgent. Singing has been identified as a promising strategy to enhance cognitive function and emotional well-being in older adults. While substantial research has [...] Read more.
Background/Objectives: As the global population ages, the need for effective nonpharmacological interventions to support cognitive health has become increasingly urgent. Singing has been identified as a promising strategy to enhance cognitive function and emotional well-being in older adults. While substantial research has focused on the neurocognitive benefits of musical training, the specific effects of singing on neuroplasticity and cognition in aging populations remain underexplored. Methods: This review synthesizes findings from PubMed, PsycINFO, and Google Scholar to examine the impact of singing on cognitive health, particularly in mitigating cognitive decline and promoting mental well-being. Results: Key benefits of singing include improvements in verbal fluency, executive function, and episodic memory. Structural changes such as increased white matter integrity and enhanced auditory–motor integration highlight the potential of singing to stimulate neuroplasticity. Among individuals with dementia, singing fosters episodic memory, mood enhancement, and social connection, while healthy older adults demonstrate improved verbal flexibility and cognitive resilience. However, methodological limitations, such as small sample sizes and cross-sectional designs, preclude definitive conclusions about long-term benefits. Conclusions: Future research should explore the specific neural mechanisms underlying these effects, with an emphasis on longitudinal studies and diverse populations. Tailored, inclusive singing programs could address individual cognitive and physical abilities while fostering sustained engagement and social connection. As a low-cost, scalable intervention, singing holds promise for addressing cognitive and emotional challenges associated with aging, offering an accessible avenue to support healthy aging and enhance quality of life across diverse populations. Full article
(This article belongs to the Special Issue Aging-Related Changes in Memory and Cognition)
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73 pages, 4804 KB  
Systematic Review
From Neural Networks to Emotional Networks: A Systematic Review of EEG-Based Emotion Recognition in Cognitive Neuroscience and Real-World Applications
by Evgenia Gkintoni, Anthimos Aroutzidis, Hera Antonopoulou and Constantinos Halkiopoulos
Brain Sci. 2025, 15(3), 220; https://doi.org/10.3390/brainsci15030220 - 20 Feb 2025
Cited by 75 | Viewed by 15646
Abstract
Background/Objectives: This systematic review presents how neural and emotional networks are integrated into EEG-based emotion recognition, bridging the gap between cognitive neuroscience and practical applications. Methods: Following PRISMA, 64 studies were reviewed that outlined the latest feature extraction and classification developments using deep [...] Read more.
Background/Objectives: This systematic review presents how neural and emotional networks are integrated into EEG-based emotion recognition, bridging the gap between cognitive neuroscience and practical applications. Methods: Following PRISMA, 64 studies were reviewed that outlined the latest feature extraction and classification developments using deep learning models such as CNNs and RNNs. Results: Indeed, the findings showed that the multimodal approaches were practical, especially the combinations involving EEG with physiological signals, thus improving the accuracy of classification, even surpassing 90% in some studies. Key signal processing techniques used during this process include spectral features, connectivity analysis, and frontal asymmetry detection, which helped enhance the performance of recognition. Despite these advances, challenges remain more significant in real-time EEG processing, where a trade-off between accuracy and computational efficiency limits practical implementation. High computational cost is prohibitive to the use of deep learning models in real-world applications, therefore indicating a need for the development and application of optimization techniques. Aside from this, the significant obstacles are inconsistency in labeling emotions, variation in experimental protocols, and the use of non-standardized datasets regarding the generalizability of EEG-based emotion recognition systems. Discussion: These challenges include developing adaptive, real-time processing algorithms, integrating EEG with other inputs like facial expressions and physiological sensors, and a need for standardized protocols for emotion elicitation and classification. Further, related ethical issues with respect to privacy, data security, and machine learning model biases need to be much more proclaimed to responsibly apply research on emotions to areas such as healthcare, human–computer interaction, and marketing. Conclusions: This review provides critical insight into and suggestions for further development in the field of EEG-based emotion recognition toward more robust, scalable, and ethical applications by consolidating current methodologies and identifying their key limitations. Full article
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25 pages, 1272 KB  
Systematic Review
Cholinesterase Inhibitors from Plants and Their Potential in Alzheimer’s Treatment: Systematic Review
by Maryam N. ALNasser, Ghadir M. Alboraiy, Eman M. Alsowig and Fatimah M. Alqattan
Brain Sci. 2025, 15(2), 215; https://doi.org/10.3390/brainsci15020215 - 19 Feb 2025
Cited by 16 | Viewed by 5862
Abstract
Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory loss and cognitive decline, primarily due to dysfunction of acetylcholine caused by acetylcholinesterase and butyrylcholinesterase. While synthetic cholinesterase inhibitors like donepezil, rivastigmine, and galantamine are commonly used, they have notable side effects, [...] Read more.
Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory loss and cognitive decline, primarily due to dysfunction of acetylcholine caused by acetylcholinesterase and butyrylcholinesterase. While synthetic cholinesterase inhibitors like donepezil, rivastigmine, and galantamine are commonly used, they have notable side effects, prompting interest in natural alternatives. Medicinal plants, rich in bioactive compounds like flavonoids and alkaloids, have shown potential as cholinesterase inhibitors with additional antioxidants and anti-inflammatory benefits. This study aimed to evaluate the cholinesterase-inhibiting effects of various plant species and their compounds to identify new therapeutic candidates and reduce side effects. Method: A PRISMA-compliant review was conducted, screening studies from multiple databases, with a final inclusion of 64 in vivo studies. Results: These studies highlighted plant extracts such as Ferula ammoniacum, Elaeagnus umbellata, Bacopa monnieri, and Centella asiatica, which improved memory, reduced oxidative stress, and provided neuroprotection. Some extracts also reduced amyloid plaques, enhanced neuronal integrity, and restored cholinesterase activity, indicating their potential as therapeutic agents for AD and other neurodegenerative diseases. Conclusions: The findings underscore the promise of plant-based compounds in treating cognitive decline and cholinergic dysfunction in AD, advocating for further research into their therapeutic potential. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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18 pages, 1124 KB  
Review
Neuroinflammatory and Immunological Aspects of Fibromyalgia
by Kate Findeisen, Emma Guymer and Geoffrey Littlejohn
Brain Sci. 2025, 15(2), 206; https://doi.org/10.3390/brainsci15020206 - 17 Feb 2025
Cited by 19 | Viewed by 10128
Abstract
Fibromyalgia is a common, high-impact condition of chronic widespread pain and sensory dysfunction associated with altered central and peripheral sensory processing. A growing body of evidence supports the role of neuroinflammation and immune changes in fibromyalgia, and a narrative review of this literature [...] Read more.
Fibromyalgia is a common, high-impact condition of chronic widespread pain and sensory dysfunction associated with altered central and peripheral sensory processing. A growing body of evidence supports the role of neuroinflammation and immune changes in fibromyalgia, and a narrative review of this literature was undertaken. Published data suggest that the interactions between the neural pain networks and the immune system in fibromyalgia appear to be bidirectional and operate both centrally and peripherally. There is a growing focus on processes occurring in the dorsal root ganglia and the role of maladaptive microglial cell activation. Ongoing insight into neuroinflammatory mechanisms in fibromyalgia opens potential avenues for the development of mechanism-based therapies in what is, at present, a challenging-to-manage condition. Full article
(This article belongs to the Special Issue Advances in Neuroinflammation and Pain Medicine)
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101 pages, 7201 KB  
Systematic Review
Challenging Cognitive Load Theory: The Role of Educational Neuroscience and Artificial Intelligence in Redefining Learning Efficacy
by Evgenia Gkintoni, Hera Antonopoulou, Andrew Sortwell and Constantinos Halkiopoulos
Brain Sci. 2025, 15(2), 203; https://doi.org/10.3390/brainsci15020203 - 15 Feb 2025
Cited by 117 | Viewed by 32936
Abstract
Background/Objectives: This systematic review integrates Cognitive Load Theory (CLT), Educational Neuroscience (EdNeuro), Artificial Intelligence (AI), and Machine Learning (ML) to examine their combined impact on optimizing learning environments. It explores how AI-driven adaptive learning systems, informed by neurophysiological insights, enhance personalized education for [...] Read more.
Background/Objectives: This systematic review integrates Cognitive Load Theory (CLT), Educational Neuroscience (EdNeuro), Artificial Intelligence (AI), and Machine Learning (ML) to examine their combined impact on optimizing learning environments. It explores how AI-driven adaptive learning systems, informed by neurophysiological insights, enhance personalized education for K-12 students and adult learners. This study emphasizes the role of Electroencephalography (EEG), Functional Near-Infrared Spectroscopy (fNIRS), and other neurophysiological tools in assessing cognitive states and guiding AI-powered interventions to refine instructional strategies dynamically. Methods: This study reviews n = 103 papers related to the integration of principles of CLT with AI and ML in educational settings. It evaluates the progress made in neuroadaptive learning technologies, especially the real-time management of cognitive load, personalized feedback systems, and the multimodal applications of AI. Besides that, this research examines key hurdles such as data privacy, ethical concerns, algorithmic bias, and scalability issues while pinpointing best practices for robust and effective implementation. Results: The results show that AI and ML significantly improve Learning Efficacy due to managing cognitive load automatically, providing personalized instruction, and adapting learning pathways dynamically based on real-time neurophysiological data. Deep Learning models such as Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs), and Support Vector Machines (SVMs) improve classification accuracy, making AI-powered adaptive learning systems more efficient and scalable. Multimodal approaches enhance system robustness by mitigating signal variability and noise-related limitations by combining EEG with fMRI, Electrocardiography (ECG), and Galvanic Skin Response (GSR). Despite these advances, practical implementation challenges remain, including ethical considerations, data security risks, and accessibility disparities across learner demographics. Conclusions: AI and ML are epitomes of redefinition potentials that solid ethical frameworks, inclusive design, and scalable methodologies must inform. Future studies will be necessary for refining pre-processing techniques, expanding the variety of datasets, and advancing multimodal neuroadaptive learning for developing high-accuracy, affordable, and ethically responsible AI-driven educational systems. The future of AI-enhanced education should be inclusive, equitable, and effective across various learning populations that would surmount technological limitations and ethical dilemmas. Full article
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23 pages, 870 KB  
Article
Architecturally Mediated Allostasis and Neurosustainability: A Proposed Theoretical Framework for the Impact of the Built Environment on Neurocognitive Health
by Cleo Valentine, Heather Mitcheltree, Isabelle A. K. Sjövall and Mohamed Hesham Khalil
Brain Sci. 2025, 15(2), 201; https://doi.org/10.3390/brainsci15020201 - 15 Feb 2025
Cited by 7 | Viewed by 5824
Abstract
The global rise in mental health-related disorders represents a significant health and wellbeing challenge, imposing a substantial social and economic burden on individuals, communities, and healthcare systems. According to the World Health Organization, one in four people globally will be affected by mental [...] Read more.
The global rise in mental health-related disorders represents a significant health and wellbeing challenge, imposing a substantial social and economic burden on individuals, communities, and healthcare systems. According to the World Health Organization, one in four people globally will be affected by mental or neurological disorders at some point in their lives, highlighting a significant global health concern that warrants carefully considered and innovative responses. While mental health challenges arise from complex, multifaceted factors, emerging research indicates that the built environment—the architecture of our homes, workplaces, and public spaces—may exert a critical but underappreciated influence on mental health outcomes. This paper outlines a novel theoretical framework for how visual stressors in the built environment might trigger neurophysiological stress responses via the HPA and SAM axes, potentially contributing over time to allostatic load. In this paper, it is proposed that chronic physiological strain can alter neuroplastic processes and neurogenesis in key brain regions—such as the hippocampus, prefrontal cortex (PFC), anterior cingulate cortex (ACC), and amygdala—thereby affecting cognitive health, emotional regulation, and overall mental wellbeing. Drawing on the principle of neurosustainability, this paper suggests that long-term exposure to stress-inducing environments may create feedback loops, particularly involving the amygdala, that have downstream effects on other brain areas and may be linked to adverse mental health outcomes such as depression. By presenting this framework, this paper aims to inspire further inquiry and applied experimental research into the intersection of neurophysiology, mental health, and the built environment, with a particular emphasis on rigorous testing and validation of the proposed mechanisms, that may then be translated into practical architectural design strategies for supporting health and wellbeing. In doing so, it is hoped that this work may contribute to a more holistic approach to improving mental health that integrates the creation of nurturing, resilient spaces into the broader public health agenda. Full article
(This article belongs to the Special Issue Neuroarchitecture: Humans in the Built Environment)
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14 pages, 23633 KB  
Article
Resting-State EEG Power Spectral Density Analysis Between Healthy and Cognitively Impaired Subjects
by Katherine F. Walters, Rohit Shukla, Vivek Kumar, Shannon Schueren, Hariom Yadav, Nathan D. Schilaty and Shalini Jain
Brain Sci. 2025, 15(2), 173; https://doi.org/10.3390/brainsci15020173 - 10 Feb 2025
Cited by 9 | Viewed by 5250
Abstract
Background/Objectives: This study evaluates the potential of electroencephalography (EEG) as a noninvasive tool for distinguishing between healthy individuals (n = 79), those with mild cognitive impairment (MCI; n = 36), and dementia patients (n = 7). Methods: Using a [...] Read more.
Background/Objectives: This study evaluates the potential of electroencephalography (EEG) as a noninvasive tool for distinguishing between healthy individuals (n = 79), those with mild cognitive impairment (MCI; n = 36), and dementia patients (n = 7). Methods: Using a 14-channel Emotiv EPOC-X headset, we analyzed power spectral density during a 2-min eyes-closed resting state. Results: Our results demonstrated that while EEG effectively differentiated dementia patients from healthy controls, it did not show significant differences between MCI and healthy controls. This indicates that EEG holds promise for identifying advanced cognitive decline but faces challenges in early-stage detection. Conclusions: The study contributes to the growing body of literature by highlighting EEG’s potential as a cost-effective alternative to invasive diagnostic methods while also identifying the need for larger sample sizes and task-oriented approaches to improve its diagnostic precision. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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16 pages, 474 KB  
Review
Gut–Brain Axis and Brain Microbiome Interactions from a Medical Perspective
by Borros Arneth
Brain Sci. 2025, 15(2), 167; https://doi.org/10.3390/brainsci15020167 - 8 Feb 2025
Cited by 7 | Viewed by 7759
Abstract
Background: The gut microbiome directly impacts brain health and activity, meaning the two are closely associated. This relationship suggests a link between microbial imbalances and diseases such as Alzheimer’s, although multiple other contributing factors, such as genetics, also play a part. Additionally, recent [...] Read more.
Background: The gut microbiome directly impacts brain health and activity, meaning the two are closely associated. This relationship suggests a link between microbial imbalances and diseases such as Alzheimer’s, although multiple other contributing factors, such as genetics, also play a part. Additionally, recent studies discovered that cerebrospinal fluid has some microbial deoxyribonucleic acid (DNA), which can be interpreted to mean a microbiome exists in the brain too. The vagus nerve and the central nervous and immune systems are responsible for the connection between the brain and gut microbiome. Aims and Objectives: The main aim of this systematic review is to analyze existing research on the gut–brain axis and the brain microbiome to fill the current knowledge gap. Materials and Methods: A search was conducted on the PubMed database based on a set of predefined MeSH terms. Results: After the search, 2716 articles meeting the MeSH parameters were found in PubMed. This list was then downloaded and analyzed according to the inclusion/exclusion criteria, and 63 relevant papers were selected. Discussion: Bacteria in the gut microbiome produce some substances that are considered neuroactive. These compounds can directly or indirectly affect brain function through the gut–brain axis. However, various knowledge gaps on the mechanisms involved in this connection need to be addressed first. Full article
(This article belongs to the Special Issue Brain-Microbiome Interactions: 2nd Edition)
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26 pages, 2250 KB  
Article
Balneotherapy as a Complementary Intervention for Stress and Cortisol Reduction: Findings from a Randomized Controlled Trial
by Lolita Rapolienė, Dovydas Rapolis, Aelita Bredelytė, Giedrė Taletavičienė, Antonella Fioravanti and Arvydas Martinkėnas
Brain Sci. 2025, 15(2), 165; https://doi.org/10.3390/brainsci15020165 - 7 Feb 2025
Cited by 8 | Viewed by 7277
Abstract
Background: In our modern era, stress has become a pervasive challenge, affecting individuals across all ages and backgrounds. Acute or chronic stress and elevated cortisol levels are known to impair neurological function and hinder rehabilitation outcomes. Therefore, effective treatment methods that reduce stress, [...] Read more.
Background: In our modern era, stress has become a pervasive challenge, affecting individuals across all ages and backgrounds. Acute or chronic stress and elevated cortisol levels are known to impair neurological function and hinder rehabilitation outcomes. Therefore, effective treatment methods that reduce stress, enhance mental health, and promote overall well-being are urgently needed. The aim of this study was to evaluate the seasonal impact of balneotherapy on distress, as measured by the General Symptoms Distress Scale (GSDS), and well-being, as assessed using the Arizona Integrative Outcomes Scale (AIOS), and the effect of winter balneotherapy on salivary cortisol levels. Methods: In 2023, a multicenter, single-blind, parallel-group, randomized controlled trial was carried out across six medical spa centers in Lithuania. Participants with a stress intensity greater than 3 points on the Visual Analogue Scale (VAS) underwent combined natural resource-based therapies over a 1- to 2-week treatment period. Outcomes were assessed using the General Symptom Distress and Arizona Integrative Outcomes scales, along with salivary cortisol measurements after winter intervention. Results: The results demonstrated a significant reduction in distress intensity by 1–3.5 points (VAS), with winter interventions showing greater efficacy compared to summer. Participants also experienced an increase in well-being by up to 3 points (VAS), improved stress management by up to 1.9 points (VAS), and a reduction in salivary cortisol levels by 0.9 units following winter-based treatments. Some gender differences emerged in specific groups. Conclusions: Our study provides robust evidence for the stress-reducing effects of balneotherapy, particularly highlighting the enhanced efficacy of winter interventions. These findings are especially relevant for neurological rehabilitation, where stress reduction and improved autonomic regulation can support neuroplasticity, recovery processes, and overall quality of life. This research offers valuable insights for developing holistic, seasonally optimized strategies to aid stress management and promote neurological health. Full article
(This article belongs to the Special Issue The Rehabilitation of Neurologic Disorders)
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19 pages, 2543 KB  
Review
Effect of N-Acetyl Cysteine as an Adjuvant Treatment in Alzheimer’s Disease
by Sarah Monserrat Lomelí Martínez, Fermín Paul Pacheco Moisés, Oscar Kurt Bitzer-Quintero, Javier Ramírez-Jirano, Daniela L. C. Delgado-Lara, Irán Cortés Trujillo, Juan Heriberto Torres Jasso, Joel Salazar-Flores and Erandis Dheni Torres-Sánchez
Brain Sci. 2025, 15(2), 164; https://doi.org/10.3390/brainsci15020164 - 7 Feb 2025
Cited by 13 | Viewed by 8949
Abstract
Oxidative stress levels are exacerbated in Alzheimer’s disease (AD). This phenomenon feeds back into the overactivation of oxidase enzymes, mitochondrial dysfunction, and the formation of advanced glycation end-products (AGEs), with the stimulation of their receptors (RAGE). These factors stimulate Aβ peptide aggregation and [...] Read more.
Oxidative stress levels are exacerbated in Alzheimer’s disease (AD). This phenomenon feeds back into the overactivation of oxidase enzymes, mitochondrial dysfunction, and the formation of advanced glycation end-products (AGEs), with the stimulation of their receptors (RAGE). These factors stimulate Aβ peptide aggregation and tau hyperphosphorylation through multiple pathways, which are addressed in this paper. The aim of this study was to evaluate the regulatory effect of N-acetyl cysteine (NAC) on oxidant/antioxidant balance as an adjuvant treatment in patients with AD. The results obtained showed that NAC supplementation produced improved cognitive performance, decreased levels of oxidative stress markers, lowered activities of oxidase enzymes, increased antioxidant responses, and attenuated inflammatory and apoptotic markers. Moreover, NAC reversed mitochondrial dysfunction, lowered AGEs-RAGE formation, attenuated Aβ peptide oligomerization, and reduced phosphorylation of tau, thereby halting the formation of neurofibrillary tangles and the progression of AD. Full article
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27 pages, 1161 KB  
Review
Emergent Aspects of the Integration of Sensory and Motor Functions
by Tiziana M. Florio
Brain Sci. 2025, 15(2), 162; https://doi.org/10.3390/brainsci15020162 - 7 Feb 2025
Cited by 12 | Viewed by 10193
Abstract
This article delves into the intricate mechanisms underlying sensory integration in the executive control of movement, encompassing ideomotor activity, predictive capabilities, and motor control systems. It examines the interplay between motor and sensory functions, highlighting the role of the cortical and subcortical regions [...] Read more.
This article delves into the intricate mechanisms underlying sensory integration in the executive control of movement, encompassing ideomotor activity, predictive capabilities, and motor control systems. It examines the interplay between motor and sensory functions, highlighting the role of the cortical and subcortical regions of the central nervous system in enhancing environmental interaction. The acquisition of motor skills, procedural memory, and the representation of actions in the brain are discussed emphasizing the significance of mental imagery and training in motor function. The development of this aspect of sensorimotor integration control can help to advance our understanding of the interactions between executive motor control, cortical mechanisms, and consciousness. Bridging theoretical insights with practical applications, it sets the stage for future innovations in clinical rehabilitation, assistive technology, and education. The ongoing exploration of these domains promises to uncover new pathways for enhancing human capability and well-being. Full article
(This article belongs to the Special Issue New Insights into Movement Generation: Sensorimotor Processes)
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15 pages, 596 KB  
Review
Small-Fiber Neuropathy: An Etiology-Oriented Review
by Alessandro Furia, Rocco Liguori and Vincenzo Donadio
Brain Sci. 2025, 15(2), 158; https://doi.org/10.3390/brainsci15020158 - 6 Feb 2025
Cited by 8 | Viewed by 17558
Abstract
Background: Small-fiber neuropathy (SFN), affecting Aδ or C nerve fibers, is characterized by alterations of pain and temperature sensation, as well as autonomic dysfunction. Its diagnosis may still remain challenging as methods specifically assessing small nerve fibers are not always readily available, and [...] Read more.
Background: Small-fiber neuropathy (SFN), affecting Aδ or C nerve fibers, is characterized by alterations of pain and temperature sensation, as well as autonomic dysfunction. Its diagnosis may still remain challenging as methods specifically assessing small nerve fibers are not always readily available, and standard techniques for large-fiber neuropathies, such as electroneuromyography, yield negative results. Still, skin biopsy for epidermal innervation and quantitative sensory testing allow for diagnosis in the presence of a congruent clinical picture. Objectives: Many different etiologies may underlie small-fiber neuropathy, of which metabolic (diabetes mellitus/impaired glucose tolerance) and idiopathic remain prevalent. The aim of this narrative review is to provide a general picture of SFN while focusing on the different etiologies described in the literature in order to raise awareness of the variegated set of different causes of SFN and promote adequate diagnostic investigation. Methods: The term “Small-Fiber Neuropathy” was searched on the PubMed database with its different recognized etiologies: the abstracts of the articles were reviewed and described in the article if relevant for a total of 40 studies. Results: Many different disorders have been associated with SFN, even though often in the form of case reports or small case series. Conclusions: Idiopathic forms of SFN remain the most prevalent in the literature, but association with different disorders (e.g., infectious, autoimmune) should prompt investigation for SFN in the presence of a congruent clinical picture (e.g., pain with neuropathic features). Full article
(This article belongs to the Special Issue Diagnosis, Therapy and Rehabilitation in Neuromuscular Diseases)
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40 pages, 1542 KB  
Review
Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges
by Michael J. Lucido and Boadie W. Dunlop
Brain Sci. 2025, 15(2), 161; https://doi.org/10.3390/brainsci15020161 - 6 Feb 2025
Cited by 11 | Viewed by 17102
Abstract
Background/Objectives: Non-response to initial treatment options for major depressive disorder (MDD) is a common clinical challenge with profound deleterious impacts for affected patients. Few treatments have received regulatory approval for treatment-resistant depression (TRD). Methods: A systematic search of United States and [...] Read more.
Background/Objectives: Non-response to initial treatment options for major depressive disorder (MDD) is a common clinical challenge with profound deleterious impacts for affected patients. Few treatments have received regulatory approval for treatment-resistant depression (TRD). Methods: A systematic search of United States and European Union clinical trials registries was conducted to identify Phase II, III, or IV clinical trials, with a last update posted on or after 1 January 2020, that were evaluating medications for TRD. For both the US and EU registries, the condition term “treatment resistant depression” and associated lower-level terms (per registry search protocol) were used. For the US registry, a secondary search using the condition term “depressive disorders” and the modifying term “inadequate” was also performed to capture registrations not tagged as TRD. Two additional searches were also conducted in the US registry for the terms “suicide” and “anhedonia” as transdiagnostic targets of investigational medications. Trials were categorized based on the primary mechanism of action of the trial’s investigational medication. Results: Fifty clinical trials for TRD, 20 for anhedonia, and 25 for suicide were identified. Glutamate system modulation was the mechanism currently with the most compounds in development, including antagonists and allosteric modulators of NMDA receptors, AMPA receptors, metabotropic type 2/3 glutamate receptors, and intracellular effector molecules downstream of glutamate signaling. Psychedelics have seen the greatest surge among mechanistic targets in the past 5 years, however, with psilocybin in particular garnering significant attention. Other mechanisms included GABA modulators, monoamine modulators, anti-inflammatory/immune-modulating agents, and an orexin type 2 receptor antagonist. Conclusions: These investigations offer substantial promise for more efficacious and potentially personalized medication approaches for TRD. Challenges for detecting efficacy in TRD include the heterogeneity within the TRD population stemming from the presumed variety of biological dysfunctions underlying the disorder, comorbid disorders, chronic psychosocial stressors, and enduring effects of prior serotonergic antidepressant medication treatments. Full article
(This article belongs to the Section Neuropsychiatry)
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