Previous Issue
Volume 15, April
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.8
2.7
Journals
Brain Sciences
Volume 15
Issue 5
share announcement

Brain Sci., Volume 15, Issue 5 (May 2025) – 54 articles

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
17 pages, 412 KiB  
Article
Cross-Cultural Biases of Emotion Perception in Music
by Marjorie G. Li, Kirk N. Olsen and William Forde Thompson
Brain Sci. 2025, 15(5), 477; https://doi.org/10.3390/brainsci15050477 (registering DOI) - 29 Apr 2025
Abstract
Objectives: Emotion perception in music is shaped by cultural background, yet the extent of cultural biases remains unclear. This study investigated how Western listeners perceive emotion in music across cultures, focusing on the accuracy and intensity of emotion recognition and the musical features [...] Read more.
Objectives: Emotion perception in music is shaped by cultural background, yet the extent of cultural biases remains unclear. This study investigated how Western listeners perceive emotion in music across cultures, focusing on the accuracy and intensity of emotion recognition and the musical features that predict emotion perception. Methods: White-European (Western) listeners from the UK, USA, New Zealand, and Australia (N = 100) listened to 48 ten-second excerpts of Western classical and Chinese traditional bowed-string music that were validated by experts to convey happiness, sadness, agitation, and calmness. After each excerpt, participants rated the familiarity, enjoyment, and perceived intensity of the four emotions. Musical features were computationally extracted for regression analyses. Results: Western listeners experienced Western classical music as more familiar and enjoyable than Chinese music. Happiness and sadness were recognised more accurately in Western classical music, whereas agitation was more accurately identified in Chinese music. The perceived intensity of happiness and sadness was greater for Western classical music; conversely, the perceived intensity of agitation was greater for Chinese music. Furthermore, emotion perception was influenced by both culture-shared (e.g., timbre) and culture-specific (e.g., dynamics) musical features. Conclusions: Our findings reveal clear cultural biases in the way individuals perceive and classify music, highlighting how these biases are shaped by the interaction between cultural familiarity and the emotional and structural qualities of the music. We discuss the possibility that purposeful engagement with music from diverse cultural traditions—especially in educational and therapeutic settings—may cultivate intercultural empathy and an appreciation of the values and aesthetics of other cultures. Full article
(This article belongs to the Special Issue Advances in Emotion Processing and Cognitive Neuropsychology)
16 pages, 3834 KiB  
Article
Reward System EEG–fMRI-Pattern Neurofeedback for Major Depressive Disorder with Anhedonia: A Multicenter Pilot Study
by Daniela Amital, Raz Gross, Nadav Goldental, Eyal Fruchter, Haya Yaron-Wachtel, Aron Tendler, Yaki Stern, Lisa Deutsch, Jeffrey D. Voigt, Talma Hendler, Tal Harmelech, Neomi Singer and Haggai Sharon
Brain Sci. 2025, 15(5), 476; https://doi.org/10.3390/brainsci15050476 - 29 Apr 2025
Abstract
Background/Objectives: Up to 75% of patients with major depressive disorder (MDD) exhibit persistent anhedonia symptoms related to abnormalities in the positive valence system. Cumulative evidence points to brain dysfunction in the reward system (RS), including in the ventral striatum, in patients with MDD [...] Read more.
Background/Objectives: Up to 75% of patients with major depressive disorder (MDD) exhibit persistent anhedonia symptoms related to abnormalities in the positive valence system. Cumulative evidence points to brain dysfunction in the reward system (RS), including in the ventral striatum, in patients with MDD with anhedonia. This study aims to evaluate the safety and efficacy of a novel neurofeedback (NF) device (termed Prism) which incorporates the EEG–FRI-Pattern biomarker of the reward system (RS-EFP) for use in self-neuromodulation training (RS-EFP-NF) for alleviating depression in patients with MDD with anhedonia. Methods: A total of 49 adults (age range: M = 39.9 ± 11.03) with a DSM-5 diagnosis of MDD with anhedonia (per a SHAPS-C score ≥ 25) were screened for the administration of ten sessions of RS-EFP-NF twice a week on nonconsecutive days. Depression and anhedonia severity was assessed, respectively, by HDRS-17 and SHAPS-C at baseline, midway, and treatment end. Results: A total of 34 patients (77%) completed the protocol and were included in the analyses. No device-related adverse events were serious or required treatment. Depression symptoms were reduced at end of treatment as indicated by the HDRS-17, with a reduction of eight points on average (95% CI: −10.5 to −5.41, p < 0.0001), a clinical improvement rate of 78.47%, and a remission rate of 32.25%. Anhedonia, as indicated by the SHAPS-C score, was diminished, showing an average reduction of 6.3 points (95% CI: −8.51 to −4.14, p < 0.0001). Conclusions: Self-neuromodulation using RS-EFP-NF is a promising and safe treatment for MDD with anhedonia. The intervention demonstrates substantial clinical effects on both depression and anhedonia symptoms, with high patient acceptability and retention. Prism may address a critical mechanism-driven treatment gap for anhedonia that often persists despite conventional therapies. Larger controlled implementation, efficacy, and dosing studies are warranted. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
►▼ Show Figures

Figure 1

3 pages, 132 KiB  
Editorial
Application of Nerve Stimulation: Current Status and Future Directions
by Hee Young Kim and Younbyoung Chae
Brain Sci. 2025, 15(5), 475; https://doi.org/10.3390/brainsci15050475 - 29 Apr 2025
Abstract
Neuromodulation is frequently used to modulate neuronal activity and influence brain function [...] Full article
(This article belongs to the Special Issue Application of Nerve Stimulation: Current Status and Future Directions)
40 pages, 5811 KiB  
Review
Metabolic Dysfunction and Dietary Interventions in Migraine Management: The Role of Insulin Resistance and Neuroinflammation—A Narrative and Scoping Review
by Cinzia Cavestro
Brain Sci. 2025, 15(5), 474; https://doi.org/10.3390/brainsci15050474 - 29 Apr 2025
Abstract
Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, [...] Read more.
Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, it has been known that certain foods can trigger migraine attacks, which led for many years to the recommendation of elimination diets—now understood to primarily target histamine-rich foods. Over the past two decades, attention has shifted toward underlying metabolic disturbances, leading to the development of dietary approaches specifically aimed at addressing these dysfunctions. Methods: A scoping literature review was conducted using PubMed and Embase to evaluate the relationships among migraine, insulin-related mechanisms, neurogenic inflammation, and dietary interventions. Initial searches focused on “MIGRAINE AND (neurogenic inflammation)” (2019–15 April 2025), followed by expanded searches from 1950 onward using terms such as “MIGRAINE AND (insulin, insulin resistance, hyperinsulinism)”, and “MIGRAINE AND (diet, dietary, nutrition, nutritional)”. A specific search also targeted “(INSULIN OR insulin resistance OR hyperinsulinism) AND (neurogenic inflammation)”. Abstracts were screened, full texts were retrieved, and duplicates or irrelevant publications were excluded. No filters were applied by article type or language. Systematic reviews and meta-analyses were prioritized when available. Results: Migraine pathogenesis involves trigeminovascular system activation, neurogenic inflammation mediated by CGRP and PACAP, immune dysregulation, mast cell activation, and cortical spreading depression (CSD). Emerging evidence highlights significant associations between migraine, insulin resistance, and hyperinsulinism. Hyperinsulinism contributes to migraine through TRPV1 sensitization, increased CGRP release, oxidative stress, mitochondrial dysfunction, and systemic inflammation. Metabolic dysfunction, including obesity and insulin resistance, exacerbates migraine severity and frequency. Dietary interventions, particularly anti-inflammatory, Mediterranean, and ketogenic diets, show promise in reducing migraine frequency and severity through mechanisms involving reduced inflammation, oxidative stress, improved mitochondrial function, and glucose metabolism stabilization. Conclusions: The interplay between insulin resistance, metabolic dysfunction, and neuroinflammation is crucial in migraine pathophysiology. Targeted dietary interventions, including ketogenic and Mediterranean diets, demonstrate significant potential in managing migraines, emphasizing the need for personalized nutritional strategies to optimize therapeutic outcomes. Full article
(This article belongs to the Special Issue Advances in Neuroinflammation and Pain Medicine)
►▼ Show Figures

Graphical abstract

16 pages, 8001 KiB  
Article
Epitranscriptomic Analysis of the Ventral Hippocampus in a Mouse Model of Post-Traumatic Stress Disorder Following Deep Brain Stimulation Treatment of the Basolateral Amygdala
by Mingxi Ma, Hao Fan, Hui Zhang, Yao Yin, Yizheng Wang and Yan Gao
Brain Sci. 2025, 15(5), 473; https://doi.org/10.3390/brainsci15050473 - 29 Apr 2025
Abstract
Background: Basolateral amygdala (BLA) deep brain stimulation (DBS) has been shown to alleviate the symptoms of post-traumatic stress disorder (PTSD), but the specific mechanisms remain incompletely understood. The hippocampus, a brain region closely connected to the amygdala, plays a key role in the [...] Read more.
Background: Basolateral amygdala (BLA) deep brain stimulation (DBS) has been shown to alleviate the symptoms of post-traumatic stress disorder (PTSD), but the specific mechanisms remain incompletely understood. The hippocampus, a brain region closely connected to the amygdala, plays a key role in the pathological processes of PTSD. The N6-methyladenosine (m6A) methylation of RNAs in the hippocampus is known to play a significant role in regulating the brain’s response to stress and emotional disorders. Methods: This study aimed to comprehensively analyze the roles of transcriptome-wide m6A modifications of the hippocampus in the BLA DBS treatment of a PTSD mouse model using m6A sequencing. Results: Significant alterations in functional connectivity between the ventral hippocampus (vHPC) and BLA were observed in foot shock (FS) mice through functional magnetic resonance imaging (fMRI) analysis. Furthermore, we observed that the expression of the key m6A methyltransferase enzyme, METTL3, in the FS and BLA DBS groups was higher than that in the control group. At the same time, both FS and BLA DBS induced the widespread m6A methylation of RNAs in the vHPC. Gene ontology (GO) enrichment analysis revealed that FS altered methylation in metabolic, developmental, and cytoskeletal pathways, while BLA DBS targeted metabolic, cell cycle, and neuroplasticity-related genes. Additionally, BLA DBS reversed the aberrant methylation of genes associated with multiple functional pathways induced by FS, including those related to cholinergic transmission, sodium and calcium ion homeostasis, and stress hormone responsiveness. We identified a set of RNAs with methylation changes that were reversed by BLA DBS in the FS vs. Ctrl (control) comparison, including those associated with cholinergic transmission, sodium and calcium ion balance, and stress hormone response. Additionally, we detected several specific BLA DBS-related genes through MeRIP-qPCR, indicating that DBS influences crucial genes linked to calcium signaling and synaptic plasticity. Conclusions: We draw two conclusions from these findings: BLA DBS may alleviate PTSD-like symptoms by reversing FS-induced methylation changes and by altering the methylation levels of crucial genes. These findings indicate that epigenetic m6A modifications in the vHPC may play an important role in the amelioration of PTSD using BLA DBS. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
►▼ Show Figures

Figure 1

11 pages, 4714 KiB  
Case Report
Cerebral Amyloid Angiopathy Related Inflammation: A Single-Center Case Series Analysis
by Syed Zahid Ali, Hanah Alley, James Johnson, Harshini Sirvisetty, Michael Sowell, Alex Glynn and Peter Hedera
Brain Sci. 2025, 15(5), 472; https://doi.org/10.3390/brainsci15050472 - 29 Apr 2025
Abstract
Background: Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare subtype of cerebral amyloid angiopathy (CAA), which presents mostly as a subacute and reversible encephalopathy. Primary symptoms include behavioral changes and cognitive decline in the form of rapidly progressive dementia, headache, seizures, and focal [...] Read more.
Background: Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare subtype of cerebral amyloid angiopathy (CAA), which presents mostly as a subacute and reversible encephalopathy. Primary symptoms include behavioral changes and cognitive decline in the form of rapidly progressive dementia, headache, seizures, and focal neurological deficits. It can also manifest as a varied range of typical and atypical presentations. Misdiagnosis is common because it shares symptoms with other infectious, ischemic and autoimmune pathologies and there is also a significant overlap of MRI findings. Methods: Gold standard diagnosis requires brain biopsy in appropriate clinical setting, but diagnostic criteria is established for probable and possible CAA-RI using clinical symptoms and MRI findings in the absence of other inflammatory, infectious or autoimmune processes. Immunomodulatory therapy is the mainstay of treatment, with variable response. Results: We present a case series of three patients with CAA-RI highlighting disease course, neuroradiological manifestation, treatment response, and clinical outcomes. We also provide a literature review to increase insight into this rare pathology. Conclusions: Early diagnosis and prompt initiation of immunosuppressive therapy is beneficial in most cases. Full article
(This article belongs to the Section Behavioral Neuroscience)
►▼ Show Figures

Figure 1

13 pages, 1616 KiB  
Review
Neurophysiological Markers of Reward Processing Can Inform Preclinical Neurorehabilitation Approaches for Cognitive Impairments Following Brain Injury
by Miranda Francoeur Koloski, Reyana Menon and Victoria Krasnyanskiy
Brain Sci. 2025, 15(5), 471; https://doi.org/10.3390/brainsci15050471 - 29 Apr 2025
Abstract
Brain stimulation therapies may be used to correct motor, social, emotional, and cognitive consequences of traumatic brain injury (TBI). Neuromodulation applied with anatomical specificity can ameliorate desired symptoms while leaving functional circuits intact. Before applying precision medicine approaches, preclinical animal studies are needed [...] Read more.
Brain stimulation therapies may be used to correct motor, social, emotional, and cognitive consequences of traumatic brain injury (TBI). Neuromodulation applied with anatomical specificity can ameliorate desired symptoms while leaving functional circuits intact. Before applying precision medicine approaches, preclinical animal studies are needed to explore potential neurophysiological signatures that could be modulated with neurostimulation. This review discusses potential neural signatures of cognition, particularly reward processing, which is chronically impaired after brain injury. Electrophysiology, compared to other types of biomarkers, can detect deficits missed by structural measures, holds translational potential between humans and animals, and directly informs neuromodulatory treatments. Disturbances in oscillatory activity underscore structural, molecular, and behavioral impairments seen following TBI. For instance, cortico-striatal beta frequency activity (15–30 Hz) during reward processing represents subjective value and is chronically disturbed after frontal TBI in rodents. We use the example of evoked beta oscillations in the cortico-striatal network as a putative marker of reward processing that could be targeted with electrical stimulation to improve decision making after TBI. This review highlights the necessity of collecting electrophysiological data in preclinical models to understand the underlying mechanisms of cognitive behavioral deficits after TBI and to develop targeted stimulation treatments in humans. Full article
(This article belongs to the Special Issue The Application of EEG in Neurorehabilitation)
►▼ Show Figures

Figure 1

13 pages, 1139 KiB  
Article
A Crossover Study of Virtual Reality Exposure for Emotional and Physiological Regulation in Mild Dementia
by Paula Latorre, Cleiton Pons Ferreira and Francisco Nieto-Escamez
Brain Sci. 2025, 15(5), 470; https://doi.org/10.3390/brainsci15050470 - 28 Apr 2025
Viewed by 28
Abstract
(1) Background: Immersive virtual reality (IVR) has emerged as a promising non-pharmacological intervention to promote relaxation and improve emotional well-being in this population. (2) Methods: This crossover study evaluated the effects of IVR on anxiety and psychological well-being in a sample of eight [...] Read more.
(1) Background: Immersive virtual reality (IVR) has emerged as a promising non-pharmacological intervention to promote relaxation and improve emotional well-being in this population. (2) Methods: This crossover study evaluated the effects of IVR on anxiety and psychological well-being in a sample of eight participants with mild dementia attending a day-care center. Participants underwent two conditions: an experimental condition involving relaxing nature-based VR scenarios (Nature Treks VR) and a control condition using personalized YouTube videos on a tablet. Each condition lasted 12 sessions. Assessments included heart rate (HR), the I-PANAS-SF, the reduced State–Trait Anxiety Inventory (STAI-r), behavioral observations, and a subjective response questionnaire. (3) Results: A significant reduction in HR over time was found during IVR exposure, suggesting a calming physiological effect not observed in the control condition. While changes in PANAS and STAI-r scores were not statistically significant, the PANAS score improvement in the experimental condition approached statistical significance (p = 0.054) and was just below the minimal clinically important difference (MCID), suggesting a potentially meaningful trend. Behavioral responses were higher during YouTube sessions, likely due to personalized content. All participants rated the IVR experience positively on the subjective questionnaire, indicating high acceptability, though social desirability bias cannot be excluded. (4) Conclusions: IVR appears to be a feasible and acceptable intervention for individuals with dementia, warranting further investigation. Full article
(This article belongs to the Special Issue The Rehabilitation of Neurologic Disorders)
►▼ Show Figures

Figure 1

17 pages, 3590 KiB  
Protocol
Simultaneous Eye Tracking and Cerebral Hemodynamic Monitoring in Infants: A Guide for Pediatric Outpatient Follow-Up
by Valéria Azevedo de Almeida, Maria Clara Lima da Cruz, Nicole Rodrigues Morais, Italo Vinicius Tavares Rodrigues, Cintia Ricaele Ferreira da Silva, Edgard Morya and Silvana Alves Pereira
Brain Sci. 2025, 15(5), 469; https://doi.org/10.3390/brainsci15050469 - 28 Apr 2025
Viewed by 94
Abstract
Simultaneous eye tracking and cerebral hemodynamic monitoring contribute to the understanding of neural responses to stimuli in infants. However, exploring the impact of complex socioeconomic and environmental adversities on neurodevelopment requires transitioning this tool from research laboratories into clinical practice to evaluate its [...] Read more.
Simultaneous eye tracking and cerebral hemodynamic monitoring contribute to the understanding of neural responses to stimuli in infants. However, exploring the impact of complex socioeconomic and environmental adversities on neurodevelopment requires transitioning this tool from research laboratories into clinical practice to evaluate its feasibility in outpatient contexts. Background/Objectives: This study aimed to present a protocol for simultaneously integrating functional near-infrared spectroscopy (fNIRS) with eye tracking (ET) in infants at risk for neurodevelopmental disorders in a clinical setting with limited resources, during a cognitive task. Methods:The protocol was applied to infants in their first 12 months of life. The infants were exposed to tasks involving the processing of social and non-social stimuli, while their brain signals were monitored using fNIRS and their eyes were tracked with ET. The protocol included three main stages: (1) pre-collection, involving the preparation and habituation of the infants and equipment setup (fNIRS and ET); (2) cognitive function monitoring, using social and non-social stimuli to assess preferential processing via fNIRS and ET; and (3) post-collection, with guidelines for data pre-processing and analysis. Results: The application of the protocol allowed for the identification of technical challenges and the adaptation of procedures for clinical use. The main methodological challenges were difficulty using the conventional cap, excessive movement, synchronization issues between fNIRS and ET, and difficulties calibrating both devices across different age groups. Conclusions: The standardization proposed in this protocol enables healthcare professionals to explore different neurocognitive aspects in pediatric clinical settings and expands the scope of neurodevelopmental assessments. Full article
(This article belongs to the Special Issue Eye-Tracking Monitoring of Neurological and Psychiatric Conditions Across Life Span)
►▼ Show Figures

Figure 1

15 pages, 816 KiB  
Study Protocol
The Effect of Fremanezumab on Pain in Patients with Complex Regional Pain Syndrome: Study Protocol of a Randomized, Double-Blind, Proof-of-Concept, Placebo-Controlled Trial
by Abarajitha Thiyagarajah, Astrid Juhl Terkelsen, Frank Birklein, Nanna Brix Finnerup and Sandra Sif Gylfadottir
Brain Sci. 2025, 15(5), 468; https://doi.org/10.3390/brainsci15050468 - 28 Apr 2025
Viewed by 100
Abstract
Background/Objectives: Complex regional pain syndrome (CRPS) is a primary pain condition that can develop in a limb after a trauma. Although the condition is rare, it may cause lifelong pain and disability. Evidence-based treatments are limited. Neurogenic inflammation induced by the release of [...] Read more.
Background/Objectives: Complex regional pain syndrome (CRPS) is a primary pain condition that can develop in a limb after a trauma. Although the condition is rare, it may cause lifelong pain and disability. Evidence-based treatments are limited. Neurogenic inflammation induced by the release of neuropeptides, such as calcitonin gene-related peptide (CGRP), is thought to play an important role in the pathophysiology of CRPS. Recently, drugs targeting CGRP have proven to be effective and well tolerated in the treatment of migraine, but their efficacy in other pain conditions, including CRPS, is unclear. The aim of this study is to assess the efficacy of the anti-CGRP antibody fremanezumab on pain in CRPS. Methods: In this randomized, double-blind, placebo-controlled, proof-of-concept study, 60 adult patients with CRPS with a disease duration of 3–36 months are randomized to treatment for eight weeks with fremanezumab 225 mg or placebo administered subcutaneously at a 1:1 rate. The primary objective is to compare the change in pain intensity from baseline to the last week of treatment between fremanezumab and the placebo. Other objectives are to assess pain relief and differences in clinical signs between the groups and to examine if the effect can be predicted by CGRP biomarkers. Adverse events and blinding will also be assessed. Conclusions: If found effective, fremanezumab and other anti-CGRP antibodies may emerge as a mechanism-based treatment option for patients with CRPS, which could hopefully improve the overall care of patients with this devastating disease. Full article
►▼ Show Figures

Figure 1

11 pages, 171 KiB  
Article
Cluster Analysis of Motor Symptoms in Early-Diagnosed Parkinson’s Disease Patients
by Renee M. Hendricks and Shreyasi Biswas
Brain Sci. 2025, 15(5), 467; https://doi.org/10.3390/brainsci15050467 - 28 Apr 2025
Viewed by 78
Abstract
Parkinson’s disease (PD) is a common movement disorder affecting adults. People diagnosed with PD can have a multitude of physical (motor) symptoms, including tremors, and rigidness, and psychological (non-motor) symptoms, including anxiety and depression. These symptoms dramatically affect daily living activities, including dressing [...] Read more.
Parkinson’s disease (PD) is a common movement disorder affecting adults. People diagnosed with PD can have a multitude of physical (motor) symptoms, including tremors, and rigidness, and psychological (non-motor) symptoms, including anxiety and depression. These symptoms dramatically affect daily living activities, including dressing oneself, preparing meals, and speaking and writing. Background/Objectives: To determine the symptom similarities and differences among PD patients, a method referred to as cluster analysis can be applied to patient data. This method can separate patients who differ by symptom presence while grouping patients with disease similarities. Previous PD cluster analysis studies provided patient groups that were defined by their age and disease duration—both numerical values—and excluded categorical values, such as patient gender, family history of the disease, and symptom presence. In addition, patient age and disease duration were limited in range in previous studies, providing a patient group that was too similar to divide into distinct clusters. Methods: This study utilized a decision tree cluster analysis method applied to categorical symptom data from PD patients. The applied cluster method automatically determines the number of clusters, reducing estimation errors, as many cluster analysis methods require the end user to estimate the number of clusters prior to applying cluster analysis. A post analysis of additional categorical and numerical variables was conducted, and this provided a means to describe the PD patient clusters in terms of gender, family history of PD, median age, disease duration, and symptom presence. The patient dataset utilized was accessed from the Parkinson’s Progression Markers Initiative (PPMI) website. Results and Conclusions: The cluster analysis results provided a means to describe seven PD patient subtypes based on motor symptom presence, with the largest PD patient cluster containing half of the patient sample, and these individuals had three of the motor symptoms present: bradykinesia, rigidity, and tremors. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
16 pages, 1760 KiB  
Systematic Review
Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Haneen Sabet, Abdallah Abbas, Mohamed El-Moslemani, Mohamed Ahmed Zanaty, Ramanathan Kadirvel and Sherief Ghozy
Brain Sci. 2025, 15(5), 466; https://doi.org/10.3390/brainsci15050466 - 28 Apr 2025
Viewed by 85
Abstract
Objective: To evaluate the safety and efficacy of recombinant human prourokinase (rhPro-UK) administered via intravenous (IV) and intra-arterial (IA) routes in acute ischemic stroke (AIS) patients compared with standard treatments. Methods: A comprehensive search was conducted in accordance with PRISMA guidelines across Scopus, [...] Read more.
Objective: To evaluate the safety and efficacy of recombinant human prourokinase (rhPro-UK) administered via intravenous (IV) and intra-arterial (IA) routes in acute ischemic stroke (AIS) patients compared with standard treatments. Methods: A comprehensive search was conducted in accordance with PRISMA guidelines across Scopus, Web of Science, and PubMed until 11 December 2024. Randomized controlled trials (RCTs) assessing rhPro-UK’s efficacy and safety were included. Outcomes included the modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), mortality, and adverse events (AEs). Data analysis used risk difference (RD) with 95% confidence intervals (CIs). Results: Six RCTs (n = 3993) met the inclusion criteria. IV rhPro-UK showed comparable efficacy to the comparator for the mRS 0–1 at 90 days (RD: 0.00, 95% CI: [−0.04, 0.04]) and the mRS 0–2 (RD: −0.01, 95% CI: [−0.03, 0.01], P = 0.23). IA rhPro-UK significantly improved the mRS 0–1 (RD: 0.13, 95% CI: [0.01, 0.26], P = 0.04). The NIHSS reduction was significant for IV rhPro-UK (MD: −0.83, 95% [CI: −1.36, −0.29]). IV rhPro-UK did not significantly reduce the risk of systemic bleeding (RD: −0.10, 95% CI: [−0.24, 0.03], P = 0.12), serious AEs (RD: −0.01, 95% CI: [−0.04, 0.02], P = 0.53), or mortality (RD: 0.01, 95% CI: −0.01, 0.02). IA rhPro-UK significantly increased hemorrhage with neurological deterioration (RD: 0.08, 95% CI: [0.01, 0.14], P = 0.02). Conclusions: IV rhPro-UK provides non-inferior efficacy to both alteplase and standard care with a better safety profile at 35 mg, while IA rhPro-UK enhances functional outcomes in middle cerebral artery occlusions, albeit with safety concerns. Further trials are needed to confirm long-term outcomes, optimal dosing, and broader applicability. Full article
(This article belongs to the Section Neurorehabilitation)
►▼ Show Figures

Figure 1

24 pages, 6899 KiB  
Article
Analysis of Epilepsy Treatment Strategies Based on an Astrocyte–Neuron-Coupled Network Model
by Jianing Lan and Rong Wang
Brain Sci. 2025, 15(5), 465; https://doi.org/10.3390/brainsci15050465 - 27 Apr 2025
Viewed by 142
Abstract
Background/Objectives: Epilepsy is a common neurological disorder that not only severely impacts patients’ health but also imposes a significant burden on families and society. However, its pathogenesis remains unclear. Astrocytes play a crucial role in epileptic seizures and may serve as potential [...] Read more.
Background/Objectives: Epilepsy is a common neurological disorder that not only severely impacts patients’ health but also imposes a significant burden on families and society. However, its pathogenesis remains unclear. Astrocytes play a crucial role in epileptic seizures and may serve as potential therapeutic targets. Establishing a network model of epileptic seizures based on the astrocyte–neuron cell coupling and the clinical electroencephalographic (EEG) characteristics of epilepsy can facilitate further research on refractory epilepsy and the development of treatment strategies. Methods: This study constructs a neuronal network dynamic model of epileptic seizures based on the Watts–Strogatz small-world network, with a particular emphasis on the biological mechanisms of astrocyte–neuron coupling. The phase-locking value (PLV) is used to quantify the degree of network synchronization and to identify the key nodes or connections influencing synchronous seizures, such that two epilepsy treatment strategies are proposed: seizure suppression through stimulation and surgical resection simulation therapy. The therapeutic effects are evaluated based on the PLV-quantified network synchronization. Results: The results indicate that the desynchronization effect of random noise and sinusoidal wave stimulation is limited, while square wave stimulation is the most effective. Among the four surgical resection strategies, the effectiveness is the highest when resecting nodes exhibiting epileptic discharges. These findings contribute to the development of rational seizure suppression strategies and provide insights into precise epileptic focus localization and personalized treatment approaches. Full article
(This article belongs to the Section Computational Neuroscience and Neuroinformatics)
►▼ Show Figures

Figure 1

11 pages, 249 KiB  
Article
Barriers to Using Mobile App-Based Cognitive Testing in Older Adults with Probable Alzheimer’s Disease: A Qualitative Study
by Mei-Lan Chen, Kun-Lin Hsieh, Sung-Lin Hsieh, Ming-Cheng Hsieh, Dan Chia-Tien Lo and Jung-Lung Hsu
Brain Sci. 2025, 15(5), 464; https://doi.org/10.3390/brainsci15050464 - 27 Apr 2025
Viewed by 115
Abstract
Background/Objectives: Smart technologies have the potential to be rapid, sensitive, and cost-effective tools for real-life monitoring of cognitive function among older adults. Identifying barriers to using remote cognitive testing in older adults’ daily lives is essential. However, obstacles of utilizing digital cognitive [...] Read more.
Background/Objectives: Smart technologies have the potential to be rapid, sensitive, and cost-effective tools for real-life monitoring of cognitive function among older adults. Identifying barriers to using remote cognitive testing in older adults’ daily lives is essential. However, obstacles of utilizing digital cognitive tests in community-dwelling older adults with probable Alzheimer’s Disease (AD) remain unclear. The purpose of this study was to investigate barriers of older adults with probable AD toward using mobile app-based cognitive assessment. Methods: This was a qualitative study. Older adults with probable AD and their family caregivers were recruited from an outpatient clinic at a hospital’s neurological department. Semi-structured interviews were performed. Characteristics of the participants were analyzed using descriptive statistics. Thematic analysis was conducted to identify barriers to using mobile app-based cognitive testing. Results: The study sample consisted of 32 older adults with probable AD and 19 family caregivers involving the use of at-home mobile app-based cognitive assessment every two weeks over 12 months. In this study, three main themes were identified, including barriers related to availability of family support, health-related barriers, and app-related barriers. Conclusions: Mobile app-based cognitive assessment could be a promising tool for detecting AD and monitoring cognition among older adults. A better understanding of the barriers to using at-home digital cognitive testing can facilitate the development of patient-centered and custom-built mobile applications for older adults with probable AD and improve their cognitive function. Full article
(This article belongs to the Section Behavioral Neuroscience)
20 pages, 2640 KiB  
Article
Repeat Resection for Recurrent Glioblastoma in the WHO 2021 Era: A Longitudinal Matched Case-Control Study
by Melike Mut, Hatice Yagmur Zengin, Aynur Azizova, Cengiz Savas Askun, David Schiff and Figen Soylemezoglu
Brain Sci. 2025, 15(5), 463; https://doi.org/10.3390/brainsci15050463 - 27 Apr 2025
Viewed by 109
Abstract
Background and Objectives: This study aims to evaluate the overall survival benefits of repeat resection in patients with recurrent glioblastoma, IDH-wildtype (rGBM), and to identify factors for long-term survival, including the role of clinical, radiological, and molecular parameters. Methods: This longitudinal matched case-control [...] Read more.
Background and Objectives: This study aims to evaluate the overall survival benefits of repeat resection in patients with recurrent glioblastoma, IDH-wildtype (rGBM), and to identify factors for long-term survival, including the role of clinical, radiological, and molecular parameters. Methods: This longitudinal matched case-control study included 60 patients with rGBM divided into two groups: one surgery (n = 30) and repeat resection (n = 30). The baseline characteristics, preoperative and postoperative volumes, and molecular markers were assessed. Survival analyses were conducted using the Log-rank test, and associated factors with long-term survival were identified in the repeat resection cohort. Results: The patients who underwent repeat resection had a significantly longer median survival of 23.9 months compared to 9.2 months in the one-surgery group (p < 0.001). Preoperative tumor volume was found to correlate with postoperative residual volume in repeat resections. The patients with no residual contrast-enhancing tumor volume (0 cm3) after repeat resection had a median survival of 19.33 months, while those with any residual volume had a median survival of 10.13 months. The patients with lower KPS (≤70) and GCS (≤13) scores at the time of the repeat resection tended to have shorter survival, underscoring the potential clinical relevance of functional status when evaluating surgical candidacy. Conclusions: Complete repeat resection may improve overall survival in patients with recurrent IDH-wildtype GBM and should be considered earlier as a therapeutic option rather than a diagnostic or salvage procedure. Early surgical intervention, before declines in the KPS and GCS or tumor volumes become unmanageable, may lead to better outcomes. Further studies with larger cohorts are needed to confirm these findings. Full article
(This article belongs to the Special Issue Current Research in Neurosurgery)
►▼ Show Figures

Figure 1

18 pages, 893 KiB  
Article
The Greek Version of the Mild Behavioral Impairment Checklist (MBI-C): Psychometric Properties in Mild Cognitive Impairment Due to Alzheimer’s Disease
by Efthalia Angelopoulou, Evangelia Stanitsa, Maria Hatzopoulou, Akylina Despoti, Niki Tsinia, Vasiliki Kamtsadeli, Marina Papadogiani, Vasilis Kyriakidis, Sokratis Papageorgiou and John D. Papatriantafyllou
Brain Sci. 2025, 15(5), 462; https://doi.org/10.3390/brainsci15050462 - 27 Apr 2025
Viewed by 207
Abstract
Background/Objectives: Mild behavioral impairment (MBI) is an early marker of Alzheimer’s disease (AD) and other neurodegenerative diseases, often preceding cognitive decline. The MBI Checklist (MBI-C) is a 34-item tool designed to detect MBI. This study aimed to assess the psychometric properties of the [...] Read more.
Background/Objectives: Mild behavioral impairment (MBI) is an early marker of Alzheimer’s disease (AD) and other neurodegenerative diseases, often preceding cognitive decline. The MBI Checklist (MBI-C) is a 34-item tool designed to detect MBI. This study aimed to assess the psychometric properties of the Greek version of the MBI-C and its ability to differentiate patients with mild cognitive impairment due to AD (MCI-AD) from cognitively unimpaired older adults (healthy participants, HPs). Methods: A total of 181 participants (104 MCI-AD, 77 HPs) were recruited from the Third Age Day Care Center IASIS (2019–2023), accompanied by a close informant. Participants underwent neuropsychological assessment [Mini-Mental State Examination (MMSE), Addenbrooke’s Cognitive Examination-Revised (ACE-R)], and informants completed the MBI-C. Internal consistency was evaluated using Cronbach’s α and known-group validity was assessed via comparing MBI-C between the MCI-AD and HPs groups. Diagnostic accuracy was determined via receiver operating characteristic (ROC) analysis. Results: The Greek MBI-C showed excellent internal consistency (Cronbach’s α = 0.899). Among its domains, impulse dyscontrol demonstrated the highest reliability (α = 0.901), whereas decreased motivation (α = 0.564) and abnormal perception/thought content (α = 0.617) exhibited lower reliability. MBI-C total and domain scores were significantly higher in patients with MCI-AD than HPs (p < 0.001). The area under the curve (AUC) was 0.871 (optimal cutoff = 9.5), indicating excellent diagnostic performance. Conclusions: Overall, the Greek MBI-C has strong psychometric properties for MCI-AD. Sociocultural factors might influence symptom identification and reporting, particularly in the domains of decreased motivation and abnormal perception/thought content. Future research should investigate its predictive value for dementia conversion and its applicability to other populations, including individuals with subjective cognitive decline and non-AD causes of MCI. Full article
(This article belongs to the Special Issue Aging-Related Changes in Memory and Cognition)
►▼ Show Figures

Graphical abstract

15 pages, 1374 KiB  
Article
A Methodological Evaluation of Four Different Paired Associative Stimulation Paradigms in Healthy Controls
by Kenan Hodzic, Magnus Thordstein, Joakim Strandberg, Elisabet Jerlhag and Caroline E. Wass
Brain Sci. 2025, 15(5), 461; https://doi.org/10.3390/brainsci15050461 - 27 Apr 2025
Viewed by 55
Abstract
Background/Objectives: Plasticity deficits play a key role in the pathophysiology of various psychiatric and neurological disorders. Paired associative stimulation (PAS) leverages Hebbian principles to induce synaptic plasticity in the human brain. By repeatedly pairing (1) the peripheral nerve stimulation of the median [...] Read more.
Background/Objectives: Plasticity deficits play a key role in the pathophysiology of various psychiatric and neurological disorders. Paired associative stimulation (PAS) leverages Hebbian principles to induce synaptic plasticity in the human brain. By repeatedly pairing (1) the peripheral nerve stimulation of the median nerve with (2) transcranial magnetic stimulation over the primary motor cortex (M1) at different inter-stimulus intervals (25 ms; PAS-25, or 10 ms; PAS-10), corticospinal excitability can be increased (PAS-25, mimicking long-term potentiation (LTP)) or decreased (PAS-10, mimicking long-term depression (LTD)). However, variations in the number of pairings and inter-pair intervals lack consensus. The aim of the study was to evaluate four different PAS paradigms, i.e., PAS-10 and PAS-25 with both 180 versus 225 pairings each, to establish the most reliable PAS protocols for LTP- and LTD-like cortical changes. Methods: In a randomized, double-blind, crossover study, 14 healthy participants underwent PAS-10 and PAS-25 with 180 and 225 pairings. Excitability was assessed by quantifying the EMG response amplitude of a hand muscle to a single stimulus. Results: PAS-25 with 225 pairings produced a robust enhancement of corticospinal excitability, while PAS-25 with 180 pairings was less effective. Surprisingly, PAS-10 with both 180 and 225 pairings also increased excitability. Conclusions: While all four PAS paradigms enhanced M1 excitability, PAS-25 with 225 pairings induced the strongest group-level effects and was most time-efficient. Significant individual variability of PAS responses suggests that optimizing PAS parameters, including pairing number and interstimulus intervals, may be necessary for personalized approaches. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
►▼ Show Figures

Figure 1

22 pages, 7640 KiB  
Article
MCL-SWT: Mirror Contrastive Learning with Sliding Window Transformer for Subject-Independent EEG Recognition
by Qi Mao, Hongke Zhu, Wenyao Yan, Yu Zhao, Xinhong Hei and Jing Luo
Brain Sci. 2025, 15(5), 460; https://doi.org/10.3390/brainsci15050460 - 27 Apr 2025
Viewed by 128
Abstract
Background: In brain–computer interfaces (BCIs), transformer-based models have found extensive application in motor imagery (MI)-based EEG signal recognition. However, for subject-independent EEG recognition, these models face challenges: low sensitivity to spatial dynamics of neural activity and difficulty balancing high temporal resolution features [...] Read more.
Background: In brain–computer interfaces (BCIs), transformer-based models have found extensive application in motor imagery (MI)-based EEG signal recognition. However, for subject-independent EEG recognition, these models face challenges: low sensitivity to spatial dynamics of neural activity and difficulty balancing high temporal resolution features with manageable computational complexity. The overarching objective is to address these critical issues. Methods: We introduce Mirror Contrastive Learning with Sliding Window Transformer (MCL-SWT). Inspired by left/right hand motor imagery inducing event-related desynchronization (ERD) in the contralateral sensorimotor cortex, we develop a mirror contrastive loss function. It segregates feature spaces of EEG signals from contralateral ERD locations while curtailing variability in signals sharing similar ERD locations. The Sliding Window Transformer computes self-attention scores over high temporal resolution features, enabling efficient capture of global temporal dependencies. Results: Evaluated on benchmark datasets for subject-independent MI EEG recognition, MCL-SWT achieves classification accuracies of 66.48% and 75.62%, outperforming State-of-the-Art models by 2.82% and 2.17%, respectively. Ablation studies validate the efficacy of both the mirror contrastive loss and sliding window mechanism. Conclusions: These findings underscore MCL-SWT’s potential as a robust, interpretable framework for subject-independent EEG recognition. By addressing existing challenges, MCL-SWT could significantly advance BCI technology development. Full article
(This article belongs to the Special Issue The Application of EEG in Neurorehabilitation)
►▼ Show Figures

Figure 1

15 pages, 603 KiB  
Article
Cognitive Impairment-Associated Risk Factors of Parkinson’s Disease: A Hospital-Based Study in a Cohort of Upper Egypt Parkinson’s Patients
by Eman M. Khedr, Khaled Aboshaera, Ahmed A. Karim, Mohammad A. Korayem, Gellan K. Ahmed and Doaa M. Mahmoud
Brain Sci. 2025, 15(5), 459; https://doi.org/10.3390/brainsci15050459 - 27 Apr 2025
Viewed by 133
Abstract
Background/Objectives: Cognitive impairment (CI) in Parkinson’s disease (PD) is a major burden and significantly affects patients’ quality of life. Previous studies found that older age at onset and presence of the akinetic–rigid (AR) subtype are associated with an increased likelihood of CI in [...] Read more.
Background/Objectives: Cognitive impairment (CI) in Parkinson’s disease (PD) is a major burden and significantly affects patients’ quality of life. Previous studies found that older age at onset and presence of the akinetic–rigid (AR) subtype are associated with an increased likelihood of CI in PD. The present study aimed to assess factors that are related to the development of CI in PD. Methods: Eighty-three PD patients were consecutively recruited. Demographic information, clinical details, Montreal cognitive assessment (MoCA), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), walking speed, and instrumental activity of daily living (IADL) were assessed. Resting motor threshold (rMT), was also assessed for subgroup of patients with versus without cognitive impairment. Results: According to the MoCA cut-off score of 26, 45 had PD without CI (PD-NCI) (54.22%) and 38 cases (45.78%) had PD with CI (PD-CI). The age and age at onset were significantly older in the PD-CI group (p = 0.006 and 0.018, respectively). The patients were reclassified into AR and tremor-dominant (TR) phenotype. PD-CI patients were more likely to have the AR (81.6%). Walking speed, MDS-UPDRS score, and IADL scores were significantly worse in PD-CI than in PD-NCI. Stepwise linear regression analysis of risk factors associated CI revealed that higher MDS-UPDRS scores, later age of onset, and higher rMT values were considered risk factors for developing CI. Conclusions: Higher UPDRS score, later age of onset, and higher rMT values were considered as risk factors associated CI in PD patients and provide valuable insights for further investigation and potential clinical considerations. Full article
(This article belongs to the Special Issue Aging-Related Changes in Memory and Cognition)
►▼ Show Figures

Figure 1

15 pages, 1541 KiB  
Article
Synergistic Effects of Joint-Biased Rehabilitation and Combined Transcranial Direct Current Stimulation (tDCS) in Chronic Ankle Instability: A Single-Blind, Three-Armed Randomized Controlled Trial
by Yunseo Kim, Hyunjoong Kim, Jihye Jung and Seungwon Lee
Brain Sci. 2025, 15(5), 458; https://doi.org/10.3390/brainsci15050458 - 27 Apr 2025
Viewed by 121
Abstract
Background/Objectives: The ankle joint is among the most frequently injured joints in daily life, with approximately 25% of young adults reporting chronic ankle instability (CAI). This study investigated the effects of transcranial direct current stimulation (tDCS), a type of non-invasive brain stimulation (NIBS) [...] Read more.
Background/Objectives: The ankle joint is among the most frequently injured joints in daily life, with approximately 25% of young adults reporting chronic ankle instability (CAI). This study investigated the effects of transcranial direct current stimulation (tDCS), a type of non-invasive brain stimulation (NIBS) technique, combined with joint mobilization and active joint mobilization on CAI. Methods: A total of 36 participants (mean age: 20.81 years; 63.89% female; mean body mass index: 21.68) were randomly divided into three groups: (1) tDCS with joint mobilization (n = 12); (2) active joint mobilization (n = 12); and (3) tDCS with active joint mobilization (n = 12). Dynamic balance, range of motion (ROM), static balance, and ankle instability (Cumberland Ankle Instability Tool, CAIT) were evaluated at multiple time points. Interventions were conducted three times per week, for 15 min per session, over four weeks (12 sessions total). Results: All three groups showed significant improvements over time in dynamic balance, ankle instability, ROM, and static balance (p < 0.05). However, no significant interaction effects were observed between time and group (p > 0.05). The tDCS with active joint mobilization group demonstrated the largest effect sizes across most outcome measures, particularly for ankle instability, ROM, and static balance, in both immediate and post-intervention assessments. Conclusions: tDCS combined with active joint mobilization appears to be particularly effective in improving CAI. This approach, targeting both top-down mechanisms through non-invasive brain stimulation and local joint function, offers a promising alternative to traditional interventions that focus solely on the ankle joint. This study was registered with the Clinical Research Information Service (CRIS) under the identifier KCT0009566. Full article
(This article belongs to the Special Issue Neural Mechanisms Underlying Sensorimotor Learning and Plasticity: Novel Advances and Future Perspectives)
►▼ Show Figures

Figure 1

19 pages, 2750 KiB  
Article
Impact of Observation Duration in Action Observation Therapy: Manual Dexterity, Mirror Neuron System Activity, and Subjective Psychomotor Effort in Healthy Adults
by Anri Sasaki, Eizaburo Suzuki, Kotaro Homma, Nariyuki Mura and Katsuhiko Suzuki
Brain Sci. 2025, 15(5), 457; https://doi.org/10.3390/brainsci15050457 - 27 Apr 2025
Viewed by 215
Abstract
Background/Objectives: Action observation therapy (AOT) has gained attention as a rehabilitation method for motor function recovery following nerve injury. Although the total observation time and daily session duration have been studied, the effective observation duration per trial remains unclear. This study examined the [...] Read more.
Background/Objectives: Action observation therapy (AOT) has gained attention as a rehabilitation method for motor function recovery following nerve injury. Although the total observation time and daily session duration have been studied, the effective observation duration per trial remains unclear. This study examined the effect of different observation durations on manual dexterity, mirror neuron system activity, and subjective psychomotor effort in healthy adults. Methods: Twenty-four healthy right-handed adults participated in this crossover study under four conditions: observing ball rotations with the dominant hand for one, two, or three minutes, or geometric patterns (control) for two minutes. The outcomes included maximum rotations and errors by both hands during a ball rotation task and interpersonal motor resonance (IMR), indicating mirror neuron system activity. These measures were compared before and after intervention. Subjective ratings of concentration, physical fatigue, and mental fatigue were assessed post-intervention. Results: Rotation performance significantly increased for the intervention hand after a 2 min observation and showed a notable effect (p = 0.113, r = 0.48) for the non-intervention hand after a 3 min observation compared to the control. The IMR was significantly greater during the 2 min observation than in the control. Compared to the 1 min observation, the 2 min and 3 min observations resulted in higher mental fatigue, and the 3 min observation showed lower concentration levels. Conclusions: These findings indicate that the observation duration has varying effects on manual dexterity and mirror neuron system activity, with optimal effects observed at specific time intervals while also highlighting the relationship between observational learning and psychomotor effort. Full article
(This article belongs to the Section Neurorehabilitation)
►▼ Show Figures

Figure 1

10 pages, 2002 KiB  
Case Report
Adult-Onset Syringomyelia in Dandy-Walker Malformation Patients: Clinical Insights and Literature Review
by Bojana Zivkovic, Mirko Micovic, Marko Todorovic, Jelena Kostic and Vladimir Bascarevic
Brain Sci. 2025, 15(5), 456; https://doi.org/10.3390/brainsci15050456 - 26 Apr 2025
Viewed by 126
Abstract
Introduction: The presence of syringomyelia associated with Dandy-Walker malformation is rarely described in adults. Case report: We report a case of a 28-year-old woman with a history of Dandy-Walker malformation who developed syringomyelia. She had been previously treated in childhood with a ventriculoperitoneal [...] Read more.
Introduction: The presence of syringomyelia associated with Dandy-Walker malformation is rarely described in adults. Case report: We report a case of a 28-year-old woman with a history of Dandy-Walker malformation who developed syringomyelia. She had been previously treated in childhood with a ventriculoperitoneal and cystoperitoneal shunt for hydrocephalus, but over time she developed progressive neurological symptoms, including numbness and weakness in the upper extremities. Magnetic resonance imaging revealed a syrinx extending from C4 to T1 associated with large posterior fossa cyst. The patient was treated with cyst fenestration and cystoperitoneal shunts were removed, with complete resolution of symptoms and disappearance of syrinx. Discussion: A literature review revealed only 6 cases of syringomyelia associated with Dandy-Walker malformation in adults. The pathophysiology of this entity is multifactorial and may be related to obstructed cerebrospinal fluid flow, altered pressure dynamics, and formation of arachnoid adhesions. Conclusions: Individualized surgical approaches are essential for optimizing outcomes in this rare condition. Further research is needed to standardize treatment protocols and clarify underlying mechanisms and help to improve the management of these patients. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
►▼ Show Figures

Figure 1

15 pages, 1253 KiB  
Article
Effectiveness of Intracerebral Hemorrhage Aspiration with Catheter Insertion: Impact on Hematoma Volume and Symptom Improvement
by Jun Kyu Hwang, Na Young Kim, Won Joo Jeong, Chang Ki Jang, Jae Whan Lee, Tae Im Yi and Kwang-Chun Cho
Brain Sci. 2025, 15(5), 455; https://doi.org/10.3390/brainsci15050455 - 26 Apr 2025
Viewed by 138
Abstract
Background: Catheter insertion is the most commonly used method for treating intracerebral hemorrhage (ICH). Simultaneous hematoma aspiration allows for faster decompression than catheter insertion alone. Methods: Between March 2020 and Apri1 2024, 49 patients (25 men and 24 women) with ICH underwent ICH [...] Read more.
Background: Catheter insertion is the most commonly used method for treating intracerebral hemorrhage (ICH). Simultaneous hematoma aspiration allows for faster decompression than catheter insertion alone. Methods: Between March 2020 and Apri1 2024, 49 patients (25 men and 24 women) with ICH underwent ICH catheter insertion. Thirty-two patients (Group A) underwent intraoperative aspiration simultaneously with ICH catheter insertion. The other seventeen patients underwent catheter insertion alone (Group B). Four patients in Group A (12.5%) and two patients in Group B (11.8%) died within one month after surgery. Consequently, a total of 43 patients were included in the final analysis (Group A-1 vs. Group B-1). The Glasgow coma scale (GCS) score and muscle strength of the four extremities in both groups were compared 2 weeks later (first period) and on the date of discharge (second period). Patients in Group A-1 were discharged 5 days earlier than those in Group B-1. (average 49 ± 20 vs. 54 ± 31 days). Results: In Group A, the preoperative ICH volume was 66.2 ± 28.8 mL, and the median aspiration volume was 30 ± 19.6 mL. The preoperative ICH volume was 55.9 ± 22.2 mL in group B. Intraoperative ICH aspiration (Group A-1) significantly improved motor scores during the second period (p = 0.001). It also showed the trend toward improved GCS scores during the first period (p = 0.095) and the second period (p = 0.069). Conclusions: Compared to ICH catheter insertion alone, additional intraoperative ICH aspiration resulted in greater motor improvement at 7 weeks postoperatively (p = 0.004). It also showed a trend toward greater improvement in the GCS scores (p = 0.12). Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
►▼ Show Figures

Figure 1

21 pages, 1331 KiB  
Review
Ischemic Stroke in Patients Under Oral Anticoagulation: The Achilles Heel of Atrial Fibrillation Management
by Kyriakos Dimitriadis, Nikolaos Pyrpyris, Konstantinos Aznaouridis, Gyanaranjan Nayak, Panagiotis Kanatas, Panagiotis Theofilis, Panagiotis Tsioufis, Eirini Beneki, Aggelos Papanikolaou, Christos Fragoulis, Konstantina Aggeli and Konstantinos Tsioufis
Brain Sci. 2025, 15(5), 454; https://doi.org/10.3390/brainsci15050454 - 26 Apr 2025
Viewed by 200
Abstract
Oral anticoagulation (OAC) is essential for preventing ischemic stroke events in patients with atrial fibrillation (AF), and leads to a significant ischemic prophylaxis, when appropriately used. However, there is still a risk of experiencing stroke events, despite being under anticoagulation. Stroke despite OAC [...] Read more.
Oral anticoagulation (OAC) is essential for preventing ischemic stroke events in patients with atrial fibrillation (AF), and leads to a significant ischemic prophylaxis, when appropriately used. However, there is still a risk of experiencing stroke events, despite being under anticoagulation. Stroke despite OAC is an increasingly common diagnosis, and pathophysiologically, it can be associated with several etiologies, ranging from AF competing mechanisms to true anticoagulation failure. While the cardioembolic origin of stroke is the most frequently identified etiology, other factors also have to be considered, as there is a significance risk of coexistence. This highlights the need for thorough diagnostic testing, evaluating each stroke etiology independently, with the use of imaging, biomarker and blood tests. Treating such patients, however, is more complex, as there is still uncertainty regarding the selection of OAC post-stroke, with data showing a superiority of direct OAC (DOAC), compared to vitamin K antagonists, in recurrent ischemic stroke prevention and conflicting results regarding OAC switch. Finally, the additive value of cardiac interventions, such as left atrial appendage occlusion (LAAO), in secondary prevention of stroke, is being explored, as it could potentially lead to significant stroke risk reduction. This review, therefore, provides an updated summary of the pathophysiology, diagnostics and therapeutics of stroke under OAC, while also discussing the future direction on the Achilles heel of AF management. Full article
►▼ Show Figures

Graphical abstract

14 pages, 216 KiB  
Review
A Window to the Brain—The Enduring Impact of Vision Research
by George Ayoub
Brain Sci. 2025, 15(5), 453; https://doi.org/10.3390/brainsci15050453 - 26 Apr 2025
Viewed by 121
Abstract
The visual system has served as an expeditious entry point for discerning the mechanism of action of many brain systems, spearheading multiple fields of neuroscience in the process. It has additionally launched the careers of countless scientists, as we have crafted new means [...] Read more.
The visual system has served as an expeditious entry point for discerning the mechanism of action of many brain systems, spearheading multiple fields of neuroscience in the process. It has additionally launched the careers of countless scientists, as we have crafted new means to understand neuronal structures and their functions, leading to advances in many areas of the sciences. Indeed, one can readily mark the onset of the scientific examination of the visual system with the 1851 invention of the ophthalmoscope by Hermann von Helmholtz, and the trichromatic theory of color vision in 1802. The Young–Helmholtz understanding the red–green–blue nature of color vision became the foundation to understanding sensory system function that visual artists and also contemporary flat panel displays rely on. It is fascinating to realize that the paintings of Georges Seurat and an iPhone display share a commonality of this application of the trichromatic theory. While it was not until 1956 that the existence of cells responsive to three different ranges of wavelengths was proven with the work of Gunnar Svaetichin, this proof in many ways marked the advancement of tools to visualize at a microscopic level, a full century after the Young–Helmholtz theory was developed. Just a decade later, in 1966, the person widely considered as the founder of modern neuroscience, Stephen Kuffler, founded the Harvard neurobiology department. It was from Kuffler’s work with his post-doctoral students that many new fields of study were created and from whom many of the neuroscience programs across the US were founded. In terms of the visual system, Kuffler and his team were key in detailing areas of retinal neuroanatomy, neurochemistry, neurophysiology, and developmental neurobiology. This paper traces areas in visual system research that provide our understanding of the disparate areas of brain sciences. As such, there are six categories that are evaluated, each of which spawned work in multiple areas that have become mainstays in neuroscience. These range from fields that were dominant a half century ago to ones that have their origins in this decade. The commonality is that all of these owe their origin to Helmholtz and Kuffler, polymaths of the nineteenth and twentieth centuries. We will examine the impact of vision research across the following fields of neuroscience: sensory system function, neuroanatomy, neurochemistry, neurophysiology, developmental neurobiology, and neurological health and disease. Full article
(This article belongs to the Special Issue The Eye as the Window to Brain Science: Fields of Neuroscience Created from Eye Research)
11 pages, 578 KiB  
Article
Abnormal Gyrus Rectus Asymmetry in Alzheimer’s Disease: An MRI-Based Parcellation Method
by Ömür Karaca, Ahmet Arman Kibar, Burcu Aslantekin and Nermin Tepe
Brain Sci. 2025, 15(5), 452; https://doi.org/10.3390/brainsci15050452 - 26 Apr 2025
Viewed by 122
Abstract
Background: The gyrus rectus is a key brain region with neural connections to the entorhinal cortex and hippocampus, both of which are among the earliest areas affected in Alzheimer’s disease (AD). Investigating volumetric differences and asymmetry in this region may provide insights into [...] Read more.
Background: The gyrus rectus is a key brain region with neural connections to the entorhinal cortex and hippocampus, both of which are among the earliest areas affected in Alzheimer’s disease (AD). Investigating volumetric differences and asymmetry in this region may provide insights into disease progression. This study aimed to assess gyrus rectus volume and asymmetry in AD patients using an MRI-based parcellation method. Methods: This cross-sectional volumetric study included 25 cognitively healthy adults and 25 AD patients recruited from the Neurology Clinic of Balıkesir University Hospital. Brain MRI scans were obtained using a 1.5 Tesla MRI scanner. Volumetric measurements were computed using MRIStudio, an atlas-based image analysis program. Group differences in brain volume and asymmetry index were examined, and their correlations with Mini-Mental State Examination (MMSE) scores were evaluated. Results: AD patients exhibited significantly greater rightward volumetric asymmetry of the gyrus rectus volume than healthy controls (p < 0.05). Additionally, a positive correlation was observed between gyrus rectus volume and MMSE scores (p < 0.05). Conclusions: These results suggest that rightward volumetric asymmetry of the gyrus rectus may represent a promising biomarker for tracking the progression of Alzheimer’s disease. Detecting asymmetry in brain structures could improve understanding of AD pathology and aid clinical evaluation. Full article
►▼ Show Figures

Figure 1

26 pages, 3268 KiB  
Article
The Neural Mechanisms of Private Speech in Second Language Learners’ Oral Production: An fNIRS Study
by Rong Jiang, Zhe Xiao, Yihan Jiang and Xueqing Jiang
Brain Sci. 2025, 15(5), 451; https://doi.org/10.3390/brainsci15050451 - 25 Apr 2025
Viewed by 95
Abstract
Background: According to Vygotsky’s sociocultural theory, private speech functions both as a tool for thought regulation and as a transitional form between outer and inner speech. However, its role in adult second language (L2) learning—and the neural mechanisms supporting it—remains insufficiently understood. [...] Read more.
Background: According to Vygotsky’s sociocultural theory, private speech functions both as a tool for thought regulation and as a transitional form between outer and inner speech. However, its role in adult second language (L2) learning—and the neural mechanisms supporting it—remains insufficiently understood. This study thus examined whether private speech facilitates L2 oral production and investigated its underlying neural mechanisms, including the extent to which private speech resembles inner speech in its regulatory function and the transitional nature of private speech. Methods: In Experiment 1, to identify natural users of private speech, 64 Chinese-speaking L2 English learners with varying proficiency levels were invited to complete a picture-description task. In Experiment 2, functional near-infrared spectroscopy (fNIRS) was used to examine the neural mechanisms of private speech in 32 private speech users identified in Experiment 1. Results: Experiment 1 showed that private speech facilitates L2 oral production. Experiment 2 revealed that private and inner speech elicited highly similar patterns of functional connectivity. Among high-proficiency learners, private speech exhibited enhanced connectivity between the language network and the thought-regulation network, indicating involvement of higher-order cognitive processes. In contrast, among low-proficiency learners, connectivity was primarily restricted to language-related regions, suggesting that private speech supports basic linguistic processing at early stages. Furthermore, both private and outer speech showed stronger connectivity in speech-related brain regions. Conclusions: This is the first study to examine the neural mechanisms of private speech in L2 learners by using fNIRS. The findings provide novel neural evidence that private speech serves as both a regulatory scaffold and a transitional form bridging outer and inner speech. Its cognitive function appears to evolve with increasing L2 proficiency. Full article
(This article belongs to the Section Behavioral Neuroscience)
►▼ Show Figures

Figure 1

15 pages, 4420 KiB  
Article
Bayesian-Optimized Convolutional Neural Networks for Classifying Primary Tumor Origin of Brain Metastases from MRI
by Jawed Nawabi, Semil Eminovic, Alexander Hartenstein, Georg Lukas Baumgaertner, Nils Schnurbusch, Madhuri Rudolph, David Wasilewski, Julia Onken, Eberhard Siebert, Edzard Wiener, Georg Bohner, Andrea Dell'Orco, Mike P. Wattjes, Bernd Hamm, Uli Fehrenbach and Tobias Penzkofer
Brain Sci. 2025, 15(5), 450; https://doi.org/10.3390/brainsci15050450 - 25 Apr 2025
Viewed by 206
Abstract
Background/Objectives: This study evaluates whether convolutional neural networks (CNNs) can be trained to determine the primary tumor origin from MRI images alone in patients with metastatic brain lesions. Methods: This retrospective, monocentric study involved the segmentation of 1175 brain lesions from [...] Read more.
Background/Objectives: This study evaluates whether convolutional neural networks (CNNs) can be trained to determine the primary tumor origin from MRI images alone in patients with metastatic brain lesions. Methods: This retrospective, monocentric study involved the segmentation of 1175 brain lesions from MRI scans of 436 patients with histologically confirmed primary tumor origins. The four most common tumor types—lung adenocarcinoma, small cell lung cancer, breast cancer, and melanoma—were selected, and a class-balanced dataset was created through under-sampling. This resulted in 276 training datasets and 88 hold-out test datasets. Bayesian optimization was employed to determine the optimal CNN architecture, the most relevant imaging sequences, and whether the masking of images was necessary. We compared the performance of the CNN with that of two expert radiologists specializing in neuro-oncological imaging. Results: The best-performing CNN from the Bayesian optimization process used masked images across all available MRI sequences. It achieved Area-Under-the-Curve (AUC) values of 0.75 for melanoma, 0.65 for small cell lung cancer, 0.64 for breast cancer, and 0.57 for lung adenocarcinoma. Masked images likely improved performance by focusing the CNN on relevant regions and reducing noise from surrounding tissues. In comparison, Radiologist 1 achieved AUCs of 0.55, 0.52, 0.45, and 0.51, and Radiologist 2 achieved AUCs of 0.68, 0.55, 0.64, and 0.43 for the same tumor types, respectively. The CNN consistently showed higher accuracy, particularly for melanoma and breast cancer. Conclusions: Bayesian optimization enabled the creation of a CNN that outperformed expert radiologists in classifying the primary tumor origin of brain metastases from MRI. Full article
(This article belongs to the Section Neuro-oncology)
►▼ Show Figures

Figure 1

22 pages, 1055 KiB  
Perspective
Non-Invasive Brain Stimulation and Artificial Intelligence in Communication Neuroprosthetics: A Bidirectional Approach for Speech and Hearing Impairments
by Thorsten Rudroff
Brain Sci. 2025, 15(5), 449; https://doi.org/10.3390/brainsci15050449 - 25 Apr 2025
Viewed by 182
Abstract
This perspective paper introduces a novel bidirectional framework for communication neuroprosthetics that integrates non-invasive brain stimulation (NIBS) with artificial intelligence (AI) to address both speech production and auditory processing impairments. Traditional approaches typically target only one aspect of communication, while this framework supports [...] Read more.
This perspective paper introduces a novel bidirectional framework for communication neuroprosthetics that integrates non-invasive brain stimulation (NIBS) with artificial intelligence (AI) to address both speech production and auditory processing impairments. Traditional approaches typically target only one aspect of communication, while this framework supports the complete communication cycle. The integration of transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) with advanced AI algorithms enables the personalized, adaptive enhancement of neural signals for both speaking and listening functions. This paper examines current evidence for NIBS efficacy in communication disorders, explores AI innovations in neural signal processing, and discusses implementation considerations for closed-loop systems. This bidirectional approach has the potential to provide more natural, effective communication support while promoting neuroplasticity for long-term recovery. The framework presented offers a roadmap for developing accessible communication interventions that could significantly improve the quality of life for individuals with speech and hearing impairments resulting from neurological conditions. Full article
(This article belongs to the Special Issue The Future of Human–Machine Collaboration: AI in Neural Rehabilitation and Assistive Technologies)
►▼ Show Figures

Figure 1

12 pages, 952 KiB  
Article
Theta Burst TMS over the Pre-SMA Improves Inhibitory Control in Gambling Disorder Subjects as Assessed with Stop Signal Task
by Gioele Gavazzi, Carlo Cavaliere, Marco Salvatore, Nikolaos Makris and Stefano Pallanti
Brain Sci. 2025, 15(5), 448; https://doi.org/10.3390/brainsci15050448 - 25 Apr 2025
Viewed by 165
Abstract
Background. Inhibitory control failure represents a central trait in substance and behavioral addictions, which includes patients affected with gambling disorder (GD). In GD patients, research on this trait of the addiction cycle has primarily focused on the use of pharmacological treatments for its [...] Read more.
Background. Inhibitory control failure represents a central trait in substance and behavioral addictions, which includes patients affected with gambling disorder (GD). In GD patients, research on this trait of the addiction cycle has primarily focused on the use of pharmacological treatments for its assessment. More recently, modification of neural activity using transcranial magnetic stimulation (TMS) has been used to explore the dimensions of GD using patient questionnaires. Methods. Herein, we evaluated the use of continuous Theta burst stimulation (cTBS) over the pre-supplementary motor area (pre-SMA) to determine if it modified inhibitory control in the stop signal task of patients affected by GD when compared with a group of healthy controls without cTBS treatment. Results. To the best of our knowledge, our study is the first to report that TMS treatment of GD patients is associated with a behavioral improvement of stop signal reaction time. Conclusion. Our results suggest that this TMS-mediated improvement in the efficiency of inhibitory control in GD patients warrants further mechanistic studies in a larger cohort to determine if can be used as a treatment modality. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-54
Previous Issue
Back to TopTop