Brain Sciences

4 pages, 177 KiB

Open AccessEditorial

Understanding Mental Health in Autism: A Lifespan Perspective

by Domingo García-Villamisar, María Álvarez-Couto and Gema Pilar Sáez-Suanes

Brain Sci. 2025, 15(7), 774; https://doi.org/10.3390/brainsci15070774 - 21 Jul 2025

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Understanding and studying the mental health of people with ASD across the spectrum, from childhood to adulthood, is undoubtedly a pressing need and a challenge [...] Full article

(This article belongs to the Special Issue Exploring the Mental Health of People with Autism)

11 pages, 1629 KiB

Open AccessArticle

The Effects of Carotid Pathologies on Short-Term Functional Outcomes After First-Ever Small Vessel Occlusion Stroke

by Minwook Bae, Yong-Suk Jeong, Sopheak Phoung, Phoeuk Borei, Dahyeon Koo and Dougho Park

Brain Sci. 2025, 15(7), 773; https://doi.org/10.3390/brainsci15070773 - 20 Jul 2025

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Abstract

Background: While carotid pathologies are well-established risk factors for stroke, their specific effects on outcomes following stroke that cannot be classified as atherosclerotic remain unclear. In this study, we aimed to determine whether carotid pathologies are associated with functional dependence (FD) 3 months [...] Read more.

Background: While carotid pathologies are well-established risk factors for stroke, their specific effects on outcomes following stroke that cannot be classified as atherosclerotic remain unclear. In this study, we aimed to determine whether carotid pathologies are associated with functional dependence (FD) 3 months after small vessel occlusion (SVO) stroke. Methods: This retrospective study included patients with a first-ever SVO stroke admitted to a single cerebrovascular-specialty hospital between October 2021 and March 2024. Standardized ultrasound criteria were used to grade the carotid plaques. The modified Rankin scale (mRS) was used to assess functional outcomes at 3 months. Logistic regression analysis was performed to identify FD predictors (mRS of ≥2). Results: Of the 372 included patients, 276 achieved functional independence and 96 experienced FD at 3 months. Univariable analysis revealed an association between carotid plaque grade III and FD (odds ratio [OR], 2.46; 95% confidence interval [CI], 1.05–6.51; p = 0.049). However, this association was not significant in the multivariable model. Overall, age (adjusted OR, 1.07; 95% CI 1.03–1.10, p < 0.001), NIHSS at initial presentation (adjusted OR, 1.84; 95% CI, 1.55–2.18; p < 0.001), and diabetes (adjusted OR, 2.84; 95% CI, 1.37–5.92; p = 0.005) were independently associated with FD 3 months after SVO stroke. Conclusions: Carotid plaque severity was not independently associated with functional outcomes 3 months after SVO stroke. Age, NIHSS at initial presentation, and diabetes were identified as independent FD predictors. Future in-depth studies are warranted to confirm the complex interplay of factors influencing functional outcomes in patients with SVO stroke and carotid pathologies simultaneously. Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

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23 pages, 16941 KiB

Open AccessArticle

Functional Importance Backbones of the Brain at Rest, Wakefulness, and Sleep

by Klaus Lehnertz and Timo Bröhl

Brain Sci. 2025, 15(7), 772; https://doi.org/10.3390/brainsci15070772 - 20 Jul 2025

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Abstract

Background: The brain is never truly at rest. Even in the absence of external tasks, it remains active, continuously organizing itself into large-scale resting-state networks involved in shaping our internal thoughts and experiences. Understanding the networks’ structure and dynamics is key to [...] Read more.

Background: The brain is never truly at rest. Even in the absence of external tasks, it remains active, continuously organizing itself into large-scale resting-state networks involved in shaping our internal thoughts and experiences. Understanding the networks’ structure and dynamics is key to uncovering how the brain functions as a whole. While previous studies have mapped resting-state networks and explored the roles of individual brain regions (network vertices), the relevance of the time-dependent functional interactions (network edges) between them remains largely unexplored. Methods: Here, we assess this relevance by elucidating the time-evolving importance of both brain regions and their interactions, associated with the networks’ constituents, using the fundamental concept of centrality. We investigate long-term electrophysiological recordings of brain dynamics from more than 100 participants and reveal new insights into how resting-state networks are organized over longer times. Results: Our findings reveal that the functional architecture of brain networks in a resting state is critically shaped by the dynamic interplay between brain regions. We identified functional importance backbones–core sets of dynamically central vertices and edges–whose configuration varies significantly between subgroups and further varies with different brain states, including wakefulness and sleep. Notably, regions associated with the default mode network exhibited adaptable patterns of centrality, challenging the notion of static network cores. Conclusions: By considering the temporal evolution of both vertices and edges, we provide a more comprehensive understanding of intrinsic brain activity and its functional relevance. This dynamic perspective reveals how the brain’s intrinsic activity is coordinated across space and time, highlighting the existence of functional importance backbones that adapt to different brain states. Full article

(This article belongs to the Special Issue Understanding the Functioning of Brain Networks in Health and Disease)

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12 pages, 1530 KiB

Open AccessArticle

Evaluation of Intracochlear Pressure and Fluid Distribution in 3D-Printed Artificial Cochlear Models and Human Petrous Bones

by Rayoung Kim, Matthias Schürmann, Lars-Uwe Scholtz and Ingo Todt

Brain Sci. 2025, 15(7), 771; https://doi.org/10.3390/brainsci15070771 - 20 Jul 2025

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Abstract

Introduction: The important factor in applying substances for inner ear therapy is the atraumatic execution, as well as effective concentration uniformly distributed in all regions of the cochlea within a reasonable time frame. This study investigates whether an additional cochlear opening (“second-hole technique”) [...] Read more.

Introduction: The important factor in applying substances for inner ear therapy is the atraumatic execution, as well as effective concentration uniformly distributed in all regions of the cochlea within a reasonable time frame. This study investigates whether an additional cochlear opening (“second-hole technique”) can improve fluid distribution and reduce intracochlear pressure during dye delivery into the cochlear models and human petrous bone. Material and Methods: Three experimental setups were used: an uncoiled scala tympani model, a full-scale 3D-printed cochlear model, and a human petrous bone. In all cases, 1% methylene blue-stained saline was infused using a cochlear catheter (MED-EL, Innsbruck, Austria) through the round window. Intracochlear pressure was measured via fiberoptic pressure sensors inserted through a burr hole (artificial cochlear models) or at the lateral semicircular canal (human petrous bone). A second hole was made on the helicotrema in the inner ear models or at the oval window of the human petrous bone to examine the effect of a second hole on intracochlear pressure and fluid distribution. Dye distribution and intracochlear pressure were measured in 3D artificial models at two flow rates (0.2 and 0.4 mL/h). The intracochlear pressure were measured in the human petrous bone at a fixed rate (0.4 mL/h). Results: The use of a second hole significantly improved dye distribution in 3D models at both flow rates (p < 0.05) and led to earlier saturation-level distribution. Intracochlear pressure remained significantly lower and more stable in models with a second hole (p < 0.05). In human petrous bones, pressure fluctuation was reduced by the second hole, though pressure still increased over time. Conclusions: Using a second-hole technique leads to a faster, uniform level of dye distribution throughout the cochlear models, as well as a lower intracochlear pressure, which can be assumed to be an essential factor for hearing preservation during dye application. Full article

(This article belongs to the Special Issue Recent Advances in Hearing Impairment: 2nd Edition)

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17 pages, 1098 KiB

Open AccessArticle

Attentional Functioning in Healthy Older Adults and aMCI Patients: Results from the Attention Network Test with a Focus on Sex Differences

by Laura Facci, Laura Sandrini and Gabriella Bottini

Brain Sci. 2025, 15(7), 770; https://doi.org/10.3390/brainsci15070770 - 19 Jul 2025

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Abstract

Background/Objectives: The prognostic uncertainty of Mild Cognitive Impairment (MCI) imposes comprehensive neuropsychological evaluations beyond mere memory assessment. However, previous investigations into other cognitive domains, such as attention, have yielded divergent findings. Furthermore, while evidence suggests the presence of sex differences across the [...] Read more.

Background/Objectives: The prognostic uncertainty of Mild Cognitive Impairment (MCI) imposes comprehensive neuropsychological evaluations beyond mere memory assessment. However, previous investigations into other cognitive domains, such as attention, have yielded divergent findings. Furthermore, while evidence suggests the presence of sex differences across the spectrum of dementia-related conditions, no study has systematically explored attentional disparities between genders within this context. The current study aims to investigate differences in the attentional subcomponents, i.e., alerting, orienting, and executive control, between patients with MCI and healthy older controls (HOCs), emphasizing interactions between biological sex and cognitive impairment. Methods: Thirty-six participants (18 MCI, and 18 HOCs) were evaluated using the Attention Network Test (ANT). Raw RTs as well as RTs corrected for general slowing were analyzed using Generalized Mixed Models. Results: Both health status and sex influenced ANT performance, when considering raw RTs. Nevertheless, after adjusting for the baseline processing speed, the effect of cognitive impairment was no longer evident in men, while it persisted in women, suggesting specific vulnerabilities in females not attributable to general slowing nor to the MCI diagnosis. Moreover, women appeared significantly slower and less accurate when dealing with conflicting information. Orienting and alerting did not differ between groups. Conclusions: To the best of our knowledge, this is the first study investigating sex differences in attentional subcomponents in the aging population. Our results suggest that previously reported inconsistencies about the decline of attentional subcomponents may be attributable to such diversities. Systematically addressing sex differences in cognitive decline appears pivotal for informing the development of precision medicine approaches. Full article

(This article belongs to the Special Issue Heterogeneity in Cognitive Aging: From Healthy Aging to Neurodegenerative Disease)

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23 pages, 1580 KiB

Open AccessArticle

Elucidating White Matter Contributions to the Cognitive Architecture of Affective Prosody Recognition: Evidence from Right Hemisphere Stroke

by Meyra S. Jackson, Yuto Uchida, Shannon M. Sheppard, Kenichi Oishi, Ciprian Crainiceanu, Argye E. Hillis and Alexandra Z. Durfee

Brain Sci. 2025, 15(7), 769; https://doi.org/10.3390/brainsci15070769 - 19 Jul 2025

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Abstract

Background/Objectives: Successful discourse relies not only on linguistic but also on prosodic information. Difficulty recognizing emotion conveyed through prosody (receptive affective aprosodia) following right hemisphere stroke (RHS) significantly disrupts communication participation and personal relationships. Growing evidence suggests that damage to white matter [...] Read more.

Background/Objectives: Successful discourse relies not only on linguistic but also on prosodic information. Difficulty recognizing emotion conveyed through prosody (receptive affective aprosodia) following right hemisphere stroke (RHS) significantly disrupts communication participation and personal relationships. Growing evidence suggests that damage to white matter in addition to gray matter structures impairs affective prosody recognition. The current study investigates lesion–symptom associations in receptive affective aprosodia during RHS recovery by assessing whether disruptions in distinct white matter structures impact different underlying affective prosody recognition skills. Methods: Twenty-eight adults with RHS underwent neuroimaging and behavioral testing at acute, subacute, and chronic timepoints. Fifty-seven healthy matched controls completed the same behavioral testing, which comprised tasks targeting affective prosody recognition and underlying perceptual, cognitive, and linguistic skills. Linear mixed-effects models and multivariable linear regression were used to assess behavioral performance recovery and lesion–symptom associations. Results: Controls outperformed RHS participants on behavioral tasks earlier in recovery, and RHS participants’ affective prosody recognition significantly improved from acute to chronic testing. Affective prosody and emotional facial expression recognition were affected by external capsule and inferior fronto-occipital fasciculus lesions while sagittal stratum lesions impacted prosodic feature recognition. Accessing semantic representations of emotions implicated the superior longitudinal fasciculus. Conclusions: These findings replicate previously observed associations between right white matter tracts and affective prosody recognition and further identify lesion–symptom associations of underlying prosodic recognition skills throughout recovery. Investigation into prosody’s behavioral components and how they are affected by injury can help further intervention development and planning. Full article

(This article belongs to the Special Issue Language, Communication and the Brain—2nd Edition)

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23 pages, 1135 KiB

Open AccessSystematic Review

Intraoperative Neurophysiological Monitoring in Contemporary Spinal Surgery: A Systematic Review of Clinical Outcomes and Cost-Effectiveness

by Luca Zanin, Laura Broglio, Pier Paolo Panciani, Riccardo Bergomi, Giorgia De Rosa, Luca Ricciardi, Giusy Guzzi, Alessandro Fiorindi, Carlo Brembilla, Francesco Restelli, Francesco Costa, Nicola Montemurro and Marco Maria Fontanella

Brain Sci. 2025, 15(7), 768; https://doi.org/10.3390/brainsci15070768 - 19 Jul 2025

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Abstract

Background: Intraoperative neurophysiological monitoring (IONM) is increasingly used during spinal surgery to reduce the risk of neurological complications. This systematic review evaluates both the clinical outcomes and cost-effectiveness of IONM in contemporary spinal surgery. Methods: A comprehensive literature search was conducted to identify [...] Read more.

Background: Intraoperative neurophysiological monitoring (IONM) is increasingly used during spinal surgery to reduce the risk of neurological complications. This systematic review evaluates both the clinical outcomes and cost-effectiveness of IONM in contemporary spinal surgery. Methods: A comprehensive literature search was conducted to identify studies evaluating IONM in spinal surgery. Twenty-three studies were included: twenty-one reporting clinical outcomes and two focusing on economic analysis. Data on neurological deficits, monitoring accuracy, and cost-effectiveness were extracted and analyzed. Results: Analysis of the included studies showed that IONM reduced the risk of neurological deficits across various types of spinal surgery. The diagnostic accuracy varied by modality, with MEP showing the highest sensitivity (90.2%) and SSEP demonstrating high specificity (97.1%). The greatest benefit was observed in deformity surgery and spinal tumors. D-wave monitoring showed efficacy for intramedullary tumors. Economic analysis demonstrated that IONM is cost-effective when the neurological complication rate exceeds 0.3%, with potential savings of over USD 23,000 per case. Conclusions: IONM significantly improves neurological outcomes in spinal surgery and is cost-effective in most clinical scenarios, particularly in high-risk procedures. Multimodal monitoring approaches provide the most comprehensive neurological assessment. These findings support the routine use of IONM in contemporary spinal surgery, especially for complex cases. Full article

(This article belongs to the Special Issue Contemporary Spinal Surgery: Surgical Optimization and Technological Innovation)

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22 pages, 1226 KiB

Open AccessReview

Neurobiology of Dystonia: Review of Genetics, Animal Models, and Neuroimaging

by Jamir Pitton Rissardo, Andrew McGarry, Yiwen Shi, Ana Leticia Fornari Caprara and Ian M. Walker

Brain Sci. 2025, 15(7), 767; https://doi.org/10.3390/brainsci15070767 - 19 Jul 2025

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Abstract

Over the past decade, substantial progress has been made in understanding the pathophysiology of dystonia. The number of identified genes has surged—exceeding 400 by 2024—with approximately 76.6% linked to neurodevelopmental disorders. Despite this, the genetic diagnostic yield remains modest (12–36%), and many newly [...] Read more.

Over the past decade, substantial progress has been made in understanding the pathophysiology of dystonia. The number of identified genes has surged—exceeding 400 by 2024—with approximately 76.6% linked to neurodevelopmental disorders. Despite this, the genetic diagnostic yield remains modest (12–36%), and many newly discovered genes have yet to reveal novel mechanistic insights. The limited number of studies exploring dystonia-related pathways in animal models restricts the generalizability of findings to human disease, raising concerns about their external validity. Developing experimental models remains a challenge, particularly given the importance of critical developmental windows—periods during central nervous system maturation when disruptions can have lasting effects. Some models also exhibit delayed symptom onset, prompting a shift toward faster-developing organisms such as Drosophila. There is a pressing need for standardized, scalable protocols that enable precise evaluation of specific neural tissues. Advances in neuroimaging have improved our understanding of dystonia-related brain networks at both regional and whole-brain levels. The emerging concept of “network kernels” has provided new perspectives on brain connectivity. However, future imaging studies should incorporate effective connectivity analyses to distinguish between hemodynamic and neuronal contributions and to clarify neurobiological pathways. This review synthesizes current knowledge from genetics, animal models, and neuroimaging to present an integrated view of dystonia’s neurobiological underpinnings. Full article

(This article belongs to the Topic Advances in Motor Control and Neuromotor Interfacing in Sports)

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13 pages, 691 KiB

Open AccessReview

Sleep and Risk of Multiple Sclerosis: Bridging the Gap Between Inflammation and Neurodegeneration via Glymphatic Failure

by Mariateresa Buongiorno, Carmen Tur, Darly Milena Giraldo, Natalia Cullell, Jerzy Krupinski, Roberta Lanzillo and Gonzalo Sánchez-Benavides

Brain Sci. 2025, 15(7), 766; https://doi.org/10.3390/brainsci15070766 - 19 Jul 2025

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Abstract

Epidemiological studies identified insufficient and poor-quality sleep as independent risk factors for multiple sclerosis (MS). The glymphatic system, active during slow-wave sleep, clears brain waste through perivascular astrocytic aquaporin-4 (AQP4) channels. The presence of antigens induces a transient, physiological lowering of glymphatic flux [...] Read more.

Epidemiological studies identified insufficient and poor-quality sleep as independent risk factors for multiple sclerosis (MS). The glymphatic system, active during slow-wave sleep, clears brain waste through perivascular astrocytic aquaporin-4 (AQP4) channels. The presence of antigens induces a transient, physiological lowering of glymphatic flux as a first step of an inflammatory response. A possible hypothesis linking infection with the Epstein–Barr virus, a well identified causal step in MS, and the development of the disease is that mechanisms such as poor sleep or less functional AQP4 polymorphisms may sustain glymphatic flow reduction. Such chronic glymphatic reduction would trigger a vicious circle in which the persistence of antigens and an inflammatory response maintains glymphatic dysfunction. In addition, viral proteins that persist in demyelinated plaques can depolarize AQP4, further restricting waste elimination and sustaining local inflammation. This review examines the epidemiological evidence connecting sleep and MS risk, and the mechanistic findings showing how poor sleep and other glymphatic modulators heighten inflammatory signaling implicated in MS pathogenesis. Deepening knowledge of glymphatic functioning in MS could open new avenues for personalized prevention and therapy. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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15 pages, 802 KiB

Open AccessArticle

Differential Cortical Activations Among Young Adults Who Fall Versus Those Who Recover Successfully Following an Unexpected Slip During Walking

by Rudri Purohit, Shuaijie Wang and Tanvi Bhatt

Brain Sci. 2025, 15(7), 765; https://doi.org/10.3390/brainsci15070765 - 18 Jul 2025

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Abstract

Background: Biomechanical and neuromuscular differences between falls and recoveries have been well-studied; however, the cortical correlations remain unclear. Using mobile brain imaging via electroencephalography (EEG), we examined differences in sensorimotor beta frequencies between falls and recoveries during an unpredicted slip in walking. Methods [...] Read more.

Background: Biomechanical and neuromuscular differences between falls and recoveries have been well-studied; however, the cortical correlations remain unclear. Using mobile brain imaging via electroencephalography (EEG), we examined differences in sensorimotor beta frequencies between falls and recoveries during an unpredicted slip in walking. Methods: We recruited 22 young adults (15 female; 18–35 years) who experienced a slip (65 cm) during walking. Raw EEG signals were band-pass filtered, and independent component analysis was performed to remove non-neural sources, eventually three participants were excluded due to excessive artifacts. Peak beta power was extracted from three time-bins: 400 milliseconds pre-, 0–150 milliseconds post and 150–300 milliseconds post-perturbation from the midline (Cz) electrode. A 2 × 3 Analysis of Covariance assessed the interaction between time-bins and group on beta power, followed by Independent and Paired t-tests for between and within-group post hoc comparisons. Results: All participants (n = 19) experienced a balance loss, seven experienced a fall. There was a time × group interaction on beta power (p < 0.05). With no group differences pre-perturbation, participants who experienced a fall exhibited higher beta power during 0–150 milliseconds post-perturbation than those who recovered (p < 0.001). However, there were no group differences in beta power during 150–300 milliseconds post-perturbation. Conclusions: Young adults exhibiting a greater increase in beta power during the early post-perturbation period experienced a fall, suggesting a higher cortical error detection due to a larger mismatch in the expected and ongoing postural state and greater cortical dependence for sensorimotor processing. Our study results provide an overview of the possible cortical governance to modulate slip-fall/recovery outcomes. Full article

(This article belongs to the Section Behavioral Neuroscience)

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18 pages, 4488 KiB

Open AccessSystematic Review

Mental Health and Quality of Life in Patients with Untreated Unruptured Intracranial Aneurysms: A Systematic Review and Meta-Analysis of 417,152 Patients with Trial Sequential Analysis

by Plamen Penchev, Kiril Ivanov, Daniela Milanova-Ilieva, Lyubomir Gaydarski, Kiril Kostov, Nikola Boyadzhiev, Petar-Preslav Petrov, Patrice Mehandzhiev, Remzi Hyusein, Vladislav Velchev, Ilko Ilyov, Valentin Kuzmanov, Gergana Dzhikova, Desislava Dobreva, Liliana Toptchiyska, Vasilena Dimitrova, Victoria Petrova, Svetoslav Yorov, Pavel Stanchev, Martin Gyulbaharov, Noor Husain and Nikolai Ramadanov Show full author list Hide full author list

Brain Sci. 2025, 15(7), 764; https://doi.org/10.3390/brainsci15070764 - 18 Jul 2025

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Abstract

Introduction: Unruptured intracranial aneurysms (UIAs) can induce psychological stress, leading to anxiety, depression, and impaired quality of life (QoL). Most studies on this topic are limited by small sample sizes, cross-sectional designs, and a focus on treated rather than untreated cases, leaving a [...] Read more.

Introduction: Unruptured intracranial aneurysms (UIAs) can induce psychological stress, leading to anxiety, depression, and impaired quality of life (QoL). Most studies on this topic are limited by small sample sizes, cross-sectional designs, and a focus on treated rather than untreated cases, leaving a gap in the literature. We aimed to conduct a systematic review and meta-analysis to evaluate mental health and QoL outcomes in patients with untreated UIAs. Methods: A systematic search was conducted up to 30 November 2024 using PubMed, Scopus, and Cochrane Central for studies comparing patients with untreated UIAs to a control group. The outcomes of interest included anxiety, depression, and QoL. Statistical analysis was performed using RevMan 5.1.7 and R 4.3.1. Heterogeneity was assessed using I² statistics and the Cochrane Q test. Risk ratios (RR) and standardized mean differences (SMD) were computed using a frequentist random-effects model. Results: We included five studies with 417,152 patients, of whom 85,668 (20.53%) had untreated UIAs. In the pooled analysis, patients with untreated UIAs had significantly higher anxiety levels (SMD 0.66; 95% CI [0.16; 1.17]; p = 0.01; I² = 76%) and lower QoL (SMD −0.82; 95% CI [−1.12; −0.53]; p = 0.01; I² = 56%) compared to the control group However, no statistically significant differences were found in depression (RR 0.94; 95% CI [0.52; 1.72]; p = 0.84; I² = 88%) between groups. Conclusions: This meta-analysis indicates a potential association between untreated UIAs and increased anxiety levels and reduced QoL. Regarding depression, no significant differences were observed between groups. Full article

(This article belongs to the Special Issue Current Advances in Intracranial Aneurysms: From Basic to Clinical Research)

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19 pages, 836 KiB

Open AccessArticle

The Multimodal Rehabilitation of Complex Regional Pain Syndrome and Its Contribution to the Improvement of Visual–Spatial Memory, Visual Information-Processing Speed, Mood, and Coping with Pain—A Nonrandomized Controlled Trial

by Justyna Wiśniowska, Iana Andreieva, Dominika Robak, Natalia Salata and Beata Tarnacka

Brain Sci. 2025, 15(7), 763; https://doi.org/10.3390/brainsci15070763 - 18 Jul 2025

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Abstract

Objectives: To investigate whether a Multimodal Rehabilitation Program (MRP) affects the change in visual–spatial abilities, especially attention, information-processing speed, visual–spatial learning, the severity of depression, and strategies for coping with pain in Complex Regional Pain Syndrome (CRPS) participants. Methods: The study [...] Read more.

Objectives: To investigate whether a Multimodal Rehabilitation Program (MRP) affects the change in visual–spatial abilities, especially attention, information-processing speed, visual–spatial learning, the severity of depression, and strategies for coping with pain in Complex Regional Pain Syndrome (CRPS) participants. Methods: The study was conducted between October 2021 and February 2023, with a 4-week rehabilitation program that included individual physiotherapy, manual and physical therapy, and psychological intervention such as psychoeducation, relaxation, and Graded Motor Imagery therapy. Twenty participants with CRPS and twenty healthy participants, forming a control group, were enlisted. The study was a 2-arm parallel: a CRPS group with MRP intervention and a healthy control group matched to the CRPS group according to demographic variables. Before and after, the MRP participants in the CRPS group were assessed for visual–spatial learning, attention abilities, severity of depression, and pain-coping strategy. The healthy control group underwent the same assessment without intervention before two measurements. The primary outcome measure was Reproduction on Rey–Osterrieth’s Complex Figure Test assessing visual–spatial learning. Results: In the post-test compared to the pre-test, the participants with CRPS obtained a significantly high score in visual–spatial learning (p < 0.01) and visual information-processing speed (p = 0.01). They made significantly fewer omission mistakes in visual working memory (p = 0.01). After the MRP compared to the pre-test, the CRPS participants indicated a decrease in the severity of depression (p = 0.04) and used a task-oriented strategy for coping with pain more often than before the rehabilitation program (p = 0.02). Conclusions: After a 4-week MRP, the following outcomes were obtained: an increase in visual–spatial learning, visual information-processing speed, a decrease in severity of depression, and a change in the pain-coping strategies—which became more adaptive. Full article

(This article belongs to the Section Neurorehabilitation)

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16 pages, 317 KiB

Open AccessPerspective

Listening to the Mind: Integrating Vocal Biomarkers into Digital Health

by Irene Rodrigo and Jon Andoni Duñabeitia

Brain Sci. 2025, 15(7), 762; https://doi.org/10.3390/brainsci15070762 - 18 Jul 2025

Viewed by 441

Abstract

The human voice is an invaluable tool for communication, carrying information about a speaker’s emotional state and cognitive health. Recent research highlights the potential of acoustic biomarkers to detect early signs of mental health and neurodegenerative conditions. Despite their promise, vocal biomarkers remain [...] Read more.

The human voice is an invaluable tool for communication, carrying information about a speaker’s emotional state and cognitive health. Recent research highlights the potential of acoustic biomarkers to detect early signs of mental health and neurodegenerative conditions. Despite their promise, vocal biomarkers remain underutilized in clinical settings, with limited standardized protocols for assessment. This Perspective article argues for the integration of acoustic biomarkers into digital health solutions to improve the detection and monitoring of cognitive impairment and emotional disturbances. Advances in speech analysis and machine learning have demonstrated the feasibility of using voice features such as pitch, jitter, shimmer, and speech rate to assess these conditions. Moreover, we propose that singing, particularly simple melodic structures, could be an effective and accessible means of gathering vocal biomarkers, offering additional insights into cognitive and emotional states. Given its potential to engage multiple neural networks, singing could function as an assessment tool and an intervention strategy for individuals with cognitive decline. We highlight the necessity of further research to establish robust, reproducible methodologies for analyzing vocal biomarkers and standardizing voice-based diagnostic approaches. By integrating vocal analysis into routine health assessments, clinicians and researchers could significantly advance early detection and personalized interventions for cognitive and emotional disorders. Full article

(This article belongs to the Topic Language: From Hearing to Speech and Writing)

18 pages, 3116 KiB

Open AccessArticle

Effects of Probiotic Supplementation on Depressive Symptoms, Sleep Quality, and Modulation of Gut Microbiota and Inflammatory Biomarkers: A Randomized Controlled Trial

by S Rehan Ahmad, Abdullah M. AlShahrani and Anupriya Kumari

Brain Sci. 2025, 15(7), 761; https://doi.org/10.3390/brainsci15070761 - 18 Jul 2025

Viewed by 1010

Abstract

Background: More than merely determining our sleep pattern, our body’s internal clock also improves the quality of our sleep, alleviates the symptoms of depression, and maintains the balance of our gut flora. Methods: We carried out a 12-week randomized controlled trial with 99 [...] Read more.

Background: More than merely determining our sleep pattern, our body’s internal clock also improves the quality of our sleep, alleviates the symptoms of depression, and maintains the balance of our gut flora. Methods: We carried out a 12-week randomized controlled trial with 99 adults from Kolkata, New Delhi, and Pune who reported sleep problems and symptoms of depression or anxiety. Participants received either a probiotic formulated to improve sleep quality and reduce depressive symptoms or a placebo. We tracked sleep using overnight studies and wearable devices, assessed depressive symptoms with standardized questionnaires, and analyzed stool samples to profile gut bacteria and their metabolites using gene sequencing and metabolomics. Advanced statistics and machine learning helped us pinpoint the key microbial and metabolic factors tied to sleep and mental health. Results: At the start, participants with disrupted sleep and depressive symptoms had fewer beneficial gut bacteria like Bifidobacterium and Lactobacillus, more inflammation-related microbes, and lower levels of helpful short-chain fatty acids. These imbalances were linked to poorer sleep efficiency, less REM sleep, and higher depression and anxiety scores. After 12 weeks, those taking the circadian-supporting probiotic saw a statistically significant increase in beneficial gut bacteria, improved sleep efficiency (+7.4%, p = 0.02), and greater reductions in depression and anxiety compared to the placebo. Increases in SCFA-producing bacteria most strongly predicted improvements. Conclusions: Our results show that taking a probiotic supplement can help bring your gut back into balance, support better sleep, and lift symptoms of depression and anxiety. This offers a hopeful and practical option for people looking for real relief from these deeply connected challenges. Full article

(This article belongs to the Special Issue Relationships Between Disordered Sleep and Mental Health)

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18 pages, 513 KiB

Open AccessPerspective

The Use of Non-Invasive Brain Stimulation for the Management of Chronic Musculoskeletal Pain: Fad or Future?

by Philippe Patricio and Hugo Massé-Alarie

Brain Sci. 2025, 15(7), 760; https://doi.org/10.3390/brainsci15070760 - 17 Jul 2025

Viewed by 457

Abstract

This article aims to offer a broad perspective on the use of non-invasive brain stimulation (NIBS) techniques in the context of chronic musculoskeletal pain (CMP) conditions. While NIBS has demonstrated promising efficacy in certain chronic pain populations, its application in the management of [...] Read more.

This article aims to offer a broad perspective on the use of non-invasive brain stimulation (NIBS) techniques in the context of chronic musculoskeletal pain (CMP) conditions. While NIBS has demonstrated promising efficacy in certain chronic pain populations, its application in the management of CMP remains limited. This paper examines the current evidence supporting the use of NIBS for pain relief in CMP, the rationale and proposed mechanisms of action, the importance of patient selection, common methodological limitations in the existing literature, and the potential adverse effects of these techniques. The authors argue that the current evidence is insufficient to support widespread clinical adoption of NIBS for CMP. Advancing the field will require more rigorous study designs, with adequately powered and properly blinded randomized controlled trials. Additionally, future research should address the identification of potential responders to brain stimulation, conduct economic evaluations, and carefully assess the benefit–risk ratio before NIBS can be integrated into routine clinical practice. Full article

(This article belongs to the Special Issue Neuromodulation for Pain Management: Evidence of Safety and Efficacy)

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25 pages, 432 KiB

Open AccessReview

Targeting CX3CR1 Signaling Dynamics: A Critical Determinant in the Temporal Regulation of Post-Stroke Neurorepair

by Quan He, Tong Zhou and Quanwei He

Brain Sci. 2025, 15(7), 759; https://doi.org/10.3390/brainsci15070759 - 17 Jul 2025

Viewed by 512

Abstract

Ischemic stroke ranks among the top global causes of disability and mortality, with a highly dynamic pathological process. Post-stroke neuroinflammation, mediated by microglia, demonstrates a dual role in both injury and repair. The CX3CR1/CX3CL1 signaling axis, highly expressed in microglia, acts as a [...] Read more.

Ischemic stroke ranks among the top global causes of disability and mortality, with a highly dynamic pathological process. Post-stroke neuroinflammation, mediated by microglia, demonstrates a dual role in both injury and repair. The CX3CR1/CX3CL1 signaling axis, highly expressed in microglia, acts as a key regulator. This review examines the spatiotemporal dynamics of the axis across the stroke process and its involvement in neural repair. Crucially, this signaling pathway demonstrates stage-dependent functional duality: its cellular sources, receptor expression profiles, and functional consequences undergo temporally orchestrated shifts, manifesting coexisting or interconverting protective and damaging properties. Ignoring this dynamism compromises the therapeutic efficacy of targeted interventions. Thus, we propose a triple precision strategy of “stroke phase—biomarker—targeted intervention”. It uses specific biomarkers for precise staging and designs interventions based on each phase’s signaling characteristics. Despite challenges like biomarker validation, mechanistic exploration, and cross-species differences, integrating cutting-edge technologies such as spatial metabolomics and AI-driven dynamic modeling promises to shift stroke therapy toward personalized spatiotemporal programming. Temporally targeting CX3CR1 signaling may offer a key basis for developing next-generation precision neural repair strategies for stroke. Full article

10 pages, 232 KiB

Open AccessArticle

Symptom-Triggered Alcohol Detoxification Compared to Fixed-Dose Regimen of Benzodiazepines: A Retrospective Case–Control Study

by Laurent Becciolini, Fabienne Wehrli, Jens Kronschnabel, Carolina Wiesendanger, Norbert Scherbaum and Patrik Roser

Brain Sci. 2025, 15(7), 758; https://doi.org/10.3390/brainsci15070758 - 17 Jul 2025

Viewed by 294

Abstract

Background: Alcohol withdrawal syndrome is a common clinical challenge that may lead to significant complications if not properly managed. Symptom-triggered therapy (STT) represents a promising alternative to fixed-dose regimens (FDRs) providing benzodiazepine prescriptions based on objectively quantified withdrawal symptoms. This study aimed to [...] Read more.

Background: Alcohol withdrawal syndrome is a common clinical challenge that may lead to significant complications if not properly managed. Symptom-triggered therapy (STT) represents a promising alternative to fixed-dose regimens (FDRs) providing benzodiazepine prescriptions based on objectively quantified withdrawal symptoms. This study aimed to evaluate the effectiveness and safety of STT using the Hamburg Alcohol Withdrawal Scale (HAES) compared to FDRs in the management of inpatient alcohol detoxification. Methods: In a retrospective case–control study, alcohol detoxification treatment in STT was compared with FDRs. During a twelve-month observation period, a total of 123 patients in the STT group were recruited and compared with 123 controls in the FDR group (matched according to sex, age, and current amount of alcohol consumption) treated in the same hospital before the implementation of STT. The study outcomes included the total benzodiazepine dosage, duration of acute detoxification phase, length of inpatient stay, and occurrence of complications such as epileptic seizures and delirium tremens. Results: STT showed a significantly lower total benzodiazepine dosage (22.50 mg vs. 115.00 mg, p < 0.001), a shorter duration of the detoxification phase (48.00 h vs. 201.75 h, p < 0.001), and a reduced length of inpatient stay (23.00 days vs. 28.00 days, p = 0.003) compared to FDRs. There were no significant differences in the rates of complications between the two settings. Linear mixed model analysis revealed that the differences remained highly significant even after adjusting for various explanatory variables (i.e., age, sex, standard units of alcohol, psychiatric comorbidities, treatment discontinuation, and occurrence of any complication). Conclusions: STT appears to be as effective and safe as traditional fixed-dose regimens of benzodiazepines for the management of inpatient alcohol detoxification. This approach may thereby minimize unnecessary pharmacological exposure, facilitate the earlier integration of patients into psychoeducational and psychosocial interventions, and reduce healthcare costs. Full article

(This article belongs to the Special Issue Psychiatry and Addiction: A Multi-Faceted Issue)

14 pages, 1359 KiB

Open AccessArticle

Delving into the Perception, Use, and Context of Duloxetine in Clinical Practice: An Analysis Based on the Experience of Healthcare Professionals

by Oscar Fraile-Martinez, Cielo Garcia-Montero, Miguel Angel Alvarez-Mon, Miguel A. Ortega, Melchor Alvarez-Mon and Javier Quintero

Brain Sci. 2025, 15(7), 757; https://doi.org/10.3390/brainsci15070757 - 17 Jul 2025

Viewed by 314

Abstract

Background and objectives: Duloxetine is widely used for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and various types of neuropathic pain. While its efficacy is well documented in clinical trials, less is known about how it is perceived and [...] Read more.

Background and objectives: Duloxetine is widely used for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and various types of neuropathic pain. While its efficacy is well documented in clinical trials, less is known about how it is perceived and utilized in routine psychiatric practice. To address this knowledge gap, we conducted a cross-sectional observational study involving 80 psychiatrists from Spain to assess real-world clinical attitudes toward duloxetine. Methods: Participants completed a 20-item multiple-choice questionnaire that examined familiarity, perceived efficacy in multiple conditions (MDD, GAD, neuropathic pain, somatization, and quality of life), and perspectives on tolerability, safety, adherence, and overall satisfaction. Results: Survey results indicated that a large majority of psychiatrists frequently prescribe duloxetine, particularly for patients with MDD and comorbid chronic pain. Notably, 94% rated it as either “more effective” or “much more effective” for diabetic peripheral neuropathic pain. Psychiatrists reported a high perceived efficacy of duloxetine: 94% rated it as “more effective” or “much more effective” for diabetic peripheral neuropathy, and 93% gave similarly positive ratings for general neuropathic pain. For somatization, 70% found it “effective” or “very effective”, and 83% observed improvements in quality of life for many of their patients. Psychiatrists generally reported favorable perceptions of duloxetine’s tolerability profile: 97.5% rated it as the antidepressant associated with the least weight gain, and 82.5% perceived fewer sexual side effects compared to other options. Sedation and gastrointestinal side effects were generally considered mild or less severe. In terms of treatment adherence, 69% rated it as “better” or “much better” than other antidepressants, and 80% found its combination with other antidepressants to be “favorable” or “very favorable”. Overall satisfaction was high, with 99% of psychiatrists reporting being either “satisfied” or “very satisfied” with its use. The side effect profile was generally viewed as manageable, with low perceived rates of weight gain, sedation, and sexual dysfunction. Furthermore, 96% of respondents expressed a willingness to recommend duloxetine to their colleagues. Conclusions: Psychiatrists reported highly favorable attitudes toward duloxetine, viewing it as a flexible treatment option in routine care. However, these findings reflect clinicians’ subjective perceptions rather than objective clinical outcomes and should be interpreted accordingly. Full article

(This article belongs to the Special Issue Anxiety, Depression and Stress)

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21 pages, 1875 KiB

Open AccessReview

Translating Exosomal microRNAs from Bench to Bedside in Parkinson’s Disease

by Oscar Arias-Carrión, María Paulina Reyes-Mata, Joaquín Zúñiga and Daniel Ortuño-Sahagún

Brain Sci. 2025, 15(7), 756; https://doi.org/10.3390/brainsci15070756 - 16 Jul 2025

Viewed by 357

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and [...] Read more.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and therapeutic intervention. Exosomes facilitate intercellular communication, cross the blood–brain barrier, and protect miRNAs from degradation, rendering them suitable for non-invasive diagnostics and targeted delivery. Specific exosomal miRNAs modulate neuroinflammatory cascades, oxidative stress, and synaptic dysfunction, and their altered expression in cerebrospinal fluid and plasma correlates with disease onset, severity, and progression. Despite their translational promise, challenges persist, including methodological variability in exosome isolation, miRNA profiling, and delivery strategies. This review integrates findings from preclinical models, patient-derived samples, and systems biology to delineate the functional impact of exosomal miRNAs in PD. We propose mechanistic hypotheses linking miRNA dysregulation to molecular pathogenesis and present an interactome model highlighting therapeutic nodes. Advancing exosomal miRNA research may transform the clinical management of PD by enabling earlier diagnosis, molecular stratification, and the development of disease-modifying therapies. Full article

(This article belongs to the Special Issue Molecular Insights in Neurodegeneration)

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17 pages, 554 KiB

Open AccessReview

Post-Concussion Syndrome and Functional Neurological Disorder: Diagnostic Interfaces, Risk Mechanisms, and the Functional Overlay Model

by Ioannis Mavroudis, Foivos Petridis, Eleni Karantali, Alin Ciobica, Sotirios Papagiannopoulos and Dimitrios Kazis

Brain Sci. 2025, 15(7), 755; https://doi.org/10.3390/brainsci15070755 - 16 Jul 2025

Viewed by 465

Abstract

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, [...] Read more.

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

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26 pages, 2058 KiB

Open AccessReview

Neuromodulation Interventions for Language Deficits in Alzheimer’s Disease: Update on Current Practice and Future Developments

by Fei Chen, Yuyan Nie and Chen Kuang

Brain Sci. 2025, 15(7), 754; https://doi.org/10.3390/brainsci15070754 - 16 Jul 2025

Viewed by 312

Abstract

Alzheimer’s disease (AD) is a leading cause of dementia, characterized by progressive cognitive and language impairments that significantly impact communication and quality of life. Neuromodulation techniques, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS), have [...] Read more.

Alzheimer’s disease (AD) is a leading cause of dementia, characterized by progressive cognitive and language impairments that significantly impact communication and quality of life. Neuromodulation techniques, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS), have emerged as promising interventions. This study employs bibliometric analysis to evaluate global research trends in neuromodulation treatments for AD-related language impairments. A total of 88 publications from the Web of Science Core Collection (2006–2024) were analyzed using bibliometric methods. Key indicators such as publication trends, citation patterns, collaboration networks, and research themes were examined to map the intellectual landscape of this field. The analysis identified 580 authors across 65 journals, with an average of 34.82 citations per article. Nearly half of the publications were produced after 2021, indicating rapid recent growth. The findings highlight a predominant focus on non-invasive neuromodulation methods, particularly rTMS and tDCS, within neurosciences and neurology. While research activity is increasing, significant challenges persist, including ethical concerns, operational constraints, and the translational gap between research and clinical applications. This study provides insights into the current research landscape and future directions for neuromodulation in AD-related language impairments. The results emphasize the need for novel neuromodulation techniques and interdisciplinary collaboration to enhance therapeutic efficacy and clinical integration. Full article

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

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30 pages, 891 KiB

Open AccessReview

Communication Abilities, Assessment Procedures, and Intervention Approaches in Rett Syndrome: A Narrative Review

by Louiza Voniati, Angelos Papadopoulos, Nafsika Ziavra and Dionysios Tafiadis

Brain Sci. 2025, 15(7), 753; https://doi.org/10.3390/brainsci15070753 - 15 Jul 2025

Viewed by 313

Abstract

Background/Objectives: Rett syndrome (RTT) is a rare neurodevelopmental disorder that affects movement and communication skills primarily in females. This study aimed to synthesize the research from the last two decades regarding the verbal and nonverbal communication abilities, assessment procedures, and intervention approaches for [...] Read more.

Background/Objectives: Rett syndrome (RTT) is a rare neurodevelopmental disorder that affects movement and communication skills primarily in females. This study aimed to synthesize the research from the last two decades regarding the verbal and nonverbal communication abilities, assessment procedures, and intervention approaches for individuals with RTT. Methods: A structured literature search was conducted using the Embase, Scopus, and PubMed databases. Fifty-seven studies were selected and analyzed based on inclusion criteria. The data were categorized into four domains (verbal communication skills, nonverbal communication skills, assessment procedures, and intervention approaches). Results: The findings indicated a wide variety of communicative behaviors across the RTT population, including prelinguistic signals, regression in verbal output, and preserved nonverbal communicative intent. Moreover, the results highlighted the importance of tailored assessments (Inventory of Potential Communicative Acts, eye tracking tools, and Augmentative and Alternative Communication) to facilitate functional communication. The individualized intervention approaches were found to be the most effective in improving communicative participation. Conclusions: The current review provides an overview of the current evidence with an emphasis on the need for personalized and evidence-based clinical practices. Additionally, it provided guidance for professionals, clinicians, and researchers seeking to improve the quality of life for individuals with RTT. Full article

(This article belongs to the Special Issue Recent Advances in Assessment and Rehabilitation of Individuals with Communication and Language Disorders)

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19 pages, 1521 KiB

Open AccessArticle

SAGEFusionNet: An Auxiliary Supervised Graph Neural Network for Brain Age Prediction as a Neurodegenerative Biomarker

by Suraj Kumar, Suman Hazarika and Cota Navin Gupta

Brain Sci. 2025, 15(7), 752; https://doi.org/10.3390/brainsci15070752 - 15 Jul 2025

Viewed by 309

Abstract

Background: The ability of Graph Neural Networks (GNNs) to analyse brain structural patterns in various kinds of neurodegenerative diseases, including Parkinson’s disease (PD), has drawn a lot of interest recently. One emerging technique in this field is brain age prediction, which estimates biological [...] Read more.

Background: The ability of Graph Neural Networks (GNNs) to analyse brain structural patterns in various kinds of neurodegenerative diseases, including Parkinson’s disease (PD), has drawn a lot of interest recently. One emerging technique in this field is brain age prediction, which estimates biological age to identify ageing patterns that may serve as biomarkers for such disorders. However, a significant problem with most of the GNNs is their depth, which can lead to issues like oversmoothing and diminishing gradients. Methods: In this study, we propose SAGEFusionNet, a GNN architecture specifically designed to enhance brain age prediction and assess PD-related brain ageing patterns using T1-weighted structural MRI (sMRI). SAGEFusionNet learns important ROIs for brain age prediction by incorporating ROI-aware pooling at every layer to overcome the above challenges. Additionally, it incorporates multi-layer feature fusion to capture multi-scale structural information across the network hierarchy and auxiliary supervision to enhance gradient flow and feature learning at multiple depths. The dataset utilised in this study was sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. It included a total of 580 T1-weighted sMRI scans from healthy individuals. The brain sMRI scans were parcellated into 56 regions of interest (ROIs) using the LPBA40 brain atlas in CAT12. The anatomical graph was constructed based on grey matter (GM) volume features. This graph served as input to the GNN models, along with GM and white matter (WM) volume as node features. All models were trained using 5-fold cross-validation to predict brain age and subsequently tested for performance evaluation. Results: The proposed framework achieved a mean absolute error (MAE) of

4.24 \pm 0.38

years and a mean Pearson’s Correlation Coefficient (PCC) of

0.72 \pm 0.03

during cross-validation. We also used 215 PD patient scans from the Parkinson’s Progression Markers Initiative (PPMI) database to assess the model’s performance and validate it. The initial findings revealed that out of 215 individuals with Parkinson’s disease, 213 showed higher and 2 showed lower predicted brain ages than their actual ages, with a mean MAE of 13.36 years (95% confidence interval: 12.51–14.28). Conclusions: These results suggest that brain age prediction using the proposed method may provide important insights into neurodegenerative diseases. Full article

(This article belongs to the Section Neurorehabilitation)

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13 pages, 590 KiB

Open AccessArticle

Subtyping Early Parkinson’s Disease by Mapping Cognitive Profiles to Brain Atrophy with Visual MRI Ratings

by Tania Álvarez-Avellón, Carmen Solares, Juan Álvarez-Carriles and Manuel Menéndez-González

Brain Sci. 2025, 15(7), 751; https://doi.org/10.3390/brainsci15070751 - 15 Jul 2025

Viewed by 321

Abstract

Background: Cognitive heterogeneity in Parkinson’s disease (PD) remains a diagnostic and prognostic challenge, particularly in early stages. In this cross-sectional study, we aimed to identify clinically relevant cognitive subtypes in early PD by integrating neuropsychological profiles with regional brain atrophy assessed via visual [...] Read more.

Background: Cognitive heterogeneity in Parkinson’s disease (PD) remains a diagnostic and prognostic challenge, particularly in early stages. In this cross-sectional study, we aimed to identify clinically relevant cognitive subtypes in early PD by integrating neuropsychological profiles with regional brain atrophy assessed via visual MRI scales. Methods: Eighty-one de novo PD patients (≤36 months from diagnosis) and twenty healthy controls underwent 3T MRI with visual atrophy ratings and completed an extensive neuropsychological battery. Results: Using a mixed a priori–a posteriori approach, we defined eight anatomocognitive subtypes reflecting distinct patterns of regional vulnerability: frontosubcortical, posterior cortical, left/right hippocampal, global, and preserved cognition. Specific MRI markers correlated with cognitive deficits in executive, visuospatial, memory, and language domains. Cluster analyses supported subtype validity (AUC range: 0.68–0.95). Conclusions: These results support a practical classification model linking cognitive performance to brain structural changes in early PD. This scalable approach may improve early patient stratification and guide personalized management strategies. Longitudinal studies are needed to assess progression patterns and therapeutic implications. Full article

(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease)

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14 pages, 2907 KiB

Open AccessArticle

Neural Dynamics of Strategic Early Predictive Saccade Behavior in Target Arrival Estimation

by Ryo Koshizawa, Kazuma Oki and Masaki Takayose

Brain Sci. 2025, 15(7), 750; https://doi.org/10.3390/brainsci15070750 - 15 Jul 2025

Viewed by 254

Abstract

Background/Objectives: Accurately predicting the arrival position of a moving target is essential in sports and daily life. While predictive saccades are known to enhance performance, the neural mechanisms underlying the timing of these strategies remain unclear. This study investigated how the timing [...] Read more.

Background/Objectives: Accurately predicting the arrival position of a moving target is essential in sports and daily life. While predictive saccades are known to enhance performance, the neural mechanisms underlying the timing of these strategies remain unclear. This study investigated how the timing of saccadic strategies—executed early versus late—affects cortical activity patterns, as measured by electroencephalography (EEG). Methods: Sixteen participants performed a task requiring them to predict the arrival position and timing of a parabolically moving target that became occluded midway through its trajectory. Based on eye movement behavior, participants were classified into an Early Saccade Strategy Group (SSG) or a Late SSG. EEG signals were analyzed in the low beta band (13–15 Hz) using the Hilbert transform. Group differences in eye movements and EEG activity were statistically assessed. Results: No significant group differences were observed in final position or response timing errors. However, time-series analysis showed that the Early SSG achieved earlier and more accurate eye positioning. EEG results revealed greater low beta activity in the Early SSG at electrode sites FC6 and P8, corresponding to the frontal eye field (FEF) and middle temporal (MT) visual area, respectively. Conclusions: Early execution of predictive saccades was associated with enhanced cortical activity in visuomotor and motion-sensitive regions. These findings suggest that early engagement of saccadic strategies supports more efficient visuospatial processing, with potential applications in dynamic physical tasks and digitally mediated performance domains such as eSports. Full article

(This article belongs to the Special Issue Recent Advances in Neuroscience: Theoretical, Applied, and Experimental Research)

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16 pages, 2725 KiB

Open AccessArticle

Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study

by Yong-Won Shin and Sang Bin Hong

Brain Sci. 2025, 15(7), 749; https://doi.org/10.3390/brainsci15070749 - 14 Jul 2025

Viewed by 383

Abstract

Background/Objectives: Epilepsy and sleep disturbances frequently co-occur, yet the causal nature of this relationship remains uncertain, particularly in relation to epilepsy subtypes and status epilepticus. We investigated potential bidirectional causal associations between sleep-related traits and epilepsy, including subtypes and status epilepticus, using [...] Read more.

Background/Objectives: Epilepsy and sleep disturbances frequently co-occur, yet the causal nature of this relationship remains uncertain, particularly in relation to epilepsy subtypes and status epilepticus. We investigated potential bidirectional causal associations between sleep-related traits and epilepsy, including subtypes and status epilepticus, using Mendelian randomization (MR). Methods: We conducted two-sample MR using genome-wide association study (GWAS) summary statistics from European ancestry cohorts. Epilepsy, its subtypes, and status epilepticus were analyzed using data from the International League Against Epilepsy Consortium on Complex Epilepsies (ILAE) and the FinnGen study. Nine self-reported sleep-related traits were derived from the UK Biobank-based GWAS. Causal estimates were primarily obtained using inverse variance weighted models with additional MR analysis methods. Pleiotropy and heterogeneity were assessed to enhance the robustness of the finding. Results: Several subtype-specific associations were identified, with direction and statistical significance varying across cohorts and subtypes. After correction for multiple testing and filtering for tests with ≥10 instrumental variables to ensure robust and reliable MR estimates, several consistent and potentially mutually reinforcing associations emerged. In the ILAE cohort, focal epilepsy with hippocampal sclerosis was associated with an increased risk of insomnia, and juvenile myoclonic epilepsy with reduced sleep duration. In the FinnGen cohort, overall epilepsy was associated with increased risk of both insomnia and daytime sleepiness. In reverse MR, daytime sleepiness and napping were associated with increased risk of epilepsy, while daytime napping and frequent insomnia symptoms were linked to elevated risk of status epilepticus. Conclusions: Our findings reveal subtype-specific and bidirectional causal links between epilepsy and sleep-related traits. These results highlight the biological interplay between epileptic networks and sleep regulation and underscore the need for further clinical and mechanistic studies. Full article

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2 pages, 167 KiB

Open AccessCorrection

Correction: MACCHINI et al. Intra-Arrest Therapeutic Hypothermia and Neurologic Outcome in Patients Admitted After Out-of-Hospital Cardiac Arrest: A Post Hoc Analysis of the Princess Trial. Brain Sci. 2022, 12, 1374

by Elisabetta MACCHINI, Emelie DILLENBECK, Martin JONSSON, Filippo ANNONI, Sune FORSBERG, Jacob HOLLENBERG, Anatolij TRUHLAR, Leif SVENSSON, Per NORDBERG and Fabio Silvio TACCONE

Brain Sci. 2025, 15(7), 748; https://doi.org/10.3390/brainsci15070748 - 14 Jul 2025

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Abstract

In the original publication [...] Full article

3 pages, 141 KiB

Open AccessComment

Redefining Clinical Perspectives on MCS: Toward an Evidence-Based, Multisystem Model. Comment on Jacques, L. Multiple Chemical Sensitivity: A Clinical Perspective. Brain Sci. 2024, 14, 1261

by Elaine Psaradellis

Brain Sci. 2025, 15(7), 747; https://doi.org/10.3390/brainsci15070747 - 14 Jul 2025

Viewed by 335

Abstract

The article “Multiple Chemical Sensitivity: A Clinical Perspective”, published in Brain Sciences, suggests that multiple chemical sensitivity (MCS) is primarily a psychogenic disorder, rooted in unresolved emotional trauma and stress responses [...] Full article

16 pages, 823 KiB

Open AccessReview

GABAergic Influences on Medulloblastoma

by Viviane Aline Buffon, Jurandir M. Ribas Filho, Osvaldo Malafaia, Isadora D. Tassinari, Rafael Roesler and Gustavo R. Isolan

Brain Sci. 2025, 15(7), 746; https://doi.org/10.3390/brainsci15070746 - 11 Jul 2025

Viewed by 339

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor in children and typically arises in the cerebellum, likely due to disruptions in neuronal precursor development. The primary inhibitory neurotransmitter in the central nervous system (CNS), γ-aminobutyric acid (GABA), exerts its effects through GABA [...] Read more.

Medulloblastoma (MB) is the most common malignant brain tumor in children and typically arises in the cerebellum, likely due to disruptions in neuronal precursor development. The primary inhibitory neurotransmitter in the central nervous system (CNS), γ-aminobutyric acid (GABA), exerts its effects through GABA_A, GABA_B, and GABA_C receptors. GABA receptor activity regulates the development and function of cerebellar neurons, including glutamatergic cerebellar granule cells (CGCs). Beyond the nervous system, GABA is also a common metabolite in non-neuronal cell types. An increasing body of evidence indicates that GABA can influence cell proliferation, differentiation, and migration in several types of adult solid tumors, including brain cancers. GABA and GABA_A receptor agonists can impair the viability and survival of MB cells, primarily acting on GABA_A receptors containing the α5 subunit. A marked expression of the gene encoding the α5 subunit is found across all MB tumor molecular subgroups, particularly Group 3 MB, which has a poor prognosis. Importantly, high levels of the γ-aminobutyric acid type A receptor subunit α5 (GABRA5) gene are associated with shorter patient overall survival in Group 3 and Group 4 MB. In contrast, high γ-aminobutyric acid type A receptor subunit β1 (GABRB1) gene expression is related to longer survival in all MB subgroups. The GABAergic system may, therefore, regulate MB cell function and tumor progression and influence patient prognosis, and is worthy of further investigation as a biomarker and therapeutic target in MB. Full article

(This article belongs to the Special Issue Editorial Board Collection Series: Advances in Neuro-Oncology)

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12 pages, 674 KiB

Open AccessArticle

Quality of Life in Multiple Sclerosis Compared to Amyotrophic Lateral Sclerosis: Fatigue and Fast Disease Progression Interferes with the Ability to Psychosocially Adjust

by Luisa T. Balz, Ingo Uttner, Jochen Weishaupt, Albert C. Ludolph, Daniela Taranu, Ioannis Vardakas, Stefanie Jung, Tanja Fangerau, Deborah K. Erhart, Makbule Senel, Hayrettin Tumani and Dorothée E. Lulé

Brain Sci. 2025, 15(7), 745; https://doi.org/10.3390/brainsci15070745 - 11 Jul 2025

Viewed by 383

Abstract

Background/Objectives: Multiple sclerosis (MS) is a complex neurological disease that is associated with a broad spectrum of physical and psychological symptoms. Psychosocial adjustment (PSA) refers to the ability to cope with these challenges, which influence quality of life (QoL) and depressiveness in [...] Read more.

Background/Objectives: Multiple sclerosis (MS) is a complex neurological disease that is associated with a broad spectrum of physical and psychological symptoms. Psychosocial adjustment (PSA) refers to the ability to cope with these challenges, which influence quality of life (QoL) and depressiveness in ways not yet fully understood. This study explores the relationship of PSA and disease-specific symptoms in MS, including fatigue, a prominent MS symptom. Additionally, PSA was compared to Amyotrophic Lateral Sclerosis (ALS) to disentangle the impact of disease trajectory on PSA. Methods: We interviewed 77 MS patients using patient-reported outcome measures on QoL and depression and compared them to 30 ALS patients. Confirmatory factor analysis and regression analysis were used to identify PSA indicators and predictors in MS, while t-tests assessed PSA differences across diseases. Results: Key PSA indicators in MS included physical (PQoL), mental (MQoL), and subjective (SQoL) quality of life, as well as depressiveness, with cognitive and motor fatigue emerging as significant predictors. MS patients had higher PQoL and SQoL and lower levels of depression compared to ALS patients, while both groups were comparable with regard to MQoL. Conclusions: PSA in MS is supported by high QoL and low depression levels, with fatigue being a significant predictor. Despite different disease trajectories, patients with MS and ALS showed comparable MQoL, indicating that both diseases similarly impact mental QoL, reflecting a partial overlap in psychosocial adjustment. Overall, psychosocial adjustment was more favorable in MS, likely due to its slower disease progression compared to ALS. Full article

(This article belongs to the Special Issue Neuropsychological Impact and Quality of Life in Chronic Illness)

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