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Brain Sci., Volume 15, Issue 2 (February 2025) – 63 articles

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26 pages, 1228 KiB  
Review
The Inflammatory Mechanism of Parkinson’s Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut–Brain Axis
by Ai Gao, Jiaqi Lv and Yanwei Su
Brain Sci. 2025, 15(2), 159; https://doi.org/10.3390/brainsci15020159 (registering DOI) - 6 Feb 2025
Abstract
Parkinson’s disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson’s disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson’s [...] Read more.
Parkinson’s disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson’s disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson’s disease, emphasizing alterations in gut microbiota and their metabolites that influence the disease’s progression through the bidirectional transmission of inflammatory signals along the gut–brain axis. Building on this mechanistic framework, this article further discusses research methodologies and treatment strategies focused on gut microbiota metabolites, including metabolomics detection techniques, animal model investigations, and therapeutic approaches such as dietary interventions, probiotic treatments, and fecal transplantation. Ultimately, this article aims to elucidate the relationship between gut microbiota metabolites and the inflammatory mechanisms underlying Parkinson’s disease, thereby paving the way for novel avenues in the research and treatment of this condition. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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15 pages, 596 KiB  
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
Viewed by 121
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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15 pages, 1055 KiB  
Article
Metagenomic Insights into Microbial Signatures in Thrombi from Acute Ischemic Stroke Patients Undergoing Endovascular Treatment
by Kasthuri Thirupathi, Sherief Ghozy, Abdullah Reda, Wasantha K. Ranatunga, Mars A. Ruben, Zarrintan Armin, Oana M. Mereuta, Sekhon Prabhjot, Daying Dai, Waleed Brinjikji, David F. Kallmes and Ramanathan Kadirvel
Brain Sci. 2025, 15(2), 157; https://doi.org/10.3390/brainsci15020157 - 6 Feb 2025
Viewed by 145
Abstract
Background: Variability in recanalization success during endovascular treatment for acute ischemic stroke (AIS) has led to increased interests in thrombus composition and associated cellular materials. While evidence suggests that bacteria may influence thrombus characteristics, limited data exist on microbiological profiles of thrombi in [...] Read more.
Background: Variability in recanalization success during endovascular treatment for acute ischemic stroke (AIS) has led to increased interests in thrombus composition and associated cellular materials. While evidence suggests that bacteria may influence thrombus characteristics, limited data exist on microbiological profiles of thrombi in stroke patients. Objectives: Characterization of bacterial communities present in thrombi of AIS patients undergoing mechanical thrombectomy, providing insights into microbial contributions to stroke pathogenesis and treatment outcomes. Methods: Thrombi were collected from 20 AIS patients. After extracting metagenome, 16S rDNA sequencing was performed. Bioinformatic analysis included taxonomy and diversity assessments. The presence of bacterial DNA and viable bacteria in thrombi was validated using polymerase chain reaction (PCR) and bacterial culturing followed by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) analysis, respectively. Results: 16S rDNA was amplified in 19/20 thrombi (95%). Analysis identified a diverse microbial community, with Corynebacterium spp. as the most prevalent genus, followed by Staphylococcus spp., Bifidobacterium spp., Methylobacterium spp., and Anaerococcus spp. Alpha diversity analyses (Shannon index: 4.0–6.0 and Simpson index: 0.8–1.0) revealed moderate to high microbial diversity across samples; beta diversity demonstrated distinct clustering, indicating inter-patient variability in microbial profiles. PCR confirmed the presence of DNA specific to dominant bacterial taxa identified through sequencing. Culturing showed the presence of Staphylococcus epidermidis and Enterococcus faecalis in some clots as identified through MALDI analysis. Conclusions: This study shows bacterial communities present in AIS patients’ thrombi, suggesting a potential link between microbial signatures and thrombus characteristics. Full article
(This article belongs to the Section Neurorehabilitation)
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12 pages, 641 KiB  
Case Report
Three Cases of Spinocerebellar Ataxia Type 2 (SCA2) and Pediatric Literature Review: Do Not Forget Trinucleotide Repeat Disorders in Childhood-Onset Progressive Ataxia
by Jacopo Sartorelli, Maria Grazia Pomponi, Giacomo Garone, Gessica Vasco, Francesca Cumbo, Vito Luigi Colona, Adele D'Amico, Enrico Bertini and Francesco Nicita
Brain Sci. 2025, 15(2), 156; https://doi.org/10.3390/brainsci15020156 - 4 Feb 2025
Viewed by 367
Abstract
Background: Childhood-onset progressive ataxias are rare neurodegenerative disorders characterized by cerebellar signs, sometimes associated with other neurological or extra-neurological features. The autosomal dominant forms, known as spinocerebellar ataxias (SCAs), linked to trinucleotide (i.e., CAG) repeat disorders, are ultra-rare in children. We describe [...] Read more.
Background: Childhood-onset progressive ataxias are rare neurodegenerative disorders characterized by cerebellar signs, sometimes associated with other neurological or extra-neurological features. The autosomal dominant forms, known as spinocerebellar ataxias (SCAs), linked to trinucleotide (i.e., CAG) repeat disorders, are ultra-rare in children. We describe three patients from two unrelated families affected by spinocerebellar ataxia type 2 (SCA2) and present a literature review of pediatric cases. Methods: The patients’ clinical and genetic data were collected retrospectively. Results: The first case was a 9.5-year-old boy, affected by ataxia with oculomotor apraxia and cerebellar atrophy, subcortical myoclonus, and peripheral axonal sensitive polyneuropathy caused by a pathologic expansion in ATXN2, inherited from his asymptomatic father. Two brothers with familial SCA2 presented neurodegeneration leading to early death in one case and progressive ataxia, parkinsonism, and epilepsy with preserved ambulation at age 18 years in the second. To date, 19 pediatric patients affected by SCA2 have been reported, 3 of whom had a phenotype consistent with progressive ataxia with shorter CAG repeats, while 16 had more severe early-onset encephalopathy, with longer alleles. Conclusions: Although they are ultra-rare, trinucleotide repeat disorders must be considered in differential diagnosis of hereditary progressive ataxias in children, especially considering that they require targeted genetic testing and can manifest even before a parental carrier becomes symptomatic. Thus, they must also be taken into account with negative family history and when Next-Generation Sequencing (NGS) results are inconclusive. Notably, the association between cerebellar ataxia and other movement disorders should raise suspicion of SCA2 among differential diagnoses. Full article
(This article belongs to the Section Neurodegenerative Diseases)
7 pages, 155 KiB  
Editorial
Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives
by Jacopo Lisoni and Stefano Barlati
Brain Sci. 2025, 15(2), 155; https://doi.org/10.3390/brainsci15020155 - 4 Feb 2025
Viewed by 365
Abstract
Currently, several Non-Invasive Brain Stimulation (NIBS) techniques are available for clinical application in psychiatric disorders (including major depressive disorder, MDD, and obsessive–compulsive disorder) or are under investigation (including schizophrenia, eating, substance use, and neurodevelopmental disorders) [...] Full article
23 pages, 442 KiB  
Systematic Review
The Use of Magnetoencephalography in the Diagnosis and Monitoring of Mild Traumatic Brain Injuries and Post-Concussion Syndrome
by Ioannis Mavroudis, Dimitrios Kazis, Foivos E. Petridis, Ioana-Miruna Balmus and Alin Ciobica
Brain Sci. 2025, 15(2), 154; https://doi.org/10.3390/brainsci15020154 - 4 Feb 2025
Viewed by 369
Abstract
Background/Objectives: The main objective of this systematic review was to explore the role of magnetoencephalography (MEG) in the diagnosis, assessment, and monitoring of mild traumatic brain injury (mTBI) and post-concussion syndrome (PCS). We aimed to evaluate the potential of some MEG biomarkers [...] Read more.
Background/Objectives: The main objective of this systematic review was to explore the role of magnetoencephalography (MEG) in the diagnosis, assessment, and monitoring of mild traumatic brain injury (mTBI) and post-concussion syndrome (PCS). We aimed to evaluate the potential of some MEG biomarkers in detecting subtle brain abnormalities often missed by conventional imaging techniques. Methods: A systematic review was conducted using 25 studies that administered MEG to examine mTBI and PCS patients. The quality of the studies was assessed based on selection, comparability, and outcomes. Studies were analyzed for their methodology, evaluated parameters, and the clinical implications of using MEG for mTBI diagnosis. Results: MEG detected abnormal brain oscillations, including increased delta, theta, and gamma waves and disruptions in functional connectivity, particularly in the default mode and frontoparietal networks of patients suffering from mTBI. MEG consistently revealed abnormalities in mTBI patients even when structural imaging was normal. The use of MEG in monitoring recovery showed significant reductions in abnormal slow-wave activity corresponding to clinical improvements. Machine learning algorithms applied to MEG data demonstrated high sensitivity and specificity in distinguishing mTBI patients from healthy controls and predicting clinical outcomes. Conclusions: MEG provides a valuable diagnostic and prognostic tool for mTBI and PCS by identifying subtle neurophysiological abnormalities. The high temporal resolution and the ability to assess functional brain networks make MEG a promising complement to conventional imaging. Future research should focus on integrating MEG with other neuroimaging modalities and standardizing MEG protocols for clinical use. Full article
(This article belongs to the Section Systems Neuroscience)
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29 pages, 5605 KiB  
Article
A Pilot Study on Video Game Training Effects on Visual Working Memory: Behavioral and Neural Insights
by Héctor Hugo Alfaro-Cortés, Sulema Torres-Ramos, Israel Román-Godínez, Vanessa Doreen Ruiz-Stovel and Ricardo Antonio Salido-Ruiz
Brain Sci. 2025, 15(2), 153; https://doi.org/10.3390/brainsci15020153 - 4 Feb 2025
Viewed by 384
Abstract
Background/Objectives: Recent research suggests that video games may serve as cognitive training tools to enhance visual working memory (VWM) capacity. However, the effectiveness of game-based cognitive training remains debated, and the underlying neural mechanisms, as well as the relationship between training efficacy and [...] Read more.
Background/Objectives: Recent research suggests that video games may serve as cognitive training tools to enhance visual working memory (VWM) capacity. However, the effectiveness of game-based cognitive training remains debated, and the underlying neural mechanisms, as well as the relationship between training efficacy and game design factors, are unclear. This study aimed to evaluate the impact of video game training on VWM capacity and explore its neural correlates. Methods: Two groups underwent 56 daily 20 min training sessions with two distinct video games targeting different cognitive skills: a reaction-time training game and a VWM-specific training game. Behavioral assessments included accuracy, hit response times, correct rejection response times, and Cowan’s K values. Neural correlates were measured through Negative Slow Wave (NSW) activity using EEG. Decision tree classification analyses were applied to NSW data across sessions and set sizes to identify patterns linked to VWM capacity. Results: Preliminary results are that both groups showed improvements in behavioral measures (accuracy, response times, and Cowan’s K values). NSW analyses revealed a main effect of set size in both groups, and classification results indicated that NSW patterns differed between groups, across sessions, and set sizes, supporting the relationship between NSW and VWM capacity. Conclusions: These findings contribute to understanding NSW as a neurophysiological correlate of VWM capacity, demonstrating its plasticity through video game training. Simple video games could effectively enhance behavioral and neural aspects of VWM, encouraging their potential as accessible cognitive training tools. Full article
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21 pages, 1260 KiB  
Article
Understanding Pediatric Bipolar Disorder Through the Investigation of Clinical, Neuroanatomic, Neurophysiological and Neurocognitive Dimensions: A Pilot Study
by Alessio Simonetti, Evelina Bernardi, Sherin Kurian, Antonio Restaino, Claudia Calderoni, Emanuela De Chiara, Francesca Bardi, Gabriele Sani, Jair C. Soares and Kirti Saxena
Brain Sci. 2025, 15(2), 152; https://doi.org/10.3390/brainsci15020152 - 3 Feb 2025
Viewed by 533
Abstract
Background: Pathophysiological models of pediatric bipolar disorder (PBD) are lacking. Multimodal approaches may provide a comprehensive description of the complex relationship between the brain and behavior. Aim: To assess behavioral, neuropsychological, neurophysiological, and neuroanatomical alterations in youth with PBD. Methods: [...] Read more.
Background: Pathophysiological models of pediatric bipolar disorder (PBD) are lacking. Multimodal approaches may provide a comprehensive description of the complex relationship between the brain and behavior. Aim: To assess behavioral, neuropsychological, neurophysiological, and neuroanatomical alterations in youth with PBD. Methods: Subjects with PBD (n = 23) and healthy controls (HCs, n = 23) underwent (a) clinical assessments encompassing the severity of psychiatric symptoms, (b) neuropsychological evaluation, (c) analyses of event-related potentials (related to the passive viewing of fearful, neutral, and happy faces during electroencephalography recording, and (d) cortical thickness and deep gray matter volume measurement using magnetic resonance imaging. Canonical correlation analyses were used to assess the relationships between these dimensions. Results: Youth with PBD had higher levels of anxiety (p < 0.001) and borderline personality features (p < 0.001), greater commission errors for negative stimuli (p = 0.003), delayed deliberation time (p < 0.001), and smaller risk adjustment scores (p = 0.002) than HCs. Furthermore, they showed cortical thinning in the frontal, parietal, and occipital areas (all p < 0.001) and greater P300 for happy faces (p = 0.29). In youth with PBD, cortical thickening and P300 amplitude positively correlated with more commission errors for negative stimuli, longer deliberation times, reduced risk adjustment, higher levels of panic and separation anxiety, and greater levels of negative relationships, whereas they negatively correlated with levels of depression (overall loadings > or <0.3). Limitations: Small sample size, cross-sectional design, and limited variables investigated. Conclusions: This preliminary work showed that multimodal assessment might be a viable tool for providing a pathophysiological model that unifies brain and behavioral alterations in youth with PBD. Full article
(This article belongs to the Section Neuropsychiatry)
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23 pages, 984 KiB  
Systematic Review
Tetrahydrobiopterin and Autism Spectrum Disorder: A Systematic Review of a Promising Therapeutic Pathway
by Clóvis Colpani Filho, Lucas Melfior, Sthephanie Luiz Ramos, Mateus Santos Oliveira Pizi, Lilian Freitas Taruhn, Margrit Ellis Muller, Thiago Kucera Nunes, Luísa de Oliveira Schmitt, Joana Margarida Gaspar, Miguel de Abreu de Oliveira, Giovanna Tassinari, Luisa Cruz and Alexandra Latini
Brain Sci. 2025, 15(2), 151; https://doi.org/10.3390/brainsci15020151 - 3 Feb 2025
Viewed by 456
Abstract
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, along with restricted and repetitive patterns of behavior, interests, or activities. ASD encompasses a wide spectrum of clinical presentations and functional impairments, ranging from mild to [...] Read more.
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, along with restricted and repetitive patterns of behavior, interests, or activities. ASD encompasses a wide spectrum of clinical presentations and functional impairments, ranging from mild to severe. Despite its prevalence, the underlying physiopathological mechanisms of ASD remain largely unknown, resulting in a lack of effective targeted therapeutic interventions, contributing to significant financial and emotional burdens on affected families and the healthcare system. Emerging evidence suggests that dysfunction in the tetrahydrobiopterin (BH4) pathway may impair the activity of monoaminergic and nitric oxide (NO)-dependent neurons in individuals with ASD. To explore this potential mechanism, we conducted a systematic review to analyze such impairments to gather information on whether the off-label use of BH4 could represent a novel pharmacological approach for managing ASD. Following the PRISMA 2020 guidelines, we systematically reviewed the literature from four databases: PubMed, Virtual Health Library, Cochrane Library, and SciELO, from January 1967 to December 2021. The quality of the included studies was assessed using the Newcastle–Ottawa scale. The inclusion criteria for this systematic review focused on identifying articles published in English that contained the following keywords, used in various combinations: autism, ASD, autism spectrum disorder, BH4, tetrahydrobiopterin, neopterin, NO, nitric oxide. The analysis was performed between December 2020 and December 2021. The collected data demonstrated that BH4 metabolism was altered in individuals with ASD. Lower levels of BH4 were reported in biological samples from ASD-affected individuals compared to age- and sex-matched controls. Additionally, neopterin levels were elevated in plasma and urine, but decreased in cerebrospinal fluid, while nitric oxide levels were consistently reported to be higher across studies. Treatment with BH4 has shown potential in improving ASD-related symptoms. The reported increase in neopterin in biological fluids indicates inflammation, while the reduction in BH4 levels suggests a potential shift in its metabolic role. Specifically, BH4 may be diverted from its primary role in neurotransmitter synthesis to function as an antioxidant or to perpetuate inflammation through NO production. Given that BH4 is a critical cofactor in monoaminergic neurotransmission, its dysfunction highlights the molecule’s therapeutic potential. BH4, already FDA-approved for other conditions, emerges as a promising off-label candidate to alleviate ASD symptomatology. Full article
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14 pages, 1094 KiB  
Article
Vinpocetine, a Phosphodiesterase Type 1 Inhibitor, Mitigates Locomotor Hyperactivity in Female Mice Exposed to Lead During Development
by Ulisses C. Araujo, Fernanda Nunes, Bruno S. Gonçalves, Regina A. A. Gomes, Maria de Fátima R. Moreira, Andre Nunes-Freitas, Thomas E. Krahe, Yael de Abreu-Villaça, Alex C. Manhães and Cláudio C. Filgueiras
Brain Sci. 2025, 15(2), 150; https://doi.org/10.3390/brainsci15020150 - 2 Feb 2025
Viewed by 633
Abstract
Background/Objectives Studies in rodents indicate that disruptions in both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways are involved in the development of hyperactive behavior. We examined whether vinpocetine, a phosphodiesterase type 1 inhibitor that enhances brain cAMP and cGMP [...] Read more.
Background/Objectives Studies in rodents indicate that disruptions in both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways are involved in the development of hyperactive behavior. We examined whether vinpocetine, a phosphodiesterase type 1 inhibitor that enhances brain cAMP and cGMP levels, could mitigate locomotor hyperactivity in mice exposed to lead during early development. Methods Swiss mice were exposed to 90 ppm of lead in their drinking water throughout gestation and the first ten postnatal days. At postnatal day 10 (PN10), blood lead levels (BLLs) were about 30 µg/dL. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or a vehicle 4 h before the evaluation of locomotor activity in the open field. Results Lead-exposed males did not display differences in locomotor activity compared to controls, while lead-exposed females showed a significant increase in locomotion. Vinpocetine treatment significantly reversed the lead-induced hyperactivity in females. Conclusions These findings suggest that the cAMP and cGMP signaling pathways play a role in the hyperactivity induced by lead exposure. Full article
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17 pages, 853 KiB  
Review
Eye-Tracking Metrics as a Digital Biomarker for Neurocognitive Disorders in Multiple Sclerosis: A Scoping Review
by Sonja Cecchetti, Andrew T. Duchowski and Marco Cavallo
Brain Sci. 2025, 15(2), 149; https://doi.org/10.3390/brainsci15020149 - 31 Jan 2025
Viewed by 532
Abstract
Multiple sclerosis (MS) is an autoimmune disease classified as neurodegenerative because it can be associated with the more or less progressive development of neurological symptoms and cognitive deficits. In recent years, various studies have started to investigate eye movements in relation to cognitive [...] Read more.
Multiple sclerosis (MS) is an autoimmune disease classified as neurodegenerative because it can be associated with the more or less progressive development of neurological symptoms and cognitive deficits. In recent years, various studies have started to investigate eye movements in relation to cognitive impairment in persons with MS by means of eye-tracking equipment. However, the high heterogeneity of the paradigms used in different studies, as well as the different methodologies included, makes it difficult to provide a complete and precise picture of this important research and clinical issue. The purpose of the present in-depth scoping review was to map the existing literature in this field to determine which metrics may be relevant when dealing with the neurocognitive profile of people with MS. From the analyses of the included studies, the anti-saccade latency and errors were the most frequently proposed metrics. Correlation analyses between these metrics and cognitive measures showed significant associations between them, calling for a deeper investigation of this promising research and clinical field. The results of the present scoping review strongly suggest that eye tracking may play a crucial role in clinical practice during the early detection of neurocognitive disorders. There is a great need for primary research that addresses the full complexity of MS in its different phenotypes and the disease-related variables from a multidisciplinary perspective. Future research should clarify whether oculomotor dysfunction in MS follows or precedes cognitive deficits. Full article
20 pages, 676 KiB  
Systematic Review
Systematic Review of Self-Assessment Scales for Negative Symptoms in Schizophrenia
by Lucie Métivier and Sonia Dollfus
Brain Sci. 2025, 15(2), 148; https://doi.org/10.3390/brainsci15020148 - 31 Jan 2025
Viewed by 413
Abstract
Background/Objectives: Negative symptoms (NSs) significantly impair the outcome of schizophrenia, primarily due to their effect on quality of life and their resistance to pharmacological treatments. Several scales have been developed to assess the various dimensions of NSs, including avolition, anhedonia, alogia, social [...] Read more.
Background/Objectives: Negative symptoms (NSs) significantly impair the outcome of schizophrenia, primarily due to their effect on quality of life and their resistance to pharmacological treatments. Several scales have been developed to assess the various dimensions of NSs, including avolition, anhedonia, alogia, social withdrawal, and blunted affect. While observer-rated scales are the most commonly used, self-assessment tools remain underutilized. However, self-assessments offer a promising approach for gaining insights into the personal experiences of individuals. The objective of this review was to identify and report the psychometric properties of self-assessment scales for NSs that are relevant for both research and clinical practice, with a focus on tools that assess multiple domains of NSs in order to support comprehensive evaluations and tailored therapeutic strategies. Methods: We conducted an exhaustive literature review following PRISMA guidelines to identify self-evaluation scales that evaluate several domains of NSs in the MEDLINE and Web of Science databases. The COSMIN checklist was used to assess the methodological quality of each tool. Results: Our review identified five self-assessment scales. Among these, two scales received a Grade A recommendation for use in clinical or research practice: the Self-evaluation Negative Symptom (SNS), which assesses the five domains of NSs, and the Motivation And Pleasure Scale Self-report (MAP-SR), which evaluates anhedonia, avolition, and social withdrawal. Conclusions: The SNS and the MAP-SR are the only tools with sufficient psychometric properties, making them reliable for use in both research and clinical practice. Despite the development of self-assessment tools for NSs, their integration into research and clinical settings remains limited, highlighting the need for increased utilization to enhance the understanding and management of these symptoms. Full article
(This article belongs to the Section Neuropsychiatry)
15 pages, 571 KiB  
Article
Binaural Pulse Modulation (BPM) as an Adjunctive Treatment for Anxiety: A Pilot Study
by Gerry Leisman, Joseph Wallach, Yanin Machado-Ferrer, Mauricio-Chinchilla Acosta, Abraham-Gérard Meyer, Robert Lebovits and Scott Donkin
Brain Sci. 2025, 15(2), 147; https://doi.org/10.3390/brainsci15020147 - 31 Jan 2025
Viewed by 470
Abstract
Background: Treating psychiatric illnesses or influencing mental states with neurofeedback is challenging, likely due to the limited spatial specificity of EEG and the complications arising from the inadequate signal-to-noise ratio reduction of single-trial EEG. Objective: This pilot study aimed to investigate the feasibility [...] Read more.
Background: Treating psychiatric illnesses or influencing mental states with neurofeedback is challenging, likely due to the limited spatial specificity of EEG and the complications arising from the inadequate signal-to-noise ratio reduction of single-trial EEG. Objective: This pilot study aimed to investigate the feasibility of employing a binaural pulse mode-modulation (BPM) device to reduce anxiety by self-regulation. We desired to determine whether anxiety could be significantly reduced or regulated using BPM-type systems. Methods: Sixty adult participants were examined with self-reported anxiety tests (COVID Stress Scale, Generalized Anxiety Disorder 7, Beck Depression Inventory-II), which were completed before treatment, after four weeks, and after 12 weeks post-treatment. This BPM device produced two frequencies which combined to create a binaural pulse through differential auditory tone presentations. The participant calibrated the suitable target tone for optimal treatment efficacy. Each participant adjusted the binaural pulse to enhance the emotional intensity felt when envisioning an experience with comparable emotional significance or while performing a cognitive task while concurrently listening to music. The “treatment” relied on the individual’s regulation of binaural pulses to obtain the desired state. The training concentrated on particular facets of their psychological challenges while listening to an auditory tone, adjusting a knob until the sound amplified the intended emotional state. Another knob was turned to intensify the emotional state associated with distress reduction. Results: On the self-reported measures, the BPM treatment group was significantly better than the sham treatment (control) groups (p < 0.01). These findings indicate that over the four-week intervention period, BPM was similarly effective. On the GAD-7, the significant difference over time was noted before treatment and at the end of treatment for the experimental group, with the average GAD-7 score at the end of treatment being significantly lower (p < 0.01). Conclusions: BPM seems to induce a short-term alteration in self-reported distress levels during therapy. This study’s limitations are examined, and recommendations for future research are provided. Full article
(This article belongs to the Special Issue Neuromodulation and Neurostimulation in Psychiatric Disorders)
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17 pages, 3841 KiB  
Article
Response Assessment in Long-Term Glioblastoma Survivors Using a Multiparametric MRI-Based Prediction Model
by Laiz Laura de Godoy, Archith Rajan, Amir Banihashemi, Thara Patel, Arati Desai, Stephen Bagley, Steven Brem, Sanjeev Chawla and Suyash Mohan
Brain Sci. 2025, 15(2), 146; https://doi.org/10.3390/brainsci15020146 - 31 Jan 2025
Viewed by 789
Abstract
Purpose: Early treatment response assessments are crucial, and the results are known to better correlate with prognosis and survival outcomes. The present study was conducted to differentiate true progression (TP) from pseudoprogression (PsP) in long-term-surviving glioblastoma patients using our previously established multiparametric MRI-based [...] Read more.
Purpose: Early treatment response assessments are crucial, and the results are known to better correlate with prognosis and survival outcomes. The present study was conducted to differentiate true progression (TP) from pseudoprogression (PsP) in long-term-surviving glioblastoma patients using our previously established multiparametric MRI-based predictive model, as well as to identify clinical factors impacting survival outcomes in these patients. Methods: We report six patients with glioblastoma that had an overall survival longer than 5 years. When tumor specimens were available from second-stage surgery, histopathological analyses were used to classify between TP (>25% characteristics of malignant neoplasms; n = 2) and PsP (<25% characteristics of malignant neoplasms; n = 2). In the absence of histopathology, modified RANO criteria were assessed to determine the presence of TP (n = 1) or PsP (n = 1). The predictive probabilities (PPs) of tumor progression were measured from contrast-enhancing regions of neoplasms using a multiparametric MRI-based prediction model. Subsequently, these PP values were used to define each lesion as TP (PP ≥ 50%) or PsP (PP < 50%). Additionally, detailed clinical information was collected. Results: Our predictive model correctly identified all patients with TP (n = 3) and PsP (n = 3) cases, reflecting a significant concordance between histopathology/modified RANO criteria and PP values. The overall survival varied from 5.1 to 12.3 years. Five of the six glioblastoma patients were MGMT promoter methylated. All patients were female, with a median age of 56 years. Moreover, all six patients had a good functional status (KPS ≥ 70), underwent near-total/complete resection, and received alternative therapies. Conclusions: Multiparametric MRI can aid in assessing treatment response in long-term-surviving glioblastoma patients. Full article
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14 pages, 506 KiB  
Article
Multidomain Cognitive Tele-Neurorehabilitation Training in Long-Term Post-Stroke Patients: An RCT Study
by Marianna Contrada, Gennarina Arabia, Martina Vatrano, Caterina Pucci, Isabel Mantia, Federica Scarfone, Giusi Torchia, Maria Quintieri, Antonio Cerasa and Loris Pignolo
Brain Sci. 2025, 15(2), 145; https://doi.org/10.3390/brainsci15020145 - 31 Jan 2025
Viewed by 470
Abstract
Purpose: Over the past decade, tele-neurorehabilitation (TNR) has emerged as a vital and effective tool for delivering continuous care to stroke patients, playing a key role in enhancing functional recovery and ensuring consistent access to rehabilitation services. In the field of TNR, various [...] Read more.
Purpose: Over the past decade, tele-neurorehabilitation (TNR) has emerged as a vital and effective tool for delivering continuous care to stroke patients, playing a key role in enhancing functional recovery and ensuring consistent access to rehabilitation services. In the field of TNR, various protocols are utilized to ensure effective cognitive stimulation at home. Recent preliminary studies highlight the employment of multidomain cognitive interventions, which would seem to induce more stable and relevant cognitive recovery in stroke patients. A randomized controlled trial (RCT) study was conducted to compare the effectiveness of a TNR multidomain cognitive approach to conventional face-to-face cognitive treatment. Methods: A total of 30 patients with stroke were equally enrolled and randomly assigned to the experimental and control groups. In the experimental group, patients received sessions of home-based cognitive virtual reality rehabilitation system (VRRS) training. The control group underwent traditional face-to-face cognitive multidomain treatment at the hospital. The therapy was given for one hour every day for four weeks in both groups. Specific cognitive domains, including memory, praxis skills, executive functions, and speech therapy, were stimulated in the procedure. Neuropsychological evaluations were performed at three timepoints: at baseline (T0), at the end of TNR (T1), and six months later (T2). Results: The TNR group demonstrated significant improvements in working memory and language abilities, as well as in depressive symptoms and caregiver burden, with an average decrease of 2.07. Most of this improvement persisted 6 months after treatment. The group that received face-to-face cognitive treatment showed improvements (not persisting at T2) after treatment in a task measuring constructive apraxia and alternating attention with the cognitive skill of set-shifting. Conclusions: According to our findings, multidomain cognitive TNR may be useful in enhancing cognitive outcomes in stroke populations (even six months after treatment concludes). TNR may also be a viable way to deliver these interventions since it boosts people’s motivation to train and, consequently, their adherence to treatment while also having a positive effect on caregivers’ distress management. Full article
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34 pages, 2413 KiB  
Review
Epigallocatechin-3-Gallate, Quercetin, and Kaempferol for Treatment of Parkinson’s Disease Through Prevention of Gut Dysbiosis and Attenuation of Multiple Molecular Mechanisms of Pathogenesis
by Alexis Kalu and Swapan K. Ray
Brain Sci. 2025, 15(2), 144; https://doi.org/10.3390/brainsci15020144 - 31 Jan 2025
Viewed by 398
Abstract
Parkinson’s disease (PD) is a neurodegenerative condition in which degeneration mostly occurs in the dopamine (DA)-producing neurons within the substantia nigra in the midbrain. As a result, individuals with this condition suffer from progressively worsening motor impairment because of the resulting DA deficiency, [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative condition in which degeneration mostly occurs in the dopamine (DA)-producing neurons within the substantia nigra in the midbrain. As a result, individuals with this condition suffer from progressively worsening motor impairment because of the resulting DA deficiency, along with an array of other symptoms that, over time, force them into a completely debilitating state. As an age-related disease, PD has only risen in prevalence over the years; thus, an emphasis has recently been placed on discovering a new treatment for this condition that is capable of attenuating its progression. The gut microbiota has become an area of intrigue among PD studies, as research into this topic has shown that imbalances in the gut microbiota (colloquially known as gut dysbiosis) seemingly promote the primary etiologic factors that have been found to be associated with PD and its pathologic progression. With this knowledge, research into PD treatment has begun to expand beyond synthetic pharmaceutical compounds, as a growing emphasis has been placed on studying plant-derived polyphenolic compounds, namely flavonoids, as a new potential therapeutic approach. Due to their capacity to promote a state of homeostasis in the gut microbiota and their long-standing history as powerful medicinal agents, flavonoids have begun to be looked at as promising therapeutic agents capable of attenuating several of the pathologic states seen amidst PD through indirect and direct means. This review article focuses on three flavonoids, specifically epigallocatechin-3-gallate, quercetin, and kaempferol, discussing the mechanisms through which these powerful flavonoids can potentially prevent gut dysbiosis, neuroinflammation, and other molecular mechanisms involved in the pathogenesis and progression of PD, while also exploring their real-world application and how issues of bioavailability and potential drug interactions can be circumvented or exploited. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
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16 pages, 454 KiB  
Article
Head Injury and Amyotrophic Lateral Sclerosis: Population-Based Study from the National ALS Registry
by Jaime Raymond, Ileana M. Howard, Jasmine Berry, Theodore Larson, D. Kevin Horton and Paul Mehta
Brain Sci. 2025, 15(2), 143; https://doi.org/10.3390/brainsci15020143 - 31 Jan 2025
Viewed by 722
Abstract
Background/Objectives: To examine if head injury (HI) is associated with age at ALS diagnosis in the United States. Methods: In this cross-sectional populationf-based analysis, we identified patients with ALS who were registered from 2015 to 2023 who completed the Registry’s head trauma survey [...] Read more.
Background/Objectives: To examine if head injury (HI) is associated with age at ALS diagnosis in the United States. Methods: In this cross-sectional populationf-based analysis, we identified patients with ALS who were registered from 2015 to 2023 who completed the Registry’s head trauma survey module. The association between HI and age at ALS diagnosis was assessed using multivariate analysis. Results: Of the 3424 respondents, 56.6% had experienced a HI. The adjusted odds ratio (aOR) for an ALS diagnosis before age 60 years for patients with a HI was 1.24 (95% CI, 1.07–1.45). One or two HIs had an aOR of 1.15 (95% CI, 0.97–1.36), and five or more HIs had an aOR of 1.58 (95% CI, 1.19–2.09). HI before age 18 years yielded an aOR of 2.03 (95% CI, 1.53–2.70) as well as HI between the ages of 18 and 30 years (aOR = 1.48, 95% CI: 1.06–2.06)). When narrowing the analysis to patients with HI before age 18 compared with patients with no HI, we found an association with HI that led to an emergency department or hospital visit (aOR = 1.50 (95% CI: 1.21–1.86)). Conclusions: In this cross-sectional analysis of ALS patients, HIs occurring in childhood and early adulthood and the number of HIs increased the odds of being diagnosed before age 60 years. These results suggest that HI continues to be a risk factor for ALS and could be associated with a younger age of diagnosis. Full article
(This article belongs to the Section Neuromuscular and Movement Disorders)
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4 pages, 143 KiB  
Editorial
Brain Mechanisms of Hypnosis
by Giuseppe De Benedittis
Brain Sci. 2025, 15(2), 142; https://doi.org/10.3390/brainsci15020142 - 31 Jan 2025
Viewed by 402
Abstract
Hypnosis is the longest-lasting of all psychotherapies and one of the oldest practiced methods for the control of pain and other stress-related chronic disorders [...] Full article
(This article belongs to the Special Issue Brain Mechanism of Hypnosis)
23 pages, 1149 KiB  
Article
Psychological Determinants of Conflict with the Law and Susceptibility to Rehabilitation in Relation to the Presence of Symptoms of Attention Deficit Hyperactivity Disorder
by Agnieszka Nowogrodzka, Mirosław Andrusiewicz and Ewa Mojs
Brain Sci. 2025, 15(2), 141; https://doi.org/10.3390/brainsci15020141 - 31 Jan 2025
Viewed by 490
Abstract
Background/Objectives: Many prison-sentenced individuals exhibit symptoms of mental dysfunctions, including attention deficit hyperactivity disorder (ADHD). The presence of co-occurring mental disorders further complicates their rehabilitation and social reintegration efforts. Given these challenges, understanding the role of specific disorders, such as ADHD, is critical [...] Read more.
Background/Objectives: Many prison-sentenced individuals exhibit symptoms of mental dysfunctions, including attention deficit hyperactivity disorder (ADHD). The presence of co-occurring mental disorders further complicates their rehabilitation and social reintegration efforts. Given these challenges, understanding the role of specific disorders, such as ADHD, is critical for developing targeted interventions tailored to the needs of incarcerated individuals and improving their outcomes. This research aimed to clarify the relationships among hyperactivity, criminal behavior, and psychological functioning to inform preventative and therapeutic strategies. Methods: This study investigated the complex interplay among attention deficit hyperactivity disorder (ADHD) symptoms, criminal behavior, and various psychological factors in a sample of 391 male inmates from low-security Polish prisons and a control group of non-offending men. Principal component analysis (PCA) and Spearman’s rank correlation were used to analyze the relationships among ADHD severity, type of crime (no crime, property crime, crime involving aggression), family functioning, childhood trauma, early maladaptive schemas, and mental health disorders. Results: The results revealed that while traumatic experiences were present across all groups, stronger family cohesion and support were associated with the absence of ADHD symptoms and criminal behavior. As ADHD severity and criminal behavior escalated, particularly in cases involving aggression, family support diminished, and maladaptive schemas, including “disconnection and rejection” and “excessive vigilance and inhibition”, became more prominent, alongside increased correlations with mental health issues (anxiety and depression). Conclusions: The findings underscore the crucial role of family environment and early intervention in mitigating the risks associated with ADHD and criminal behavior, highlighting the need for comprehensive interventions targeting maladaptive schemas and providing support for both internalizing and externalizing symptoms. Limitations include the retrospective nature of data collection and the exclusive focus on male inmates in low-security facilities. Full article
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14 pages, 339 KiB  
Article
Efficacy of Body Representation Rehabilitation Training for Adults with Unilateral Brain Damage: A Preliminary Study
by Maria Cropano, Mariachiara Gaita, Erica Dolce, Silvia Canino, Valentina Gerarda Angelillo, Antonella Di Vita, Maddalena Boccia, Simona Raimo and Liana Palermo
Brain Sci. 2025, 15(2), 140; https://doi.org/10.3390/brainsci15020140 - 30 Jan 2025
Viewed by 415
Abstract
Background/Objectives: Body representations (BRs) are essential for guiding movements, maintaining spatial awareness, and achieving effective interactions with the environment. Several studies suggest that BRs are frequently impaired following unilateral brain damage, emphasising the need for tailored rehabilitation interventions; however, there is a lack [...] Read more.
Background/Objectives: Body representations (BRs) are essential for guiding movements, maintaining spatial awareness, and achieving effective interactions with the environment. Several studies suggest that BRs are frequently impaired following unilateral brain damage, emphasising the need for tailored rehabilitation interventions; however, there is a lack of studies evaluating the effectiveness of training specifically designed to improve different kinds of functional BRs after stroke. Therefore, the present study aimed to present and implement a specific rehabilitation training program for BR alterations and evaluate its effectiveness in a sample of adults with unilateral brain damage. Methods: Nine adults with unilateral brain damage and seven age- and education-matched healthy controls were recruited. Both groups underwent a neuropsychological assessment to evaluate BR (action- and nonaction-oriented). Additionally, functional autonomy and motor functioning were assessed in the patient group. Following an initial assessment (T0), the patients participated in a BR-specific rehabilitation intervention. At the end of the rehabilitation program (T1), both groups were re-evaluated with the same tasks used at T0. Results: At T0, the patient group performed worse on BR tasks than the controls. At T1, a significant improvement in the nonaction-oriented BR and functional autonomy was observed in the patient group. Conclusions: This preliminary study suggests the effectiveness of a targeted rehabilitation intervention for BR in promoting enhanced body boundary awareness and greater accuracy in the perception of body part positions, possibly leading to increased functional autonomy. These findings highlight the importance of incorporating BR training in rehabilitation programs for adults with acquired brain damage, alongside motor rehabilitation. Full article
(This article belongs to the Section Neurorehabilitation)
24 pages, 1422 KiB  
Article
Processing of Scene-Grammar Inconsistencies in Children with Developmental Language Disorder—Insights from Implicit and Explicit Measures
by Daniela Bahn, Dilara Deniz Türk, Nikol Tsenkova, Gudrun Schwarzer, Melissa Le-Hoa Võ and Christina Kauschke
Brain Sci. 2025, 15(2), 139; https://doi.org/10.3390/brainsci15020139 - 30 Jan 2025
Viewed by 411
Abstract
Background/Objectives: Developmental language disorders (DLD) are often associated with co-occurring neurodevelopmental difficulties, including attentional or social–emotional problems. Another nonverbal domain, i.e., visual cognition and its relationship to DLD, is virtually unexplored. However, learning visuospatial regularities – a scene-grammar - is crucial for navigating [...] Read more.
Background/Objectives: Developmental language disorders (DLD) are often associated with co-occurring neurodevelopmental difficulties, including attentional or social–emotional problems. Another nonverbal domain, i.e., visual cognition and its relationship to DLD, is virtually unexplored. However, learning visuospatial regularities – a scene-grammar - is crucial for navigating our daily environment. These regularities show certain similarities to the structure of language and there is preliminary evidence for a relationship between scene processing and language competence in preschoolers with and without DLD. This study compared implicit and explicit visuospatial knowledge of everyday indoor scenes in older children, aged 6 to 10 years, of both groups. Methods: We measured ‘dwell times’ on semantic and syntactic object – scene inconsistencies via eye-tracking and performance in an object-placement task, and their associations with children’s language, visual, and cognitive skills. Results: Visual attention towards object-scene inconsistencies was highly comparable between groups, but children with DLD scored lower in a visual perception test and higher language skills were associated with higher visuo-cognitive performance in both tasks. In the explicit scene-grammar measurement, this relationship only existed for children with DLD and disappeared when nonverbal cognitive performance was controlled. Conclusions: Our study suggests the existence of mild problems in visuospatial processing co-occurring with DLD, which is partly influenced by age and nonverbal cognitive ability. The acquisition of visual cognition and linguistic knowledge is an interactive, multimodal process where the perception of objects in scenes might affect how the words for these objects are learned and vice versa. A better understanding of this interplay could eventually have impact on the diagnosis and treatment of DLD. Full article
(This article belongs to the Special Issue Neurodevelopmental Disorders and Early Language Acquisition)
18 pages, 2885 KiB  
Article
Effect of Vibro-Tactile Stimulation Sequence and Support Surface Inclination on Gait and Balance Measures
by Christopher P. Engsberg, Nathaniel H. Hunt, Steven Barlow and Mukul Mukherjee
Brain Sci. 2025, 15(2), 138; https://doi.org/10.3390/brainsci15020138 - 30 Jan 2025
Viewed by 459
Abstract
The plantar surfaces of the feet are important for balance control during walking, specifically by allowing for the perception of pressure movements during stance. Background/Objectives: The current study aimed to perturb CoP movement perception in healthy individuals by applying vibrations to the [...] Read more.
The plantar surfaces of the feet are important for balance control during walking, specifically by allowing for the perception of pressure movements during stance. Background/Objectives: The current study aimed to perturb CoP movement perception in healthy individuals by applying vibrations to the soles of the feet in different stimulation sequences: a natural pattern that followed CoP movement (gait-like) and a perturbing pattern that did not follow the CoP (random) during walking. We hypothesized that the gait-like stimulation sequence would be similar to walking without any stimulation and therefore have no effect on balance measures and that the random sequence would negatively affect balance measures such as the anteroposterior (AP) and mediolateral (ML) margins of stability (MoSs) and foot placement area. Methods: Subjects walked at a level angle and 5.0 and 8.0 degrees of incline and with low visual conditions to increase reliance on tactile sensations from the feet. Results: No significant effect of the stimulation sequence was found at any incline, while there was a significant effect of incline. As the incline increased from level to 5 deg, subjects reduced their AP MoS measured at heel strikes from 4.36 ± 0.56 cm to 1.95 ± 1.07 cm and increased their foot placement area from 24.04 ± 11.13 cm2 to 38.98 ± 17.47 cm2. However, the AP MoS measured at midstance did not significantly change as the incline increased. Conclusions: The stimulation sequence had no effect on the dependent measures, but the subjects could still feel the vibrations on the plantar surfaces during walking; this implies that similar stimulation techniques could be a useful method for applying directive biofeedback without negatively impacting gait. Overall, this study demonstrates the detailed control of our tactile system and the adaptability of healthy individuals while walking with a perturbing stimulation. Full article
(This article belongs to the Special Issue Multisensory Perception of the Body and Its Movement)
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25 pages, 653 KiB  
Review
The Role of Immune Cells in Moyamoya Disease
by Sheng Wang, Qian Jiang, Yuan Liu, Xincheng Zhang, Yimin Huang and Huaqiu Zhang
Brain Sci. 2025, 15(2), 137; https://doi.org/10.3390/brainsci15020137 - 30 Jan 2025
Viewed by 319
Abstract
Moyamoya disease (MMD) is a rare progressive cerebrovascular disorder characterized by the stenosis or occlusion of the terminal segments of the internal carotid arteries, leading to the development of abnormal collateral vascular networks. These networks are a compensatory mechanism for reduced blood flow [...] Read more.
Moyamoya disease (MMD) is a rare progressive cerebrovascular disorder characterized by the stenosis or occlusion of the terminal segments of the internal carotid arteries, leading to the development of abnormal collateral vascular networks. These networks are a compensatory mechanism for reduced blood flow to the brain. Despite extensive research, the exact etiology of MMD remains unknown, although recent studies suggest that immune system dysfunction plays a critical role in its pathogenesis. In particular, the involvement of immune cells such as T cells, macrophages, and dendritic cells has been increasingly recognized. These immune cells contribute to the inflammatory process and vascular remodeling observed in MMD patients, further complicating the disease’s progression. Inflammation and immune-mediated damage to the vessel walls may accelerate the narrowing and occlusion of arteries, exacerbating ischemic events in the brain. Additionally, studies have revealed that certain genetic and environmental factors can influence immune system activation in MMD, linking these pathways to disease development. This review aims to provide a comprehensive overview of the immune mechanisms at play in MMD, focusing on how immune cells participate in vascular injury and remodeling. Understanding these immunological processes may offer new therapeutic targets to halt or reverse disease progression, potentially leading to more effective treatment strategies for MMD. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
32 pages, 5318 KiB  
Review
Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours
by Smita Khilar, Antonina Dembinska-Kenner, Helen Hall, Nikolaos Syrmos, Gianfranco K. I. Ligarotti, Puneet Plaha, Vasileios Apostolopoulos, Salvatore Chibbaro, Giuseppe Maria Vincenzo Barbagallo and Mario Ganau
Brain Sci. 2025, 15(2), 136; https://doi.org/10.3390/brainsci15020136 - 30 Jan 2025
Viewed by 823
Abstract
(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the [...] Read more.
(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood–brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following the PRISMA-ScR guidelines and checklist was conducted using key terms input into PubMed to find articles that reflect emerging trends in the utilisation of nanomedicine in drug delivery for primary and secondary brain tumours. (3) Results: The review highlights various strategies by which different nanoparticles can be exploited to bypass the BBB; we provide a synthesis of the literature on the ongoing contributions to therapeutic protocols based on chemotherapy, immunotherapy, focused ultrasound, radiotherapy/radiosurgery, and radio-immunotherapy. (4) Conclusions: The emerging trends summarised in this scoping review indicate encouraging advantageous properties of nanoparticles as potential effective drug delivery mechanisms; however, there are still nanotoxicity issues that largely remain to be addressed before the translation of these innovations from laboratory to clinical practice. Full article
(This article belongs to the Special Issue Advanced Clinical Technologies in Treating Neurosurgical Diseases)
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14 pages, 2079 KiB  
Article
The Problem with Time: Application of Partial Least Squares Analysis on Time-Frequency Plots to Account for Varying Time Intervals with Applied EEG Data
by Jessie M. H. Szostakiwskyj, Filomeno Cortese, Raneen Abdul-Rhaman, Sarah J. Anderson, Amy L. Warren, Rebecca Archer, Emma Read and Kent G. Hecker
Brain Sci. 2025, 15(2), 135; https://doi.org/10.3390/brainsci15020135 - 30 Jan 2025
Viewed by 424
Abstract
Background/Objectives: When attempting to study neurocognitive mechanisms with electroencephalography (EEG) in applied ecologically valid settings, responses to stimuli may differ in time, which presents challenges to traditional EEG averaging methods. In this proof-of-concept paper, we present a method to normalize time over unequal [...] Read more.
Background/Objectives: When attempting to study neurocognitive mechanisms with electroencephalography (EEG) in applied ecologically valid settings, responses to stimuli may differ in time, which presents challenges to traditional EEG averaging methods. In this proof-of-concept paper, we present a method to normalize time over unequal trial lengths while preserving frequency content. Methods: Epochs are converted to time-frequency space where they are resampled to contain an equal number of timepoints representing the proportion of trial complete rather than true time. To validate this method, we used EEG data recorded from 8 novices and 4 experts in veterinary medicine while completing decision-making tasks using two question types: multiple-choice and script concordance questions used in veterinary school exams. Results: The resulting resampled time-frequency data were analyzed with partial least squares (PLS), a multivariate technique that extracts patterns of data that support a contrast between conditions and groups while controlling for Type I error. We found a significant latent variable representing a difference between question types for experts only. Conclusions: Despite within and between subject differences in timing, we found consistent differences between question types in experts in gamma and beta bands that are consistent with changes resulting from increased information load and decision-making. This novel analysis method may be a viable path forward to preserve ecological validity in EEG studies. Full article
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23 pages, 2560 KiB  
Review
Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials
by Ladan Dawoody Nejad and Erik P. Pioro
Brain Sci. 2025, 15(2), 134; https://doi.org/10.3390/brainsci15020134 - 30 Jan 2025
Viewed by 431
Abstract
Amyotrophic lateral sclerosis (ALS) is a terminal complex neurodegenerative disease, with 10–15% of cases being familial and the majority being sporadic with no known cause. There are no animal models for the 85–90% of sporadic ALS cases. More creative, sophisticated models of ALS [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a terminal complex neurodegenerative disease, with 10–15% of cases being familial and the majority being sporadic with no known cause. There are no animal models for the 85–90% of sporadic ALS cases. More creative, sophisticated models of ALS disease are required to unravel the mysteries of this complicated disease. While ALS patients urgently require new medications and treatments, suitable preclinical in vitro models for drug screening are lacking. Therefore, human-derived induced pluripotent stem cell (hiPSC) technology offers the opportunity to model diverse and unreachable cell types in a culture dish. In this review, we focus on recent hiPSC-derived ALS neuronal and non-neuronal models to examine the research progress of current ALS 2D monocultures, co-cultures, and more complex 3D-model organoids. Despite the challenges inherent to hiPSC-based models, their application to preclinical drug studies is enormous. Full article
15 pages, 796 KiB  
Article
Emotional Availability in Autism Intervention: A Mother–Father Comparative Analysis
by Silvia Perzolli, Giulio Bertamini, Paola Venuti and Arianna Bentenuto
Brain Sci. 2025, 15(2), 133; https://doi.org/10.3390/brainsci15020133 - 29 Jan 2025
Viewed by 521
Abstract
Background/Objectives: The literature highlights the importance of parental involvement in autism treatment. However, much research has predominantly focused on child outcomes and cognitive dimensions. This study explores the impact of an early intensive intervention with parental involvement, focusing on changes in parents’ affective [...] Read more.
Background/Objectives: The literature highlights the importance of parental involvement in autism treatment. However, much research has predominantly focused on child outcomes and cognitive dimensions. This study explores the impact of an early intensive intervention with parental involvement, focusing on changes in parents’ affective exchanges. Notably, given the paucity of studies on fathers in the intervention context, this study examines the comparative trajectory of change considering both caregivers. Methods: Twenty autistic preschoolers were monitored for one year during a parental-based intervention. Child–mother and child–father play interactions were coded with the Emotional Availability Scales at baseline and at 12 months. Repeated measures linear mixed-effect models were employed to investigate time and caregiver effects and their interaction. Results: Results highlighted both similarities and differences in change trajectories between caregivers. Parental sensitivity, structuring, and non-intrusiveness significantly increased for both parents with fathers showing more prominent gains in structuring the interaction while being non-intrusive. Child responsiveness and involvement significantly increased, showing similar trajectories with both caregivers. Children were generally more involved while interacting with their fathers. Conclusion: Parent–child interactions with caregivers evolved toward more adaptive exchanges regarding emotional availability for children’s and parents’ dimensions. Fathers appeared to be particularly receptive regarding acquiring structuring abilities and non-intrusive behaviors. Our results underscore the importance of investigating parental features as well as the importance of actively involving caregivers to support distal outcomes and generalization. Full article
(This article belongs to the Section Developmental Neuroscience)
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14 pages, 380 KiB  
Review
Natural Source of Drugs Targeting Central Nervous System Tumors—Focus on NAD(P)H Oxidoreductase 1 (NQO1) Activity
by Nikola M. Stojanovic, Milica Mitić, Jovan Ilić, Milica Radić, Miša Radisavljević, Marko Baralić and Miljan Krstić
Brain Sci. 2025, 15(2), 132; https://doi.org/10.3390/brainsci15020132 - 29 Jan 2025
Viewed by 403
Abstract
Central nervous system (CNS) tumors involve a large and diverse group of malignancies that arise from various cell types within the brain tissue. Although there are advances in treatments, CNS tumors still remain challenging, due to their complex biology and the delicate nature [...] Read more.
Central nervous system (CNS) tumors involve a large and diverse group of malignancies that arise from various cell types within the brain tissue. Although there are advances in treatments, CNS tumors still remain challenging, due to their complex biology and the delicate nature of the surrounding tissue. NAD(P)H O=oxidoreductase 1 (NQO1) is an enzyme that plays a critical role in the detoxification of quinones, protecting cells from oxidative stress. In CNS tumors this enzyme is often overexpressed, which contributes to the resistance of tumor cells to chemotherapy by enhancing their antioxidant defenses. NQO1 influences the progression of CNS tumors by affecting downstream signaling pathways, such as those involving the transcription factor SNAIL, as well as others that are associated with tumor behavior. Plants represent a valuable source of numerous constituents with different chemical structures known to affect different molecular signaling pathways associated with different pathologies. Full article
(This article belongs to the Special Issue Brain Tumors: From Molecular Basis to Therapy)
22 pages, 4307 KiB  
Article
A Computational Analysis of the Effect of Hard Choices on the Individuation of Values
by Norberto M. Grzywacz
Brain Sci. 2025, 15(2), 131; https://doi.org/10.3390/brainsci15020131 - 29 Jan 2025
Viewed by 439
Abstract
Background/Objectives: Experimental studies show that when an individual makes choices, they affect future decisions. Future choices tend to be consistent with past ones. This tendency matters in the context of ambivalent situations because they may not lead to clear choices, often leading people [...] Read more.
Background/Objectives: Experimental studies show that when an individual makes choices, they affect future decisions. Future choices tend to be consistent with past ones. This tendency matters in the context of ambivalent situations because they may not lead to clear choices, often leading people to make “arbitrary” decisions. Thus, because of choice consistency with the past, people’s decision-making values diverge. Thus, hard choices may contribute to the individuation of values. Methods: Here, we develop a Bayesian framework for the effects of cognitive choice consistency on decision-making. This framework thus extends earlier cognitive-science Bayesian theories, which focus on other tasks, such as inference. The minimization of total surprisals considering the history of stimuli and chosen actions implements choice consistency in our framework. We then use a computational model based on this framework to study the effect of hard choices on decision-making values. Results: The results for action selection based on sensory stimuli show that hard choices can cause the spontaneous symmetry breaking of the decision-making space. This spontaneous symmetry breaking is different across individuals, leading to individuation. If in addition, rewards are given to certain choices, then the direction of the symmetry breaking can be guided by these incentives. Finally, we explore the effects of the parametric complexity of the model, the number of choices, and the length of choice memory. Conclusions: Considering the brain’s mechanism of choice consistency and the number of hard choices made in life, we hypothesize that they contribute to individuality. We assess this hypothesis by placing our study in the context of the cognition-of-individuality literature and proposing experimental tests of our computational results. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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17 pages, 1316 KiB  
Article
Mitochondrial Dysfunction Correlates with Brain Amyloid Binding, Memory, and Executive Function in Down Syndrome: Implications for Alzheimer’s Disease in Down Syndrome
by Jessica A. Beresford-Webb, Catherine J. McAllister, Alison Sleigh, Madeleine J. Walpert, Anthony J. Holland and Shahid H. Zaman
Brain Sci. 2025, 15(2), 130; https://doi.org/10.3390/brainsci15020130 - 28 Jan 2025
Viewed by 465
Abstract
Background/Objectives: Mitochondrial dysfunction is increasingly recognized as a central contributor to neurodegenerative diseases and age-related cognitive decline. Individuals with Down syndrome (DS) are at high risk of neurodegeneration due to Alzheimer’s disease (AD). This study aims to explore the relationship between mitochondrial dysfunction, [...] Read more.
Background/Objectives: Mitochondrial dysfunction is increasingly recognized as a central contributor to neurodegenerative diseases and age-related cognitive decline. Individuals with Down syndrome (DS) are at high risk of neurodegeneration due to Alzheimer’s disease (AD). This study aims to explore the relationship between mitochondrial dysfunction, brain amyloid-beta (Aβ) deposition, and cognitive decline in this population. Methods: We investigated mitochondrial function, brain amyloid-beta burden, and cognitive performance in a pilot study of a cohort of 10 eligible adults with DS selected from a sample of 28 individuals with DS. Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) was used to assess mitochondrial function in skeletal muscle using a post-exercise paradigm, while positron emission tomography using 11C-Pittsburgh compound B (PiB-PET) measured brain Aβ deposition. Cognitive performance was evaluated using the Cambridge Cognitive Examination adapted for individuals with Down syndrome (CAMCOG-DS) and executive function batteries. Results: Significant correlations were observed between slowed phosphocreatine (PCr) recovery in muscle and increased Aβ deposition in key brain regions, particularly the striatum. Cognitive performance inversely correlated with mitochondrial function, with pronounced deficits in memory and executive function tasks. Notably, an individual carrying the APOE-ε4 allele exhibited the poorest mitochondrial function, highest Aβ burden, and most severe cognitive impairment, suggesting a potential interaction between genetic risk and mitochondrial health. Conclusions: These findings highlight the role of mitochondrial dysfunction in DS-associated AD (DSAD) and its impact on cognition in adults. The results support targeting mitochondrial pathways as a potential therapeutic strategy to mitigate AD progression in DS populations. Further research with larger cohorts and longitudinal designs is needed to clarify causative mechanisms and develop effective interventions. Full article
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