Brain Sciences

13 pages, 718 KB

Open AccessArticle

Quantitative Analysis of Intracranial Atherosclerosis and Its Correlation with Ischemic Cerebrovascular Disease and Prognosis

by Jingjing Cai, Sizhan Chen, Shiyu Hu, Lijie Ren and Gelin Xu

Brain Sci. 2025, 15(9), 1009; https://doi.org/10.3390/brainsci15091009 - 18 Sep 2025

Abstract

Background: Intracranial atherosclerosis disease (ICAD) represents a significant etiology of stroke. This study aimed to evaluate correlations between intracranial atherosclerotic burden and risk of ischemic events. Methods: In this prospective observational study, all enrolled patients underwent High-Resolution Magnetic Resonance vessel wall Imaging [...] Read more.

Background: Intracranial atherosclerosis disease (ICAD) represents a significant etiology of stroke. This study aimed to evaluate correlations between intracranial atherosclerotic burden and risk of ischemic events. Methods: In this prospective observational study, all enrolled patients underwent High-Resolution Magnetic Resonance vessel wall Imaging (HR MR-VMI) within two weeks of onset, or of enrollment. Baseline assessments included modified American Heart Association plaque type, stenosis degree, intra-plaque hemorrhage (IPH), plaque thickness, plaque length, and vessel wall enhancement. Modified Rankin Scale (mRS) was followed with one-year treatment in adherence to the guidelines. Comparative analyses were conducted between symptomatic and asymptomatic groups, culprit versus non-culprit plaques, and favorable versus poor prognosis groups. Results: The study included 129 symptomatic and 42 asymptomatic patients. Hypertension, diabetes, and smoking were more prevalent in patients in the symptomatic group. Vulnerable plaque (97.7% vs. 64.3%, p = 0.003), IPH (17.8% vs. 4.8%, p = 0.022) and higher stenosis degree (χ² = 2.675, p = 0.008) were significantly more prevalent in the symptomatic group. Culprit plaques were predominantly located in the superior wall of the middle cerebral artery (MCA) (χ² = 15.561, p = 0.001) and the left wall of the basilar artery (χ² = 34.138, p = 0.008). Factors associated with poor prognosis included older age (63.63 ± 8.19 vs. 55.63 ± 13.15, p = 0.001), presence of IPH (31.82% vs. 14.29%, p = 0.037), and elevated D-dimer levels (0.77 ± 0.60 vs. 0.40 ± 0.36, p = 0.022). Conclusions: Vulnerable plaque, specific lesion locations, and higher stenosis degree are significantly associated with ischemic events in ICAD. While plaque enhancement and stenosis correlate with stroke occurrence, they show no clear association with prognosis. Neither the length nor the thickness of plaques manifests a significant correlation with either stroke events or the prognostic outcomes. Full article

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

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12 pages, 262 KB

Open AccessArticle

Sex-Specific Association Between XPC rs2228001 Polymorphism and Parkinson’s Disease Risk in a Mexican Population: A Case–Control Study Exploring Gene–Environment Interactions

by Karla Mariana Alvarado-Retana, Daniel Francisco Ramos-Rosales, Elizabeth Irasema Antuna-Salcido, Sergio Manuel Salas-Pacheco, Francisco Xavier Castellanos-Juárez, Edna Madai Méndez-Hernández, Alma Cristina Salas-Leal, Osmel La Llave-León, Gerardo Quiñones-Canales, Oscar Arias-Carrión, Ada Sandoval-Carrillo and José Manuel Salas-Pacheco

Brain Sci. 2025, 15(9), 1008; https://doi.org/10.3390/brainsci15091008 - 18 Sep 2025

Abstract

Background/Objectives: Emerging evidence implicates impaired DNA repair mechanisms in the pathogenesis of Parkinson’s disease (PD), particularly in the context of oxidative stress and environmental exposures. This study investigated the association between five polymorphisms in nucleotide excision repair (NER) pathway genes and PD susceptibility [...] Read more.

Background/Objectives: Emerging evidence implicates impaired DNA repair mechanisms in the pathogenesis of Parkinson’s disease (PD), particularly in the context of oxidative stress and environmental exposures. This study investigated the association between five polymorphisms in nucleotide excision repair (NER) pathway genes and PD susceptibility in a northern Mexican mestizo population. Methods: We conducted a case–control study including 137 patients with clinically diagnosed PD and 137 age- and sex-matched controls. Genomic DNA was isolated from peripheral blood, and genotyping of ERCC1 (rs11615), ERCC2 (rs13181), XPA (rs1800975), XPC (rs2228001), and XPF (rs1799801) was performed using TaqMan real-time PCR assays. Associations between genotype frequencies and PD were evaluated using logistic regression models adjusted for age, sex, and pesticide exposure. Results: A significantly higher prevalence of pesticide exposure was observed in PD patients than in controls (OR 2.08, 95% CI 1.18–3.68; p = 0.01). The XPC rs2228001 C/C genotype was independently associated with increased PD risk in males (OR 3.25, 95% CI 1.07–9.85; p = 0.042), even after adjusting for uric acid, pesticide exposure, and cognitive status (MMSE score). No significant associations were found for other NER-related polymorphisms. Male PD patients also exhibited significantly lower serum uric acid levels than controls (p = 0.046), supporting a link between oxidative stress and disease vulnerability. Conclusions: Our findings suggest a sex-specific genetic contribution to PD susceptibility involving the XPC rs2228001 variant, particularly in the context of pesticide exposure. These results underscore the relevance of DNA repair pathways in PD pathogenesis and highlight the importance of integrated models incorporating genetic and environmental risk factors. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Neurodegenerative Diseases)

20 pages, 966 KB

Open AccessSystematic Review

Effectiveness of AI-Assisted Digital Therapies for Post-Stroke Aphasia Rehabilitation: A Systematic Review

by Yamil Liscano, Lina Marcela Bernal and Jhony Alejandro Díaz Vallejo

Brain Sci. 2025, 15(9), 1007; https://doi.org/10.3390/brainsci15091007 - 18 Sep 2025

Abstract

Background: Traditional aphasia therapy is often limited by insufficient dosage, a barrier that AI-assisted digital therapies are poised to overcome. However, it remains unclear whether gains on specific tasks translate to functional, real-world communication. This systematic review evaluates the effectiveness of these novel [...] Read more.

Background: Traditional aphasia therapy is often limited by insufficient dosage, a barrier that AI-assisted digital therapies are poised to overcome. However, it remains unclear whether gains on specific tasks translate to functional, real-world communication. This systematic review evaluates the effectiveness of these novel interventions and investigates the potential for a “generalization gap” when compared to conventional treatments for post-stroke aphasia rehabilitation. Methods: Following PRISMA guidelines, we systematically reviewed randomized controlled trials (2010–2024) from six databases. We included studies examining AI-powered digital platforms for adults with chronic post-stroke apha-sia that reported standardized language outcomes. Results: Our analysis of five trials (n = 366) shows that AI-assisted therapies successfully deliver high-dose interventions, leading to significant improvements in trained language skills, including word retrieval (up to 16.4% gain) and auditory comprehension. However, a critical “generalization gap” was consistently identified: these impairment-level gains rarely transferred to functional, real-world communication. Conclusions: AI-assisted digital therapies effectively solve the dosage problem in aphasia care and improve specific linguistic deficits. Their primary limitation is the failure to generalize skills to everyday use. Future platforms must therefore be strategically redesigned to incorporate therapeutic principles that explicitly target the transfer of skills, bridging the gap between clinical improvement and functional communication. Full article

(This article belongs to the Special Issue Clinical Research on Neurological Rehabilitation After Stroke)

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33 pages, 1053 KB

Open AccessSystematic Review

Clinical Management of Synthetic-Cannabinoid-Induced Psychosis: A Systematic Review of Treatment Strategies and Outcomes

by Alessio Mosca, Stefania Chiappini, Andrea Miuli, Clara Cavallotto, Mauro Pettorruso, Giovanni Martinotti and Fabrizio Schifano

Brain Sci. 2025, 15(9), 1006; https://doi.org/10.3390/brainsci15091006 - 17 Sep 2025

Abstract

Background: Synthetic cannabinoid receptor agonists (SCRAs, commercially known as “Spice”) have become a leading cause of substance-induced psychosis worldwide. These compounds show strong associations not only with acute psychotic episodes but also, in a subset of patients, with persistent or relapsing psychotic disorders, [...] Read more.

Background: Synthetic cannabinoid receptor agonists (SCRAs, commercially known as “Spice”) have become a leading cause of substance-induced psychosis worldwide. These compounds show strong associations not only with acute psychotic episodes but also, in a subset of patients, with persistent or relapsing psychotic disorders, patterns that raise concern about progression to schizophrenia. Yet clinicians still lack clear, evidence-based guidance, and the optimal management of SCRA-induced psychosis remains inadequately defined. Methods: We carried out a systematic search of PubMed, Scopus, and Web of Science on 2 April 2025, identifying 35 primary studies that together describe roughly 4600 clinical presentations (≈77% male; mean age: 24.7 years). Results: Across diverse settings a convergent three-step pharmacological strategy emerged. First, rapid tranquillization with parenteral benzodiazepines consistently controlled severe agitation and autonomic instability. Second, when florid psychosis persisted beyond 30–60 min, clinicians introduced a second-generation antipsychotic—most commonly olanzapine, risperidone, or aripiprazole—often at doses exceeding those used for primary psychoses. Third, for the minority of refractory or relapse-prone cases, escalation to long-acting injectable formulations or low-dose clozapine achieved symptom control, even at plasma levels below those required in treatment-resistant schizophrenia. Although the evidence base consists largely of uncontrolled clinical descriptions, across studies, a recurrent clinical pattern was observed: initial benzodiazepines for agitation, followed by antipsychotics when psychosis persisted and escalation to clozapine or long-acting injectables in refractory cases. This approach appears to be associated with symptom improvement, although the certainty of the evidence is low to very low. Conclusions. Prospective, comparative studies are urgently needed to refine dosing, directly compare antipsychotic classes, and evaluate emerging cannabinoid-modulating interventions. Full article

(This article belongs to the Special Issue Drug Development for Schizophrenia)

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11 pages, 1656 KB

Open AccessArticle

Spinal Cord Injury in Real Time: Intra-Operative Ultrasound for Acute Phase Examination in Non-Human Primates

by Eleni Sinopoulou, Michelle W. Chow, Numaira Obaid, Emily Chong, Yvette S. Nout-Lomas, Rachele Wurr, Ryan Macon, J. Russell Huie, Adam R. Ferguson, Mark H. Tuszynski, Michael S. Beattie, Jacqueline C. Bresnahan and Carolyn J. Sparrey

Brain Sci. 2025, 15(9), 1005; https://doi.org/10.3390/brainsci15091005 - 17 Sep 2025

Abstract

Background: A spinal cord contusion injury is among the most clinically relevant models for studying pathophysiology and for developing potential therapeutic interventions for spinal cord injuries (SCI). Methods: In this study, we implemented an intra-operative ultrasound (IOU) approach to precisely locate and examine [...] Read more.

Background: A spinal cord contusion injury is among the most clinically relevant models for studying pathophysiology and for developing potential therapeutic interventions for spinal cord injuries (SCI). Methods: In this study, we implemented an intra-operative ultrasound (IOU) approach to precisely locate and examine the lesion site at 5 and 10 min post-injury after a cervical hemi-contusion injury in a non-human primate (NHP) model. We assessed acute lesion progression from 5 to 10 min and then compared that to the lesion extent as measured by MRI 3 weeks later. Results: We observed a small increase in the rostrocaudal and mediolateral lesion area (mm²) from 5 to 10 min and a further 26% increase in the mediolateral lesion extent when comparing 5 and 10 min to 3 weeks post-injury. Conclusions: By enabling high-resolution ultrasound visualization of the hemicontusion lesion in vivo, this approach can provide critical insights into the early progression of SCI. It can help with further refining this preclinical SCI model and provide significant predictive value for the animals’ recovery post-injury. Full article

(This article belongs to the Special Issue Spinal Cord Injury)

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23 pages, 2647 KB

Open AccessReview

Primary Cilia and Cardiovascular Risk Factors in Alzheimer’s Disease

by Clare L. Sunderman, Kathleen V. Forero, Qasim Alorjani, Raghad Buqaileh, Gillian M. Gallagher, Sestina M. Ventresca, William S. Messer, Jr. and Wissam A. AbouAlaiwi

Brain Sci. 2025, 15(9), 1004; https://doi.org/10.3390/brainsci15091004 - 17 Sep 2025

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia worldwide due to an aging population. AD is characterized as a progressive neurodegenerative disease that leads to atrophy of brain tissue, causing cognitive deficits. Amyloid beta plaques and neurofibrillary tangles are pathological hallmarks [...] Read more.

Alzheimer’s disease (AD) is the most common cause of dementia worldwide due to an aging population. AD is characterized as a progressive neurodegenerative disease that leads to atrophy of brain tissue, causing cognitive deficits. Amyloid beta plaques and neurofibrillary tangles are pathological hallmarks of AD, yet the cause is still highly debated. Many other cardiovascular diseases and vascular manifestations share the same symptoms as patients with AD. In this review, the current understanding of AD is summarized with a brief discussion on how primary cilia dysfunction and impaired nitric oxide (NO) signaling contribute to cardiovascular risk factors, vascular pathology, and cognitive decline in AD. Finally, we highlight primary cilia as a possible therapeutic target and any future directions for treating AD. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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20 pages, 1125 KB

Open AccessReview

Beyond Hot Flashes: The Role of Estrogen Receptors in Menopausal Mental Health and Cognitive Decline

by Jung Min Cho, Jihye Lee, Eun-Mi Ahn and Jaehoon Bae

Brain Sci. 2025, 15(9), 1003; https://doi.org/10.3390/brainsci15091003 - 16 Sep 2025

Abstract

Menopause is a natural phase in a woman’s life marked by the cessation of menstruation, typically accompanied by hormonal fluctuations that have significant impacts on physical and mental health. While much attention has been given to the physical symptoms of menopause, such as [...] Read more.

Menopause is a natural phase in a woman’s life marked by the cessation of menstruation, typically accompanied by hormonal fluctuations that have significant impacts on physical and mental health. While much attention has been given to the physical symptoms of menopause, such as hot flashes and osteoporosis, the neurocognitive consequences of hormonal fluctuations during the menopausal transition and the subsequent sustained estrogen loss after menopause have received less focus. Estrogen receptors (ERs), specifically ERα and ERβ, play a critical role in maintaining brain health, influencing mood, memory, and cognition. This review explores the connection between estrogen receptor signaling and mental health during menopause, focusing on mood disorders such as depression and anxiety, as well as cognitive decline and dementia. We discuss the molecular mechanisms by which ERs modulate brain function, including their effects on neuroplasticity, neurotransmitter systems, and gene expression. The review also examines current clinical approaches to managing menopausal cognitive and mental health issues, including hormone replacement therapy and selective ER modulators, while emphasizing the need for further research into alternative therapies and individualized treatments. The importance of estrogen receptors in the menopausal brain and their potential as therapeutic targets is critically evaluated, aiming to shed light on this often-overlooked aspect of menopause and aging. Full article

(This article belongs to the Section Neuropsychology)

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12 pages, 1361 KB

Open AccessArticle

Age and Self-Expansion Behaviors Correlate with Spatial Navigation in Healthy Adults

by Melissa Ansara, MaKayla Duggan, Alana Schafer, Karina Villalobos, Alexis N. Chargo, Ana M. Daugherty, Taylor N. Takla and Nora E. Fritz

Brain Sci. 2025, 15(9), 1002; https://doi.org/10.3390/brainsci15091002 - 16 Sep 2025

Abstract

Background: Spatial navigation is one’s ability to travel through their environment to reach a goal location. Self-expansion is the motivation to increase one’s self-perception through engaging in novel activities. Our objective was to examine the relations among self-expansion, age, and navigation ability and [...] Read more.

Background: Spatial navigation is one’s ability to travel through their environment to reach a goal location. Self-expansion is the motivation to increase one’s self-perception through engaging in novel activities. Our objective was to examine the relations among self-expansion, age, and navigation ability and investigate how one’s internal motivation may influence navigation performance across paradigms. Methods: In total, 33 younger adults (YAs; 19F, 14M, mean age = 25.0 ± 1.6) and 74 older adults (OAs; 52F, 22M, mean age = 69.5 ± 8.0) completed the following: Self-Expansion Preference Scale (SEPS), Wayfinding Questionnaire (WQ), Virtual Supermarket Task, Virtual Morris Water Maze (vMWM), and a Floor Maze Task (FMT). Mann–Whitney U tests and Spearman ρ correlations were used to examine differences in navigation performance between YAs vs. OAs and self-expanders vs. self-conservers, and relations among the measures, respectively. Results: YAs had lower vMWM completion times compared to OAs (p < 0.001). Self-expanders had better recall of the vMWM environment compared to self-conservers (p = 0.049), independent of age. Greater self-expansion in YAs was correlated with lower spatial anxiety (ρ = −0.356, p = 0.042) and faster completion of the FMT (ρ = −0.36, p = 0.042). Discussion: Our results build on established age-related deficits in navigation abilities to identify correlations of self-expansion and better performance in various navigation tasks. Independent of age, individuals with greater inclination towards self-expansion exhibit superior navigation abilities. Future research should explore underlying mechanisms driving these associations and investigate intervention strategies aimed at improving navigation skills in aging populations through increasing self-expansion. Full article

(This article belongs to the Special Issue Neuropsychological Exploration of Spatial Cognition and Navigation)

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21 pages, 3208 KB

Open AccessArticle

Analysis of Neurophysiological Correlates of Mental Fatigue in Both Monotonous and Demanding Driving Conditions

by Francesca Dello Iacono, Luca Guinti, Marianna Cecchetti, Andrea Giorgi, Dario Rossi, Vincenzo Ronca, Alessia Vozzi, Rossella Capotorto, Fabio Babiloni, Pietro Aricò, Gianluca Borghini, Marteyn Van Gasteren, Javier Melus, Manuel Picardi and Gianluca Di Flumeri

Brain Sci. 2025, 15(9), 1001; https://doi.org/10.3390/brainsci15091001 - 16 Sep 2025

Abstract

Background/Objectives: Mental fatigue during driving, whether passive (arising from monotony) or active (caused by cognitive overload), is a critical factor for road safety. Despite the growing interest in monitoring techniques based on neurophysiological signals, current biomarkers are primarily validated only for detecting [...] Read more.

Background/Objectives: Mental fatigue during driving, whether passive (arising from monotony) or active (caused by cognitive overload), is a critical factor for road safety. Despite the growing interest in monitoring techniques based on neurophysiological signals, current biomarkers are primarily validated only for detecting passive mental fatigue under monotonous conditions. The objective of this study is to evaluate the sensitivity of the MDrow index, which is based on EEG Alpha band activity, previously validated for detecting passive mental fatigue, with respect to active mental fatigue, i.e., the mental fatigue occurring in cognitively demanding driving scenarios. Methods: A simulated experimental protocol was developed featuring three driving scenarios with increasing complexity: monotonous, urban, and urban with dual tasks. Nineteen participants took part in the experiment, during which electroencephalogram (EEG), photoplethysmogram (PPG), and electrodermal activity (EDA) data were collected in addition to subjective assessments, namely the Karolinska Sleepiness Scale (KSS) and the Driving Activity Load Index (DALI) questionnaires. Results:The findings indicate that MDrow shows sensitivity to both passive and active mental fatigue (p < 0.001), thereby demonstrating stability even in the presence of additional cognitive demands. Furthermore, Heart Rate (HR) and Heart Rate Variability (HRV) increased significantly during the execution of more complex tasks, thereby suggesting a heightened response to mental workload in comparison to mental fatigue alone. Conversely, electrodermal measures evidenced no sensitivity to mental fatigue-related changes. Conclusions: These findings confirm the MDrow index’s validity as an objective and continuous marker of mental fatigue, even under cognitively demanding conditions. Full article

(This article belongs to the Section Cognitive, Social and Affective Neuroscience)

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19 pages, 1603 KB

Open AccessArticle

Cross-Linguistic Influences on L2 Prosody Perception: Evidence from English Interrogative Focus Perception by Mandarin Listeners

by Xing Liu, Xiaoxiang Chen, Chen Kuang and Fei Chen

Brain Sci. 2025, 15(9), 1000; https://doi.org/10.3390/brainsci15091000 - 16 Sep 2025

Abstract

Background/Objectives: This study sets out to explore how L1 Mandarin speakers with varying lengths of L2 experience perceived English focus interrogative tune, L*H-H%, within the framework of the autosegmental–metrical model. Methods: Eighteen Mandarin speakers with varying lengths of residence in the United States [...] Read more.

Background/Objectives: This study sets out to explore how L1 Mandarin speakers with varying lengths of L2 experience perceived English focus interrogative tune, L*H-H%, within the framework of the autosegmental–metrical model. Methods: Eighteen Mandarin speakers with varying lengths of residence in the United States and eighteen English native speakers were invited to perceive prosodic prominence and judge the naturalness of focus prosody tunes. Results: For the perception of on-focus pitch accent L*, Mandarin speakers performed well in the prominence detection task but not in the focus identification task. For post-focus edge tones, we found that phrase accents were more susceptible to L1 influences than boundary tones due to the varying degrees of cross-linguistic similarity between these intonational categories. The results also show that even listeners with extended L2 experience were not proficient in their perception of L2 interrogative focus tunes. Conclusions: This study reveals the advantage of considering the degree of L1-L2 similarity and the necessity to examine cross-linguistic influences on L2 perception of prosody separately in phonological and phonetic dimensions. Full article

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

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23 pages, 1586 KB

Open AccessReview

Statistical Parametric Mapping and Voxel-Based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD): Principles and Clinical Applications

by Shinji Yamamoto, Nobukiyo Yoshida, Noriko Sakurai, Yukinori Okada, Norikazu Ohno, Masayuki Satoh, Koji Takeshita, Masanori Ishida and Kazuhiro Saito

Brain Sci. 2025, 15(9), 999; https://doi.org/10.3390/brainsci15090999 - 16 Sep 2025

Abstract

Background: The voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) allows quantitative evaluation of the degree of an individual’s brain atrophy through statistical comparison of brain magnetic resonance imaging (MRI) of their brain to a normative database of healthy Japanese individuals. [...] Read more.

Background: The voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) allows quantitative evaluation of the degree of an individual’s brain atrophy through statistical comparison of brain magnetic resonance imaging (MRI) of their brain to a normative database of healthy Japanese individuals. Currently, the VSRAD is used in routine clinical practice in the diagnosis of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Recent studies using VSRAD have explored its utility in the assessment of brain atrophy associated with various conditions, including diabetes, oral health status, and olfactory dysfunction. This review summarizes the principles of the VSRAD and its foundational method, voxel-based morphometry (VBM), and their clinical and research applications. Methods: This narrative review was conducted by performing a literature search of PubMed to identify articles regarding VBM and the VSRAD that were published between 2005 and 2025. Results: VSRAD yields four indices for quantifying the severity and extent of gray matter atrophy, especially in the medial temporal lobe. Studies have demonstrated its high diagnostic accuracy in distinguishing among AD, mild cognitive impairment (MCI), and DLB. Furthermore, it is correlated with neuropsychological test scores and has been applied to evaluate brain changes associated with diabetes, olfactory dysfunction, and physical inactivity. Motion-corrected MR images, which utilize AI techniques, have also been validated using VSRAD-derived metrics. Conclusions: Quantifying brain atrophy using the VSRAD allows objective evaluation and facilitates the investigation of its association with various diseases. Specifically, VSRAD can be considered a useful adjunctive tool for diagnosing AD and DLB. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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19 pages, 1875 KB

Open AccessArticle

Boosting Working Memory in ADHD: Adaptive Dual N-Back Training Enhances WAIS-IV Performance, but Yields Mixed Corsi Outcomes

by Alessandra Lintas, Michel Bader and Alessandro E. P. Villa

Brain Sci. 2025, 15(9), 998; https://doi.org/10.3390/brainsci15090998 - 16 Sep 2025

Abstract

Background/Objectives: This study investigates the efficacy of working memory training (WMT) using the dual N-back (DNB) task on cognitive performance in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: Over the course of at least 18 daily sessions conducted within one month, 106 participants [...] Read more.

Background/Objectives: This study investigates the efficacy of working memory training (WMT) using the dual N-back (DNB) task on cognitive performance in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: Over the course of at least 18 daily sessions conducted within one month, 106 participants (33 non-medicated ADHD, 42 medicated ADHD, and 45 controls) were randomly assigned to either a fixed dual 1-back (FD1B) training condition or an adaptive DNB condition, wherein the N-back level increased following successful completion of each trial block. Cognitive performance was assessed pre- and post-intervention using the Wechsler Adult Intelligence Scale–Fourth Edition (WAIS-IV) Working Memory Index (WMI) and the Corsi Block-Tapping Task. Results: A mixed-design ANOVA revealed significant improvements in DNB performance across all groups, with the adaptive training condition producing larger gains (e.g., a 204.6% improvement in controls, Cohen’s

d = 1.85

). WAIS-IV WMI scores—particularly the Digit Span Backward subtest—also improved significantly post-training, with greater effect sizes in the adaptive condition (

d = 0.46

) than in FD1B (

d = 0.27

). Corsi performance showed very modest gains, showing a surprising tendency to be more associated with the FD1B condition than the adaptive condition. Control participants outperformed the medicated ADHD group on WAIS-IV subtests, although no significant differences emerged between medicated and non-medicated ADHD participants. Correlational analyses indicated task-specific training effects, with adaptive training enhancing associations between DNB and Corsi performance in both controls (

r = 0.60

) and medicated ADHD participants (

r = 0.51

). Conclusions: This study demonstrates that dual N-back training improves verbal working memory in young adults with ADHD, specifically in a sample without psychiatric comorbidities. Transfer benefit to visuospatial domains appears limited and may not generalize to adolescents, older adults, or individuals with complex clinical profiles. The results underscore the importance of tailoring training protocols to maximize cognitive outcomes across different domains. Full article

(This article belongs to the Section Neurorehabilitation)

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18 pages, 687 KB

Open AccessReview

Positive Clinical Signs in Functional Neurological Disorders: A Narrative Review and Development of a Clinical Decision Tool

by Ioannis Mavroudis, Katerina Franekova, Foivos Petridis, Alin Ciobica, Sotirios Papagiannopoulos and Dimitrios Kazis

Brain Sci. 2025, 15(9), 997; https://doi.org/10.3390/brainsci15090997 - 16 Sep 2025

Abstract

Background: Functional Neurological Disorders (FNDs) encompass a spectrum of disabling conditions, including functional limb weakness, tremor, gait disorders, seizures, and cognitive impairments. While previously diagnosed by exclusion, a growing consensus now supports the use of positive clinical signs as a basis for [...] Read more.

Background: Functional Neurological Disorders (FNDs) encompass a spectrum of disabling conditions, including functional limb weakness, tremor, gait disorders, seizures, and cognitive impairments. While previously diagnosed by exclusion, a growing consensus now supports the use of positive clinical signs as a basis for diagnosis. Despite this paradigm shift, frontline clinicians lack an integrated, accessible clinical tool for guiding diagnostic reasoning across FND subtypes. Objectives: This study aims to (1) synthesize the contemporary evidence on positive clinical signs across major FND subtypes and (2) develop a structured Clinical Decision Tool to support early and confident diagnosis in routine clinical settings. Methods: A focused narrative review was conducted using peer-reviewed publications and neurology reference texts, identifying reproducible positive clinical signs relevant to FND diagnosis. Signs were extracted, tabulated by subtype, and integrated into a modular decision-making framework designed for usability across outpatient, emergency, and specialist contexts. Results: The review identified 60+ positive signs across seven FND subtypes. These include Hoover’s sign for limb weakness, entrainment for tremor, variable responsiveness in NESs, and paradoxical memory performance in Functional Cognitive Disorder. A Clinical Decision Tool was developed, featuring subtype-specific checklists, diagnostic confidence indicators, and red flag alerts, and it is currently available in printable format. Conclusions: This study offers a novel, evidence-based decision tool to facilitate the positive diagnosis of FND. By consolidating observable signs into a practical format, it aims to reduce diagnostic delays, avoid unnecessary investigations, and enhance patient–clinician communication. Future efforts will focus on clinical validation and digital implementation. Full article

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14 pages, 464 KB

Open AccessArticle

Does Music Experience Impact the Vascular Endothelial Response to Singing?

by Mehri Bagherimohamadipour, Muhammad Hammad, Alexis Visotcky, Rodney Sparapani and Jacquelyn Kulinski

Brain Sci. 2025, 15(9), 996; https://doi.org/10.3390/brainsci15090996 - 16 Sep 2025

Abstract

Background: Vascular endothelial function is closely related to brain health, especially in individuals with cardiovascular risk factors. In a randomized, crossover clinical trial (NCT04121741), we have previously shown that 30 min of singing improves microvascular endothelial function in older adults with coronary artery [...] Read more.

Background: Vascular endothelial function is closely related to brain health, especially in individuals with cardiovascular risk factors. In a randomized, crossover clinical trial (NCT04121741), we have previously shown that 30 min of singing improves microvascular endothelial function in older adults with coronary artery disease. Here, we report on secondary and exploratory analyses, including (1) changes in cortisol and cytokine levels and their impact on vascular endothelial function, and (2) the impact of personal music experience on vascular function. Methods: Participants had three study visits separated by 2–7 days, according to a randomized, researcher-blinded, crossover, controlled design: (1) a 30-min period of live singing with an in-person music therapist, (2) a 30-min period of singing along to an instructional video and (3) a 30-min rest (control). Primary outcomes included macrovascular endothelial function assessed by brachial artery flow-mediated dilation (BA FMD%) and microvascular function assessed by peripheral arterial tonometry [Framingham reactive hyperemia index (fRHI) and reactive hyperemia index (RHI)]. Exploratory outcomes included (log) changes in salivary cortisol and cytokine (IL-6, TNF-α, IL-1β, IL-8) levels. Participants were asked to complete the Brief Music Experience Questionnaire (BMEQ), a 53-item validated self-report questionnaire designed to measure an individual’s overall experience with music. The BMEQ assesses how people perceive, react to, and engage with music in various aspects of their lives. Results: Sixty-five subjects (mean age 67.7 ± 6.6 years, 40% female) completed the study. Compared to those subjects completing the BMEQ (n = 31), there were no significant differences in age, sex, race, or presence of diabetes mellitus, hypertension, high cholesterol, heart failure, chronic kidney disease, or chronic respiratory disease in subjects who did not complete the BMEQ (n = 34). Total BMEQ score did not impact changes in BA FMD% (−3.49 ± 2.00, p = 0.086), changes in fRHI (0.58 ± 0.93, p = 0.535), or changes in RHI (0.73 ± 0.65, p = 0.262). When we decompose the sum of squares based on intervention, sex, race, and age, the BMEQ score does not predict changes in vascular function measures. In cross-over analyses, there were no acute changes in salivary cortisol or cytokine levels with 30 min of singing compared to control. Changes in IL-8 were directly related to changes in microvascular endothelial function (0.470 ± 0.184, p = 0.012 for RHI and 0.780 ± 0.248, p = 0.002 for fRHI). Changes in TNF-α were inversely related to changes in fRHI (−0.547 ± 0.263, p = 0.040). Changes in cortisol concentrations were not related to measures of vascular function. Conclusions: The beneficial changes in microvascular endothelial function are not modified by personal music experience in older subjects with known coronary artery disease. There were no changes in salivary cortisol or cytokine levels after 30 min of singing compared to control. Full article

(This article belongs to the Special Issue Rethinking the Role of Applied Auditory and Music Neuroscience to Neurorehabilitation)

20 pages, 1600 KB

Open AccessReview

Acute Vertigo, Dizziness and Imbalance in the Emergency Department—Beyond Stroke and Acute Unilateral Vestibulopathy—A Narrative Review

by Sun-Uk Lee, Jonathan A. Edlow and Alexander A. Tarnutzer

Brain Sci. 2025, 15(9), 995; https://doi.org/10.3390/brainsci15090995 - 15 Sep 2025

Abstract

New-onset vertigo, dizziness and gait imbalance are amongst the most common symptoms presenting to the emergency department, accounting for 2.1–4.4% of all patients. The broad spectrum of underlying causes in these patients cuts across many specialties, which often results in diagnostic challenges. For [...] Read more.

New-onset vertigo, dizziness and gait imbalance are amongst the most common symptoms presenting to the emergency department, accounting for 2.1–4.4% of all patients. The broad spectrum of underlying causes in these patients cuts across many specialties, which often results in diagnostic challenges. For patients meeting the diagnostic criteria for acute vestibular syndrome (AVS, i.e., presenting with acute-onset prolonged vertigo/dizziness with accompanying gait imbalance, motion intolerance, nausea/vomiting, with or without nystagmus), the typical differential diagnosis is vertebrobasilar stroke and acute unilateral vestibulopathy. However, other disorders may also present with AVS. These include non-neurological causes such as drug side-effects or intoxication, electrolyte disturbances, cardiac disease, severe anemia, carbon monoxide poisoning, endocrine disorders and others. Other non-stroke neurological disorders may also present with AVS or episodic vertigo/dizziness, including demyelinating CNS diseases, posterior fossa mass lesions, acute thiamine deficiency and vestibular migraine. Furthermore, acute physiological abnormalities (e.g., hypotension, fever, severe anemia) may unmask previous vestibular impairments that had been well-compensated. Here, we review the diagnostic approach to patients with acute-onset dizziness in the emergency room and discuss the most important differential diagnoses beyond stroke and acute unilateral vestibulopathy. Full article

(This article belongs to the Section Sensory and Motor Neuroscience)

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26 pages, 1276 KB

Open AccessArticle

Adaptation of Better Conversations with Primary Progressive Aphasia to Norwegian

by Ingvild Winsnes, Monica Norvik and Anna Volkmer

Brain Sci. 2025, 15(9), 994; https://doi.org/10.3390/brainsci15090994 - 15 Sep 2025

Abstract

Background/Objectives: People with primary progressive aphasia (PPA) and their communication partners report that having conversations becomes more difficult over time. They want speech and language therapy to help them have better conversations. Communication partner training has shown promise as an approach for people [...] Read more.

Background/Objectives: People with primary progressive aphasia (PPA) and their communication partners report that having conversations becomes more difficult over time. They want speech and language therapy to help them have better conversations. Communication partner training has shown promise as an approach for people with PPA and their communication partners. However, there are currently no communication partner training programs available in Norwegian for people with PPA. The Better Conversations with Primary Progressive Aphasia (BCPPA) is a communication partner training program developed in the UK. In this study, we aimed to culturally adapt the BCPPA to meet the needs of Norwegian people with PPA. Methods: Guided by adaptation elements identified in a systematic review of frameworks for cultural adaptation, we translated the BCPPA into Norwegian before piloting it with four participant dyads, comprising people with PPA and their communication partners. The translated BCPPA was compared to the original BCPPA to identify adherence with core intervention components. Semi-structured interviews were used to explore the acceptability of the intervention to participant dyads. Outcome data, including Goal Attainment Scaling, coding of conversation behaviours from video samples, the Aphasia Impact Questionnaire, and the Communicative Effectiveness Index, were recorded pre-, post-, and three months after intervention delivery to explore outcomes for Norwegian participant dyads. We used the Framework for Reporting Adaptations and Modifications-Enhanced to document the modifications. Results: The results indicate high adherence to the core components in the original BCPPA. The pilot demonstrated that the participant dyads found the BCPPA acceptable, but they made some additional suggestions to complete the cultural adaptation further. Despite the progressive nature of PPA, the participant dyads achieved their goals on the Goal Attainment Scaling, and group analysis demonstrated maintenance on the Aphasia Impact Questionnaire and the Communicative Effectiveness Index over the three time points. Conclusions: This study demonstrates that the Norwegian version of the BCPPA was acceptable to the participants with PPA and their communication partner in this study. As the first communication partner training program for people with PPA and their communication partners in Norwegian, the BCPPA has the potential to be a valuable treatment tool to support people affected by PPA to have better conversations. Full article

(This article belongs to the Special Issue Primary Progressive Aphasia: What Happens to Speech and Language? What Can We Do to Help?)

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14 pages, 302 KB

Open AccessArticle

Validity of the Japanese Version of the Weekly Calendar Planning Activity (WCPA)-10 on Assessing Executive Function in Patients with Acquired Brain Injury (ABI)

by Asako Matsubara, Yasuhiro Higashi, Mio Kawabata and Katsunobu Sugihara

Brain Sci. 2025, 15(9), 993; https://doi.org/10.3390/brainsci15090993 - 15 Sep 2025

Abstract

Background: The Weekly Calendar Planning Activity (WCPA) is one of the assessments of functional cognition, including executive function, by the cognitive instrumental activities of daily living (C-IADL). It is translated and adapted in many countries, but not in Japan. Methods: This [...] Read more.

Background: The Weekly Calendar Planning Activity (WCPA) is one of the assessments of functional cognition, including executive function, by the cognitive instrumental activities of daily living (C-IADL). It is translated and adapted in many countries, but not in Japan. Methods: This study aimed to examine the validity of the Japanese version of the WCPA-10 (WCPA-10-J) in patients with acquired brain injury (ABI), and to explore the characteristics of cognitive strategy use among that population. Fifty-three patients with ABI aged 27–81 years and 52 healthy controls (HCs) completed the WCPA-10-J, three neuropsychological tests, and the assessment of the instrumental activities of daily living (IADL). Results: Results demonstrated that the WCPA-10-J was able to discriminate between the patients with ABI and the HCs. We found significant limitations in ABI patients’ ability to use strategies. Concurrent, convergent, and ecological validities were partly demonstrated through correlations between the neuropsychological test scores, IADL, and the WCPA-10-J performance. Conclusions: This study provides initial evidence for the validity of the WCPA-10-J for patients with ABI and suggests the need to use performance-based tests even in patients with normal cognitive screening test results. The WCPA-10-J could provide useful information for strategy-based interventions for patients with ABI. Full article

(This article belongs to the Special Issue The Impact of Stroke on Functional Cognition and Rehabilitation Approaches)

15 pages, 265 KB

Open AccessArticle

Challenges in the Management of Cavernoma-Related Epilepsy: Seizure Outcomes, Antiseizure Medication Practices, and Access to Intraoperative Technologies in Kazakhstan

by Karashash Menlibayeva, Chingiz Nurimanov, Iroda Mammadinova, Ainur Turzhanova, Serik Akshulakov and Yerbol Makhambetov

Brain Sci. 2025, 15(9), 992; https://doi.org/10.3390/brainsci15090992 - 15 Sep 2025

Abstract

Objective: This study aims to analyze the diagnostic patterns of cavernoma-related epilepsy, the management of antiseizure medications, and clinical outcomes following microsurgical treatment in patients with late-diagnosed epilepsy secondary to cavernous malformations in the Central Asian region. Methods: A retrospective cross-sectional study was [...] Read more.

Objective: This study aims to analyze the diagnostic patterns of cavernoma-related epilepsy, the management of antiseizure medications, and clinical outcomes following microsurgical treatment in patients with late-diagnosed epilepsy secondary to cavernous malformations in the Central Asian region. Methods: A retrospective cross-sectional study was conducted on 60 patients who underwent microsurgical resection for brain cavernous malformations over a 12-year period (2010–2022) at the National Centre for Neurosurgery, Astana, Kazakhstan. All participants were 18 years or older and presented with seizures. Follow-up evaluations were conducted by neurologists, and seizure outcomes were assessed using the 2017 classification criteria of the International League Against Epilepsy. Results: The mean follow-up period was 83.77 ± 39.81 months. In total, 51.67% of participants demonstrated positive ILAE outcomes, 33.33% had moderate ILAE outcomes, and the remaining 15.00% experienced negative ILAE outcomes. Approximately 47% of patients received antiseizure medication before surgery, primarily as monotherapy with carbamazepine (33%), and administered at a low dose (40%). Early microsurgical resection showed a positive post-surgery seizure outcome. Approximately 67% of patients who experienced seizures within one year prior to surgery showed positive ILAE outcomes, whereas those with a seizure history extending beyond five years were roughly 32% seizure-free (p = 0.01). Conclusions. Cavernoma-related epilepsy in Central Asia remains a significant clinical challenge, particularly with respect to diagnostic accuracy and antiseizure medication management. In our cohort, only approximately half of patients achieved favorable seizure control following microsurgical resection. Notably, early surgical intervention within one year of seizure onset was associated with improved outcomes, whereas delayed surgery, restricted availability of intraoperative technologies, and suboptimal antiseizure medication practices were linked to less favorable outcomes. Strengthening diagnostic pathways, antiseizure medication management, and expanding access to advanced surgical technologies are critical steps to improving treatment outcomes in a studied patient population. Full article

(This article belongs to the Special Issue The Latest Exploration of Cerebrovascular Diseases: From Preclinical Research to Treatment)

16 pages, 2716 KB

Open AccessArticle

Language Learning as a Non-Pharmacological Intervention in Older Adults with (Past) Depression

by Jelle Brouwer, Floor van den Berg, Remco Knooihuizen, Hanneke Loerts and Merel Keijzer

Brain Sci. 2025, 15(9), 991; https://doi.org/10.3390/brainsci15090991 - 15 Sep 2025

Abstract

Background: Language learning has been proposed as a non-pharmacological intervention to promote healthy aging. This intervention has not been studied in older adults with a history of depression, who experience high prevalence of cognitive dysfunction. This small-scale study was the first to investigate [...] Read more.

Background: Language learning has been proposed as a non-pharmacological intervention to promote healthy aging. This intervention has not been studied in older adults with a history of depression, who experience high prevalence of cognitive dysfunction. This small-scale study was the first to investigate the potential efficacy of language learning in older adults with (past) depression. Methods: Data on psychosocial well-being, cognitive functioning, and language outcomes were collected in nineteen participants with (past) depression (M = 69.7 years old, SD = 2.9; 79% women, 21% men) and a control group of fifteen older adults without depression in the past 25 years (M = 70.1 years old, SD = 3.8; 60% women, 40% men). Data were collected before, immediately after, and four months after completing a three-month language course. Results: Participants with (past) depression showed significant decreases in apathy, social loneliness, and cognitive failures, and increases in associative memory and global cognition. The control group improved on associative memory and letter-number sequencing. Both groups improved in linguistic self-confidence and lexical access to English, while the group with (past) depression also improved on listening and speaking proficiency. Conclusions: The intervention had limited benefits for cognition and psychosocial well-being, but (longer) group-based learning interventions may build up social and motivational reserves protecting against morbidity. Research with larger samples and a no-training control sample is needed to further support these findings. Full article

(This article belongs to the Special Issue Advances in Speech and Language Research for Cognitive Well-Being in Aging)

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