Brain Sciences

3 pages, 148 KiB

Open AccessCorrection

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

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

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

Abstract

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

(This article belongs to the Section Neurodegenerative Diseases)

16 pages, 2443 KiB

Open AccessArticle

Contralateral Structure and Molecular Response to Severe Unilateral Brain Injury

by Xixian Liao, Xiaojian Xu, Ming Li, Runfa Tian, Yuan Zhuang and Guoyi Gao

Brain Sci. 2025, 15(8), 837; https://doi.org/10.3390/brainsci15080837 (registering DOI) - 5 Aug 2025

Abstract

Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, [...] Read more.

Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, can help discover potential treatment strategies to promote recovery after severe brain trauma on one side. Methods: In our study, the right motor cortex was surgically removed to simulate severe unilateral brain injury, and changes in glial cells and synaptic structure in the contralateral cortex were subsequently assessed through immunohistological, morphological, and Western blot analyses. We conducted transcriptomic studies to explore changes in gene expression levels associated with the inflammatory response. Results: Seven days after corticotomy, levels of reactive astrocytes and hypertrophic microglia increased significantly in the experimental group, while synapsin-1 and PSD-95 levels in the contralateral motor cortex increased. These molecular changes are associated with structural changes, including destruction of dendritic structures and the encapsulation of astrocytes by synapses. Genome-wide transcriptome analysis showed a significant increase in gene pathways involved in inflammatory responses, synaptic activity, and nerve fiber regeneration in the contralateral cortex after corticorectomy. Key transcription factors such as NF-κB1, Rela, STAT3 and Jun were identified as potential regulators of these contralateral changes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the mRNA expression levels of Cacna1c, Tgfb1 and Slc2a1 genes related to STAT3, JUN, and NF-κB regulation significantly increased in the contralateral cortex of the experimental group. Conclusions: After unilateral brain damage occurs, changes in the contralateral cerebral hemisphere are closely related to processes involving inflammation and synaptic function. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms Regulating Neuronal Function, Homeostasis, and Disease)

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10 pages, 209 KiB

Open AccessArticle

“Hangry” in Forensic Psychiatry? Analysis of the Relationship Between Eating Disorders and Aggressive Behavior in Patients with Substance Use Disorders

by Judith Streb, Tinatin Deisenhofer, Samira Schneider, Victoria Peters and Manuela Dudeck

Brain Sci. 2025, 15(8), 836; https://doi.org/10.3390/brainsci15080836 (registering DOI) - 4 Aug 2025

Abstract

Background/Objectives: Substance use disorders and eating disorders frequently co-occur and are both associated with increased aggression. As a result, individuals with these conditions are overrepresented in prison populations. The present study investigated whether symptoms of eating disorders in male forensic psychiatric inpatients [...] Read more.

Background/Objectives: Substance use disorders and eating disorders frequently co-occur and are both associated with increased aggression. As a result, individuals with these conditions are overrepresented in prison populations. The present study investigated whether symptoms of eating disorders in male forensic psychiatric inpatients with substance use disorders are associated with heightened aggression. To this end, various forms of aggressive behavior—including spontaneous and reactive aggression, excitability, and violent offenses—were analyzed. Methods: Fifty-six male patients from two forensic psychiatric hospitals in Germany participated in the study. Symptoms of eating disorders were evaluated with the German version of the Eating Disorder Examination Questionnaire (EDE-Q), and aggression was measured with the Short Questionnaire for the Assessment of Aggression Factors (K-FAF) and by considering the violent index offense. Data were analyzed by generalized linear models, with age and body mass index (BMI) included as covariates. Results: Higher EDE-Q scores significantly predicted increased spontaneous aggression and excitability. However, no significant association was found between eating disorder symptoms and reactive aggression or the likelihood of a violent index offense. Age and BMI did not significantly influence any aggression subscales. Conclusions: The findings suggest that in patients with substance use disorder, eating disorder symptoms may be linked to heightened internalized forms of aggression. These results support the clinical relevance of screening for eating disorder symptoms in forensic psychiatric settings and integrating dietary interventions into therapeutic efforts to manage aggression. Full article

(This article belongs to the Special Issue Substance Abuse in the Psychiatric Population)

27 pages, 1766 KiB

Open AccessArticle

A Novel Optimized Hybrid Deep Learning Framework for Mental Stress Detection Using Electroencephalography

by Maithili Shailesh Andhare, T. Vijayan, B. Karthik and Shabana Urooj

Brain Sci. 2025, 15(8), 835; https://doi.org/10.3390/brainsci15080835 (registering DOI) - 4 Aug 2025

Abstract

Mental stress is a psychological or emotional strain that typically occurs because of threatening, challenging, and overwhelming conditions and affects human behavior. Various factors, such as professional, environmental, and personal pressures, often trigger it. In recent years, various deep learning (DL)-based schemes using [...] Read more.

Mental stress is a psychological or emotional strain that typically occurs because of threatening, challenging, and overwhelming conditions and affects human behavior. Various factors, such as professional, environmental, and personal pressures, often trigger it. In recent years, various deep learning (DL)-based schemes using electroencephalograms (EEGs) have been proposed. However, the effectiveness of DL-based schemes is challenging because of the intricate DL structure, class imbalance problems, poor feature representation, low-frequency resolution problems, and complexity of multi-channel signal processing. This paper presents a novel hybrid DL framework, BDDNet, which combines a deep convolutional neural network (DCNN), bidirectional long short-term memory (BiLSTM), and deep belief network (DBN). BDDNet provides superior spectral–temporal feature depiction and better long-term dependency on the local and global features of EEGs. BDDNet accepts multiple EEG features (MEFs) that provide the spectral and time-domain features of EEGs. A novel improved crow search algorithm (ICSA) was presented for channel selection to minimize the computational complexity of multichannel stress detection. Further, the novel employee optimization algorithm (EOA) is utilized for the hyper-parameter optimization of hybrid BDDNet to enhance the training performance. The outcomes of the novel BDDNet were assessed using a public DEAP dataset. The BDDNet-ICSA offers improved recall of 97.6%, precision of 97.6%, F1-score of 97.6%, selectivity of 96.9%, negative predictive value NPV of 96.9%, and accuracy of 97.3% to traditional techniques. Full article

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

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34 pages, 1876 KiB

Open AccessArticle

The Interaction of Target and Masker Speech in Competing Speech Perception

by Sheyenne Fishero, Joan A. Sereno and Allard Jongman

Brain Sci. 2025, 15(8), 834; https://doi.org/10.3390/brainsci15080834 (registering DOI) - 4 Aug 2025

Abstract

Background/Objectives: Speech perception typically takes place against a background of other speech or noise. The present study investigates the effectiveness of segregating speech streams within a competing speech signal, examining whether cues such as pitch, which typically denote a difference in talker, [...] Read more.

Background/Objectives: Speech perception typically takes place against a background of other speech or noise. The present study investigates the effectiveness of segregating speech streams within a competing speech signal, examining whether cues such as pitch, which typically denote a difference in talker, behave in the same way as cues such as speaking rate, which typically do not denote the presence of a new talker. Methods: Native English speakers listened to English target speech within English two-talker babble of a similar or different pitch and/or a similar or different speaking rate to identify whether mismatched properties between target speech and masker babble improve speech segregation. Additionally, Dutch and French masker babble was tested to identify whether an unknown language masker improves speech segregation capacity and whether the rhythm patterns of the unknown language modulate the improvement. Results: Results indicated that a difference in pitch or speaking rate between target and masker improved speech segregation, but when both pitch and speaking rate differed, only a difference in pitch improved speech segregation. Results also indicated improved speech segregation for an unknown language masker, with little to no role of rhythm pattern of the unknown language. Conclusions: This study increases the understanding of speech perception in a noisy ecologically valid context and suggests that there is a link between a cue’s potential to denote a new speaker and its ability to aid in speech segregation during competing speech perception. Full article

(This article belongs to the Special Issue Language Perception and Processing)

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20 pages, 681 KiB

Open AccessReview

Unraveling Glioblastoma Heterogeneity: Advancing Immunological Insights and Therapeutic Innovations

by Joshua H. Liu, Maksym Horiachok, Santosh Guru and Cecile L. Maire

Brain Sci. 2025, 15(8), 833; https://doi.org/10.3390/brainsci15080833 (registering DOI) - 2 Aug 2025

Abstract

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new [...] Read more.

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article

(This article belongs to the Special Issue Recent Advances in Translational Neuro-Oncology)

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11 pages, 770 KiB

Open AccessArticle

Acute Ischemic Stroke Treatment in Germany (2015–2023): Nationwide Trends in Thrombolysis and Thrombectomy by Age and Sex

by Sara Hirsch, Karel Kostev, Christian Tanislav and Ali Hammed

Brain Sci. 2025, 15(8), 832; https://doi.org/10.3390/brainsci15080832 (registering DOI) - 2 Aug 2025

Abstract

Background: The implementation of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in acute ischemic stroke (AIS) has proven effective, offering significant benefits for patient outcomes. We therefore investigated trends in the implementation of IVT and MT in Germany between 2015 and 2023. Methods: [...] Read more.

Background: The implementation of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in acute ischemic stroke (AIS) has proven effective, offering significant benefits for patient outcomes. We therefore investigated trends in the implementation of IVT and MT in Germany between 2015 and 2023. Methods: We conducted a retrospective analysis using German Diagnosis-Related Group (DRG) statistics from 2015 to 2023. Treatment numbers were analyzed annually based on OPS codes. We examined the age and sex distribution of patients undergoing these treatments. Additionally, we analyzed all hospital cases coded with ICD-10 for acute ischemic stroke (AIS). Results: Between 2015 and 2023, the number of AIS cases in Germany slightly declined from 250,802 to 248,107 (−1.1%), with the largest annual decrease (−4.3%) occurring during the COVID-19 pandemic (2019–2020). Despite this, the use of IVT increased from 40,766 cases (16.25%) in 2015 to 48,378 (19.50%) in 2023. MT usage rose even more sharply, from 7840 cases (3.13%) to 22,445 (9.05%). Among MT recipients, the proportion of patients aged ≥80 years rose significantly, from 27.2% to 42.1%. In this age group, women consistently comprised the majority of MT patients—65.4% in 2015 and 65.5% in 2023. Conclusions: Despite a stable stroke incidence, the use of IVT—and particularly MT—continued to increase in Germany from 2015 to 2023, even during the COVID-19 pandemic. MT usage nearly tripled, especially among patients aged ≥80 years. These trends highlight a resilient stroke care system and underscore the need for future planning to meet the rising demand for endovascular treatment in an aging population. Full article

(This article belongs to the Special Issue Management of Acute Stroke)

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30 pages, 919 KiB

Open AccessSystematic Review

Advances in Research on Brain Structure and Activation Characteristics in Patients with Anterior Cruciate Ligament Reconstruction: A Systematic Review

by Jingyi Wang, Yaxiang Jia, Qiner Li, Longhui Li, Qiuyu Dong and Quan Fu

Brain Sci. 2025, 15(8), 831; https://doi.org/10.3390/brainsci15080831 (registering DOI) - 1 Aug 2025

Abstract

Objectives: To synthesize evidence on structural and functional neuroplasticity in patients after anterior cruciate ligament reconstruction (ACLR) and its clinical implications. Methods: Adhering to the PRISMA guidelines for systematic reviews and meta-analyses, a literature search was conducted using PubMed, Embase, Web of [...] Read more.

Objectives: To synthesize evidence on structural and functional neuroplasticity in patients after anterior cruciate ligament reconstruction (ACLR) and its clinical implications. Methods: Adhering to the PRISMA guidelines for systematic reviews and meta-analyses, a literature search was conducted using PubMed, Embase, Web of Science, Scopus, and Cochrane CENTRAL (2018–2025) using specific keyword combinations, screening the results based on predetermined inclusion and exclusion criteria. Results: Among the 27 included studies were the following: (1) sensory cortex reorganization with compensatory visual dependence (5 EEG/fMRI studies); (2) reduced motor cortex efficiency evidenced by elevated AMT (TMS, 8 studies) and decreased γ-CMC (EEG, 3 studies); (3) progressive corticospinal tract degeneration (increased radial diffusivity correlating with postoperative duration); (4) enhanced sensory-visual integration correlated with functional recovery. Conclusions: This review provides a novel synthesis of evidence from transcranial magnetic stimulation (TMS), electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), diffusion tensor imaging (DTI), and functional magnetic resonance imaging (fMRI) studies. It delineates characteristic patterns of post-ACLR structural and functional neural reorganization. Targeting visual–cognitive integration and corticospinal facilitation may optimize rehabilitation. Full article

(This article belongs to the Special Issue Diagnosis, Therapy and Rehabilitation in Neuromuscular Diseases)

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15 pages, 1033 KiB

Open AccessArticle

Transcranial Pulse Stimulation in Alzheimer’s: Long-Term Feasibility and a Multifocal Treatment Approach

by Celine Cont-Richter, Nathalie Stute, Anastasia Galli, Christina Schulte and Lars Wojtecki

Brain Sci. 2025, 15(8), 830; https://doi.org/10.3390/brainsci15080830 (registering DOI) - 1 Aug 2025

Abstract

Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and [...] Read more.

Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and potential cognitive benefits of TPS over one year in patients with Alzheimer’s disease, focusing on domains such as memory, speech, orientation, visuo-construction, and depressive symptoms. Methods: We analyzed preliminary data from the first ten out of thirty-five patients enrolled in a prospective TPS study who completed one year of follow-up and were included in a dedicated long-term database. The protocol consisted of six initial TPS sessions over two weeks, followed by monthly booster sessions delivering 6000 pulses each for twelve months. Patients underwent regular neuropsychological assessments using the Alzheimer Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI-II). All adverse events (AEs) were documented and monitored throughout the study. Results: Adverse events occurred in less than 1% of stimulation sessions and mainly included mild focal pain or transient unpleasant sensations, as well as some systemic behavioral or vigilance changes, particularly in patients with underlying medical conditions, with some potentially related to the device’s stimulation as adverse device reactions (ADRs). Cognitive test results showed significant improvement after the initial stimulation cycle (ADAS total improved significantly after the first stimulation cycle (M_pre = 28.44, M_post = 18.56; p = 0.001, d = 0.80, 95% CI (0.36, 1.25)), with stable scores across all domains over one year. Improvements were most notable in memory, speech, and mood. Conclusions: TPS appears to be a generally safe and feasible add-on treatment for AD, although careful patient selection and monitoring are advised. While a considerable number of participants were lost to follow-up for various reasons, adverse events and lack of treatment effect were unlikely primary causes. A multifocal stimulation approach (F-TOP2) is proposed to enhance effects across more cognitive domains. Full article

(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)

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29 pages, 3958 KiB

Open AccessArticle

Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy

by Somaiyeh Azmoun, Freeman C. Lewis, Daniel Shoieb, Yan Jin, Elena Colicino, Isha Mhatre-Winters, Haiwei Gu, Hari Krishnamurthy, Jason R. Richardson, Donatella Placidi, Luca Lambertini and Roberto G. Lucchini

Brain Sci. 2025, 15(8), 829; https://doi.org/10.3390/brainsci15080829 (registering DOI) - 31 Jul 2025

Abstract

Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on [...] Read more.

Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m³ (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article

(This article belongs to the Special Issue From Bench to Bedside: Motor–Cognitive Interactions—2nd Edition)

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18 pages, 778 KiB

Open AccessArticle

The Effects of Handedness Consistency on the Identification of Own- and Cross-Race Faces

by Raymond P. Voss, Jr., Ryan Corser, Stephen Prunier and John D. Jasper

Brain Sci. 2025, 15(8), 828; https://doi.org/10.3390/brainsci15080828 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: People are better at recognizing the faces of racial in-group members than out-group members. This own-race bias relies on pattern recognition and memory processes, which rely on hemispheric specialization. We hypothesized that handedness, a proxy for hemispheric specialization, would moderate own-race [...] Read more.

Background/Objectives: People are better at recognizing the faces of racial in-group members than out-group members. This own-race bias relies on pattern recognition and memory processes, which rely on hemispheric specialization. We hypothesized that handedness, a proxy for hemispheric specialization, would moderate own-race bias. Specifically, consistently handed individuals perform better on tasks that require the hemispheres to work independently, while inconsistently handed individuals perform better on tasks that require integration. This led to the hypothesis that inconsistently handed individuals would show less own-race bias, driven by an increase in accuracy. Methods: 281 participants completed the study in exchange for course credit. Of those, the sample was isolated to Caucasian (174) and African American individuals (41). Participants were shown two target faces (one Caucasian and one African American), given several distractor tasks, and then asked to identify the target faces during two sequential line-ups, each terminating when participants made an identification judgment. Results: Continuous handedness score and the match between participant race and target face race were entered into a binary logistic regression predicting correct/incorrect identifications. The overall model was statistically significant, Χ² (3, N = 430) = 11.036, p = 0.012, Nagelkerke R² = 0.038, culminating in 76% correct classifications. Analyses of the parameter estimates showed that the racial match, b = 0.53, SE = 0.23, Wald Χ² (1) = 5.217, p = 0.022, OR = 1.703 and the interaction between handedness and the racial match, b = 0.51, SE = 0.23, Wald test = 4.813, p = 0.028, OR = 1.671 significantly contributed to the model. The model indicated that the probability of identification was similar for own- or cross-race targets amongst inconsistently handed individuals. Consistently handed individuals, by contrast, showed an increase in accuracy for the own-race target and a decrease in accuracy for cross-race targets. Conclusions: Results partially supported the hypotheses. Inconsistently handed individuals did show less own-race bias. This finding, however, seemed to be driven by differences in accuracy amongst consistently handed individuals rather than a hypothesized increase in accuracy amongst inconsistently handed individuals. Underlying hemispheric specialization, as measured by proxy with handedness, may impact the own-race bias in facial recognition. Future research is required to investigate the mechanisms, however, as the directional differences were different than hypothesized. Full article

(This article belongs to the Special Issue Advances in Face Perception and How Disorders Affect Face Perception)

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18 pages, 616 KiB

Open AccessReview

Reinforcing Gaps? A Rapid Review of Innovation in Borderline Personality Disorder (BPD) Treatment

by Lionel Cailhol, Samuel St-Amour, Marie Désilets, Nadine Larivière, Jillian Mills and Rémy Klein

Brain Sci. 2025, 15(8), 827; https://doi.org/10.3390/brainsci15080827 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: Borderline Personality Disorder (BPD) involves emotional dysregulation, interpersonal instability and impulsivity. Although treatments have advanced, evaluating the latest innovations remains essential. This rapid review aimed to (1) identify and classify recent therapeutic innovations for BPD, (2) assess their effects on clinical [...] Read more.

Background/Objectives: Borderline Personality Disorder (BPD) involves emotional dysregulation, interpersonal instability and impulsivity. Although treatments have advanced, evaluating the latest innovations remains essential. This rapid review aimed to (1) identify and classify recent therapeutic innovations for BPD, (2) assess their effects on clinical and functional outcomes, and (3) highlight research gaps to inform future priorities. Methods: Employing a rapid review design, we searched PubMed/MEDLINE, PsycINFO, and Embase for publications from 1 January 2019 to 28 March 2025. Eligible studies addressed adult or adolescent BPD populations and novel interventions—psychotherapies, pharmacological agents, digital tools, and neuromodulation. Two independent reviewers conducted screening, full-text review, and data extraction using a standardised form. Results: Sixty-nine studies—predominantly from Europe and North America—were included. Psychotherapeutic programmes dominated, ranging from entirely novel models to adaptations of established treatments (for example, extended or modified Dialectical Behavior Therapy). Pharmacological research offered fresh insights, particularly into ketamine, while holistic approaches such as adventure therapy and digital interventions also emerged. Most investigations centred on symptom reduction; far fewer examined psychosocial functioning, mortality, or social inclusion. Conclusions: Recent innovations show promise in BPD treatment but underserve the needs of mortality and societal-level outcomes. Future research should adopt inclusive, equity-focused agendas that align with patient-centred and recovery-oriented goals, supported by a coordinated, integrated research strategy. Full article

(This article belongs to the Section Neuropsychiatry)

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12 pages, 937 KiB

Open AccessTechnical Note

Usefulness of Direct Auricular Artery Injection as Refinement of the Well-Established Rabbit Blood Shunt Subarachnoid Hemorrhage Model

by Stefan Wanderer, Michael von Gunten, Daniela Casoni, Stefano Di Santo, Jürgen Konczalla and Ali-Reza Fathi

Brain Sci. 2025, 15(8), 826; https://doi.org/10.3390/brainsci15080826 (registering DOI) - 31 Jul 2025

Abstract

Introduction: Given the impact of aneurysmal subarachnoid hemorrhage (aSAH) on patients’ health, preclinical research is substantial to understand its pathophysiology and improve treatment strategies, which necessitates reliable and comprehensive animal models. Traditionally, aSAH models utilize iliac or subclavian access for angiography, requiring invasive [...] Read more.

Introduction: Given the impact of aneurysmal subarachnoid hemorrhage (aSAH) on patients’ health, preclinical research is substantial to understand its pathophysiology and improve treatment strategies, which necessitates reliable and comprehensive animal models. Traditionally, aSAH models utilize iliac or subclavian access for angiography, requiring invasive procedures that are associated with significant risks and animal burden. This pilot study explores a less invasive method of digital subtraction angiography (DSA) by using the auricular artery (AA) as an alternative access point. Our aim was to demonstrate the feasibility of this refined technique, with the intention of reducing procedural risks, providing shorter operation times with enhanced neurological recovery, and simplifying the process for both researchers and animals. Materials and Methods: In this study, six female New Zealand white rabbits (3.2–4.1 kg body weight) underwent experimental induction of aSAH via a subclavian-cisternal shunt. The initial steps of this procedure followed traditional techniques, consisting of subclavian access through microsurgical preparation, followed by DSA to analyze retrograde filling of the basilar artery (BA). To evaluate the alternative method, on day 3 after induction of aSAH, DSA was performed via the AA instead of the traditional subclavian or femoral access. A catheter was placed in the AA to allow retrograde filling of the BA. This approach aimed to simplify the procedure while maintaining comparable imaging quality. Results: All rabbits survived until the study endpoint. Postoperatively, two rabbits showed signs of hemisyndrome, which significantly improved by the time of follow-up. No additional morbidities were observed. Upon euthanasia and necropsy, all animals showed clear subarachnoid bleeding patterns. DSA via the AA produced strong contrasting of the BA comparable to the traditional method. Conclusions: This technical note presents an initial evaluation of AA access as a feasible and potentially advantageous method for DSA in a rabbit model of blood shunt subarachnoid hemorrhage. The method shows promise in reducing invasiveness and procedural complexity, but further studies are required to fully establish its efficacy and safety. Future research should focus on expanding the sample size, refining the anatomical understanding of the AA, and continuing to align with ethical considerations regarding animal welfare. Full article

(This article belongs to the Special Issue Current Research in Neurosurgery)

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18 pages, 2207 KiB

Open AccessArticle

CSF1R-Dependent Microglial Repopulation and Contact-Dependent Inhibition of Proliferation In Vitro

by Rie Nakai, Kuniko Kohyama, Yasumasa Nishito and Hiroshi Sakuma

Brain Sci. 2025, 15(8), 825; https://doi.org/10.3390/brainsci15080825 (registering DOI) - 31 Jul 2025

Abstract

Murine microglia exhibit rapid self-renewal upon removal from the postnatal brain. However, the signaling pathways that regulate microglial repopulation remain largely unclear. To address this knowledge gap, we depleted microglia from mixed glial cultures using anti-CD11b magnetic particles and cultured them for 4 [...] Read more.

Murine microglia exhibit rapid self-renewal upon removal from the postnatal brain. However, the signaling pathways that regulate microglial repopulation remain largely unclear. To address this knowledge gap, we depleted microglia from mixed glial cultures using anti-CD11b magnetic particles and cultured them for 4 weeks to monitor their repopulation ability in vitro. Flow cytometry and immunocytochemistry revealed that anti-CD11b bead treatment effectively eliminated >95% of microglia in mixed glial cultures. Following removal, the number of CX3CR1-positive microglia gradually increased; when a specific threshold was reached, repopulation ceased without any discernable rise in cell death. Cell cycle and 5-ethynyl-2′-deoxyuridine incorporation assays suggested the active proliferation of repopulating microglia at d7. Time-lapse imaging demonstrated post-removal division of microglia. Colony-stimulating factor 1 receptor-phosphoinositide 3-kinase-protein kinase B signaling was identified as crucial for microglial repopulation, as pharmacological inhibition or neutralization of the pathway significantly abrogated repopulation. Transwell cocultures revealed that resident microglia competitively inhibited microglial proliferation probably through contact inhibition. This in vitro microglial removal system provides valuable insights into the mechanisms underlying microglial proliferation. Full article

(This article belongs to the Section Neuroglia)

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Graphical abstract

31 pages, 638 KiB

Open AccessSystematic Review

Exploring the Autistic Brain: A Systematic Review of Diffusion Tensor Imaging Studies on Neural Connectivity in Autism Spectrum Disorder

by Giuseppe Marano, Georgios D. Kotzalidis, Maria Benedetta Anesini, Sara Barbonetti, Sara Rossi, Miriam Milintenda, Antonio Restaino, Mariateresa Acanfora, Gianandrea Traversi, Giorgio Veneziani, Maria Picilli, Tommaso Callovini, Carlo Lai, Eugenio Maria Mercuri, Gabriele Sani and Marianna Mazza

Brain Sci. 2025, 15(8), 824; https://doi.org/10.3390/brainsci15080824 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific [...] Read more.

Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article

(This article belongs to the Special Issue Chronic Non-Infectious Diseases with a High Impact on the Central Nervous System)

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12 pages, 899 KiB

Open AccessArticle

Combining Coronal and Axial DWI for Accurate Diagnosis of Brainstem Ischemic Strokes: Volume-Based Correlation with Stroke Severity

by Omar Alhaj Omar, Mesut Yenigün, Farzat Alchayah, Priyanka Boettger, Francesca Culaj, Toska Maxhuni, Norma J. Diel, Stefan T. Gerner, Maxime Viard, Hagen B. Huttner, Martin Juenemann, Julia Heinrichs and Tobias Braun

Brain Sci. 2025, 15(8), 823; https://doi.org/10.3390/brainsci15080823 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: Brainstem ischemic strokes comprise 10% of ischemic strokes and are challenging to diagnose due to small lesion size and complex presentations. Diffusion-weighted imaging (DWI) is crucial for detecting ischemia, yet it can miss small lesions, especially when only axial slices are employed. [...] Read more.

Background/Objectives: Brainstem ischemic strokes comprise 10% of ischemic strokes and are challenging to diagnose due to small lesion size and complex presentations. Diffusion-weighted imaging (DWI) is crucial for detecting ischemia, yet it can miss small lesions, especially when only axial slices are employed. This study investigated whether ischemic lesions visible in a single imaging plane correspond to smaller volumes and whether coronal DWI enhances detection compared to axial DWI alone. Methods: This retrospective single-center study examined 134 patients with brainstem ischemic strokes between December 2018 and November 2023. All patients underwent axial and coronal DWI. Clinical data, NIH Stroke Scale (NIHSS) scores, and modified Rankin Scale (mRS) scores were recorded. Diffusion-restricted lesion volumes were calculated using multiple models (planimetric, ellipsoid, and spherical), and lesion visibility per imaging plane was analyzed. Results: Brainstem ischemic strokes were detected in 85.8% of patients. Coronal DWI alone identified 6% of lesions that were undetectable on axial DWI; meanwhile, axial DWI alone identified 6.7%. Combining both improved overall sensitivity to 86.6%. Ischemic lesions visible in only one plane were significantly smaller across all volume models. Higher NIHSS scores were strongly correlated with larger diffusion-restricted lesion volumes. Coronal DWI correlated better with clinical severity than axial DWI, especially in the midbrain and medulla. Conclusions: Coronal DWI significantly improves the detection of small brainstem infarcts and should be incorporated into routine stroke imaging protocols. Infarcts visible in only one plane are typically smaller, yet still clinically relevant. Combined imaging enhances diagnostic accuracy and supports early and precise intervention in posterior circulation strokes. Full article

(This article belongs to the Special Issue Management of Acute Stroke)

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18 pages, 2644 KiB

Open AccessArticle

The Synergistic Effect of Heat Therapy and Electroacupuncture Treatment in Inflammatory Pain Mouse Models

by Boon Khai Teoh, Sharmely Sharon Ballon Romero, Tran Van Bao Quach, Hsin-Yi Chung and Yi-Hung Chen

Brain Sci. 2025, 15(8), 822; https://doi.org/10.3390/brainsci15080822 (registering DOI) - 31 Jul 2025

Abstract

Background: Heat therapy (HT) and electroacupuncture (EA) are widely utilized pain relief methods, but the analgesic mechanisms of their combined application remain unclear. Methods: In acetic acid (AA)-induced writhing test and complete Freund’s adjuvant (CFA)-induced inflammatory pain tests, mice received one of three [...] Read more.

Background: Heat therapy (HT) and electroacupuncture (EA) are widely utilized pain relief methods, but the analgesic mechanisms of their combined application remain unclear. Methods: In acetic acid (AA)-induced writhing test and complete Freund’s adjuvant (CFA)-induced inflammatory pain tests, mice received one of three treatments: EA at bilateral ST36, HT via a 45 °C heating pad, or the combination (EA + HT). To probe underlying pathways, separate groups were pretreated with caffeine, DPCPX (a selective adenosine A₁ receptor antagonist), or naloxone (an opioid receptor antagonist). Spinal expression of glial fibrillary acidic protein (GFAP) and phosphorylated p38 (p-p38) was examined by Western blot and immunofluorescence. Results: Both EA and HT individually reduced AA-induced writhing, with the combination (EA + HT) exhibiting the greatest analgesic effect. EA’s analgesic effect was reversed by caffeine and DPCPX and partially by naloxone, while HT’s effect was reversed by caffeine and DPCPX but was unaffected by naloxone. AA injection elevated spinal p-p38 and GFAP expression, which were attenuated by either EA or HT, with the most substantial suppression observed in the EA + HT group. In the CFA model, both treatments alleviated mechanical allodynia, while the combined treatment resulted in significantly greater analgesia compared to either treatment alone. Conclusions: EA combined with HT synergistically enhances analgesia in both AA and CFA pain models, accompanied by reduced spinal inflammation and astrocyte activation. EA’s analgesic effects appear to involve adenosine A₁ receptor pathways and, to a lesser extent, opioid receptor mechanisms, whereas HT’s effects involve adenosine A₁ receptor pathways. Full article

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

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10 pages, 2282 KiB

Open AccessArticle

AI-Assisted Edema Map Optimization Improves Infarction Detection in Twin-Spiral Dual-Energy CT

by Ludwig Singer, Daniel Heinze, Tim Alexius Möhle, Alexander Sekita, Angelika Mennecke, Stefan Lang, Stefan T. Gerner, Stefan Schwab, Arnd Dörfler and Manuel Alexander Schmidt

Brain Sci. 2025, 15(8), 821; https://doi.org/10.3390/brainsci15080821 (registering DOI) - 31 Jul 2025

Abstract

Objective: This study aimed to evaluate whether modifying the post-processing algorithm of Twin-Spiral Dual-Energy computed tomography (DECT) improves infarct detection compared to conventional Dual-Energy CT (DECT) and Single-Energy CT (SECT) following endovascular therapy (EVT) for large vessel occlusion (LVO). Methods: We retrospectively analyzed [...] Read more.

Objective: This study aimed to evaluate whether modifying the post-processing algorithm of Twin-Spiral Dual-Energy computed tomography (DECT) improves infarct detection compared to conventional Dual-Energy CT (DECT) and Single-Energy CT (SECT) following endovascular therapy (EVT) for large vessel occlusion (LVO). Methods: We retrospectively analyzed 52 patients who underwent Twin-Spiral DECT after endovascular stroke therapy. Ten patients were used to generate a device-specific parameter (“y”) using an AI-based neural network (SynthSR). This parameter was integrated into the post-processing algorithm for edema map generation. Quantitative Hounsfield unit (HU) measurements were used to assess density differences in ischemic brain tissue across conventional virtual non-contrast (VNC) images and edema maps. Results: The median HU of infarcted tissue in conventional mixed DECT was 33.73 ± 4.58, compared to 22.96 ± 3.81 in default VNC images. Edema maps with different smoothing filter settings showed values of 14.39 ± 4.96, 14.50 ± 3.75, and 15.05 ± 2.65, respectively. All edema maps demonstrated statistically significant HU differences of infarcted tissue compared to conventional VNC images (

p < 0.001

) while maintaining the density values of non-infarcted brain tissue. Conclusions: Enhancing the post-processing algorithm of conventional virtual non-contrast imaging improves infarct detection compared to standard mixed or virtual non-contrast reconstructions in Dual-Energy CT. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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22 pages, 1589 KiB

Open AccessArticle

Musical Distractions: Music-Based Rhythmic Auditory Stimulation Fails to Improve Gait in Huntington’s Disease

by Sidney T. Baudendistel, Lauren E. Tueth, Allison M. Haussler and Gammon M. Earhart

Brain Sci. 2025, 15(8), 820; https://doi.org/10.3390/brainsci15080820 (registering DOI) - 31 Jul 2025

Abstract

Background/Objectives: Huntington’s disease (HD) is a neurodegenerative disorder involving the basal ganglia and is characterized by psychiatric, cognitive, and movement dysfunction, including gait and balance impairment. Given the limited efficacy of pharmacological treatments for HD motor symptoms, nonpharmacological approaches like rhythmic auditory stimulation [...] Read more.

Background/Objectives: Huntington’s disease (HD) is a neurodegenerative disorder involving the basal ganglia and is characterized by psychiatric, cognitive, and movement dysfunction, including gait and balance impairment. Given the limited efficacy of pharmacological treatments for HD motor symptoms, nonpharmacological approaches like rhythmic auditory stimulation are being explored. This study aims to describe walking performance in people with HD during rhythmic auditory stimulation using external musical cues and internal singing cues. Methods: Individuals in the manifest stage of HD performed walking in four conditions: (1) comfortable pace, (2) cognitive dual task, (3) musical cue (music was played aloud), and (4) singing cue (participants sang aloud). Sensors measured cadence, velocity, stride length, and variability. Relationships between change in cadence and motor and cognitive measures were explored. Results: While no direct measurements of synchronization were performed, limiting our interpretation, neither the external musical cue nor the singing cue significantly improved walking performance. Both cues increased variability, similar to what was observed during the dual task. Greater subjective balance confidence and better cognitive performance were associated with positive cadence change during cueing. Conclusions: Musical cues may be too cognitively demanding for individuals with Huntington’s disease as they worsen gait variability without increasing gait speed, cadence, or stride length. Although global cognition and perceived balance confidence were related to the ability to increase cadence, very few people were able to increase their cadence during either cue. Therefore, the results do not support the use of musical cues to improve gait for individuals with Huntington’s disease. Full article

(This article belongs to the Special Issue Focusing on the Rhythmic Interventions in Movement Disorders)

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