Brain Sciences

14 pages, 257 KiB

Open AccessArticle

Instrumental Activities of Daily Living in Neurocognitive Disorders: Determinants and Clinical Implications for Health Promotion

by Anna Tsiakiri, Spyridon Plakias, Christos Kokkotis, Pinelopi Vlotinou, Sotiria Kyriazidou, Georgios Giarmatzis, Stylianos Kallivoulos, Aikaterini Terzoudi, Dimitrios Tsiptsios, Souzana Merai, Chrysoula Emmanouilidou, Christos Kariotis, Anna Kanidou, Nikolaos Aggelousis, Konstantinos Vadikolias and Foteini Christidi

Brain Sci. 2025, 15(4), 417; https://doi.org/10.3390/brainsci15040417 (registering DOI) - 19 Apr 2025

Abstract

Background/Objectives: Instrumental Activities of Daily Living (IADL) are the key indicators of the autonomy and functional ability in older adults with neurocognitive disorders (NCDs). However, the specific predictors of IADL performance across the NCD spectrum remains insufficiently characterized. This study aimed to [...] Read more.

Background/Objectives: Instrumental Activities of Daily Living (IADL) are the key indicators of the autonomy and functional ability in older adults with neurocognitive disorders (NCDs). However, the specific predictors of IADL performance across the NCD spectrum remains insufficiently characterized. This study aimed to identify the cognitive, motor, and caregiver-related determinants of the IADL in individuals with minor and major NCDs. Methods: A cross-sectional study was conducted involving 117 participants referred from a university-based dementia clinic. Standardized tools were administered to evaluate their IADL performance (Lawton IADL Scale), cognition [Addenbrooke’s Cognitive Examination III (ACE-III)], Functional Cognitive Assessment Scale (FUCAS)], motor functions, balance, and mobility [Tinetti Test, Timed Up and Go (TUG)], emotional status [Geriatric Depression Scale (GDS)], neuropsychiatric symptoms [Neuropsychiatric Inventory (NPI)], and caregiver burden [Zarit Burden Interview (ZBI)]. Multiple regression analyses were performed to identify the significant predictors of IADL performance. Results: In the total sample (n = 117), the IADL performance was significantly predicted via ACE-III, FUCAS, and Tinetti-balance (adjusted R² = 0.729). In the minor NCD group (n = 41), the significant predictors included sex, FUCAS, GDS, Tinetti-balance, and TUG (adjusted R² = 0.725). In the major NCD group (n = 76), ACE-III, FUCAS, and Tinetti-balance remained the significant predictors (adjusted R² = 0.634). Female sex and a worse profile on the other variables were associated with lower IADL scores. Conclusions: Global cognitive decline, executive dysfunction in everyday problem-solving situations, and balance impairment are the key determinants of IADL performance across both minor and major NCDs. Female sex and depressive symptoms further predicted the IADL performance in the minor NCD group. These findings highlight the need for multidisciplinary assessment and intervention strategies to promote health and autonomy and preserve the functional independence in older adults with NCDs. Full article

(This article belongs to the Special Issue Challenges and Perspectives of Neurological Disorders: Series II)

14 pages, 5854 KiB

Open AccessArticle

Homocysteine Mediates Cognitive Inflexibility Induced by Stress via Targeting PIN1

by Xiaobing Chen, Ling Zhang, Bing Liu, Huafeng Dong, Shijia Zhang, Xue Wang, Zhaowei Sun, Fang Xie, Lingjia Qian and Yun Zhao

Brain Sci. 2025, 15(4), 416; https://doi.org/10.3390/brainsci15040416 (registering DOI) - 19 Apr 2025

Abstract

Background: Increasing evidence shows that HCY plays an important role in stress-induced cognitive dysfunction, and HCY significantly promotes the decline of cognitive function. Stress has been reported to cause elevated HCY in the hippocampus of mice. Cognitive flexibility refers to the ability of [...] Read more.

Background: Increasing evidence shows that HCY plays an important role in stress-induced cognitive dysfunction, and HCY significantly promotes the decline of cognitive function. Stress has been reported to cause elevated HCY in the hippocampus of mice. Cognitive flexibility refers to the ability of individuals to quickly adjust their neurobehavioral strategies to different situations or to solve different tasks. Aims: This study aims to explore the role of HCY in the impairment of cognitive flexibility induced by stress and its possible regulatory mechanism. Methods: First, we examined changes in the protein and mRNA levels of the cognitive flexibility effector molecule, PIN1, during stress in mice. The results show that stress can cause a decline in cognitive flexibility in mice and lead to an increase in PIN1. Moreover, through the use of in vitro experiments, we found that HCY could induce an increase in PIN1 expression in neurons. Further in vivo experiments were used to investigate the effect of VitB on HCY and PIN1 and evaluated the therapeutic effect of VitB on stress-induced impairment of cognitive flexibility. The results show that VitB decreased the levels of HCY in plasma and the hippocampus, alleviated the stress-induced impairment of cognitive flexibility, and reduced the expression of PIN1. Conclusions: These results suggest that the impairment of cognitive flexibility induced by stress can be inhibited by regulating the content of HCY. Collectively, our findings highlight therapeutic strategies aimed at improving HCY treatment for impairments in cognitive flexibility. Full article

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20 pages, 259 KiB

Open AccessArticle

Attachment, Shame, and Trauma

by Carol George

Brain Sci. 2025, 15(4), 415; https://doi.org/10.3390/brainsci15040415 (registering DOI) - 19 Apr 2025

Abstract

Background/Objectives: Early parent–child attachment interactions guided by right-to-right brain synchrony are the foundation of emotional development and the quality of attachment relationships. Interactive failures are the hallmark of not only insecurity and trauma but also the internalization of shame. The purpose of this [...] Read more.

Background/Objectives: Early parent–child attachment interactions guided by right-to-right brain synchrony are the foundation of emotional development and the quality of attachment relationships. Interactive failures are the hallmark of not only insecurity and trauma but also the internalization of shame. The purpose of this study was to advance our understanding of the relation between attachment and shame. The study explored a range of shame experiences, from normal socialization to harsh treatment and abuse. Debilitating shame was expected for individuals who had not mourned attachment trauma. Methods: Attachment was assessed using The Adult Attachment Projective (AAP) system in a sample of 245 adults. The AAP identifies the traditional regulated attachment classifications (Secure, Dismissing, Preoccupied) and, in addition to Unresolved attachment, three forms of incomplete mourning—Failed Mourning, Preoccupied with Personal Suffering, and Traumatized Secure. The study used participants’ narratives regarding three AAP classifications when “alone” to examine individual differences in representations of the shamed self contexts portraying the self in Private, Exposed, and Threatening situations. Results: All study hypotheses were confirmed. Adults with regulated attachments (Secure, Dismissing, Preoccupied) were significantly less likely to ascribe shame to the AAP pictures than traumatized adults. The patterns of results were the same when comparing differences in shame intensity and outcomes. There were no differences in shame intensity in the regulated group. Shame intensity for the Traumatized Secures was somewhat greater. There was a significant increase observed in the traumatized groups, with the Unresolved group showing the highest ratings. Reparative outcomes were significantly related to attachment security, although not to the extent expected. Secure, regulated insecure (Dismissing, Preoccupied), and some traumatized individuals described reconciliation and functional restitution. Unresolved individuals left shame unremedied. Regression analysis demonstrated that attachment classification was a greater predictor of shame intensity than outcomes. Conculusions: Attachment and neurological development are intertwined. Childhood interactive failures are deeply traumatic. If not mourned, shame takes its place in the identity core. This study provides clinicians with an in-depth perspective on attachment and shame assessment for goal-setting in therapy, consonant with their patients’ attachment representations. Full article

(This article belongs to the Special Issue State of the Art in Human Attachment)

13 pages, 1264 KiB

Open AccessArticle

Equidistant Landmarks Fail to Produce the Blocking Effect in Spatial Learning Using a Virtual Water Maze Task with Healthy Adults: A Role for Cognitive Mapping?

by Róisín Deery and Seán Commins

Brain Sci. 2025, 15(4), 414; https://doi.org/10.3390/brainsci15040414 (registering DOI) - 19 Apr 2025

Abstract

Background/Objectives: Cue competition is a feature of associative learning, whereby during learning, cues compete with each other, based on their relative salience, to influence subsequent performance. Blocking is a feature of cue competition where prior knowledge of a cue (X) will interfere with [...] Read more.

Background/Objectives: Cue competition is a feature of associative learning, whereby during learning, cues compete with each other, based on their relative salience, to influence subsequent performance. Blocking is a feature of cue competition where prior knowledge of a cue (X) will interfere with the subsequent learning of a second cue (XY). When tested with the second cue (Y) alone, participants show an impairment in responding. While blocking has been observed across many domains, including spatial learning, previous research has raised questions regarding replication and the conditions necessary for it to occur. Furthermore, two prominent spatial learning theories predict contrary results for blocking. Associative learning accounts predict that the addition of a cue will lead to a blocking effect and impaired performance upon testing. Whereas the cognitive map theory suggests that the novel cue will be integrated into a map with no subsequent impairment in performance. Methods: Using a virtual water maze task, we investigated the blocking effect in human participants. Results: Results indicated that the cue learned in phase 1 of the experiment did not interfere with learning of a subsequent cue introduced in phase 2. Conclusions: This suggests that blocking did not occur and supports a cognitive mapping approach in human spatial learning. However, the relative location of the cues relative to the goal and how this might determine the learning strategy used by participants was discussed. Full article

(This article belongs to the Section Neuropsychology)

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19 pages, 7750 KiB

Open AccessSystematic Review

Risk of Cerebrovascular Events in Deep Brain Stimulation for Parkinson’s Disease Focused on STN and GPi: Systematic Review and Meta-Analysis

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

Brain Sci. 2025, 15(4), 413; https://doi.org/10.3390/brainsci15040413 - 18 Apr 2025

Abstract

Background/Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder treated with deep brain stimulation (DBS) for advanced stages, targeting the subthalamic nucleus (STN) or the internal globus pallidus (GPi). Despite DBS’s symptomatic benefits, cerebrovascular events (CVEs) remain a concern. This study assessed [...] Read more.

Background/Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder treated with deep brain stimulation (DBS) for advanced stages, targeting the subthalamic nucleus (STN) or the internal globus pallidus (GPi). Despite DBS’s symptomatic benefits, cerebrovascular events (CVEs) remain a concern. This study assessed CVE risk in PD patients undergoing DBS. Methods: We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. Studies published between 2014 and 2024 that reported CVEs in PD patients treated with STN-DBS or GPi-DBS were included. Data on CVEs, DBS targets, perioperative period, and microelectrode recording (MER) use were extracted, and probability proportions were pooled using a random-effects model. Results: Twenty-three studies (4795 patients) were included. The overall CVE probability was 2.71% (95% CI: 2.27–3.18%). Descriptive probabilities were 2.56% (95% CI: 1.94–3.24%) for STN and 0.93% (95% CI: 0.00–3.08%) for GPi. Hemorrhagic events were most common (STN: 2.47%; GPi: 1.98%), while ischemic events were rare (STN: 0.07%; GPi: 1.98%). Note that GPi estimates are based on a considerably smaller population and should be interpreted with caution. Postoperative CVEs (1.74%) were more frequent than intraoperative events (0.17%), and MER use did not significantly alter risk (MER: 2.89% vs. Non-MER: 2.92%). Conclusions: Our results suggest that DBS in PD is associated with a relatively low CVE risk (~2.7%), with hemorrhage being the most frequent type; CVEs remain a potential risk factor. Comprehensive evaluation of patient-specific factors and further prospective studies focusing on CVE outcomes are essential to optimize DBS safety in managing PD. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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Graphical abstract

13 pages, 2762 KiB

Open AccessArticle

Research on Adaptive Discriminating Method of Brain–Computer Interface for Motor Imagination

by Jifeng Gong, Huitong Liu, Fang Duan, Yan Che and Zheng Yan

Brain Sci. 2025, 15(4), 412; https://doi.org/10.3390/brainsci15040412 - 18 Apr 2025

Abstract

(1) Background: Brain–computer interface (BCI) technology represents a cutting-edge field that integrates brain intelligence with machine intelligence. Unlike BCIs that rely on external stimuli, motor imagery-based BCIs (MI-BCIs) generate usable brain signals based on an individual’s imagination of specific motor actions. Due [...] Read more.

(1) Background: Brain–computer interface (BCI) technology represents a cutting-edge field that integrates brain intelligence with machine intelligence. Unlike BCIs that rely on external stimuli, motor imagery-based BCIs (MI-BCIs) generate usable brain signals based on an individual’s imagination of specific motor actions. Due to the highly individualized nature of these signals, identifying individuals who are better suited for MI-BCI applications and improving its efficiency is critical. (2) Methods: This study collected four motor imagery tasks (left hand, right hand, foot, and tongue) from 50 healthy subjects and evaluated MI-BCI adaptability through classification accuracy. Functional networks were constructed using the weighted phase lag index (WPLI), and relevant graph theory parameters were calculated to explore the relationship between motor imagery adaptability and functional networks. (3) Results: Research has demonstrated a strong correlation between the network characteristics of tongue imagination and MI-BCI adaptability. Specifically, the nodal degree and characteristic path length in the right hemisphere were found to be significantly correlated with classification accuracy (p < 0.05). (4) Conclusions: The findings of this study offer new insights into the functional network mechanisms of motor imagery, suggesting that tongue imagination holds potential as a predictor of MI-BCI adaptability. Full article

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

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19 pages, 2581 KiB

Open AccessArticle

The Neural Markers of Perceptual Uncertainty/Curiosity—A Functional Near-Infrared Spectroscopy Pilot Study

by Adrian Korniluk, Barbara Gawda, Małgorzata Chojak and Anna Gawron

Brain Sci. 2025, 15(4), 411; https://doi.org/10.3390/brainsci15040411 - 18 Apr 2025

Abstract

Background: Curiosity is an immanent aspect of human experience linked to motivation, information-seeking, and learning processes. Previous research has highlighted the significant role of the orbitofrontal cortex (OFC) in curiosity-driven behaviors, particularly in processing uncertainty and evaluating information. Methods: This study aimed to [...] Read more.

Background: Curiosity is an immanent aspect of human experience linked to motivation, information-seeking, and learning processes. Previous research has highlighted the significant role of the orbitofrontal cortex (OFC) in curiosity-driven behaviors, particularly in processing uncertainty and evaluating information. Methods: This study aimed to examine cortical activation during the induction of perceptual uncertainty using a modified blurred picture paradigm. A total of 15 participants were tested with fNIRS (functional near-infrared spectroscopy) while viewing pairs of images designed to induce perceptual uncertainty. Results: The results revealed a differential hemodynamic response in one of the analyzed channels associated with orbitofrontal cortex activation, with higher activity when uncertainty was reduced (the matching condition compared to the non-matching condition). Conclusions: These findings confirm the existence of neural pathways of curiosity. Furthermore, our study also highlights the spatial limitations of fNIRS in precisely localizing OFC activity. Full article

(This article belongs to the Section Behavioral Neuroscience)

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12 pages, 456 KiB

Open AccessCase Report

EMG-Triggered Functional Electrical Stimulation for Central Facial Palsy Following Stroke: A Clinical Case Report

by Frauke Johannes, Anna Maria Pekacka-Egli, Simone Köhler, Andreas Disko, Jan von Meyenburg and Bartosz Bujan

Brain Sci. 2025, 15(4), 410; https://doi.org/10.3390/brainsci15040410 - 17 Apr 2025

Abstract

Background: Central facial palsy (CFP) is a common condition following stroke, typically affecting the lower face and causing symptoms such as drooling, dysarthria, and facial asymmetry. Despite available rehabilitation methods, the evidence supporting their effectiveness is limited. Electromyography (EMG)-triggered Functional Electrical Stimulation (FES) [...] Read more.

Background: Central facial palsy (CFP) is a common condition following stroke, typically affecting the lower face and causing symptoms such as drooling, dysarthria, and facial asymmetry. Despite available rehabilitation methods, the evidence supporting their effectiveness is limited. Electromyography (EMG)-triggered Functional Electrical Stimulation (FES) has shown promise in neurorehabilitation for motor impairments, but its application to CFP remains unclear. Methods: This case report explores the use of EMG-triggered FES in a 77-year-old patient with CFP following a severe ischemic stroke of the middle cerebral artery (MCA). Therapy, focused on stimulating the orbicularis oris muscle to address persistent drooling and improve facial symmetry, was alongside usual care. The stimulation duration was 5–15 min, frequency 35 Hz, and pulse duration 300 µs, applied 5 times a week. Stimulation duration was adjusted based on the patient’s progress. Results: The patient underwent 16 sessions of EMG-triggered FES over four weeks. Post-therapy reassessment with the Sunnybrook Facial Grading System (SFGS) showed an improvement in facial motor function, with the score increasing from 58/100 to 78/100. Reassessment of the Facial Disability Index (FDI) revealed significant improvement in physical function (55 to 85 points), though the social function score slightly decreased (76 to 64 points). Improvements in dysarthria and the complete resolution of drooling were reflected in the physical function domain of the FDI and the Allensbach Dysarthria Severity Scale. Conclusions: The results highlight that EMG-triggered FES was well tolerated and effectively supported therapy, contributing to the resolution of drooling, improved facial symmetry, and enhanced speech function. Future research should focus on randomized controlled trials to confirm its effectiveness and determine optimal therapy parameters. Full article

(This article belongs to the Special Issue Recent Advances in Neurorehabilitation: Emerging Techniques and Technologies)

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31 pages, 988 KiB

Open AccessReview

Prevention and Management of Spinal Cord Ischemia After Aortic Surgery: An Umbrella Review

by Alexandros G. Brotis, Adamantios Kalogeras, Metaxia Bareka, Eleni Arnaoutoglou, Kostas Spanos, Miltiadis Matsagkas and Kostas N. Fountas

Brain Sci. 2025, 15(4), 409; https://doi.org/10.3390/brainsci15040409 - 17 Apr 2025

Abstract

Background/Objectives: Spinal cord injury is a devastating complication of aortic surgery, with significant morbidity and mortality. This review aimed to summarize the current literature on preventing and managing spinal cord ischemia after open and endovascular aortic repair. Methods: We conducted a comprehensive [...] Read more.

Background/Objectives: Spinal cord injury is a devastating complication of aortic surgery, with significant morbidity and mortality. This review aimed to summarize the current literature on preventing and managing spinal cord ischemia after open and endovascular aortic repair. Methods: We conducted a comprehensive review of PubMed, Scopus, and the Web of Science, focusing on systematic reviews and meta-analyses of the pathophysiology, risk factors, and strategies for mitigating the risk of spinal cord injury after aortic repair. We assessed the quality of the reporting for the eligible studies using the AMSTAR-2 tool and evaluated the strength of the evidence using the GRADE approach. Due to the absence of homogeneous clinical data, the evidence was synthesized in a narrative form. Results: Spinal cord ischemia can occur after both open and endovascular aortic repair, with a higher incidence reported in more extensive thoraco-abdominal aortic aneurysm repairs. The underlying pathogenesis is largely understudied. Several preventive strategies have been partially investigated, including cerebrospinal fluid drainage, hypothermia, and distal aortic perfusion. While the employment of neuromonitoring has been established in spine surgery, its efficacy in aortic repair remains uncertain due to confounding factors like hypothermia, anesthesia medications, and cardiopulmonary bypass. The prompt management of spinal cord complications is crucial to optimizing outcomes. No clear treatment algorithm has been universally adopted. Conclusions: Spinal cord ischemia remains a major challenge in aortic surgery, with a significant impact on patient outcomes. Further research is needed to elucidate the relevant pathophysiology and develop more effective intraoperative monitoring and management strategies. Full article

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

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17 pages, 4138 KiB

Open AccessArticle

Longitudinal Trajectories of Cognitive Function Among Chinese Middle-Aged and Older Adults: The Role of Sarcopenia and Depressive Symptoms

by Shengxuan Jin, Jianqian Chao, Qian Jin, Beibei Yang, Gangrui Tan, Leixia Wang and Yanqian Wu

Brain Sci. 2025, 15(4), 408; https://doi.org/10.3390/brainsci15040408 - 17 Apr 2025

Abstract

Objectives: The longitudinal relationship between sarcopenia, depression, and cognitive impairment has been insufficiently studied in China. This study aimed to characterize the association between sarcopenia and cognitive impairment and the mediating role of depression using nationally representative data. Methods: 7091 middle-aged and older [...] Read more.

Objectives: The longitudinal relationship between sarcopenia, depression, and cognitive impairment has been insufficiently studied in China. This study aimed to characterize the association between sarcopenia and cognitive impairment and the mediating role of depression using nationally representative data. Methods: 7091 middle-aged and older adults were analyzed from the China Health and Retirement Longitudinal Study (CHARLS) across three waves (2011, 2013, and 2015). Cognitive trajectories were modeled using a group-based trajectory model (GBTM), while multivariable ordinal logistic regression was employed to evaluate the associations with cognitive trajectories. The mediating role of depressive symptoms was assessed through bootstrap mediation analysis and cross-lagged panel modeling (CLPM). Results: Trajectory analysis identified four distinct cognitive function patterns: “High and Stable” trajectory (n = 2563, 36.73%), “Middle and Stable” group (n = 2860, 38.76%), “Middle and Decline” group (n = 1280, 18.62%), and “Low and Decline” group (n = 388, 5.90%). Sarcopenia and depressive symptoms were associated with the “Low and Decline” trajectory of cognitive function [Overall: OR (95%CI) of 0.315 (0.259, 0.382) and 0.417 (0.380, 0.459)]. Mediation analysis indicated that depressive symptoms accounted for 11.78% of the relationship between sarcopenia and cognitive trajectories. The cross-lagged panel modeling demonstrated a significant mediation pathway of “T1 cognitive function → T2 depression → T3 sarcopenia”, with T2 depression mediating 5.31% of the total effect. Conclusions: Our study identified four distinct cognitive trajectories, with sarcopenia and depressive symptoms significantly associated with worse cognitive trajectories over time. Depressive symptoms mediated the relationship between sarcopenia and cognitive function. This highlights the importance of integrating mental health and physical health interventions to address the interconnected risks associated with aging. Full article

(This article belongs to the Section Neuropsychiatry)

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20 pages, 3039 KiB

Open AccessReview

The Multifaceted Role of LRRK2 in Parkinson’s Disease

by Dong Hwan Ho, Sun Jung Han and Ilhong Son

Brain Sci. 2025, 15(4), 407; https://doi.org/10.3390/brainsci15040407 - 17 Apr 2025

Abstract

Leucine-rich repeat kinase 2 (LRRK2) is a multifunctional protein kinase intricately involved in the pathogeneses of various neurodegenerative diseases, particularly Parkinson’s disease (PD). LRRK2 plays a pivotal role in mitochondrial function and cellular senescence by regulating key processes such as autophagy, oxidative stress, [...] Read more.

Leucine-rich repeat kinase 2 (LRRK2) is a multifunctional protein kinase intricately involved in the pathogeneses of various neurodegenerative diseases, particularly Parkinson’s disease (PD). LRRK2 plays a pivotal role in mitochondrial function and cellular senescence by regulating key processes such as autophagy, oxidative stress, and protein aggregation. LRRK2 is also associated with ciliogenesis in regulating neuronal development. In addition, LRRK2 has been implicated as a putative mediator in neuroinflammation via promoting the reactivation of microglia and influencing cytokine production, a factor that may have therapeutic implications. Furthermore, mutations in LRRK2 have been found to impact the production of neurotrophic factors in astrocytes, the star-shaped glial cells of the central nervous system, thereby affecting neuronal health and contributing to the pathology of neurodegenerative diseases like PD. The multifaceted roles of LRRK2 in cellular senescence, interaction with LRS, neuroinflammation, the maintenance of mitochondria, and astrocyte function highlight its significance as a therapeutic target for neurodegenerative disorders. Full article

(This article belongs to the Special Issue Physiological Functions of LRRK2 and Its Pathogenesis)

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24 pages, 4969 KiB

Open AccessArticle

Adrenergic Modulation of Cortical Gain and Sensory Processing in the Mouse Visual Cortex

by Ricardo Medina-Coss y León, Elí Lezama, Inmaculada Márquez and Mario Treviño

Brain Sci. 2025, 15(4), 406; https://doi.org/10.3390/brainsci15040406 - 17 Apr 2025

Abstract

Background/Objectives: Sensory perception is influenced by internal neuronal variability and external noise. Neuromodulators such as norepinephrine (NE) regulate this variability by modulating excitation–inhibition balance, oscillatory dynamics, and interlaminar connectivity. While NE is known to modulate cortical gain, it remains unclear how it shapes [...] Read more.

Background/Objectives: Sensory perception is influenced by internal neuronal variability and external noise. Neuromodulators such as norepinephrine (NE) regulate this variability by modulating excitation–inhibition balance, oscillatory dynamics, and interlaminar connectivity. While NE is known to modulate cortical gain, it remains unclear how it shapes sensory processing under noisy conditions. This study investigates how adrenergic modulation affects signal-to-noise processing and perceptual decision-making in the primary visual cortex (V1) of mice exposed to varying levels of visual noise. Methods: We performed in vivo local field potential (LFP) recordings from layers 2/3 and 4 of V1 in sedated mice to assess the impact of visual noise and systemic administration of atomoxetine, a NE reuptake inhibitor, on cortical signal processing. In a separate group of freely moving mice, we used a two-alternative forced-choice to evaluate the behavioral effects of systemic and intracortical adrenergic manipulations on visual discrimination. Results: Moderate visual noise enhanced cortical signal processing and visual choices, consistent with stochastic resonance. High noise levels impaired both. Systemic atomoxetine administration flattened the cortical signal-to-noise ratio function, suggesting disrupted gain control. Behaviorally, clonidine impaired accuracy at moderate noise levels, while atomoxetine reduced discrimination performance and increased response variability. Intracortical NE infusions produced similar effects. Conclusions: Our findings demonstrate that NE regulates the balance between signal amplification and noise suppression in a noise- and context-dependent manner. These results extend existing models of neuromodulatory function by linking interlaminar communication and cortical variability to perceptual decision-making. Full article

(This article belongs to the Special Issue Perceptual Learning and Cortical Plasticity)

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14 pages, 2634 KiB

Open AccessArticle

Effects of Whole-Body Vibration on Ankle Control and Walking Speed in Individuals with Incomplete Spinal Cord Injury

by Jasmine M. Hope, Anastasia Zarkou, Cazmon Suri and Edelle C. Field-Fote

Brain Sci. 2025, 15(4), 405; https://doi.org/10.3390/brainsci15040405 - 17 Apr 2025

Abstract

Background/Objectives: After spinal cord injury (SCI), poor dorsiflexor control and involuntary plantar-flexor contraction impair walking. As whole-body vibration (WBV) improves voluntary muscle activation and modulates reflex excitability, it may improve ankle control. In this study, the dosage effects of WBV on walking speed, [...] Read more.

Background/Objectives: After spinal cord injury (SCI), poor dorsiflexor control and involuntary plantar-flexor contraction impair walking. As whole-body vibration (WBV) improves voluntary muscle activation and modulates reflex excitability, it may improve ankle control. In this study, the dosage effects of WBV on walking speed, dorsiflexion, and spinal reflex excitability were examined. Methods: Sixteen people with chronic motor-incomplete SCI participated in this randomized sham-control wash-in study. Two weeks of sham stimulation (wash-in phase) were followed by either 2 weeks of eight repetitions (short bout) or sixteen repetitions of WBV (long bout; intervention phase) per session. Walking speed, ankle angle at mid-swing, and low-frequency depression of the soleus H-reflex were measured before and after the wash-in phase and before and after the intervention phase. Results: A significant dosage effect of WBV was not observed on any of the measures of interest. There were no between-phase or within-phase differences in ankle angle during the swing phase or in low-frequency depression. When dosage groups were pooled together, there was a significant change in walking speed during the intervention phase (mean = 0.04 m/s, standard deviation = 0.06, p = 0.02). There was not a significant correlation between overall change in walking speed and dorsiflexion angle or low-frequency depression during the study. Conclusions: Whole-body vibration did not have a dosage-dependent effect on dorsiflexion during the swing phase or on spinal reflex excitability. Future studies assessing the role of corticospinal tract (CST) descending drive on increased dorsiflexor ability and walking speed are warranted. Full article

(This article belongs to the Special Issue Neural Mechanisms Underlying Sensorimotor Learning and Plasticity: Novel Advances and Future Perspectives)

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16 pages, 1392 KiB

Open AccessReview

The Assessment of the Motor and Non-Motor Aspects of Anosognosia for Hemiplegia: A Historical Review

by Maddalena Beccherle, Sara Bertagnoli and Valentina Moro

Brain Sci. 2025, 15(4), 404; https://doi.org/10.3390/brainsci15040404 - 17 Apr 2025

Abstract

Anosognosia for hemiplegia is a complex, multifaceted phenomenon. Due to the various different forms in which it manifests and the few tools available to treat it, it can create difficulties for both clinicians and researchers. Since the first definition established by Babinski, a [...] Read more.

Anosognosia for hemiplegia is a complex, multifaceted phenomenon. Due to the various different forms in which it manifests and the few tools available to treat it, it can create difficulties for both clinicians and researchers. Since the first definition established by Babinski, a great deal of research has been performed and has shown that this deficit in motor awareness involves not only motor aspects but also other, non-motor dimensions. These dimensions all need to be taken into consideration during the process of diagnosis, in particular when planning a rehabilitation programme. This article reviews the main instruments currently available for the diagnosis of anosognosia for hemiplegia. After a description of the best tests to assess motor dimensions (such as explicit and implicit anosognosia, emergent awareness and awareness for daily life activities), non-motor dimensions are analysed. The literature on the subject provides ideas and tools for the evaluation of cognitive (i.e., motor imagery), emotional and social (i.e., theory of mind) aspects. Finally, the importance of differential diagnoses in relation to disorders often associated with anosognosia is discussed. Full article

(This article belongs to the Special Issue Anosognosia and the Determinants of Self-Awareness)

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16 pages, 458 KiB

Open AccessReview

A Brief Review of Inherited Neuropathies: A Perspective from Saudi Arabia

by Ahmed K. Bamaga, Anas S. Alyazidi and Feryal K. Alali

Brain Sci. 2025, 15(4), 403; https://doi.org/10.3390/brainsci15040403 - 17 Apr 2025

Abstract

Inherited neuropathies are a heterogeneous group of disorders that affect the peripheral nervous system, leading to motor, sensory, and autonomic dysfunction. These disorders are classified into various subgroups, including hereditary sensory and motor neuropathies, distal hereditary motor neuropathies, hereditary sensory and autonomic neuropathies, [...] Read more.

Inherited neuropathies are a heterogeneous group of disorders that affect the peripheral nervous system, leading to motor, sensory, and autonomic dysfunction. These disorders are classified into various subgroups, including hereditary sensory and motor neuropathies, distal hereditary motor neuropathies, hereditary sensory and autonomic neuropathies, and more complex forms. Advances in genetic testing, particularly next-generation sequencing (NGS), have significantly improved the identification of these disorders. Emerging therapies, such as gene therapy, small molecule therapies, and antisense oligonucleotides, offer promising treatment options. However, current treatments remain limited, and their clinical benefits in humans are not yet fully established. This review provides a comprehensive overview of recent developments and evolving therapeutic options for hereditary neuropathies, focusing on gene therapy, small molecule therapies, and antisense oligonucleotides. It also highlights the current state of inherited neuropathies in Saudi Arabia, emphasizing the need for national guidelines, patient registries, and collaborative research efforts. By integrating advanced genomic technologies and fostering international collaboration, we can improve the diagnosis, management, and treatment outcomes for patients with inherited neuropathies. Full article

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

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7 pages, 166 KiB

Open AccessEditorial

Human Brain Responses and Functional Brain Networks Across the Lifespan

by Birgit Mathes and Canan Başar-Eroǧlu

Brain Sci. 2025, 15(4), 402; https://doi.org/10.3390/brainsci15040402 - 16 Apr 2025

Abstract

Measuring brain responses in real time using electrophysiology enriches our understanding of changes in behavior and cognitive function across the lifespan [...] Full article

(This article belongs to the Special Issue Human Brain Responses and Functional Brain Networks across the Lifespan)

21 pages, 1890 KiB

Open AccessArticle

Musical Expertise Reshapes Cross-Domain Semantic Integration: ERP Evidence from Language and Music Processing

by Xing Wang and Tao Zeng

Brain Sci. 2025, 15(4), 401; https://doi.org/10.3390/brainsci15040401 - 16 Apr 2025

Abstract

Background/Objectives: Both language and music are capable of encoding and communicating semantic concepts, suggesting a potential overlap in neurocognitive mechanisms. Moreover, music training not only enhances domain-specific musical processing but also facilitates cross-domain language processing. However, existing research has predominantly focused on Indo-European [...] Read more.

Background/Objectives: Both language and music are capable of encoding and communicating semantic concepts, suggesting a potential overlap in neurocognitive mechanisms. Moreover, music training not only enhances domain-specific musical processing but also facilitates cross-domain language processing. However, existing research has predominantly focused on Indo-European languages, with limited evidence from paratactic languages such as Mandarin Chinese. In addition, the impact of variations in musical expertise on these shared processing mechanisms remains unclear, leaving a critical gap in our understanding of the shared neural bases for semantic processing in language and music. This event-related potential (ERP) study investigated whether Chinese sentences and musical chord sequences share semantic processing mechanisms and how musical expertise modulates these mechanisms. Methods: This study recruited 46 college students (22 musicians and 24 non-musicians). Participants read Chinese sentences presented word-by-word visually, while chord sequences were delivered auditorily, with each word temporally aligned to one chord. Sentences included semantically acceptable or unacceptable classifier–noun pairs and chord sequences ended with in-key or out-of-key chords. Participants were instructed to focus on reading sentences while ignoring the concurrent music. ERP signals were recorded, and time-locked to final words to capture neural dynamics during semantic integration. Results: The behavioral results showed that musicians were influenced by musical regularity when reading (acceptable: F(1, 44) = 25.70, p < 0.001, η_p² = 0.38; unacceptable: F(1, 44) = 11.45, p = 0.002, η_p² = 0.21), but such effect was absent in non-musicians (ps > 0.05). ERP results showed that musical semantic processing had a substantial impact on both P200 (F(1, 44) = 9.95, p = 0.003, η_p² = 0.18), N400 (musicians: F(1, 44) = 15.80, p < 0.001, η_p² = 0.26; non-musicians: F(1, 44) = 4.34, p = 0.043, η_p² = 0.09), and P600 (musicians: F(1, 44) = 5.55, p = 0.023, η_p² = 0.11; non-musicians: F(1, 44) = 8.68, p = 0.005, η_p² = 0.17) components. Furthermore, musical expertise exerted modulatory effects during later stages, as evidenced by divergent N400 and P600 latency patterns between musicians and non-musicians. Specifically, ERP amplitudes exhibited opposing trends: musicians showed an enhanced N400 and diminished P600, while non-musicians displayed a weaker N400 and stronger P600. Conclusions: Our findings provide novel evidence that Mandarin Chinese and chord sequences engage partially overlapping neural mechanisms for semantic processing both in the early (P200) and the late (N400 and P600) stages. Crucially, this study is the first to demonstrate that musical expertise may gradually reorganize these shared mechanisms, enabling two initially independent but functionally analogous semantic mechanisms into a domain-general processing system. These insights deepen our understanding of the neurocognitive mechanisms underlying linguistic and musical semantic processing and highlight how expertise shapes the neural architecture of cross-domain mechanisms. Full article

(This article belongs to the Section Neurolinguistics)

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21 pages, 1040 KiB

Open AccessReview

Neuroplasticity and Nervous System Recovery: Cellular Mechanisms, Therapeutic Advances, and Future Prospects

by Ligia Gabriela Tataranu and Radu Eugen Rizea

Brain Sci. 2025, 15(4), 400; https://doi.org/10.3390/brainsci15040400 - 15 Apr 2025

Abstract

Neuroplasticity, the ability of the nervous system to adapt structurally and functionally in response to environmental interactions and injuries, is a cornerstone of recovery in the central (CNS) and peripheral nervous systems (PNS). This review explores the mechanisms underlying neuroplasticity, focusing on the [...] Read more.

Neuroplasticity, the ability of the nervous system to adapt structurally and functionally in response to environmental interactions and injuries, is a cornerstone of recovery in the central (CNS) and peripheral nervous systems (PNS). This review explores the mechanisms underlying neuroplasticity, focusing on the dynamic roles of cellular and molecular processes in recovery from nervous system injuries. Key cellular players, including Schwann cells, oligodendrocytes, and neural stem cells, are highlighted for their contributions to nerve repair, myelination, and regeneration. Advances in therapeutic interventions, such as electrical stimulation, bioluminescent optogenetics, and innovative nerve grafting techniques, are discussed alongside their potential to enhance recovery and functional outcomes. The molecular underpinnings of plasticity, involving synaptic remodeling, homeostatic mechanisms, and activity-dependent regulation of gene expression, are elucidated to illustrate their role in learning, memory, and injury repair. Integrating emerging technologies and therapeutic approaches with a foundational understanding of neuroplasticity offers a pathway toward more effective strategies for restoring nervous system functionality after injury. Full article

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

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14 pages, 2191 KiB

Open AccessArticle

Machine Learning-Based Classification of Anterior Circulation Cerebral Infarction Using Computational Fluid Dynamics and CT Perfusion Metrics

by Xulong Yin, Yusheng Zhao, Fuping Huang, Hui Wang and Qi Fang

Brain Sci. 2025, 15(4), 399; https://doi.org/10.3390/brainsci15040399 - 15 Apr 2025

Abstract

Background: Intracranial atherosclerotic stenosis (ICAS) is a leading cause of ischemic stroke, particularly in the anterior circulation. Understanding the underlying stroke mechanisms is essential for guiding personalized treatment strategies. This study proposes an integrated framework that combines CT perfusion imaging, vascular anatomical features, [...] Read more.

Background: Intracranial atherosclerotic stenosis (ICAS) is a leading cause of ischemic stroke, particularly in the anterior circulation. Understanding the underlying stroke mechanisms is essential for guiding personalized treatment strategies. This study proposes an integrated framework that combines CT perfusion imaging, vascular anatomical features, computational fluid dynamics (CFD), and machine learning to classify stroke mechanisms based on the Chinese Ischemic Stroke Subclassification (CISS) system. Methods: A retrospective analysis was conducted on 118 patients with intracranial atherosclerotic stenosis. Key indicators were selected using one-way ANOVA with nested cross-validation and visualized through correlation heatmaps. Optimal thresholds were identified using decision trees. The classification performance of six machine learning models was evaluated using ROC and PR curves. Results: Time to Maximum (Tmax) > 4.0 s, wall shear stress ratio (WSSR), pressure ratio, and percent area stenosis were identified as the most predictive indicators. Thresholds such as Tmax > 4.0 s = 134.0 mL and WSSR = 86.51 effectively distinguished stroke subtypes. The Logistic Regression model demonstrated the best performance (AUC = 0.91, AP = 0.85), followed by Naive Bayes models. Conclusions: This multimodal approach effectively differentiates stroke mechanisms in anterior circulation ICAS and holds promise for supporting more precise diagnosis and personalized treatment in clinical practice. Full article

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

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