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16 pages, 1489 KiB  
Article
Gamma Transcranial Alternating Current Stimulation Enhances Working Memory Ability in Healthy People: An EEG Microstate Study
by Binbin Gao, Jinyan Zhang, Jianxu Zhang, Guangying Pei, Tiantian Liu, Li Wang, Shintaro Funahashi, Jinglong Wu, Zhilin Zhang and Jian Zhang
Brain Sci. 2025, 15(4), 381; https://doi.org/10.3390/brainsci15040381 (registering DOI) - 7 Apr 2025
Abstract
Background:Working memory (WM) is a core cognitive function closely linked to various cognitive processes including language, decision making, and reasoning. Transcranial alternating current stimulation (tACS), a non-invasive brain stimulation technique, has been shown to modulate cognitive abilities and treat psychiatric disorders. Although gamma [...] Read more.
Background:Working memory (WM) is a core cognitive function closely linked to various cognitive processes including language, decision making, and reasoning. Transcranial alternating current stimulation (tACS), a non-invasive brain stimulation technique, has been shown to modulate cognitive abilities and treat psychiatric disorders. Although gamma tACS (γ-tACS) has demonstrated positive effects on WM, its underlying neural mechanisms remain unclear. Methods: In this study, we employed electroencephalogram (EEG) microstate analysis to investigate the spatiotemporal dynamics of γ-tACS effects on WM performance. Healthy participants (N = 104) participated in two-back and three-back WM tasks before and after two types (sine and triangular) of γ-tACS, with sham stimulation as a control. Results: Our results revealed that γ-tACS improved performance in both the two-back and three-back tasks, with triangular γ-tACS showing greater accuracy improvement in the three-back task than the sham group. Furthermore, γ-tACS significantly modulated EEG microstate dynamics, specifically downregulating microstate Class C and upregulating microstate Classes D and B. These changes were positively correlated with reduced reaction times in the three-back task. Conclusions: Our findings establish microstate analysis as an effective approach for evaluating γ-tACS-induced changes in global brain activity and advance the understanding of how γ-tACS influences WM. Full article
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29 pages, 1960 KiB  
Review
Lactoferrin as a Candidate Multifunctional Therapeutic in Synucleinopathies
by Caroline A. Barros and Tuane C. R. G. Vieira
Brain Sci. 2025, 15(4), 380; https://doi.org/10.3390/brainsci15040380 (registering DOI) - 6 Apr 2025
Abstract
Lactoferrin (Lf) is a multifunctional glycoprotein with well-established antimicrobial, anti-inflammatory, and iron-binding properties. Emerging evidence suggests that Lf also plays a neuroprotective role, particularly in neurodegenerative disorders characterized by protein aggregation, such as Parkinson’s disease (PD). Alpha-synuclein (aSyn) aggregation is a pathological hallmark [...] Read more.
Lactoferrin (Lf) is a multifunctional glycoprotein with well-established antimicrobial, anti-inflammatory, and iron-binding properties. Emerging evidence suggests that Lf also plays a neuroprotective role, particularly in neurodegenerative disorders characterized by protein aggregation, such as Parkinson’s disease (PD). Alpha-synuclein (aSyn) aggregation is a pathological hallmark of PD and other synucleinopathies, contributing to neuronal dysfunction and disease progression. Recent studies indicate that Lf may interfere with aSyn aggregation, iron chelation, and modulation of oxidative stress and neuroinflammation. Additionally, Lf’s ability to cross the blood-brain barrier and its potential impact on the gut-brain axis highlight its promise as a therapeutic agent. This review explores Lf’s mechanisms of action in synucleinopathies, its potential as a disease-modifying therapy, and innovative delivery strategies that could enhance its clinical applicability. By addressing the pathological and therapeutic dimensions of aSyn aggregation, we propose Lf as a compelling candidate for future research and clinical development in neurodegenerative diseases. Full article
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12 pages, 804 KiB  
Review
TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression
by Paolo Alonge, Carmela Rita Balistreri, Angelo Torrente, Daniele Magro, Elisa Rubino and Roberto Monastero
Brain Sci. 2025, 15(4), 379; https://doi.org/10.3390/brainsci15040379 (registering DOI) - 5 Apr 2025
Viewed by 61
Abstract
Background/Objectives: The activation of microglia and the activity of innate immunity have recently been recognized as part of Parkinson’s Disease (PD) pathophysiology. Triggering receptor expressed on myeloid cells 2 (TREM2) is a gene with neuroprotective roles. Its variations are associated with microglial-associated [...] Read more.
Background/Objectives: The activation of microglia and the activity of innate immunity have recently been recognized as part of Parkinson’s Disease (PD) pathophysiology. Triggering receptor expressed on myeloid cells 2 (TREM2) is a gene with neuroprotective roles. Its variations are associated with microglial-associated neurodegeneration. The objective of the present review is to investigate the current evidence on the role of TREM2 in PD pathophysiology. Methods: A comprehensive search was performed using PubMed, Medline, and Web of Science, looking for English papers investigating the role of TREM2 in PD, or more in general, the genetic profile of microglia. Results: Thirty-one papers were considered relevant. Preclinical studies with PD models showed some contradictory results, even if a loss of function of TREM2 is generally associated with a microglial activation in α-synuclein-induced inflammatory processes. The role for TREM2 genetic variations in PD patients should be taken with even more caution. The increase in the soluble extracellular segment of TREM2 (sTREM2) in cerebrospinal fluid of PD patients seems to be associated with increased risk of cognitive decline. Conclusions: There is increasing evidence that TREM2 may have an important role in PD pathophysiology as demonstrated by preclinical and clinical studies. Further investigations are needed to confirm this role and may lead the way for future targeted therapies for different neurodegenerative disorders. Full article
(This article belongs to the Special Issue New Advances in Neuroimmunology and Neuroinflammation)
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13 pages, 817 KiB  
Article
Creative Cognitive Reappraisal Promotes Estimation Strategy Execution in Individuals with Trait Anxiety
by Huan Song, Chenghui Tan, Chuanlin Zhu, Dianzhi Liu and Wenbo Peng
Brain Sci. 2025, 15(4), 378; https://doi.org/10.3390/brainsci15040378 - 4 Apr 2025
Viewed by 68
Abstract
Objectives: This study aimed to investigate the impact of the creative cognitive reappraisal on the estimation strategies execution in college students with trait anxiety. Methods: Using the Trait Anxiety Scale, 47 participants with high (HTA) and low trait anxiety (LTA) were selected from [...] Read more.
Objectives: This study aimed to investigate the impact of the creative cognitive reappraisal on the estimation strategies execution in college students with trait anxiety. Methods: Using the Trait Anxiety Scale, 47 participants with high (HTA) and low trait anxiety (LTA) were selected from a total of 803 college students. These participants then completed a two-digit multiplication estimation task after using cognitive reappraisal to regulate negative emotions. Results: The results showed that for individuals with low trait anxiety, both standard cognitive reappraisal and creative cognitive reappraisal effectively improved their negative emotional experiences, with creative cognitive reappraisal demonstrating a superior regulatory effect. For individuals with high trait anxiety, creative cognitive reappraisal was effective in regulating negative emotions, whereas the effect of standard cognitive reappraisal on emotion regulation was not significant. Conclusions: Both standard cognitive reappraisal and creative cognitive reappraisal can enhance the speed of estimation strategy execution in college students with trait anxiety after regulating negative emotions, with creative cognitive reappraisal showing a more pronounced facilitative effect. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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15 pages, 3256 KiB  
Article
The Neural Correlates of Consciousness: A Spectral Exponent Approach to Diagnosing Disorders of Consciousness
by Ying Zhao, Anqi Wang, Weiqiao Zhao, Nantu Hu, Steven Laureys and Haibo Di
Brain Sci. 2025, 15(4), 377; https://doi.org/10.3390/brainsci15040377 - 4 Apr 2025
Viewed by 59
Abstract
Background/Objectives: Disorder of consciousness (DoC) poses diagnostic challenges due to behavioral assessment limitations. This study evaluates the spectral exponent (SE)—a neurophysiological biomarker quantifying the decay slope of electroencephalography (EEG) aperiodic activity—as an objective tool for consciousness stratification and clinical behavior scores correlation. Methods: [...] Read more.
Background/Objectives: Disorder of consciousness (DoC) poses diagnostic challenges due to behavioral assessment limitations. This study evaluates the spectral exponent (SE)—a neurophysiological biomarker quantifying the decay slope of electroencephalography (EEG) aperiodic activity—as an objective tool for consciousness stratification and clinical behavior scores correlation. Methods: The study involved 15 DoC patients, nine conscious brain-injured controls (BI), and 23 healthy controls (HC). Resting-state 32-channel EEG data were analyzed to compute SE across broadband (1–40 Hz) and narrowband (1–20 Hz, 20–40 Hz). Statistical frameworks included Bonferroni-corrected Kruskal–Wallis H tests, Bayesian ANOVA, and correlation analyses with CRS-R behavioral scores. Results: Narrowband SE (1–20 Hz) showed superior diagnostic sensitivity, differentiating DoC from controls (HC vs. DoC: p < 0.0001; BI vs. DoC: p = 0.0006) and MCS from VS/UWS (p = 0.0014). SE correlated positively with CRS-R index (1–20 Hz: r = 0.590, p = 0.021) and visual subscale (1–20 Hz: r = 0.684, p = 0.005). High-frequency (20–40 Hz) SE exhibited inconsistent results. Longitudinal tracking in an individual revealed a reduction in SE negativity, a flattening of the 1/f slope, and behavioral recovery occurring in parallel. Conclusions: Narrowband SE (1–20 Hz) is a robust biomarker for consciousness quantification, overcoming behavioral assessment subjectivity. Its correlation with visual function highlights potential clinical utility. Future studies should validate SE in larger cohorts and integrate multimodal neuroimaging. Full article
(This article belongs to the Section Neurorehabilitation)
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8 pages, 186 KiB  
Opinion
Evidence for Cognitive Spatial Models from Ancient Roman Land-Measurement
by Andrew M. Riggsby
Brain Sci. 2025, 15(4), 376; https://doi.org/10.3390/brainsci15040376 - 4 Apr 2025
Viewed by 80
Abstract
Influential studies in the history of cartography have argued that map-like representations of space were (virtually) unknown in the Classical Mediterranean world and that the cause of this was an absence of underlying cognitive maps. That is, persons in that time/place purportedly had [...] Read more.
Influential studies in the history of cartography have argued that map-like representations of space were (virtually) unknown in the Classical Mediterranean world and that the cause of this was an absence of underlying cognitive maps. That is, persons in that time/place purportedly had only route/egocentric-type mental representations, not survey/allocentric ones. The present study challenges that cognitive claim by examining the verbal descriptions of plots of land produced by ancient Roman land-measurers. Despite the prescription of a route-based form, actual representations persistently show a variety of features which suggest the existence of underlying survey-type mental models and the integration of those with the route-type ones. This fits better with current views on interaction between types of spatial representation and of cultural difference in this area. The evidence also suggests a linkage between the two kinds of representations. Full article
22 pages, 1558 KiB  
Review
Stroke in Young Adults: An Overview and Non-Pharmacological Preventive Strategies
by Aleksandar Sič, Nikola Andrejić, Jovana Ivanović, Vidna Karadžić Ristanović, Selena Gajić, Danka Bjelić, Marko Baralić and Nikola Stojanovic
Brain Sci. 2025, 15(4), 375; https://doi.org/10.3390/brainsci15040375 - 3 Apr 2025
Viewed by 79
Abstract
Stroke is one of the most common causes of death and disability worldwide, with significant impact on both physical and cognitive health. Although strokes are less common in young adults, they still occur in this population, particularly in those with certain comorbidities, such [...] Read more.
Stroke is one of the most common causes of death and disability worldwide, with significant impact on both physical and cognitive health. Although strokes are less common in young adults, they still occur in this population, particularly in those with certain comorbidities, such as Autosomal Dominant Polycystic Kidney Disease (ADPKD). Despite the lack of specific guidelines for stroke prevention in young adults, certain preventive measures can be implemented. Smoking cigarettes is the most significant stroke risk factor in this group. Additionally, psychosocial stress, often exacerbated by academic, career, and financial pressures, is emerging as a modifiable risk factor for stroke in young adults. Key preventive measures include dietary changes, management of underlying health conditions, incorporating regular physical activity into daily routines, smoking cessation, and effective stress management techniques such as mindfulness-based stress reduction (MBSR) and cognitive–behavioral therapy (CBT). Promoting mental health awareness, directing public health campaigns toward young adults, educating them on recognizing stroke symptoms and administering first aid, and improving the quality of healthcare for this population all play a vital role in preventing stroke in young adults. Full article
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14 pages, 246 KiB  
Article
Psychological and Clinical Parameters as Predictors of Relapse in Alcohol-Dependent Patients During and After Extensive Inpatient Rehabilitation Treatment
by Josef Rabl, Dieter Geyer, Katharina Steiner, Fabrizio Schifano and Norbert Scherbaum
Brain Sci. 2025, 15(4), 374; https://doi.org/10.3390/brainsci15040374 - 3 Apr 2025
Viewed by 40
Abstract
Background: Psychological parameters related to alcohol dependence (AD) affect patients’ behavioral and cognitive control, decision making, impulsivity and inhibitory control. People with AD often have a chronic course with a relapse to dependent substance use even after extensive treatment. This study investigated whether [...] Read more.
Background: Psychological parameters related to alcohol dependence (AD) affect patients’ behavioral and cognitive control, decision making, impulsivity and inhibitory control. People with AD often have a chronic course with a relapse to dependent substance use even after extensive treatment. This study investigated whether the psychological parameters of patients with AD predict (a) premature termination of treatment, and/or (b) relapse into consumption of alcohol from admission until 6 weeks after discharge from an inpatient rehabilitation treatment. Methods: Participants: Alcohol-dependent patients consecutively admitted for a duration of about three months to inpatient rehabilitation treatment in a hospital specialized in substance use disorders. Craving (OCDS-G) and impulsivity (BIS-11; UPPS) were assessed with computerized questionnaires. Attentional bias and inhibitory control were measured with two computer-based experiments (dot-probe task; stop-signal task (SST)). Investigations were conducted at entry (T1); after 6 weeks (T2); and during the last two weeks of the inpatient treatment (T3). Some N = 128 patients finished the first, N = 102 the second and N = 83 the third assessments. Outcome variables were discontinuation of treatment and abstinence or relapse until follow-up 6 weeks after discharge; participants were contacted via telephone. Results: None of the variables are associated with discontinuation of treatment. Poor inhibitory control (SST) and high craving (OCDS-5) levels, measured at T1, are significantly associated with relapse. Higher impulsivity (UPPS) measured at T2 and T3 is significantly associated with relapse. Exploratory analyses showed that older age, longer inpatient treatment duration and time spent in abstinence before rehabilitation treatment were significantly associated with a reduced risk of relapse. Conclusions: Psychological parameters, craving and impulsivity levels did not predict relapse to a high degree. It is assumed that discontinuation of treatment and relapse may be associated with different issues, such as social context, and individual motivation levels. In contrast, the length of both abstinence before admission and of inpatient treatment were significantly associated with abstinence; it is here suggested that recovery time duration may be an underestimated influencing factor regarding relapse in AD patients. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
4 pages, 175 KiB  
Editorial
Integrating Body Schema and Body Image in Neurorehabilitation: Where Do We Stand and What’s Next?
by Rocco Salvatore Calabrò
Brain Sci. 2025, 15(4), 373; https://doi.org/10.3390/brainsci15040373 - 3 Apr 2025
Viewed by 97
Abstract
Given the widespread debate surrounding the definitions and functional roles of “Body Schema” and “Body Image”, these constructs have become central to understanding motor control and rehabilitation, particularly for individuals with neurological impairments [...] Full article
(This article belongs to the Section Neurorehabilitation)
14 pages, 278 KiB  
Article
Emotional Eating, Impulsivity, and Affective Temperaments in a Sample of Obese Candidates for Bariatric Surgery: Which Linkage?
by Davide Gravina, Miriam Violi, Andrea Bordacchini, Elisa Diadema, Sara Fantasia, Marly Simoncini and Claudia Carmassi
Brain Sci. 2025, 15(4), 372; https://doi.org/10.3390/brainsci15040372 - 3 Apr 2025
Viewed by 170
Abstract
Background/Objectives: Obesity is a major public health challenge of the 21st century, with prevalence rates steadily rising globally. Disordered eating behaviors, particularly emotional eating (EE), complicate the clinical management of obesity and hinder long-term outcomes, such as maintaining weight loss after bariatric [...] Read more.
Background/Objectives: Obesity is a major public health challenge of the 21st century, with prevalence rates steadily rising globally. Disordered eating behaviors, particularly emotional eating (EE), complicate the clinical management of obesity and hinder long-term outcomes, such as maintaining weight loss after bariatric surgery. Studies reveal that EE affects 65–75% of overweight or obese adults, and such behavior may stem from a disrupted brain reward system linked to emotional dysregulation and impulsivity. Impulsivity in obesity involves deficient cognitive inhibitory control, creating an imbalance between impulsive and reflective systems. While problematic eating behaviors and obesity are well studied, the role of affective temperaments—innate traits influencing mood, energy, and responses to stimuli—remains underexplored. This study aims to examine the interplay between emotional eating, impulsivity, and affective temperaments in obese patients preparing for bariatric surgery. Methods: A total sample of 304 obese outpatients was consecutively enrolled at the Psychiatry Clinic of the Department of Clinical and Experimental Medicine of the University of Pisa during the presurgical mental health evaluation routinely performed before the bariatric intervention. Sociodemographic and clinical data were collected by psychiatrists during a single consultation. Assessments also included the following psychometric tests: the Structured Clinical Interview (SCID-5), the Emotional Eating Scale (EES), the Barratt Impulsivity Scale-Version 11 (BIS-11), and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Auto-questionnaire (TEMPS-A). Results: A significant correlation was observed between the EES total score and the BIS total score (p = 0.003), as well as with the sub-dimensions of attentional impulsivity (p < 0.001) and motor impulsivity (p = 0.024). In addition, a significant correlation has been found between the total score of EES and the cyclothymic (p < 0.001), depressive (p < 0.001), irritable (p = 0.013), and anxious (0.020) temperaments. When comparing obese patients with EE and without EE (No-EE), higher rates of both current (p = 0.007) and lifetime (p = 0.024) psychiatric comorbidities were observed in the EE group, namely for anxiety disorders (p = 0.008) and eating disorders (p = 0.014). Conclusions: Our study highlights a significant association between EE in obese patients with the cyclothymic, irritable, anxious, and depressive temperaments, and impulsivity dimension. Thus, problematic eating behaviors and temperamental traits may have a bidirectional psychopathological influence in obese patients and need to be carefully evaluated in subjects seeking bariatric surgery. Full article
14 pages, 1939 KiB  
Article
Marital Status-Specific Associations Between Multidomain Leisure Activities and Cognitive Reserve in Clinically Unimpaired Older Adults: Based on a National Chinese Cohort
by Cheng Cai, Junyi Wang, Dan Liu, Jing Liu, Juan Zhou, Xiaochang Liu, Dan Song, Shiyue Li, Yuyang Cui, Qianqian Nie, Feifei Hu, Xinyan Xie, Guirong Cheng and Yan Zeng
Brain Sci. 2025, 15(4), 371; https://doi.org/10.3390/brainsci15040371 - 3 Apr 2025
Viewed by 134
Abstract
Background: It is unclear how marital status moderates the association between multidomain leisure activities and the progression of cognitive decline in community-dwelling older adults. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey with up to 10 years of follow-up were used. The [...] Read more.
Background: It is unclear how marital status moderates the association between multidomain leisure activities and the progression of cognitive decline in community-dwelling older adults. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey with up to 10 years of follow-up were used. The study included participants aged ≥65 years without cognitive impairment at baseline. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Linear mixed-effect models were used to evaluate the modifying effect of marriage on leisure activities (multiple types, frequency, and single type) and cognitive decline. Results: A total of 5286 participants (aged 79.01 ± 9.54 years, 50.0% women, and 61.4% rural residents) were enrolled. The results indicated that marital status moderates the relationship between leisure activities and cognitive decline. In the unmarried group, multi-type and high-frequency leisure activities were more strongly associated with slower cognitive decline. Specific activities such as gardening, reading, performing household chores, and playing cards were found to significantly contribute to cognitive protection exclusively within the unmarried group, with no such effect observed in the married group. Conclusions: Marital status affects the relationship between participation in multiple leisure activities and cognitive decline in cognitively intact elderly people. For unmarried older adults, regular participation in leisure activities may be an effective intervention. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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23 pages, 13995 KiB  
Article
The Effect of Dopaminergic Therapy in Parkinson’s Disease: A Graph Theory Analysis
by Karthik Siva, Palanisamy Ponnusamy, Vishal Chavda and Nicola Montemurro
Brain Sci. 2025, 15(4), 370; https://doi.org/10.3390/brainsci15040370 - 2 Apr 2025
Viewed by 126
Abstract
Background: Dopaminergic therapy (DT) is the gold standard pharmacological treatment for Parkinson’s disease (PD). Currently, understanding the neuromodulation effect in the brain of PD after DT is important for doctors to optimize doses and identify the adverse effects of medication. The objective [...] Read more.
Background: Dopaminergic therapy (DT) is the gold standard pharmacological treatment for Parkinson’s disease (PD). Currently, understanding the neuromodulation effect in the brain of PD after DT is important for doctors to optimize doses and identify the adverse effects of medication. The objective of this study is to investigate the brain connectivity alteration with and without DT in PD using resting-state EEG. Methods: Graph theory (GT) is an efficient technique for analyzing brain connectivity alteration in healthy and patient groups. We applied GT analyses on three groups, namely healthy control (HC), Parkinson with medication OFF (PD-OFF), and Parkinson with medication ON (PD-ON). Results: Using the clustering coefficient (CC), participation coefficient (PC), and small-worldness (SW) properties of GT, we showed that PD-ON patients’ brain connectivity normalized towards healthy group brain connectivity due to DT. This normalization effect appeared in the brain connectivity of all EEG frequency bands, such as theta, alpha, beta-1, beta-2, and gamma except the delta band. We also analyzed region-wise brain connectivity between 10 regions of interest (ROIs) (right and left frontal, right and left temporal, right and left parietal, right and left occipital, upper and lower midline regions) at the scalp level and compared across conditions. During PD-ON, we observed a significant decrease in alpha band connectivity between right frontal and left parietal (p-value 0.0432) and right frontal and left occipital (p-value 0.008) as well as right frontal and right temporal (p-value 0.041). Conclusion: These findings offer new insights into how dopaminergic therapy modulates brain connectivity across frequency bands and highlight the continuous elevation of both the segregation and small-worldness of the delta band even after medication as a potential biomarker for adverse effects due to medication. Additionally, reduced frontal alpha band connectivity is associated with cognitive impairment and levodopa-induced dyskinesia, highlighting its potential role in Parkinson’s disease progression. This study underscores the need for personalized treatments that address both motor and non-motor symptoms in PD patients. Full article
(This article belongs to the Special Issue Brain Network Connectivity Analysis in Neuroscience)
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16 pages, 2662 KiB  
Article
Vitamin C Modulates the PI3K/AKT Pathway via Glutamate and Nitric Oxide in Developing Avian Retina Cells in Culture
by Aline T. Duarte-Silva, Ivan Domith, Isabele Gonçalves-da-Silva and Roberto Paes-de-Carvalho
Brain Sci. 2025, 15(4), 369; https://doi.org/10.3390/brainsci15040369 - 2 Apr 2025
Viewed by 97
Abstract
Background: In addition to its known antioxidant function, the reduced form of vitamin C, ascorbate, also acts as a neuromodulator in the nervous system. Previous work showed a reciprocal interaction of ascorbate with glutamate in chicken embryo retinal cultures. Ascorbate modulates extracellular glutamate [...] Read more.
Background: In addition to its known antioxidant function, the reduced form of vitamin C, ascorbate, also acts as a neuromodulator in the nervous system. Previous work showed a reciprocal interaction of ascorbate with glutamate in chicken embryo retinal cultures. Ascorbate modulates extracellular glutamate levels by inhibiting excitatory amino acid transporter 3 and promoting the activation of NMDA receptors and the consequent activation of intracellular signaling pathways involved in transcription and survival. Objective: In the present work, we investigated the regulation of AKT phosphorylation by ascorbate in chicken embryo retina cultures. Methodology: Cultures of chicken embryo retina cells were tested using Western blot, immunocytochemistry, fluorescent probe transfection, and cellular imaging techniques. Results: Our results show that ascorbate induces a concentration and time-dependent increase in AKT phosphorylation via the accumulation of extracellular glutamate, the activation of glutamate receptors, and the activation of the PI3K pathway. Ascorbate produces an increase in intracellular calcium accumulation and, accordingly, AKT phosphorylation by ascorbate is blocked by the calcium chelator BAPTA-AM. Moreover, AKT phosphorylation is also blocked by the nitric oxide synthase inhibitor 7-nitroindazole, indicating that it is mediated by calcium and nitric oxide-dependent mechanisms. Conclusions: We demonstrate that ascorbate modulates the PI3K/AKT pathway in retinal cultures through the activation of glutamate receptors and NO production in a calcium-dependent manner. Given that previous research has shown that glutamate induces ascorbate release in retinal cultures, our findings emphasize the significance of the reciprocal interactions between ascorbate and glutamate in retinal development. These findings provide further evidence supporting the role of ascorbate as a neuromodulator in retinal development. Full article
(This article belongs to the Special Issue Retinal Neurochemistry and Development)
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19 pages, 11005 KiB  
Article
The Bulb, the Brain and the Being: New Insights into Olfactory System Anatomy, Organization and Connectivity
by Anton Stenwall, Aino-Linnea Uggla, David Weibust, Markus Fahlström, Mats Ryttlefors and Francesco Latini
Brain Sci. 2025, 15(4), 368; https://doi.org/10.3390/brainsci15040368 - 31 Mar 2025
Viewed by 100
Abstract
Background/Objectives: Olfaction is in many ways the least understood sensory modality. Its organization and connectivity are still under debate. The aim of this study was to investigate the anatomy of the olfactory system by using a cadaver fiber dissection technique and in vivo [...] Read more.
Background/Objectives: Olfaction is in many ways the least understood sensory modality. Its organization and connectivity are still under debate. The aim of this study was to investigate the anatomy of the olfactory system by using a cadaver fiber dissection technique and in vivo tractography to attain a deeper understanding of the subcortical connectivity and organization. Methods: Ten cerebral hemispheres were used in this study for white matter dissection according to Klingler’s technique. Measurements of different cortical structures and interhemispheric symmetry were compared. Diffusion tensor imaging sequences from twenty-five healthy individuals from the Human Connectome Project dataset were used to explore the connectivity of the olfactory system using DSI Studio. White matter connectivity between the following were reconstructed in vivo: (1) Olfactory bulb to primary olfactory cortices; (2) Olfactory bulb to secondary olfactory cortices; (3) Primary to secondary olfactory cortices. The DTI metrics of the identified major associative, projection and commissural pathways were subsequently correlated with olfactory function and cognition in seventy-five healthy individuals with Spearman’s rank correlation and the Benjamini–Hochberg method for false discoveries (CI 95%, p < 0.05) using R. Results: 1. The dissection showed that the lateral stria was significantly longer on the left side and projected towards the amygdala, the entorhinal and piriform cortex. 2. The medial stria was not evident as a consistent white matter structure. 3. Both dissection and tractography showed that major associative white matter pathways such as the uncinate fasciculus, the inferior fronto-occipital fasciculus and cingulum supported the connectivity between olfactory areas together with the anterior commissure. 4. No significant correlation was found between DTI metrics and sensory or cognition test results. Conclusions: We present the first combined fiber dissection analysis and tractography of the olfactory system. We propose a novel definition where the primary olfactory network is defined by the olfactory tract/bulb and primary olfactory cortices through the lateral stria only. The uncinate fasciculus, inferior fronto-occipital fasciculus and cingulum are the associative pathways supporting the connectivity between primary and secondary olfactory areas together with the anterior commissure. We suggest considering these structures as a secondary olfactory network. Further work is needed to attain a deeper understanding of the pathological and physiological implications of the olfactory system. Full article
(This article belongs to the Special Issue Plasticity and Regeneration in the Olfactory System)
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19 pages, 473 KiB  
Review
Effectiveness of Lee Silverman Voice Treatment (LSVT)-BIG for Neurological Diseases Other than Parkinson’s Disease: Mini Review
by Changyeon Won, Woohyuk Jang and Sunwook Park
Brain Sci. 2025, 15(4), 367; https://doi.org/10.3390/brainsci15040367 - 31 Mar 2025
Viewed by 61
Abstract
Background: Lee Silverman Voice Treatment-BIG (LB) was developed for Parkinson’s disease patients to improve patients’ movement amplitude and accuracy through large movements and enhance movements through self-awareness and recalibration. This study aimed to review studies on LB for neurological diseases other than Parkinson’s [...] Read more.
Background: Lee Silverman Voice Treatment-BIG (LB) was developed for Parkinson’s disease patients to improve patients’ movement amplitude and accuracy through large movements and enhance movements through self-awareness and recalibration. This study aimed to review studies on LB for neurological diseases other than Parkinson’s disease and examine its potential as an intervention tool. Method: The main search databases included Google Scholar, PubMed, and ScienceDirect. ‘Neurological disease’, ‘LSVT-BIG’, ‘Treatment or Rehabilitation’, ‘Intervention’, and ‘Therapy’ were used as search keywords until December 2024, and eight articles were finally selected. Results: As a result of analyzing eight studies, there were four studies on stroke (all conducted by occupational therapists) and four studies on other diseases, including two studies on progressive supranuclear palsy, one study on idiopathic normal pressure hydrocephalus, and one study on Huntington’s disease (all conducted by physical therapists). Conclusions: LB had a positive effect on improving physical function and overall motor control in patients with neurological diseases other than Parkinson’s disease, indicating its potential as an intervention tool. In the future, studies that have high-level evidence-based study designs and complement small sample sizes are needed to demonstrate the effectiveness of LB. Full article
(This article belongs to the Section Neurorehabilitation)
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