Brain Sciences

34 pages, 3067 KB

Open AccessArticle

NRGAMTE: Neurophysiological Residual Gated Attention Multimodal Transformer Encoder for Sleep Disorder Detection

by Jayapoorani Subramaniam, Aruna Mogarala Guruvaya, Anupama Vijaykumar and Puttamadappa Chaluve Gowda

Brain Sci. 2025, 15(9), 985; https://doi.org/10.3390/brainsci15090985 (registering DOI) - 13 Sep 2025

Background/Objective: Sleep is significant for human mental and physical health. Sleep disorders represent a crucial risk to human health, and a large portion of the world population suffers from them. The efficient identification of sleep disorders is significant for effective treatment. However, the [...] Read more.

Background/Objective: Sleep is significant for human mental and physical health. Sleep disorders represent a crucial risk to human health, and a large portion of the world population suffers from them. The efficient identification of sleep disorders is significant for effective treatment. However, the precise and automatic detection of sleep disorders remains challenging due to the inter-subject variability, overlapping symptoms, and reliance on single-modality physiological signals. Methods: To address these challenges, a Neurophysiological Residual Gated Attention Multimodal Transformer Encoder (NRGAMTE) model was developed for robust sleep disorder detection using multimodal physiological signals, including Electroencephalogram (EEG), Electromyogram (EMG), and Electrooculogram (EOG). Initially, raw signals are segmented into 30-s windows and processed to capture the significant time- and frequency-domain features. Every modality is independently embedded by a One-Dimensional Convolutional Neural Network (1D-CNN), which preserves signal-specific characteristics. A Modality-wise Residual Gated Cross-Attention Fusion (MRGCAF) mechanism is introduced to select significant cross-modal interactions, while the learnable residual path ensures that the most relevant features are retained during the gating process. Results: The developed NRGAMTE model achieved an accuracy of 94.51% on the Sleep-EDF expanded dataset and 99.64% on the Cyclic Alternating Pattern (CAP Sleep database), significantly outperforming the existing single- and multimodal algorithms in terms of robustness and computational efficiency. Conclusions: The results shows that NRGAMTE obtains high performance across multiple datasets, significantly improving detection accuracy. This demonstrated their potential as a reliable tool for clinical sleep disorder detection. Full article

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

► Show Figures

Figure 1

32 pages, 1172 KB

Open AccessViewpoint

From Bacillus Criminalis to the Legalome: Will Neuromicrobiology Impact 21st Century Criminal Justice?

by Alan C. Logan, Barbara Cordell, Suresh D. Pillai, Jake M. Robinson and Susan L. Prescott

Brain Sci. 2025, 15(9), 984; https://doi.org/10.3390/brainsci15090984 (registering DOI) - 13 Sep 2025

Abstract

The idea that gut microbes or a “bacillus of crime” might promote criminal behavior was popularized in the early 20th century. Today, advances in neuromicrobiology and related omics technologies are lending credibility to the idea. In recent cases of dismissal of driving while [...] Read more.

The idea that gut microbes or a “bacillus of crime” might promote criminal behavior was popularized in the early 20th century. Today, advances in neuromicrobiology and related omics technologies are lending credibility to the idea. In recent cases of dismissal of driving while intoxicated charges, courts in the United States and Europe have acknowledged that gut microbes can manufacture significant amounts of systemically available ethanol, without a defendant’s awareness. Indeed, emergent research is raising difficult questions for criminal justice systems that depend on prescientific notions of free moral agency. Evidence demonstrates that gut microbes play a role in neurophysiology, influencing cognition and behaviors. This may lead to justice involvement via involuntary intoxication, aggression, anger, irritability, and antisocial behavior. Herein, we discuss these ‘auto-brewery syndrome’ court decisions, arguing that they portend a much larger incorporation of neuromicrobiology and multi-omics science within the criminal justice system. The legalome, which refers to the application of gut microbiome and omics sciences in the context of forensic psychiatry/psychology, will likely play an increasing role in 21st century criminal justice. The legalome concept is bolstered by epidemiology, mechanistic bench science, fecal transplant studies, multi-omics and polygenic research, Mendelian randomization work, microbiome signature research, and human intervention trials. However, a more robust body of microbiota–gut–brain axis research is needed, especially through the lens of prevention, intervention, and rehabilitation. With ethical guardrails in place, greater inclusion of at-risk or justice-involved persons in brain science and microbiome research has the potential to transform justice systems for the better. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

► Show Figures

Figure 1

33 pages, 1073 KB

Open AccessReview

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 (registering DOI) - 13 Sep 2025

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

(This article belongs to the Special Issue Unraveling Autism: Neurobiological Mechanisms and Emerging Therapeutic Advances)

► Show Figures

Figure 1

20 pages, 821 KB

Open AccessArticle

Non-Invasive Cervical Spinal Stimulation and Respiratory Recovery After Spinal Cord Injury: A Randomized Controlled Trial with a Partial Crossover Design

by Hatice Kumru, Agustin Hernandez-Navarro, Sergiu Albu and Loreto García-Alén

Brain Sci. 2025, 15(9), 982; https://doi.org/10.3390/brainsci15090982 (registering DOI) - 12 Sep 2025

Abstract

Background/Objectives: Respiratory impairment is the leading cause of morbidity and mortality in participants with spinal cord injury (SCI). Cervical SCI (cSCI) severely compromises respiratory function due to paralysis and weakness of the respiratory muscles. Recent evidence suggests that transcutaneous electrical spinal cord [...] Read more.

Background/Objectives: Respiratory impairment is the leading cause of morbidity and mortality in participants with spinal cord injury (SCI). Cervical SCI (cSCI) severely compromises respiratory function due to paralysis and weakness of the respiratory muscles. Recent evidence suggests that transcutaneous electrical spinal cord stimulation (tSCS) may enhance motor strength and promote functional recovery. Therefore, cervical tSCS, applied at cervical segments, holds potential as a therapeutic strategy to improve respiratory function in participants with cervical SCI. Methods: This randomized controlled trial with a partial crossover design included participants with both complete and incomplete cSCI. Neurological assessments were used, as well as tests to evaluate pulmonary function maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and spirometric measurements. These assessments were conducted at baseline and after the last session. The experimental group received tSCS at the C3–C4 and C6–C7 cervical spinal levels, delivered at a frequency of 30 Hz during occupational therapy. The control group underwent identical occupational therapy sessions without stimulation. Each session lasted 30 min and was conducted over eight days. Results: Fifteen participants with cSCI received tSCS, while 11 cSCI participants were included in the control group. Seven participants took part in both groups. Only the tSCS group showed significant improvements in MIP, MEP, and forced vital capacity (p < 0.05), while no significant changes were observed in the control group. Conclusions: tSCS applied at the cervical segments can promote respiratory function following cervical SCI. This approach may support neuroplasticity and help reduce long-term respiratory complications in participants with cervical SCI. However, to confirm these effects, long-term stimulation protocols and follow-up studies in larger SCI populations are required. Full article

(This article belongs to the Special Issue Spinal Cord Injury: Biomarkers, Neuroimaging and Therapeutic Approaches)

33 pages, 4276 KB

Open AccessArticle

Brain Cortical Area Characterization and Machine Learning-Based Measure of Rasmussen’s S-R-K Model

by Daniele Amore, Daniele Germano, Gianluca Di Flumeri, Pietro Aricò, Vincenzo Ronca, Andrea Giorgi, Alessia Vozzi, Rossella Capotorto, Stefano Bonelli, Fabrice Drogoul, Jean-Paul Imbert, Géraud Granger, Fabio Babiloni and Gianluca Borghini

Brain Sci. 2025, 15(9), 981; https://doi.org/10.3390/brainsci15090981 - 12 Sep 2025

Abstract

Background: the Skill, Rule, and Knowledge (S-R-K) model is a framework used to describe and analyze human behaviour and decision-making in complex environments based on the nature of the task and kind of cognitive control required. The S-R-K model is particularly useful in [...] Read more.

Background: the Skill, Rule, and Knowledge (S-R-K) model is a framework used to describe and analyze human behaviour and decision-making in complex environments based on the nature of the task and kind of cognitive control required. The S-R-K model is particularly useful in fields like human factor engineering, system design, and safety-critical industries because it helps to understand human errors and how they relate to different levels of cognitive control. However, the S-R-K model is still qualitative and lacks specific and quantifiable metrics for determining what kind of cognitive control a person is using at any given time. This aspect makes difficult to directly measure and compare performance across the three levels. This study aimed therefore to characterize the S-R-K model from a neurophysiological perspective by analyzing the operator’s cerebral cortical activity. Methods: in this study, participants carried out experimental tasks able to replicate the Skill (tracking task), Rule (rule-based navigation) and Knowledge conditions (unfamiliar situations). Results: participants’ Electroencephalogram (EEG) was recorded during tasks execution and then Global Field Power (GFP) was estimated in the different EEG frequency bands. Brodmann areas (BAs) and EEG features were then used to characterize the S-R-K pattern over the cerebral cortex and as inputs to build up the machine learning-based model to estimate participants’ cognitive control behaviours while dealing with tasks. Conclusions: the results demonstrate the possibility of objectively measuring the different S, R and K levels in terms of brain activations. Furthermore, such evidence is consistent with the scientific literature in terms of cognitive functions corresponding to the different levels of cognitive control. Full article

(This article belongs to the Special Issue Computational Intelligence and Brain Plasticity)

26 pages, 356 KB

Open AccessReview

Emerging Interventions in Behavioral Addictions: A Narrative Review of Psychedelics and Neuromodulation

by Krista Ulisse, Jehad Albitar, Jourdan T. Aromin and James Berry

Brain Sci. 2025, 15(9), 980; https://doi.org/10.3390/brainsci15090980 - 12 Sep 2025

Abstract

Addiction remains a persistent public health crisis, marked by poor treatment retention and limited pharmacotherapy options. Emerging treatments, such as psychedelic-assisted psychotherapy and neuromodulation, offer promising avenues for circuit-level interventions in behavioral addictions. This narrative review synthesizes the current landscape of psychedelic compounds [...] Read more.

Addiction remains a persistent public health crisis, marked by poor treatment retention and limited pharmacotherapy options. Emerging treatments, such as psychedelic-assisted psychotherapy and neuromodulation, offer promising avenues for circuit-level interventions in behavioral addictions. This narrative review synthesizes the current landscape of psychedelic compounds and neuromodulation techniques with a focus on their mechanisms of action, applications in specific behavioral addictions, and translational potential. By targeting disrupted reward, executive control, and stress regulation networks, these interventions may facilitate meaningful recovery and long-term remission in otherwise treatment refractory cases. We highlight key findings, current research limitations, and future directions in integrating these novel therapies into the treatment of gambling disorder; internet gaming disorder/gaming disorder, predominantly online; internet use disorder; and compulsive sexual behavior disorder. Full article

(This article belongs to the Special Issue Psychedelic and Interventional Psychiatry)

29 pages, 8282 KB

Open AccessArticle

Dopaminergic Inhibition of the Inwardly Rectifying Potassium Current in Direct Pathway Medium Spiny Neurons in Normal and Parkinsonian Striatum

by Qian Wang, Yuhan Wang, Francesca-Fang Liao and Fu-Ming Zhou

Brain Sci. 2025, 15(9), 979; https://doi.org/10.3390/brainsci15090979 - 12 Sep 2025

Abstract

Background: Despite the profound behavioral effects of the striatal dopamine (DA) activity and the inwardly rectifying potassium channel (Kir) being a key determinant of striatal medium spiny neuron (MSN) activity that strongly affects behavior, previously reported DA regulations of Kir are conflicting and [...] Read more.

Background: Despite the profound behavioral effects of the striatal dopamine (DA) activity and the inwardly rectifying potassium channel (Kir) being a key determinant of striatal medium spiny neuron (MSN) activity that strongly affects behavior, previously reported DA regulations of Kir are conflicting and incompatible with MSN function in behavior. Methods and Results: Here, we used DA depletion mouse models that have hyperfunctional DA receptors such that potential DA regulation of Kir may be enhanced and relatively large and thus detected reliably. We show that in striatal brain slices from normal mice with an intact striatal DA system, the predominant effect of DA activation of D1Rs in D1-MSNs is to cause a modest depolarization and an increase in input resistance by inhibiting Kir, thus moderately increasing the spike outputs from behavior-promoting D1-MSNs. In brain slices from parkinsonian (DA-depleted) striatum, DA increases D1-MSN intrinsic excitability more strongly than in normal striatum, consequently more strongly increasing D1-MSN spike firing that is behavior-promoting. This DA inhibition of Kir is occluded by the Kir blocker barium chloride (BaCl₂). In behaving parkinsonian mice, BaCl₂ microinjection into the dorsal striatum stimulates movement and also occludes the motor stimulation of D1R agonism. Conclusions: Taken together, our results resolve the long-standing question about what D1R agonism does to D1-MSN excitability in normal and parkinsonian striatum and strongly indicate that D1R inhibition of Kir is a key ion channel mechanism that mediates the profound motoric and behavioral stimulation of striatal D1R activation in normal and parkinsonian animals. Full article

(This article belongs to the Special Issue How to Rewire the Brain—Neuroplasticity)

► Show Figures

Figure 1

34 pages, 1088 KB

Open AccessReview

Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?

by Elena Rossini, Luca Leonardi, Stefania Morino, Giovanni Antonini and Laura Fionda

Brain Sci. 2025, 15(9), 978; https://doi.org/10.3390/brainsci15090978 - 11 Sep 2025

Abstract

Background: Generalized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies. Objective: This review aims to synthesize [...] Read more.

Background: Generalized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies. Objective: This review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes. Methods: A narrative review was conducted, integrating recent findings from clinical trials, immunogenetic studies, and preclinical research to describe subtype-specific immune mechanisms and corresponding therapeutic innovations. Results: gMG subtypes—characterized by autoantibody profiles (AChR, MuSK, LRP4, or seronegative), thymic histopathology, and age of onset—demonstrate distinct immunological pathways. Early-onset MG is associated with thymic hyperplasia and Th17-driven inflammation; thymoma-associated MG involves central tolerance breakdown; late-onset MG shows immune senescence and altered T-cell regulation. MuSK- and LRP4-positive MG exhibit unique cytokine and antibody signatures. Novel therapeutic strategies include B cell- and T cell-targeted therapies (e.g., anti-CD19, anti-CD38, JAK inhibitors), cytokine inhibitors (IL-6, IL-17, IL-23), FcRn antagonists, complement inhibitors, and gene- or cell-based therapies such as CAR-T and CAAR-T cells. Conclusion: The evolving landscape of gMG treatment reflects a shift toward immunopathology-based precision medicine. Better characterization of subtype-specific molecular signatures and immune dysfunctions is essential to guide clinical decision-making and improve outcomes for treatment-refractory patients. Full article

(This article belongs to the Special Issue Diagnosis, Treatment, and Prognosis of Neuromuscular Disorders)

► Show Figures

Figure 1

31 pages, 19306 KB

Open AccessArticle

Predicting Depression Therapy Outcomes Using EEG-Derived Amplitude Polar Maps

by Hesam Akbari, Wael Korani, Sadiq Muhammad, Reza Rostami, Reza Kazemi and Muhammad Tariq Sadiq

Brain Sci. 2025, 15(9), 977; https://doi.org/10.3390/brainsci15090977 - 11 Sep 2025

Abstract

Background/Objectives: Depression is a mental disorder that can lead to self-harm or suicidal thoughts if left untreated. Psychiatrists often face challenges in identifying the most effective courses of treatment for patients with depression. Two widely recommended depression-related therapies are selective serotonin reuptake [...] Read more.

Background/Objectives: Depression is a mental disorder that can lead to self-harm or suicidal thoughts if left untreated. Psychiatrists often face challenges in identifying the most effective courses of treatment for patients with depression. Two widely recommended depression-related therapies are selective serotonin reuptake inhibitors (SSRIs) and repetitive transcranial magnetic stimulation (rTMS). However, their response rates are approximately 50%, which is relatively low. This study introduces a computer-aided decision (CAD) system designed to determine the effectiveness of depression therapies and recommends the most appropriate treatments for patients. Methods: Each channel of the EEG is plotted in two-dimensional (2D) space via a novel technique called the amplitude polar map (APM). In each channel, the 2D plot of APM is utilized to extract distinctive features via the binary pattern of five successive lines method. The extracted features from each channel are fused to generalize the pattern of EEG signals. The most relevant features are selected via the neighborhood component analysis algorithm. The chosen features are input into a simple feed-forward neural network architecture to classify the EEG signal of a depressed patient into either a respondent to depression therapies or not. The 10-fold cross-validation strategy is employed to ensure unbiased results. Results: The results of our proposed CAD system show accuracy rates of 98.06% and 97.19% for predicting the outcomes of SSRI and rTMS therapies, respectively. In SSRI predictions, prefrontal and parietal channels such as F7, Fz, Fp2, P4, and Pz were the most informative, reflecting brain regions involved in emotional regulation and executive function. In contrast, rTMS prediction relied more on frontal, temporal, and occipital channels such as F4, O2, T5, T3, Cz, and T6, indicating broader network modulation via neuromodulation. Conclusions: The proposed CAD framework holds considerable promise as a clinical decision-support tool, assisting mental health professionals in identifying the most suitable therapeutic interventions for individuals with depression. Full article

(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)

► Show Figures

Figure 1

18 pages, 1476 KB

Open AccessArticle

Electroacupuncture Attenuates Fibromyalgia Pain Through Increased PD-1 Expression in Female Mice

by I-Han Hsiao, Wei-Hung Chen, Ming-Chia Lin, Hsin-Cheng Hsu, Hsien-Yin Liao and Yi-Wen Lin

Brain Sci. 2025, 15(9), 976; https://doi.org/10.3390/brainsci15090976 - 11 Sep 2025

Abstract

Background/Objectives: Fibromyalgia causes chronic long-term pain, with symptoms lasting for months to years. Given the lack of evidence-based methods for diagnosing and assessing fibromyalgia, it ranks among the most difficult chronic pain conditions to treat. Programmed cell death ligand 1 (PD-L1) can inhibit [...] Read more.

Background/Objectives: Fibromyalgia causes chronic long-term pain, with symptoms lasting for months to years. Given the lack of evidence-based methods for diagnosing and assessing fibromyalgia, it ranks among the most difficult chronic pain conditions to treat. Programmed cell death ligand 1 (PD-L1) can inhibit acute and chronic pain transmission by inhibiting neuronal ion channels. Methods: Here, we aimed to explore the analgesic efficacy and mechanism of PD-L1/PD1 in an intermittent cold stress-induced fibromyalgia pain mouse model. Results: Von Frey and Hargreaves tests were performed, showing that the mouse model exhibited mechanical (day 4: 2.08 ± 0.13 g, n = 9) and thermal hyperalgesia (day 4: 3.93 ± 0.45 s, n = 9). Electroacupuncture (EA) or intraventricular PD-L1 injection effectively alleviated the nociceptive response and led to low PD-1 levels in the mouse dorsal root ganglia, spinal cord, thalamus, somatosensory cortex, and cerebellum, as measured through Western blots. In contrast, the pain-related kinase levels increased after fibromyalgia induction; these effects were reversed by EA and PD-L1 via the inhibition of microglia/astrocytes and Toll-like receptor 4. Conclusions: Our results show that EA can treat fibromyalgia pain in mice through effects on the PD-L1/PD1 pathway, indicating its potential as a therapeutic target in fibromyalgia. Full article

(This article belongs to the Special Issue Application of Nerve Stimulation: Current Status and Future Directions—2nd Edition)

► Show Figures

Figure 1

14 pages, 796 KB

Open AccessArticle

Brain Connectivity Estimation Network for the Identification of Dementia

by Ji Xi, Zhengwang Xia, Weiqi Zhang and Li Zhao

Brain Sci. 2025, 15(9), 975; https://doi.org/10.3390/brainsci15090975 - 10 Sep 2025

Abstract

Objectives: The brain network serves as a reliable tool for diagnosing neurological disorders. However, the current modeling algorithms for brain networks often rely on several assumptions regarding the interactions between brain regions, which can be inaccurate. For instance, some studies assume linear [...] Read more.

Objectives: The brain network serves as a reliable tool for diagnosing neurological disorders. However, the current modeling algorithms for brain networks often rely on several assumptions regarding the interactions between brain regions, which can be inaccurate. For instance, some studies assume linear relationships among brain regions. Additionally, some research suggests that certain brain regions do not significantly influence outcomes when assessing directional influence between paired regions. Methods: To address this issue, we introduced a novel method for modeling brain connectivity structures that estimates interactions among regions from a different perspective. More importantly, this method considers all the relevant brain regions during evaluation rather than isolating individual relationships. Results: To validate its effectiveness, we conducted extensive experiments using publicly available datasets. The proposed method achieved superior performance across all tasks. Conclusions: The results demonstrate that our method not only excels in identifying various brain disorders but also uncovers new biomarkers, providing fresh insights into neurological disorder research. Full article

(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)

12 pages, 536 KB

Open AccessArticle

The Association Between Schizophrenia and Cardiovascular Diseases: A Retrospective Cohort Study of Primary Care Routine Data in Germany

by Ira Rodemer, Marcel Konrad, Mark Luedde and Karel Kostev

Brain Sci. 2025, 15(9), 974; https://doi.org/10.3390/brainsci15090974 - 10 Sep 2025

Abstract

Background: This novel study addresses the question of whether schizophrenia is associated with an increased risk of cardiovascular diseases (CVDs) by controlling for metabolic syndrome-related conditions through propensity score matching, using real-world primary care data from Germany. Methods: This retrospective cohort [...] Read more.

Background: This novel study addresses the question of whether schizophrenia is associated with an increased risk of cardiovascular diseases (CVDs) by controlling for metabolic syndrome-related conditions through propensity score matching, using real-world primary care data from Germany. Methods: This retrospective cohort study analyzed 12,527 patients aged 18 or older with schizophrenia from 1209 general practices (GPs) in Germany between 2005 and 2023 from the IQVIA Disease Analyzer database. Patients were matched 1:5 with individuals without schizophrenia based on sex, age, index year, consultation frequency, and chronic conditions. CVDs cumulative incidence was assessed using Kaplan–Meier curves and hazard ratios (HRs) were calculated using univariable Cox regression analysis. Results: Over a 10-year follow-up, schizophrenia was associated with a higher risk of heart failure (HR: 1.33, 95% CI: 1.20–1.48) and a lower risk of atrial fibrillation and flutter (HR: 0.77, 95% CI: 0.67–0.89). No significant associations were observed for acute myocardial infarction (HR: 0.97, 95% CI: 0.76–1.25), angina pectoris (HR: 0.78, 95% CI: 0.63–0.96), or chronic ischaemic heart disease (HR: 0.91, 95% CI: 0.82–1.02). Stratified analyses showed that schizophrenia was most strongly associated with heart failure in women aged 41–50 years (HR: 3.34, 95% CI: 2.11–5.31), followed by women aged 61–70 years (HR: 1.88, 95% CI: 1.45–2.44) and men aged 51–60 years (HR: 1.81, 95% CI: 1.34–2.45). Conclusions: This study highlights significant differences in the 10-year cumulative incidence of CVDs between individuals with and without schizophrenia. While patients with schizophrenia appear less likely to be diagnosed with milder or asymptomatic CVDs, they are at increased risk for severe outcomes. The study’s findings underscore the need for sex-specific and symptom-sensitive public health strategies to improve early detection and prevention of CVDs in patients with schizophrenia. Full article

(This article belongs to the Section Neuropsychiatry)

► Show Figures

Figure 1

14 pages, 1585 KB

Open AccessArticle

Management and Outcomes of Multiple Unruptured Cerebral Aneurysms: A Descriptive Cohort Analysis

by Oday Atallah, Khadeja Alrefaie and Amr Badary

Brain Sci. 2025, 15(9), 973; https://doi.org/10.3390/brainsci15090973 - 10 Sep 2025

Abstract

Background: Unruptured cerebral aneurysms pose a significant neurosurgical challenge due to their potential for rupture, which can lead to devastating subarachnoid hemorrhage. Advances in imaging have increased incidental detection of multiple unruptured aneurysms, necessitating tailored management strategies to balance rupture risk against treatment [...] Read more.

Background: Unruptured cerebral aneurysms pose a significant neurosurgical challenge due to their potential for rupture, which can lead to devastating subarachnoid hemorrhage. Advances in imaging have increased incidental detection of multiple unruptured aneurysms, necessitating tailored management strategies to balance rupture risk against treatment complications. Methods: We retrospectively analyzed 41 patients with 101 unruptured cerebral aneurysms, assessing demographics, aneurysm size and location, treatment modalities, and clinical outcomes. Descriptive statistics and correlation analyses examined associations between aneurysm characteristics, comorbidities, and post-treatment complications. Results: Most aneurysms were small (<10 mm, 48.5%), primarily located at the Middle Cerebral Artery Bifurcation (27.7%). Hypertension (56.1%) and smoking (53.7%) were prevalent risk factors. Clipping was the most common intervention (81.2%), with 41.4% of patients experiencing post-operative complications and 36.6% developing neurological deficits. Conclusions: This study underscores the difficulties in managing multiple unruptured cerebral aneurysms owing to diverse aneurysm characteristics and patient risk factors such as hypertension, hyperlipidaemia, and smoking. Clipping was the predominant intervention, with time customized for each individual case. Despite the occurrence of problems such as vasospasm and neurological difficulties, the majority of patients maintained functional independence. The results provide significant insights into the clinical attributes, therapeutic strategies, and outcomes for this patient cohort. Full article

(This article belongs to the Special Issue Advances in the Diagnosis, Visualization and Treatment of Intracranial Aneurysms and Subarachnoid Hemorrhage)

► Show Figures

Figure 1

14 pages, 2352 KB

Open AccessReview

A Comprehensive Overview of Subacute Combined Degeneration: MRI Diagnostic Challenges and Treatment Pathways

by Caterina Bernetti, Laura Cea, Andrea Buoso, Federico Greco, Mariagrazia Rossi, Fabio Pilato, Rosalinda Calandrelli, Gianfranco Di Gennaro, Vincenzo Di Lazzaro, Bruno Beomonte Zobel and Carlo Augusto Mallio

Brain Sci. 2025, 15(9), 972; https://doi.org/10.3390/brainsci15090972 - 10 Sep 2025

Abstract

Subacute combined degeneration (SCD) is a neurological disorder primarily caused by vitamin B12 deficiency. This condition leads to progressive demyelination and axonal damage, predominantly affecting the dorsal and lateral columns of the spinal cord. This review provides a comprehensive overview of SCD, detailing [...] Read more.

Subacute combined degeneration (SCD) is a neurological disorder primarily caused by vitamin B12 deficiency. This condition leads to progressive demyelination and axonal damage, predominantly affecting the dorsal and lateral columns of the spinal cord. This review provides a comprehensive overview of SCD, detailing its complex etiology, pathophysiology, and clinical presentation. We highlight the critical role of magnetic resonance imaging (MRI) in the diagnostic process, discussing both the characteristic spinal cord findings and the more subtle intracranial abnormalities. Furthermore, we address the diagnostic challenges presented by conditions that mimic SCD in MRI, such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). We conclude by outlining current treatment pathways and identifying key areas for future research, including the use of advanced neuroimaging techniques and the potential for new therapeutic approaches. This updated synthesis aims to provide a clear framework for clinicians and researchers to better understand and manage SCD. Full article

(This article belongs to the Special Issue Application of MRI in Brain Diseases)

► Show Figures

Figure 1

23 pages, 703 KB

Open AccessReview

Botulinum Toxin: An Unconventional Tool for the Treatment of Depression?

by Matteo Gambini, Riccardo Gurrieri, Gerardo Russomanno, Gianmatteo Cecchini, Federico Mucci, Manuel Glauco Carbone and Donatella Marazziti

Brain Sci. 2025, 15(9), 971; https://doi.org/10.3390/brainsci15090971 - 10 Sep 2025

Abstract

Background/Objectives: Major depressive disorder (MDD) represents a leading cause of global disability, with approximately one-third of patients exhibiting treatment resistance (TRD) despite adequate pharmacological interventions. This treatment gap underscores the urgent need for novel therapeutic strategies. Recently, a series of data suggests that [...] Read more.

Background/Objectives: Major depressive disorder (MDD) represents a leading cause of global disability, with approximately one-third of patients exhibiting treatment resistance (TRD) despite adequate pharmacological interventions. This treatment gap underscores the urgent need for novel therapeutic strategies. Recently, a series of data suggests that botulinum neurotoxin of type A (BoNT-A), traditionally used for neuromuscular and cosmetic indications, could constitute a potential antidepressant tool. This narrative review critically examines the current preclinical and clinical findings of BoNT-A in MDD. Methods: A comprehensive search of PubMed, Scopus, and Web of Science was conducted up to June 2025, including randomized controlled trials, observational studies, animal models, and mechanistic investigations. Search terms included “Botulinum Toxin,” “BoNT type A”, “Depression”, “Major Depressive Disorder”, “Facial Feedback”, and “Neurobiology”. Results: Some randomized and observational studies would indicate that glabellar BoNT-A injections might lead to significant reductions in depressive symptoms in patients with MDD and TRD. Proposed mechanisms include both peripheral modulation of emotional expression and brain effects, such as reduced amygdala hyperactivity, increased BDNF expression, and enhanced monoaminergic transmission. Preclinical studies confirm that BoNT-A modulates limbic and brainstem circuits, possibly implicated in affective regulation. The few comparative studies suggest therapeutic efficacy comparable to that of SSRIs, with a more rapid onset. Preliminary data also support its application in bipolar depression and comorbid anxiety disorders. Conclusions: The available literature would indicate that BoNT-A might constitute a promising candidate at least as an adjunctive treatment in MDD, although the impact of current findings is limited due to the methodological heterogeneity and the small sample sizes of patients examined. Further large-scale, placebo-controlled trials are warranted to elucidate the mode of action of BoNT-A and to validate or not its clinical effectiveness. Full article

(This article belongs to the Section Neuropsychiatry)

► Show Figures

Graphical abstract

13 pages, 426 KB

Open AccessArticle

Application of Concomitant Transcranial Direct Current Stimulation (tDCS) and Cognitive Behavioral-Oriented Training (CBT) for Pragmatic Skills Improvement in Young Adults with Autism Spectrum Disorder (ASD): Preliminary Data from a Pilot Study

by Lucrezia Arturi, Chiara Scoppola, Assia Riccioni, Martina Siracusano, Luigi Iasevoli, Giulia Civetta, Gianfranco Spalletta, Valentina Fiori and Luigi Mazzone

Brain Sci. 2025, 15(9), 970; https://doi.org/10.3390/brainsci15090970 - 10 Sep 2025

Abstract

Objectives: Individuals with Autism Spectrum Disorder (ASD) exhibit difficulties in the social use of language, regardless of age, cognitive abilities, and symptom severity. The left Broca’s area and adjacent cortex are crucial for socio-pragmatic language, particularly in retrieving and integrating context-dependent words. Neuroimaging [...] Read more.

Objectives: Individuals with Autism Spectrum Disorder (ASD) exhibit difficulties in the social use of language, regardless of age, cognitive abilities, and symptom severity. The left Broca’s area and adjacent cortex are crucial for socio-pragmatic language, particularly in retrieving and integrating context-dependent words. Neuroimaging studies in ASD have shown hypoactivation of the Broca’s area and an aberrant pattern of functional connectivity between language-related regions, suggesting their potential involvement in socio-communicative deficits. Given the potential of tDCS to modulate brain activity, its application targeting Broca’s areas in addition to psychological intervention may represent a promising approach for enhancing socio-communicative skills in ASD. Thus, this study aims to investigate the effect of concomitant anodal tDCS and cognitive behavioral-oriented training (CBT) on pragmatic and communicative skills in young adults with ASD. Methods: A sample of 10 ASD individuals (18–25 years) underwent treatment with both active and sham tDCS targeting the left Broca’s area during concomitant CBT. Each condition was delivered for five consecutive days, and the order of the conditions was blindly randomized. Results: Active tDCS significantly improved global communicative and pragmatic abilities compared to sham. A negative correlation was observed between communicative skills improvement and Intelligence Quotient (IQ); no significant association was found between IQ and ASD symptoms’ severity. Conclusions: Multisession tDCS targeting the left Broca’s area, combined with CBT, may enhance social language in terms of both production and comprehension of non-literal meanings, supporting Broca’s area as a central neural hub for social language. Full article

(This article belongs to the Section Behavioral Neuroscience)

► Show Figures

Figure 1

14 pages, 652 KB

Open AccessSystematic Review

Transcranial Magnetic Stimulation as a Diagnostic Tool in Mild Cognitive Impairment: A Systematic Review

by Elisa Dognini, Simona Finazzi, Elena Campana, Rosa Manenti, Maria Cotelli and Barbara Borroni

Brain Sci. 2025, 15(9), 969; https://doi.org/10.3390/brainsci15090969 - 9 Sep 2025

Abstract

Background/Objective: Mild cognitive impairment (MCI) often represents the prodromal stage of neurodegenerative dementia. Identification of Alzheimer disease (AD) and other dementias in the MCI stage is essential for early intervention. Transcranial magnetic stimulation (TMS) has gained interest as a non-invasive method to [...] Read more.

Background/Objective: Mild cognitive impairment (MCI) often represents the prodromal stage of neurodegenerative dementia. Identification of Alzheimer disease (AD) and other dementias in the MCI stage is essential for early intervention. Transcranial magnetic stimulation (TMS) has gained interest as a non-invasive method to evaluate cortical excitability and neurotransmitter function. This systematic review aims to evaluate the diagnostic utility of TMS-derived indices, such as short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) in MCI populations. Methods: Following PRISMA guidelines, 14 studies were selected, encompassing 476 MCI patients. Reported outcomes related to TMS measures (SAI, SICI, ICF, LICI) were reviewed across various MCI phenotypes. Results: Most studies report reduced SAI, a marker of cholinergic dysfunction, in amnestic MCI and MCI due to AD. Alterations in SICI and ICF, markers of GABAergic and glutamatergic dysfunction, were more variable, mainly observed in MCI of non-AD type. LICI showed no consistent changes. One study demonstrated increased clinicians’ diagnostic confidence when TMS data were incorporated. Conclusions: TMS measures hold promise as a non-invasive tool for early and differential diagnosis of MCI. Further standardized and longitudinal research is needed to confirm its clinical applicability. Full article

(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)

► Show Figures

Figure 1

11 pages, 588 KB

Open AccessArticle

Adherence to Non-Invasive Ventilation in Steinert Disease: Clinical and Psychological Insights

by Anna Annunziata, Francesca Simioli, Giorgio Emanuele Polistina, Anna Michela Gaeta, Maria Cardone, Camilla Di Somma, Raffaella Manzo, Antonella Marotta, Cecilia Calabrese and Giuseppe Fiorentino

Brain Sci. 2025, 15(9), 968; https://doi.org/10.3390/brainsci15090968 - 6 Sep 2025

Abstract

Introduction: Myotonic dystrophies (DM) are progressive genetic disorders with multisystemic involvement, particularly affecting the muscular, respiratory, and neuropsychological systems. Myotonic dystrophy type 1 (DM1), or Steinert’s disease, may lead to severe respiratory complications, including sleep-disordered breathing and hypercapnia, often requiring noninvasive ventilation to [...] Read more.

Introduction: Myotonic dystrophies (DM) are progressive genetic disorders with multisystemic involvement, particularly affecting the muscular, respiratory, and neuropsychological systems. Myotonic dystrophy type 1 (DM1), or Steinert’s disease, may lead to severe respiratory complications, including sleep-disordered breathing and hypercapnia, often requiring noninvasive ventilation to manage respiratory failure. However, adherence to NIV remains a major challenge, often influenced by cognitive and psychological factors such as apathy and depression. This study aims to investigate the presence of depression and SDB in patients with DM1 initiating NIV, and to evaluate factors influencing adherence to ventilatory support. Materials and Methods: We selected 13 adult patients (≥18 years) with diagnosis of Steinert’s disease with respiratory impairment who needed to start respiratory support. Dysphagia was assessed in all patients at baseline by a videofluoroscopic swallow study. Beck’s Depression Inventory II was administered for measuring the severity of depression. The Montreal Cognitive Assessment was used as a screening tool to detect signs of neurocognitive disorders. We evaluated adherence to NIV. Results: The study population presented with sleep-disordered breathing, as indicated by a median apnea–hypopnea index (AHI) of 24 events per hour (IQR: 14.2–34.5) and an oxygen desaturation index (ODI) of 25 events per hour (IQR: 18–33). Adherence to NIV was obtained in seven patients. No difference in baseline lung function was observed. Adherent subjects had moderate hypercapnia at baseline; pCO2 was 52 vs. 49 mmHg. Non-adherent patients showed a higher prevalence of depression with a median BDI-II score of 18 vs. 6 in adherent patients. The findings highlight that psychological factors, especially depression, play a crucial role in adherence to NIV. Interestingly, depression was not linked to initial respiratory measurements but showed a significant association with nocturnal oxygen desaturation. This suggests that relying solely on clinical and respiratory assessments may not be adequate to predict or improve treatment adherence. Conclusions: Incorporating psychological evaluations and addressing mental health issues, such as depression, are essential steps to enhance NIV compliance and overall DM1 patient outcomes. A multidisciplinary approach combining respiratory and psycho-emotional interventions is crucial for effective disease management. Full article

(This article belongs to the Special Issue Diagnosis, Treatment, and Prognosis of Neuromuscular Disorders)

► Show Figures

Figure 1

15 pages, 255 KB

Open AccessArticle

The First Shall Be First: Letter-Position Coding and Spatial Invariance in Two Cases of Attentional Dyslexia

by Jeremy J. Tree and David R. Playfoot

Brain Sci. 2025, 15(9), 967; https://doi.org/10.3390/brainsci15090967 - 6 Sep 2025

Abstract

Background/Objectives: Previous research has demonstrated that the initial letters of a word likely play a privileged role in visual word recognition, such that reading and visual recognition errors reflecting changes in this position are much less likely. For example, prior case studies of [...] Read more.

Background/Objectives: Previous research has demonstrated that the initial letters of a word likely play a privileged role in visual word recognition, such that reading and visual recognition errors reflecting changes in this position are much less likely. For example, prior case studies of attentional dyslexia reported that participants were most accurate at rejecting nonwords formed by transposing a word’s first two letters (e.g., WONER from OWNER) compared to transpositions in later positions. The current study aimed to replicate and extend this finding in patients with posterior cortical atrophy (PCA), a neurodegenerative condition associated with visuospatial and attentional impairments. Methods: Two PCA patients completed lexical decision tasks involving five-letter real words and nonwords created either by transposing adjacent letters (in positions 1 + 2, 2 + 3, 3 + 4, or 4 + 5) or using matched nonword controls. To assess robustness, tasks were repeated across test–retest sessions. Stimuli were presented in both canonical horizontal and non-canonical vertical (marquee) formats. Accuracy, response bias, and sensitivity (d′) were estimated, with 95% confidence intervals derived from a nonparametric bootstrap procedure. Within-case logistic regressions were also conducted to illustrate the findings. Results: Both patients showed significantly higher accuracy and lower response bias for 1 + 2 transposition nonwords relative to other positions. This early-letter advantage persisted across test–retest observations and was maintained when words were presented in the vertical format, suggesting orientation-invariant effects. The bootstrap and regression analyses provided convergent support for these results. Conclusions: The findings provide novel evidence in PCA that the encoding of early letter positions operates independently of visual orientation and persists despite attentional deficits. This supports models in which the initial letters serve as a key anchor point in orthographic processing, highlighting the privileged and resilient status of early letter encoding in visual word recognition. Full article

(This article belongs to the Special Issue Language Dysfunction in Posterior Cortical Atrophy)

Journal Description

Brain Sciences

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI