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Brain Sciences
Volume 15
Issue 3
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Brain Sci., Volume 15, Issue 3 (March 2025) – 110 articles

Cover Story (view full-size image): Sleep appears to have a central role in Freud’s original model, since dreaming is considered the guardian of sleep. The function of dreaming is to protect sleep from disruption, thereby preserving its biological integrity. Freud also recognized sleep as an active process, given that human beings voluntarily withdraw from the external world to sleep. The discovery of REM sleep in the 1950s led psychoanalysts to view sleep as the necessary backdrop against which dreaming occurs. Although Freud dismissed the clinical importance of sleep disturbances, authors have since suggested that sleep disturbances might have specific psychological significance. Thanks to Freud’s work, the desire to sleep assumes an important role as a psychological, active factor that contributes to the occurrence and function of sleep. View this paper
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14 pages, 5489 KiB  
Article
Naringenin Exhibits Antiglioma Activity Related to Aryl Hydrocarbon Receptor Activity and IL-6, CCL2, and TNF-α Expression
by Monique Reis de Santana, Deivison Silva Argolo, Irlã Santos Lima, Cleonice Creusa dos Santos, Maurício Moraes Victor, Gabriel dos Santos Ramos, Ravena Pereira do Nascimento, Henning Ulrich and Silvia Lima Costa
Brain Sci. 2025, 15(3), 325; https://doi.org/10.3390/brainsci15030325 - 20 Mar 2025
Viewed by 348
Abstract
Background: Glioblastoma (GBM) is a highly aggressive brain tumor characterized by rapid cell proliferation, invasive behavior, and chemoresistance. The aryl hydrocarbon receptor (AhR) is implicated in chemoresistance and immune evasion, making it a promising therapeutic target. Natural compounds such as flavonoids have gained [...] Read more.
Background: Glioblastoma (GBM) is a highly aggressive brain tumor characterized by rapid cell proliferation, invasive behavior, and chemoresistance. The aryl hydrocarbon receptor (AhR) is implicated in chemoresistance and immune evasion, making it a promising therapeutic target. Natural compounds such as flavonoids have gained attention for their anti-inflammatory, antioxidant, and anticancer properties. Among them, naringenin, a citrus-derived flavonoid, exerts antiproliferative, pro-apoptotic, and immunomodulatory effects. Objectives: This study investigated the antiglioma effects of the flavonoid naringenin on the viability, growth, and migration of glioma cells and its potential role as an AhR modulator. Methods: Human (U87) and rat (C6) glioma cell lines were exposed to naringenin (10–300 µM) alone or in combination with the AhR agonist indole-3-carbinol (50 µM) for 24 to 48 h. Cell viability, scratch wound, and cell migration assays were performed. The expression of inflammatory markers was also analyzed by RT-qPCR. Results: Naringenin exerted dose- and time-dependent inhibition of cell viability and migration. The treatment decreased the gene expression of interleukin-6 (IL-6) and chemokine (CCL2), alongside increased tumor necrosis factor-alpha (TNF-α) expression, an effect reversed by the AhR agonist. Conclusions: These findings highlight naringenin’s potential as an antiglioma agent and its role in AhR signaling. Full article
(This article belongs to the Special Issue New Advances in the Development of New Drugs and Treatment Targets for Brain Cancers (2nd Edition))
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23 pages, 1077 KiB  
Systematic Review
Mindfulness-Based Intervention Effects on EEG and Executive Functions: A Systematic Review
by Gilberto Galindo-Aldana, Luis Arturo Montoya-Rivera, Jose Jaime Esqueda-Elizondo, Everardo Inzunza-Gonzalez, Enrique Efren Garcia-Guerrero, Alfredo Padilla-Lopez, Tara G. Bautista and Cynthia Torres-González
Brain Sci. 2025, 15(3), 324; https://doi.org/10.3390/brainsci15030324 - 20 Mar 2025
Viewed by 573
Abstract
Background. Mindfulness-based interventions (MBIs) have emerged as an alternative intervention for symptoms of psychological and psychiatric conditions, such as depression, anxiety, and emotional discomfort. Over the last ten years, MBIs have established a growing body of evidence that shows cognitive and neurophysiological benefits. [...] Read more.
Background. Mindfulness-based interventions (MBIs) have emerged as an alternative intervention for symptoms of psychological and psychiatric conditions, such as depression, anxiety, and emotional discomfort. Over the last ten years, MBIs have established a growing body of evidence that shows cognitive and neurophysiological benefits. Depression and anxiety are conditions with a high prevalence in the world population. In developing countries, it is reported that, given the conditions of being at a social disadvantage, anxiety and depression are higher, resulting in compromised psychological well-being and mental health. Objectives. This systematic review aims to quantitatively and qualitatively assess changes in the neuropsychological, particularly executive functioning and social cognition domains, and electroencephalographical (EEG) effects of MBIs. Methods. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in three databases, Web of Science, Scopus, and EBSCO MedLine complete; 14,464 articles were found, 141 articles evaluated the effects of MBI on executive functioning, and 16 included both as in qualitative and quantitative variables. Results. The qualitative results show that the research on the effects of MBI on behavior and cognitive skills, including executive function, social cognition, and EEG analysis, is very scarce but consistent in suggesting strong correlations on cognitive and electrophysiological alpha–beta proportions asymmetry on frontal areas. Undoubtedly, executive functions, as a behavioral regulatory and self-monitoring system, are the most popular study of interest in the literature, including emotional regulation, awareness, planning, social skills, and focused attention. Although there are fewer studies assessing the effects of MBIs on social cognition skills. The funnel plot showed a symmetrical distribution but ranked out of significant correlation. Most estimates of treatment effects are positive (58%); however, the average outcome observed did not significantly differ from zero. Conclusions. This study concludes that the research integrating the analysis of the electrophysiological and executive function effects of MBI shows important methodological variations and clinical conditions, which explains the significant results reported individually. Even when most of the literature reports positive effects of MBIs on several behavioral and neurophysiological domains, there are still confounding factors that must be taken into consideration by researchers and clinicians before attributing possible inaccurate or generalizable benefits. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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13 pages, 945 KiB  
Article
Can the Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and C-Reactive Protein-to-Albumin Ratio Always Predict Mortality in Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy? A Single-Center Experience
by Şennur Delibaş Katı and Firdevs Ezgi Uçan Tokuç
Brain Sci. 2025, 15(3), 323; https://doi.org/10.3390/brainsci15030323 - 20 Mar 2025
Viewed by 266
Abstract
Background: Predicting mortality in patients with acute ischemic stroke who need endovascular treatment (EVT) has previously been shown to be related to inflammation. In this study, we aimed to examine the effects of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hypersensitive [...] Read more.
Background: Predicting mortality in patients with acute ischemic stroke who need endovascular treatment (EVT) has previously been shown to be related to inflammation. In this study, we aimed to examine the effects of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hypersensitive C-reactive protein-to-albumin ratio (CAR) values on mortality and hemorrhagic transformation. Methods: A total of 225 adult patients who underwent EVT between 2022 and 2024 were retrospectively analyzed. The presence of intracranial hemorrhage (ICH) after the procedure; good and poor clinical outcomes according to modified Rankin Scores; mortality status; and NLR, PLR, and CAR values were collected. Results: The average age of the patients was 66.95 ± 12.74 years, and 133 (59.1%) patients were male. Thirty-eight (30.4%) patients had symptomatic ICH. While 164 (72.9%) patients had a poor outcome, 80 (35.6%) patients died. There was a correlation between the NLR and PLR values and symptomatic ICH (p = 0.013, 0.009, respectively) in the univariate analysis, but this relationship was not found in the multivariate analyses (p: 0.212 and p: 0.459). No statistically significant relationship was observed between the CAR and symptomatic ICH and mortality (p = 0.784, 0.079, respectively). When the laboratory data were compared according to the mortality status, the NLR and PLR were observed to be statistically significantly higher in the patients with mortality (p < 0.001, 0.005, respectively) in univariate analyses. But, as a result, the NLR, PLR, and CAR were not associated with ICH and mortality according to the multivariable logistic regression analysis. Conclusions: Our findings highlight the need to better understand the post-stroke immune response. Our study demonstrated that the NLR, PLR, and CAR were not associated with ICH and mortality according to the multivariable logistic regression analysis. Full article
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22 pages, 1278 KiB  
Review
Murine Non-Transgenic Models of Alzheimer’s Disease Pathology: Focus on Risk Factors
by Maricarmen Hernández-Rodríguez, Juan Manuel Vega López, Martín Martínez-Rosas, María Inés Nicolás-Vázquez and Elvia Mera Jiménez
Brain Sci. 2025, 15(3), 322; https://doi.org/10.3390/brainsci15030322 - 19 Mar 2025
Viewed by 258
Abstract
Alzheimer’s disease (AD) represents a significant challenge among neurodegenerative disorders, as effective treatments and therapies remain largely undeveloped. Despite extensive research efforts employing various methodologies and diverse genetic models focused on amyloid-β (Aβ) pathology, the research for effective therapeutic strategies remains inconclusive. The [...] Read more.
Alzheimer’s disease (AD) represents a significant challenge among neurodegenerative disorders, as effective treatments and therapies remain largely undeveloped. Despite extensive research efforts employing various methodologies and diverse genetic models focused on amyloid-β (Aβ) pathology, the research for effective therapeutic strategies remains inconclusive. The key pathological features of AD include Aβ senile plaques, neurofibrillary tangles (NFTs), and the activation of neuroinflammatory pathways. Presently, investigations into AD and assessing potential treatments predominantly utilize Aβ transgenic models. Conversely, non-transgenic models may provide valuable insights into the multifaceted pathological states associated with AD. Thus, these models may serve as practical complementary tools for evaluating therapeutic and intervention strategies, since the primary AD risk factors are most frequently modeled. This review aims to critically assess the existing literature on AD non-transgenic models induced by streptozotocin, scopolamine, aging, mechanical stress, metals, and dietary patterns to enhance their application in AD research. Full article
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
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11 pages, 981 KiB  
Perspective
Advancing Rehabilitation Medicine with the Metaverse: Opportunities and Challenges
by Rocco Salvatore Calabrò and Giovanni Morone
Brain Sci. 2025, 15(3), 321; https://doi.org/10.3390/brainsci15030321 - 19 Mar 2025
Viewed by 270
Abstract
The metaverse, an immersive virtual environment, is emerging as a transformative tool in rehabilitation, offering innovative modalities for motor and cognitive treatments. Virtual reality and augmented reality within the metaverse facilitate interactive exercises, allowing patients to perform rehabilitative tasks in a gamified context, [...] Read more.
The metaverse, an immersive virtual environment, is emerging as a transformative tool in rehabilitation, offering innovative modalities for motor and cognitive treatments. Virtual reality and augmented reality within the metaverse facilitate interactive exercises, allowing patients to perform rehabilitative tasks in a gamified context, which can improve motivation and adherence. Furthermore, the metaverse supports treatments that are not easy to carry out during conventional therapy, such as the rehabilitation of social participation, and creates a real individuals-based platform of continuum of care thanks to its interoperability. However, challenges such as technological accessibility, user adaptability, and the need for comprehensive clinical guidelines remain. Future research should focus on long-term efficacy, integration into traditional rehabilitation frameworks, and addressing ethical considerations, ultimately positioning the metaverse as a valuable adjunct in rehabilitative practices. Full article
(This article belongs to the Special Issue Recent Advances in Neurorehabilitation: Emerging Techniques and Technologies)
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19 pages, 675 KiB  
Review
Vocal Feature Changes for Monitoring Parkinson’s Disease Progression—A Systematic Review
by Helen Wright and Vered Aharonson
Brain Sci. 2025, 15(3), 320; https://doi.org/10.3390/brainsci15030320 - 19 Mar 2025
Viewed by 367
Abstract
Background: Parkinson’s disease has a significant impact on vocal characteristics and speech patterns, making them potential biomarkers for monitoring disease progression. To effectively utilise these biomarkers, it is essential to understand how they evolve over time as this degenerative disease progresses. Objectives: This [...] Read more.
Background: Parkinson’s disease has a significant impact on vocal characteristics and speech patterns, making them potential biomarkers for monitoring disease progression. To effectively utilise these biomarkers, it is essential to understand how they evolve over time as this degenerative disease progresses. Objectives: This review aims to identify the most used vocal features in Parkinson’s disease monitoring and to track the temporal changes observed in each feature. Methods: An online database search was conducted to identify studies on voice and speech changes associated with Parkinson’s disease progression. The analysis examined the features and their temporal changes to identify potential feature classes and trends. Results: Eighteen features were identified and categorised into three main aspects of speech: articulation, phonation and prosody. While twelve of these features exhibited measurable variations in Parkinsonian voices compared to those of healthy individuals, insights into long-term changes were limited. Conclusions: Vocal features can effectively discriminate Parkinsonian voices and may be used to monitor changes through disease progression. These changes remain underexplored and necessitate more evidence from long-term studies. The additional evidence could provide clinical insights into the disease and enhance the effectiveness of automated voice-based monitoring. Full article
(This article belongs to the Special Issue New Approaches in the Exploration of Parkinson’s Disease)
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3 pages, 137 KiB  
Editorial
New Insights in Psychiatric Disorder Psychopharmacology
by Mohammadreza Shalbafan and Laura Orsolini
Brain Sci. 2025, 15(3), 319; https://doi.org/10.3390/brainsci15030319 - 19 Mar 2025
Viewed by 315
Abstract
Psychopharmacological interventions are the treatment cornerstone of most psychiatric disorders such as depression, schizophrenia, obsessive–compulsive disorder, and bipolar disorders, with a huge number of studies including clinical trials and review articles deepening knowledge in the field in recent decades [...] Full article
(This article belongs to the Special Issue New Insights in Psychiatric Disorder Psychopharmacology)
18 pages, 1576 KiB  
Article
Dual Assessment of Developmental Topographical Disorientation: Comparing Self-Reported Measures with Actual Navigational Performance
by Alessia Bonavita, Sofia Pepe, Raffaella Nori, Massimiliano Palmiero, Cecilia Guariglia and Laura Piccardi
Brain Sci. 2025, 15(3), 318; https://doi.org/10.3390/brainsci15030318 - 18 Mar 2025
Viewed by 394
Abstract
Background/Objectives: This study aimed to (i) evaluate the effectiveness of the Familiarity and Spatial Cognitive Style Scale (FSCS) and the short Computerized Ecological Navigational Battery (LBS) in predicting navigational performance by comparing self-reported scores with actual results; (ii) investigate the FSCS’s potential as [...] Read more.
Background/Objectives: This study aimed to (i) evaluate the effectiveness of the Familiarity and Spatial Cognitive Style Scale (FSCS) and the short Computerized Ecological Navigational Battery (LBS) in predicting navigational performance by comparing self-reported scores with actual results; (ii) investigate the FSCS’s potential as a screening tool for Developmental Topographical Disorientation (DTD), which affects about 3% of youth, focusing on early detection; and (iii) examine gender differences in self-reported data versus real-world performance to understand how stereotypes affect self-assessment. Methods: The study involved 185 college students (125 female), aged 18–35 years, who completed the FSCS and performed navigation tasks using a new version of the LBS. Participants’ performances were analysed using MAD-based z-scores to identify potential DTD cases, with scores below the fifth percentile flagged for further investigation. The relationship between self-reported abilities and actual performance was assessed through correlation analyses and robust linear regressions. Results: The SOD subscale of FSCS emerged as a comprehensive predictor of navigation performance, correlating significantly with accuracy across multiple tasks. The study identified a 5.42% prevalence of DTD using FSCS criteria, aligning with previous research, while LBS identified 11.96% of participants with navigational difficulties. Gender differences were observed in Survey Knowledge and Landmark Ordering tasks, with males showing higher performances. Only two participants were flagged as DTD cases by both assessment methods, suggesting they may evaluate distinct aspects of navigational ability. Conclusions: The findings validate FSCS as an initial screening tool for DTD while highlighting the need for comprehensive assessment using multiple tools. The study suggests the existence of at least two distinct forms of DTD: one affecting navigational memory (detectable by both FSCS and LBS) and another impacting perceptual navigation aspects (more readily identified by LBS). These results emphasise the importance of developing a detailed DTD taxonomy and implementing personalised interventions based on specific navigational challenges. Full article
(This article belongs to the Special Issue Neuropsychological Exploration of Spatial Cognition and Navigation)
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17 pages, 3293 KiB  
Article
Comparative Effects of Temporal Interference and High-Definition Transcranial Direct Current Stimulation on Spontaneous Neuronal Activity in the Primary Motor Cortex: A Randomized Crossover Study
by Zhiqiang Zhu, Lang Qin, Dongsheng Tang, Zhenyu Qian, Jie Zhuang and Yu Liu
Brain Sci. 2025, 15(3), 317; https://doi.org/10.3390/brainsci15030317 - 18 Mar 2025
Viewed by 466
Abstract
Background: Modulating spontaneous neuronal activity is critical for understanding and potentially treating neurological disorders, yet the comparative effects of different non-invasive brain stimulation techniques remain underexplored. Objective: This study aimed to systematically compare the effects of temporal interference (TI) stimulation and high-definition transcranial [...] Read more.
Background: Modulating spontaneous neuronal activity is critical for understanding and potentially treating neurological disorders, yet the comparative effects of different non-invasive brain stimulation techniques remain underexplored. Objective: This study aimed to systematically compare the effects of temporal interference (TI) stimulation and high-definition transcranial direct current stimulation (HD-tDCS) on spontaneous neuronal activity in the primary motor cortex. Methods: In a randomized, crossover design, forty right-handed participants underwent two 20 min sessions of either TI or HD-tDCS. Resting-state fMRI data were collected at four stages: pre-stimulus baseline (S1), first half of stimulation (S2), second half of stimulation (S3), and post-stimulation (S4). We analyzed changes in regional homogeneity (ReHo), dynamic ReHo (dReHo), fractional amplitude of low-frequency fluctuations (fALFFs), and dynamic fALFFs (dfALFFs) to assess the impact on spontaneous neuronal activity. Results: The analysis revealed that TI had a more significant impact on ReHo, especially in the left superior temporal gyrus and postcentral gyrus, compared with HD-tDCS. Both stimulation methods exhibited their strongest effects during the second half of the stimulation period, but only TI maintained significant activity in the post-stimulation phase. Additionally, both TI and HD-tDCS enhanced fALFFs in real-time, with TI showing more pronounced effects in sensorimotor regions. Conclusions: These findings suggest that TI exerts a more potent and sustained influence on spontaneous neuronal activity than HD-tDCS. This enhanced understanding of their differential effects provides valuable insights for optimizing non-invasive brain stimulation protocols for therapeutic applications. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
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15 pages, 1481 KiB  
Article
Personal Quality of Life as an Outcome Measure of Antipsychotic Drug Management of Problem Behaviours in Adults with Intellectual Developmental Disorders with or Without Autism Spectrum Disorder
by Marco O. Bertelli, Annamaria Bianco, Micaela Piva Merli, Maria Stella Vescio, Michele Rossi and Elisabetta F. Buonaguro
Brain Sci. 2025, 15(3), 316; https://doi.org/10.3390/brainsci15030316 - 18 Mar 2025
Viewed by 368
Abstract
Background/Objectives: First-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) are frequently prescribed for the management of problem behaviours (PBs) in people with intellectual developmental disorders (IDDs) with or without autism spectrum disorder (ASD). However, the different effectiveness of these two groups of drugs has [...] Read more.
Background/Objectives: First-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) are frequently prescribed for the management of problem behaviours (PBs) in people with intellectual developmental disorders (IDDs) with or without autism spectrum disorder (ASD). However, the different effectiveness of these two groups of drugs has not been adequately investigated, especially in terms of person-centred outcomes, such as quality of life (QoL). The aim of the present observational study was to compare the personal QoL of two groups of people with IDDs with and without ASD, attending the same residential facility, but receiving FGAs and SGAs, respectively, for the management of PBs. Methods: Twenty-two people with IDDs (ten with ASD) receiving FGAs and twenty-three (eleven with ASD) receiving SGAs for the management of PBs were consecutively recruited. The participants underwent a complex clinical and instrumental evaluation, including the systematic psychopathological assessment for persons with intellectual and developmental disabilities—general screening (SPAIDD-G), the Wing’s handicaps, behaviours, and skills schedule (HBS), the DOTES, and the BASIQ (QoL Assessment tool battery). Follow-up evaluations were carried out after 6, 12, and 18 months. Results: The use of antipsychotics was withdrawn only in 16 cases, of which only 4 were for significant improvement. Treatment with FGAs was associated with more frequent discontinuation, a higher incidence of side effects, and a trend toward a lower efficacy on PBs than treatment with SGAs. FGAs also improved generic QoL significantly less than SGAs. Conclusions: The present pilot study is the first to compare FGAs and SGAs with respect to the generic QoL in people with IDDs and PBs. SGAs resulted to have a significantly greater positive impact on QoL than FGAs, despite demonstrating similar efficacy in treating PBs. Full article
(This article belongs to the Section Neuropsychiatry)
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13 pages, 546 KiB  
Systematic Review
Skin Lesions as Signs of Neuroenhancement in Sport
by Sorana-Cristiana Popescu, Roman Popescu, Vlad Voiculescu and Carolina Negrei
Brain Sci. 2025, 15(3), 315; https://doi.org/10.3390/brainsci15030315 - 17 Mar 2025
Viewed by 700
Abstract
Background: Neuroenhancement in sports, through pharmacological and non-pharmacological methods, is a complex and highly debated topic with no definitive regulatory framework established by the World Anti-Doping Agency (WADA). The hypothesis that dermatological changes could serve as observable biomarkers for neurodoping introduces a novel [...] Read more.
Background: Neuroenhancement in sports, through pharmacological and non-pharmacological methods, is a complex and highly debated topic with no definitive regulatory framework established by the World Anti-Doping Agency (WADA). The hypothesis that dermatological changes could serve as observable biomarkers for neurodoping introduces a novel and promising approach to detecting and understanding the physiological impacts of cognitive enhancers in athletes. As neurodoping methods become increasingly sophisticated, developing objective, reliable, and non-invasive detection strategies is imperative. Utilizing dermatological signs as a diagnostic tool for internal neurophysiological changes could offer critical insights into the safety, fairness, and ethical considerations of cognitive enhancement in competitive sports. A systematic correlation between skin manifestations, the timeline of neurodoping practices, and the intensity of cognitive enhancement methods could provide healthcare professionals valuable tools for monitoring athletes’ health and ensuring strict compliance with anti-doping regulations. Methods: Due to the limited body of research on this topic, a systematic review of the literature was conducted, spanning from 2010 to 31 December 2024, using databases such as PubMed, Science Direct, and Google Scholar. This study followed the 2020 PRISMA guidelines and included English-language articles published within the specified period, focusing on skin lesions as adverse reactions to pharmacological and non-pharmacological neuroenhancement methods. The research employed targeted keywords, including “skin lesions AND rivastigmine”, “skin lesions AND galantamine”, “skin lesions AND donepezil”, “skin lesions AND memantine”, and “skin lesions AND transcranial direct electrical stimulation”. Given the scarcity of studies directly addressing neurodoping in sports, the search criteria were broadened to include skin reactions associated with cognitive enhancers and brain stimulation. Eighteen relevant articles were identified and analyzed. Results: The review identified rivastigmine patches as the most used pharmacological method for neuroenhancement, with pruritic (itchy) skin lesions as a frequent adverse effect. Donepezil was associated with fewer and primarily non-pruritic skin reactions. Among non-pharmacological methods, transcranial direct current stimulation (tDCS) was notably linked to skin burns, primarily due to inadequate electrode–skin contact, prolonged exposure, or excessive current intensity. These findings suggest that specific dermatological manifestations could serve as potential indicators of neurodoping practices in athletes. Conclusions: Although specific neuroenhancement methods demonstrate distinctive dermatological side effects that might signal neurodoping, the current lack of robust clinical data involving athletes limits the ability to draw definitive conclusions. Athletes who engage in neurodoping without medical supervision are at an elevated risk of adverse dermatological and systemic reactions. Skin lesions, therefore, could represent a valuable early diagnostic marker for the inappropriate use or overuse of cognitive-enhancing drugs or neuromodulation therapies. The findings emphasize the need for focused clinical research to establish validated dermatological criteria for detecting neurodoping. This research could contribute significantly to the ongoing neuroethical discourse regarding the legitimacy and safety of cognitive enhancement in sports. Full article
(This article belongs to the Section Behavioral Neuroscience)
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28 pages, 4195 KiB  
Systematic Review
Brain Markers of Resilience to Psychosis in High-Risk Individuals: A Systematic Review and Label-Based Meta-Analysis of Multimodal MRI Studies
by Guusje Collin, Joshua E. Goldenberg, Xiao Chang, Zhenghan Qi, Susan Whitfield-Gabrieli, Wiepke Cahn, Jijun Wang, William S. Stone, Matcheri S. Keshavan and Martha E. Shenton
Brain Sci. 2025, 15(3), 314; https://doi.org/10.3390/brainsci15030314 - 17 Mar 2025
Viewed by 547
Abstract
Background/Objectives: Most individuals who have a familial or clinical risk of developing psychosis remain free from psychopathology. Identifying neural markers of resilience in these at-risk individuals may help clarify underlying mechanisms and yield novel targets for early intervention. However, in contrast to [...] Read more.
Background/Objectives: Most individuals who have a familial or clinical risk of developing psychosis remain free from psychopathology. Identifying neural markers of resilience in these at-risk individuals may help clarify underlying mechanisms and yield novel targets for early intervention. However, in contrast to studies on risk biomarkers, studies on neural markers of resilience to psychosis are scarce. The current study aimed to identify potential brain markers of resilience to psychosis. Methods: A systematic review of the literature yielded a total of 43 MRI studies that reported resilience-associated brain changes in individuals with an elevated risk for psychosis. Label-based meta-analysis was used to synthesize findings across MRI modalities. Results: Resilience-associated brain changes were significantly overreported in the default mode and language network, and among highly connected and central brain regions. Conclusions: These findings suggest that the DMN and language-associated areas and central brain hubs may be hotspots for resilience-associated brain changes. These neural systems are thus of key interest as targets of inquiry and, possibly, intervention in at-risk populations. Full article
(This article belongs to the Special Issue Multimodal Imaging in Brain Development)
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17 pages, 7312 KiB  
Article
Altered Hemispheric Asymmetry of Functional Hierarchy in Schizophrenia
by Yi Zhen, Hongwei Zheng, Yi Zheng, Zhiming Zheng, Yaqian Yang and Shaoting Tang
Brain Sci. 2025, 15(3), 313; https://doi.org/10.3390/brainsci15030313 - 16 Mar 2025
Viewed by 430
Abstract
Background/Objectives: Schizophrenia is a severe psychiatric disorder characterized by deficits in perception and advanced cognitive functions. Prior studies have reported abnormal lateralization in cortical morphology and functional connectivity in schizophrenia. However, it remains unclear whether schizophrenia affects hemispheric asymmetry in the hierarchical organization [...] Read more.
Background/Objectives: Schizophrenia is a severe psychiatric disorder characterized by deficits in perception and advanced cognitive functions. Prior studies have reported abnormal lateralization in cortical morphology and functional connectivity in schizophrenia. However, it remains unclear whether schizophrenia affects hemispheric asymmetry in the hierarchical organization of functional connectome. Methods: Here, we apply a gradient mapping framework to the hemispheric functional connectome to estimate the first three gradients, which characterize unimodal-to-transmodal, visual-to-somatomotor, and somatomotor/default mode-to-multiple demand hierarchy axes. We then assess between-group differences in intra- and inter-hemispheric asymmetries of these three functional gradients. Results: We find that, compared to healthy controls, patients with schizophrenia exhibit significantly altered hemispheric asymmetry in functional gradient across multiple networks, including the dorsal attention, ventral attention, visual, and control networks. Region-level analyses further reveal that patients with schizophrenia show significantly abnormal hemispheric gradient asymmetries in several cortical regions in the dorsal prefrontal gyrus, medial superior frontal gyrus, and somatomotor areas. Lastly, we find that hemispheric asymmetries in functional gradients can differentiate between patients and healthy controls and predict the severity of positive symptoms in schizophrenia. Conclusions: Collectively, these findings suggest that schizophrenia is associated with altered hemispheric asymmetry in functional hierarchy, providing novel perspectives for understanding the atypical brain lateralization in schizophrenia. Full article
(This article belongs to the Section Neuropsychiatry)
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15 pages, 531 KiB  
Article
Differences in Gaze Behavior Between Male and Female Elite Handball Goalkeepers During Penalty Throws
by Wojciech Jedziniak, Krystian Panek, Piotr Lesiakowski, Beata Florkiewicz and Teresa Zwierko
Brain Sci. 2025, 15(3), 312; https://doi.org/10.3390/brainsci15030312 - 15 Mar 2025
Viewed by 596
Abstract
Background: Recent research suggests that an athlete’s gaze behavior plays a significant role in expert sport performance. However, there is a lack of studies investigating sex differences in gaze behavior during technical and tactical actions. Objectives: Therefore, the purpose of this study was [...] Read more.
Background: Recent research suggests that an athlete’s gaze behavior plays a significant role in expert sport performance. However, there is a lack of studies investigating sex differences in gaze behavior during technical and tactical actions. Objectives: Therefore, the purpose of this study was to analyze the eye movements of elite female and male handball goalkeepers during penalty throws. Methods: In total, 40 handball goalkeepers participated in the study (female: n = 20; male: n = 20). Eye movements were recorded during a series of five penalty throws in real-time conditions. The number of fixations and dwell time, including quiet eye, for selected areas of interest were recorded using a mobile eye-tracking system. Results: Significant differences were found in quiet-eye duration between effective and ineffective goalkeeper interventions (females: mean difference (MD) = 92.26; p = 0.005; males: MD = 122.83; p < 0.001). Significant differences in gaze behavior between female and male handball goalkeepers were observed, specifically in the number of fixations and fixation duration on the selected areas of interest (AOIs). Male goalkeepers primarily observed the throwing upper arm AOI, the throwing forearm (MD = 15.522; p < 0.001), the throwing arm AOI (MD = 6.83; p < 0.001), and the ball (MD = 7.459; z = 3.47; p < 0.001), whereas female goalkeepers mainly observed the torso AOI (MD = 14.264; p < 0.001) and the head AOI (MD = 11.91; p < 0.001) of the throwing player. Conclusions: The results suggest that female goalkeepers’ gaze behavior is based on a relatively constant observation of body areas to recall task-specific information from memory, whilst male goalkeepers mainly observe moving objects in spatio-temporal areas. From a practical perspective, these results can be used to develop perceptual training programs tailored to athletes’ sex. Full article
(This article belongs to the Special Issue Advances in Assessment and Training of Perceptual-Motor Performance)
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12 pages, 641 KiB  
Article
Presence of Psychotic Spectrum Symptoms Before Age 12 in Schizophrenia Patients: A Retrospective Study on Clinical Implications for Early Detection and Intervention
by Pietro Carmellini, Alessandro Cuomo, Annarita Vignapiano, Francesco Monaco, Simone Pardossi, Bernardo Firenzuoli and Andrea Fagiolini
Brain Sci. 2025, 15(3), 311; https://doi.org/10.3390/brainsci15030311 - 15 Mar 2025
Viewed by 463
Abstract
Background/Objectives: Schizophrenia is a severe psychiatric disorder, with onset typically occurring in late adolescence or early adulthood. Early identification of psychotic symptoms, especially those occurring before age 12, has been linked to better long-term outcomes. This study aims to assess the presence [...] Read more.
Background/Objectives: Schizophrenia is a severe psychiatric disorder, with onset typically occurring in late adolescence or early adulthood. Early identification of psychotic symptoms, especially those occurring before age 12, has been linked to better long-term outcomes. This study aims to assess the presence of psychotic spectrum symptoms before the age of 12 in adult schizophrenia patients and explore their clinical implications for early detection and intervention. Methods: This retrospective, observational study included 170 adult patients diagnosed with schizophrenia, confirmed by the SCID-5. Patients were recruited from the University of Siena Medical Center and completed the modified lifetime version of the Psychotic Spectrum Self-Report (PSY-SR) questionnaire, which assessed the onset of specific psychotic symptoms before and after age 12. Symptom severity was evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale (CGI). This study also examined the impact of the duration of untreated psychosis (DUP) on symptom severity. Results: In our cohort, 21% of patients exhibited prodromal symptoms before age 12 (95% CI: 15–27%). Prodromal symptoms were linked to a 9.53-point increase in the BPRS scores (p = 0.0478) and a 0.50-point increase in the CGI scores (p = 0.0347). The age of symptom onset negatively correlated with the BPRS scores (p < 0.0001), with each year of delay resulting in a 1.33-point decrease. The DUP correlated significantly with both the BPRS (ρ = 0.97) and CGI scores (ρ = 0.94). The multivariate analysis revealed that a longer DUP was associated with significant increases in both scores: a 27.16-point increase in the BPRS (p < 0.0001) for a moderate DUP and a 67.51-point increase (p < 0.0001) for a severe DUP. The CGI scores increased by 1.11 points with a moderate DUP and 3.17 points with a severe DUP (p < 0.0001). However, the interaction between the DUP and prodromal symptoms at age 12 was not significant, indicating similar impacts of the DUP regardless of early symptom onset. Conclusions: The results support the critical importance of early detection and intervention in schizophrenia. Early psychotic spectrum symptoms, particularly those occurring before age 12, are significant predictors of later severity and functional impairment. This study underscores the value of screening tools like the PSY-SR for identifying prodromal symptoms and facilitating timely intervention. Our findings highlight the need for the early identification of psychotic symptoms, particularly in at-risk populations, to improve long-term outcomes. Intervening before the onset of full-blown psychosis may reduce the severity of schizophrenia and promote better clinical outcomes. Full article
(This article belongs to the Section Neuropsychiatry)
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19 pages, 2199 KiB  
Article
Olfactory Testing and Gray Matter Volume: A Combined Approach to Predict the Conversion to Alzheimer
by Claudia Casadio, Daniela Ballotta, Francesco Ricci, Vanessa Zanelli, Omar Carpentiero, Maria Giulia Corni, Elisa Bardi, Nicola Filippini, Fausta Lui, Paolo Frigio Nichelli, Maria Angela Molinari and Francesca Benuzzi
Brain Sci. 2025, 15(3), 310; https://doi.org/10.3390/brainsci15030310 - 15 Mar 2025
Viewed by 554
Abstract
Background/Objectives: Olfactory decline is common in normal aging and frequent in neurodegenerative diseases such as Alzheimer’s disease (AD). Therefore, it has been suggested as a marker for the Mild Cognitive Impairment (MCI) progression to AD. Although suggested, the relationship between olfactory deficits [...] Read more.
Background/Objectives: Olfactory decline is common in normal aging and frequent in neurodegenerative diseases such as Alzheimer’s disease (AD). Therefore, it has been suggested as a marker for the Mild Cognitive Impairment (MCI) progression to AD. Although suggested, the relationship between olfactory deficits and cerebral atrophy in MCI conversion to AD is still debated. This study aims at investigating the olfaction-related morphological and behavioural alterations in MCI in order to understand whether they can predict the progression to AD. Methods: Twenty-seven MCI patients and thirty-five healthy controls (HCs) took part in the study, with follow-up showing conversion to AD in thirteen patients (converter-MCI, cMCI). The Burgarth Sniffin’ Sticks Tests (threshold—TT, discrimination—DT, identification—IT) assessed the olfactory capacities. The Voxel-Based Morphometry (VBM) analysis investigated the atrophic patterns. Results: The Receiving Operating Characteristics analyses demonstrated that DT and IT could distinguish HC from MCI (DT Area Under Curve—AUC = 0.8; IT AUC = 0.8), as well as cMCI from sMCI (stable) patients (DT AUC = 0.7; IT AUC = 0.6), similarly to memory and executive functions tests. Olfactory performance positively correlated with memory tests in sMCI (all rhos ≥ 0.8, all ps < 0.01), whereas it positively correlated with executive functions in cMCI (all rhos ≥ 0.6, all ps < 0.05). VBM results revealed distinct atrophic patterns in cMCI, especially in the olfactory cortex, that were already present at the MCI diagnosis, before AD conversion. A larger volume of the olfactory cortex was associated with better memory and executive functions. Conclusions: Quantitative olfactory and morphological patterns represent non-invasive, predictive biomarkers of the MCI progression to AD; thus, their assessments at MCI onset allows earlier interventions for MCI patients. Full article
(This article belongs to the Special Issue Brain Magnetic Resonance Imaging in Neurological Disorders: 2nd Edition)
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20 pages, 1357 KiB  
Review
Current Applications of Single-Cell RNA Sequencing in Glioblastoma: A Scoping Review
by Edgar G. Ordóñez-Rubiano, Nicolás Rincón-Arias, William J. Shelton, Andres F. Salazar, María Alejandra Sierra, Raphael Bertani, Diego F. Gómez-Amarillo, Fernando Hakim, Matías Baldoncini, César Payán-Gómez, Alba Lucia Cómbita, Sandra C. Ordonez-Rubiano and Rafael Parra-Medina
Brain Sci. 2025, 15(3), 309; https://doi.org/10.3390/brainsci15030309 - 14 Mar 2025
Viewed by 783
Abstract
Background and Objective: The discovery of novel molecular biomarkers via next-generation sequencing technologies has revolutionized how glioblastomas (GBMs) are classified nowadays. This has resulted in more precise diagnostic, prognostic, and therapeutic approaches to address this malignancy. The present work examines the applications of [...] Read more.
Background and Objective: The discovery of novel molecular biomarkers via next-generation sequencing technologies has revolutionized how glioblastomas (GBMs) are classified nowadays. This has resulted in more precise diagnostic, prognostic, and therapeutic approaches to address this malignancy. The present work examines the applications of single-cell RNA sequencing (scRNA-seq) in GBM, focusing on its potential to address tumor complexity and therapeutic resistance and improve patient outcomes. Methods: A scoping review of original studies published between 2009 and 2024 was conducted using the PUBMED and EMBASE databases. Studies in English or Spanish related to single-cell analysis and GBM were included. Key Findings: The database search yielded 453 publications. Themes related to scRNA-seq applied for the diagnosis, prognosis, treatment, and understanding of the cancer biology of GBM were used as criteria for article selection. Of the 24 studies that were included in the review, 11 focused on the tumor microenvironment and cell subpopulations in GBM samples, 5 investigated the use of sequencing to elucidate the GBM cancer biology, 3 examined disease prognosis using sequencing models, 3 applied translational research through scRNA-seq, and 2 addressed treatment-related problems in GBM elucidated by scRNA-seq. Conclusions: This scoping review explored the various clinical applications of scRNA-seq technologies in approaching GBM. The findings highlight the utility of this technology in unraveling the complex cellular and immune landscapes of GBM, paving the way for improved diagnosis and personalized treatments. This cutting-edge approach might strengthen treatment strategies against tumor progression and recurrence, setting the stage for multi-targeted interventions that could significantly improve outcomes for patients with aggressive, treatment-resistant GBMs. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
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14 pages, 723 KiB  
Review
Methodological Approaches to Pain Memory Assessment in Chronic Pain: A Scoping Review
by Carlos Forner-Álvarez and Ferran Cuenca-Martínez
Brain Sci. 2025, 15(3), 308; https://doi.org/10.3390/brainsci15030308 - 14 Mar 2025
Viewed by 390
Abstract
Background/Objectives: Pain memory refers to the ability to encode, store, and recall information related to a specific pain event. Reviewing its common features is crucial, as it provides researchers with a foundational guide for designing studies that assess pain memory in individuals with [...] Read more.
Background/Objectives: Pain memory refers to the ability to encode, store, and recall information related to a specific pain event. Reviewing its common features is crucial, as it provides researchers with a foundational guide for designing studies that assess pain memory in individuals with chronic pain. The primary objective of this study was to examine the common characteristics—particularly the methodological approaches—of existing research on pain memory in adults with chronic pain. Methods: A scoping review was conducted using PubMed and Embase as search databases. Studies were included if they met the following criteria. (a) It involved only adults with chronic pain and (b) assessed at least one of the following parameters: pain intensity or pain unpleasantness. The exclusion criteria were the following: (a) not having pain memory assessment as a primary objective, (b) including participants under 18 years of age, (c) involving individuals without chronic pain (e.g., those with acute pain or healthy participants), (d) lacking essential information, or (e) unavailability of the full text. Results: From an initial pool of 4585 papers, 11 studies met the inclusion criteria. All studies exclusively involved adults with chronic pain, and all reported pain intensity, while only 27% assessed pain unpleasantness. Additionally, psychosocial variables were the most frequently reported non-pain-related outcomes. Regarding study protocols, most relied on daily data collection, with the most common recall period being within the first 48 h. Conclusions: The methodological characteristics identified in this review—particularly those with a high frequency of occurrence—should serve as fundamental guidelines for future research on pain memory in adults with chronic pain, and should be carefully considered by investigators in this field. Full article
(This article belongs to the Special Issue Pain Memory: Assessment and Clinical Implications)
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19 pages, 2229 KiB  
Review
Neurobiological Relationships Between Neurodevelopmental Disorders and Mood Disorders
by Amanda Gollo Bertollo, Camila Ferreira Puntel, Brunna Varela da Silva, Marcio Martins, Margarete Dulce Bagatini and Zuleide Maria Ignácio
Brain Sci. 2025, 15(3), 307; https://doi.org/10.3390/brainsci15030307 - 14 Mar 2025
Viewed by 886
Abstract
According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), neurodevelopmental disorders (NDDs) are a group of conditions that arise early in development and are characterized by deficits in personal, social, academic, or occupational functioning. These disorders frequently co-occur and include conditions [...] Read more.
According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), neurodevelopmental disorders (NDDs) are a group of conditions that arise early in development and are characterized by deficits in personal, social, academic, or occupational functioning. These disorders frequently co-occur and include conditions such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Mood disorders (MDs), such as major depressive disorder and bipolar disorder, also pose significant global health challenges due to their high prevalence and substantial impact on quality of life. Emerging evidence highlights overlapping neurobiological mechanisms between NDDs and MDs, including shared genetic susceptibilities, neurotransmitter dysregulation (e.g., dopaminergic and serotonergic pathways), neuroinflammation, and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Environmental factors such as early-life adversity further exacerbate these vulnerabilities, contributing to the complexity of their clinical presentation and comorbidity. Functional neuroimaging studies reveal altered connectivity in brain regions critical for emotional regulation and executive function, such as the prefrontal cortex and amygdala, across these disorders. Despite these advances, integrative diagnostic frameworks and targeted therapeutic strategies remain underexplored, limiting effective intervention. This review synthesizes current knowledge on the shared neurobiological underpinnings of NDDs and MDs, emphasizing the need for multidisciplinary research, including genetic, pharmacological, and psychological approaches, for unified diagnosis and treatment. Addressing these intersections can improve clinical outcomes and enhance the quality of life for individuals affected by these disorders. Full article
(This article belongs to the Special Issue Mental Health: From a Neurobiology Perspective)
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19 pages, 1110 KiB  
Article
Identifying Cardiovascular Risk by Nonlinear Heart Rate Dynamics Analysis: Translational Biomarker from Mice to Humans
by Torben Hager, Agorastos Agorastos, Sven Ove Ögren and Oliver Stiedl
Brain Sci. 2025, 15(3), 306; https://doi.org/10.3390/brainsci15030306 - 14 Mar 2025
Viewed by 1525
Abstract
Background: The beat-by-beat fluctuation of heart rate (HR) in its temporal sequence (HR dynamics) provides information on HR regulation by the autonomic nervous system (ANS) and its dysregulation in pathological states. Commonly, linear analyses of HR and its variability (HRV) are used to [...] Read more.
Background: The beat-by-beat fluctuation of heart rate (HR) in its temporal sequence (HR dynamics) provides information on HR regulation by the autonomic nervous system (ANS) and its dysregulation in pathological states. Commonly, linear analyses of HR and its variability (HRV) are used to draw conclusions about pathological states despite clear statistical and translational limitations. Objective: The main aim of this study was to compare linear and nonlinear HR measures, including detrended fluctuation analysis (DFA), based on ECG recordings by radiotelemetry in C57BL/6N mice to identify pathological HR dynamics. Methods: We investigated different behavioral and a wide range of pharmacological interventions which alter ANS regulation through various peripheral and/or central mechanisms including receptors implicated in psychiatric disorders. This spectrum of interventions served as a reference system for comparison of linear and nonlinear HR measures to identify pathological states. Results: Physiological HR dynamics constitute a self-similar, scale-invariant, fractal process with persistent intrinsic long-range correlations resulting in physiological DFA scaling coefficients of α~1. Strongly altered DFA scaling coefficients (α ≠ 1) indicate pathological states of HR dynamics as elicited by (1) parasympathetic blockade, (2) parasympathetic overactivation and (3) sympathetic overactivation but not inhibition. The DFA scaling coefficients are identical in mice and humans under physiological conditions with identical pathological states by defined pharmacological interventions. Conclusions: Here, we show the importance of tonic vagal function for physiological HR dynamics in mice, as reported in humans. Unlike linear measures, DFA provides an important translational measure that reliably identifies pathological HR dynamics based on altered ANS control by pharmacological interventions. Central ANS dysregulation represents a likely mechanism of increased cardiac mortality in psychiatric disorders. Full article
(This article belongs to the Topic Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models, from Animals to Humans, from Qualitative to Quantitative Methods, 3rd Edition)
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11 pages, 394 KiB  
Article
Enhancing Grip Strength and Manual Dexterity in Unilateral Cerebral Palsy: A Randomized Trial of Mirror Visual Feedback vs. Modified Constraint-Induced Movement Therapy
by Mohamed A. Abdel Ghafar, Osama R. Abdelraouf, Nouf H. Alkhamees, Mariam E. Mohamed, Eman M. Harraz, Mohamed K. Seyam, Zizi M. Ibrahim, Amani Alnamnakani, Amal A. Elborady and Rafik E. Radwan
Brain Sci. 2025, 15(3), 305; https://doi.org/10.3390/brainsci15030305 - 13 Mar 2025
Viewed by 799
Abstract
Background/Objectives: Manual dexterity and hand strength are common challenges in children with unilateral cerebral palsy (UCP), limiting the use of their affected upper limb and impacting daily activities. The efficacy of a long-duration Mirror Visual Feedback (MVF) program compared to Modified Constraint-Induced [...] Read more.
Background/Objectives: Manual dexterity and hand strength are common challenges in children with unilateral cerebral palsy (UCP), limiting the use of their affected upper limb and impacting daily activities. The efficacy of a long-duration Mirror Visual Feedback (MVF) program compared to Modified Constraint-Induced Movement Therapy (mCIMT) in addressing these issues remains unreported. This study was conducted to compare the efficacy of mCIMT and MVF in improving manual dexterity and hand strength in children with UCP. Methods: Fifty children with UCP (aged 5–9 years) were randomly assigned to either the MVF or mCIMT group. Children in both groups received their respective interventions for 30 min, five times per week, over 12 weeks. Additionally, all participants underwent traditional physical therapy for 12 weeks, three times per week, with each session lasting 45 to 60 min. Manual dexterity was assessed using the Box and Block Test (BBT), and maximum isometric hand strength was measured with a hydraulic handheld dynamometer. Evaluations were conducted before the intervention and 12 weeks later. Results: Repeated measures of MANOVA revealed significant enhancements in manual dexterity and hand strength in both groups after the intervention. However, the mCIMT group demonstrated significantly greater gains in BBT scores (p = 0.014) and maximum isometric hand strength (p = 0.017) compared to the MVF group, with effect sizes of 0.75 and 0.79, respectively. Conclusions: Incorporating either mCIMT or MVF into rehabilitation significantly enhances manual dexterity and hand strength in children with UCP, with mCIMT yielding superior outcomes. Full article
(This article belongs to the Special Issue Recent Advances in Neurorehabilitation: Emerging Techniques and Technologies)
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14 pages, 1080 KiB  
Review
Global Perspectives on Sleep Health: Definitions, Disparities, and Implications for Public Health
by Lourdes M. DelRosso
Brain Sci. 2025, 15(3), 304; https://doi.org/10.3390/brainsci15030304 - 13 Mar 2025
Viewed by 1320
Abstract
Sleep health is a multidimensional construct encompassing sleep quality, duration, efficiency, regularity, and alignment with circadian rhythms, playing a crucial role in overall well-being. Sleep health remains inconsistently defined across research and clinical settings despite its importance, limiting the ability to standardize assessments [...] Read more.
Sleep health is a multidimensional construct encompassing sleep quality, duration, efficiency, regularity, and alignment with circadian rhythms, playing a crucial role in overall well-being. Sleep health remains inconsistently defined across research and clinical settings despite its importance, limiting the ability to standardize assessments and interventions. Recent studies have emphasized the significance of defining sleep health beyond the absence of sleep disorders, integrating subjective and objective measures to assess its impact on physical and mental health outcomes. Disparities in sleep health exist across gender, socioeconomic status, and geographic regions, particularly in low- and middle-income countries where inconsistent work schedules, economic stress, and healthcare access influence sleep patterns. Poor sleep health is associated with increased risks of cardiovascular disease, obesity, metabolic dysfunction, and mental health disorders, reinforcing its role as a modifiable risk factor in public health. Lifestyle factors such as caffeine consumption, physical activity, and irregular eating patterns also contribute to sleep disturbances, highlighting the need for behavioral interventions. This narrative review aims to synthesize the current knowledge on sleep health, focusing on its definitions, measurement tools, global disparities, and associations. Full article
(This article belongs to the Special Issue Advances in Global Sleep and Circadian Health)
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10 pages, 536 KiB  
Article
Infarct Growth Rate Predicts Early Neurological Improvement in Ischemic Stroke After Endovascular Thrombectomy
by Zhihang Huang, Shuaiyu Chen, Bin Wei, Yan E, Jingwen Qi, Xiaohao Zhang and Teng Jiang
Brain Sci. 2025, 15(3), 303; https://doi.org/10.3390/brainsci15030303 - 13 Mar 2025
Viewed by 479
Abstract
Background and Purpose: The infarct growth rate (IGR) is a major modifier of the therapeutic effect of endovascular thrombectomy. The objective of this paper was to explore the utility of the IGR measured by perfusion the imaging in predicting early neurological improvement (ENI) [...] Read more.
Background and Purpose: The infarct growth rate (IGR) is a major modifier of the therapeutic effect of endovascular thrombectomy. The objective of this paper was to explore the utility of the IGR measured by perfusion the imaging in predicting early neurological improvement (ENI) of patients treated with EVT. Methods: We reviewed consecutive large vessel occlusive stroke in the anterior circulation and treated by thrombectomy between October 2019 to July 2024. The IGR was defined as the ischemic core volume (apparent diffusion coefficient ≤ 620 × 10−6 mm2/s or relative cerebral blood flow < 30%) divided by the time from stroke onset to imaging. ENI was defined as a reduction ≥ 6 points in the NIH Stroke Scale score at 24 h after the procedure, or an NIH Stroke Scale score of 0 or 1 on day 7 of hospitalization or at discharge if it occurred before day 7. Results: A total of 407 patients (mean age, 69.3 ± 12.5 years; 63.1% of male) were included, of whom 149 (36.6%) achieved ENI. Among all enrolled patients, 281 patients were classified as slow (IGR < 10 mL/h) and 126 fast progressors (IGR ≥ 10 mL/h). In multivariable analyses, fast progressors had a lower likelihood of achieving ENI after endovascular thrombectomy (odds ratio, 0.442; 95% confidence intervals, 0.269–0.729, p = 0.001) as compared to slow progressors. Subgroup analyses further confirmed these results. Furthermore, the odds of ENI decreased by 7.3% for each 5 mL/h increase in the IGR (odds ratio, 0.927; 95% confidence intervals, 0.875–0.982, p = 0.011). Conclusions: The present study found that the pre-treatment IGR was associated with ENI in thrombectomy patients. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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10 pages, 1126 KiB  
Brief Report
Treatment of Insomnia in Forensic Psychiatric Patients: A Randomized Controlled Trial
by Maaike Marina Van Veen, Gretha Johanna Boersma, Julie Karsten and Marike Lancel
Brain Sci. 2025, 15(3), 302; https://doi.org/10.3390/brainsci15030302 - 12 Mar 2025
Viewed by 458
Abstract
Background: Insomnia is common in forensic psychiatric patients. Not only does insomnia severely impair general mental health, but it has specifically been associated with poor emotion regulation and self-control, potentially leading to problems in impulsivity, hostility, and even aggression. Cognitive behavioral therapy for [...] Read more.
Background: Insomnia is common in forensic psychiatric patients. Not only does insomnia severely impair general mental health, but it has specifically been associated with poor emotion regulation and self-control, potentially leading to problems in impulsivity, hostility, and even aggression. Cognitive behavioral therapy for insomnia (CBT-I) could therefore be beneficial in this patient group. Methods: We conducted a 14-week randomized controlled trial of the effects of cognitive behavioral therapy for insomnia (CBT-I) on sleep, general psychopathology, hostility, impulsivity, and aggression in 31 male forensic psychiatric patients. Results: The CBT-I group (n = 11) showed a stronger reduction in self-reported insomnia symptoms and hostility than the waitlist group (n = 11). No differences were found in post-treatment self-reported general psychopathology, impulsivity, or aggression, nor on actigraphy-measured sleep efficiency. Conclusions: This study demonstrates the effectiveness of CBT-I in forensic psychiatric patients and indicates the importance of insomnia treatment in this population, especially considering the effect on hostility. Full article
(This article belongs to the Special Issue Clinical Research on Sleep Disorders: Opportunities and Challenges)
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16 pages, 467 KiB  
Article
Social Media Mindsets and Well-Being in Emerging Adults: A Serial Mediation of Facebook Addiction and Stress
by Dariusz Krok and Magdalena Półtorak
Brain Sci. 2025, 15(3), 301; https://doi.org/10.3390/brainsci15030301 - 12 Mar 2025
Viewed by 722
Abstract
Background/Objectives: Emerging adults live in a time of rapid technological change, with social media playing a central role in their daily lives. While frequent use of social media is linked to reduced well-being, it also supports personal growth and the pursuit of individual [...] Read more.
Background/Objectives: Emerging adults live in a time of rapid technological change, with social media playing a central role in their daily lives. While frequent use of social media is linked to reduced well-being, it also supports personal growth and the pursuit of individual goals. This study aims to identify the relationships between attitudes toward social media and psychological well-being in the context of the mediating roles of Facebook addiction and perceived stress in emerging adulthood. Methods: The study included 294 participants, with a mean age of 23.76 years (SD = 3.23). The following tools were used to measure the variables: the Social Media Mindsets Scale (translated by the authors), the Bergen Facebook Addiction Scale, the Perceived Stress Scale, the Psychological Well-Being Scale, and the Satisfaction with Life Scale. Correlation and mediation analyses were conducted. Results: The findings confirmed most of the assumptions. Attitudes toward social media were positively correlated with psychological well-being. Furthermore, Facebook addiction and perceived stress serve as serial mediators between attitudes toward social media and well-being. Conclusions: Based on the results, practical interventions can be developed to prevent addictions and reinforce stress management, which will help young people maintain their well-being and mental health. Full article
(This article belongs to the Special Issue Focus on Mental Health and Mental Illness in Adolescents)
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9 pages, 67781 KiB  
Technical Note
QEVO®-Assisted Anatomical Inspection of Adjacent Perforators in Microsurgical Clipping—Technical Note
by Adi Ahmetspahic, Eldin Burazerovic, Hana Rizvanovic, Ema Selimovic, Eleonora Kujaca, Mirza Pojskic, Alberto Feletti and Kenan Arnautovic
Brain Sci. 2025, 15(3), 300; https://doi.org/10.3390/brainsci15030300 - 12 Mar 2025
Viewed by 597
Abstract
Introduction: Aneurysms of brain vessels are life-threatening conditions with various adverse outcomes, some stemming from microsurgical intervention, particularly when major vessel perforators are inadequately protected. The use of endoscopes enhances the approach to aneurysms by providing closer visualization (180–360 degrees) of the local [...] Read more.
Introduction: Aneurysms of brain vessels are life-threatening conditions with various adverse outcomes, some stemming from microsurgical intervention, particularly when major vessel perforators are inadequately protected. The use of endoscopes enhances the approach to aneurysms by providing closer visualization (180–360 degrees) of the local anatomy, potentially reducing accidental damage. To improve visualization and efficiency, a microscope-integrated 45-degree angled microinspection endoscopic tool (QEVO®, Carl Zeiss, OberkochenTM) has been developed and employed in various neurosurgical procedures. Methods: Between 2021 and 2025, 27 brain aneurysms were treated with QEVO® assistance at the Department of Neurosurgery, Clinical Center of the University of Sarajevo. The choice of the videos corresponds to the best image quality in videos and on the microscopic determination of adjacent vessel perforators, which were not adequately seen purely by the surgical microscope in specific cases. Exclusion criteria included cases without a need for QEVO® assistance in perforator visualization, severe brain edema, intraoperative aneurysm rupture, posterior circulation, or low video quality. Results: Case 1 demonstrates an anterior choroidal artery (AchA) aneurysm; Case 2 presents an anterior communicating artery (AcommA) aneurysm; and Case 3 features contralateral middle cerebral artery (MCA) microsurgical clipping with QEVO® assistance. Conclusions: The QEVO® tool significantly improves the visualization of aneurysm–perforator relationships, increasing the likelihood of preserving perforators during standard microsurgical clipping. This innovative approach may reduce surgical complications and enhance patient outcomes, highlighting the tool’s potential as an adjunct in aneurysm microsurgery. Full article
(This article belongs to the Special Issue Current Research in Neurosurgery)
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14 pages, 430 KiB  
Article
I Got Rhythm and Executive Function, Memory, and More: The Automated Test of Embodied Cognition (ATEC)
by Morris D. Bell, Yarani Gonzalez, Andrea J. Weinstein, David Ciosek, Yan Wang and Gihyun Yoon
Brain Sci. 2025, 15(3), 299; https://doi.org/10.3390/brainsci15030299 - 12 Mar 2025
Viewed by 500
Abstract
Background: The Automated Test of Embodied Cognition (ATEC) is a new system for measuring cognition in action that uses cognitively demanding physical tasks and motion capture technology. Rhythm is one of the domains assessed by the ATEC across a number of tasks [...] Read more.
Background: The Automated Test of Embodied Cognition (ATEC) is a new system for measuring cognition in action that uses cognitively demanding physical tasks and motion capture technology. Rhythm is one of the domains assessed by the ATEC across a number of tasks and is a domain for which there is no broadly accepted neurocognitive measure. Method: Rhythm was assessed in a sample of 104 participants that included those at risk of cognitive decline and community controls. At-risk participants were also administered standard measures of executive functioning (EF), verbal list-learning, story memory, visual memory, and pre-morbid IQ. Results: The ATEC Rhythm Domain was found in the factor analysis with Varimax rotation to be loaded distinctly on the EF factor. ATEC Rhythm was significantly correlated with EF neurocognitive measures, and, in a Chi-square analysis, significantly differentiated the community control participants from those at risk for cognitive decline. ATEC Rhythm was significantly correlated with story memory and visual memory but not verbal list-learning. Age was negatively correlated with ATEC Rhythm, and women performed slightly better than men. ATEC Rhythm was also significantly correlated with the years of education and an estimate of pre-morbid IQ. Discussion: ATEC Rhythm was found to have discriminant and concurrent validity with EF measures and was significantly correlated with measures of story memory and visual memory, but not verbal list-learning. We speculate on rhythm’s relationship to story narrative and visual sequencing, and on rhythm’s relationship to cognitive reserve, as represented by education and the pre-morbid IQ estimate. Conclusions: The ATEC is a promising new measure that provides a systematic assessment of rhythm as a domain of embodied cognition. It may be useful in studies of neurodevelopment and neurocognitive decline, and it may be especially useful in assessing the effects of interventions that use physical activities, including dance and music therapies. Full article
(This article belongs to the Special Issue State of the Art in Multisensory Integration: Predicting Age-Related Clinical Outcomes)
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13 pages, 1396 KiB  
Article
Phonemic–Phonological Profile of People with 22q11.2 Deletion Syndrome: A Pilot Study
by Esther Moraleda-Sepúlveda, María Rubio-Lorca, Noelia Pulido-García, Noelia Santos-Muriel and Javiera Espinosa-Villarroel
Brain Sci. 2025, 15(3), 298; https://doi.org/10.3390/brainsci15030298 - 12 Mar 2025
Viewed by 551
Abstract
Background: 22q11.2 deletion syndrome is considered as a rare disease. It is considered one of the most prevalent genetic disorders with multiple systemic and neuropsychological alterations. At present, there are few studies that define the linguistic profile in Spanish of children with this [...] Read more.
Background: 22q11.2 deletion syndrome is considered as a rare disease. It is considered one of the most prevalent genetic disorders with multiple systemic and neuropsychological alterations. At present, there are few studies that define the linguistic profile in Spanish of children with this syndrome. Objectives: Therefore, the aim of the present study was to define the phonemic–phonological characteristics of people with 22q11.2 Syndrome. Method: Eight boys and girls between 5 and 16 years old participated in an evaluation using the following tests: Induced Phonological Register and Laura Bosh’s Phonological Assessment and Children’s Speech. Results: After analyzing the results obtained, it was observed that more than half of the participants presented a delay in the acquisition of phonemes. Conclusions: The conclusion of this study points out the importance of working on language, especially the phonetic-phonological area, throughout the development of people with 22q11.2 Syndrome. Full article
(This article belongs to the Section Neuropsychology)
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17 pages, 2368 KiB  
Article
Can Amygdala-Derived-EEG-fMRI-Pattern (EFP) Neurofeedback Treat Sleep Disturbances in PTSD?
by Aron Tendler, Yaki Stern and Tal Harmelech
Brain Sci. 2025, 15(3), 297; https://doi.org/10.3390/brainsci15030297 - 12 Mar 2025
Viewed by 1892
Abstract
Background: Sleep disturbances are a core feature of post-traumatic stress disorder (PTSD), affecting up to 90% of patients and often persisting after standard PTSD treatment. As all the current interventions have limitations, amygdala-targeted neuromodulation may offer a novel treatment pathway. Methods: Secondary analysis [...] Read more.
Background: Sleep disturbances are a core feature of post-traumatic stress disorder (PTSD), affecting up to 90% of patients and often persisting after standard PTSD treatment. As all the current interventions have limitations, amygdala-targeted neuromodulation may offer a novel treatment pathway. Methods: Secondary analysis of a prospective, single-arm trial (n = 58) was carried out evaluating Prism™ amygdala-derived-EEG-fMRI-Pattern neurofeedback (Amyg-EFP-NF). Sleep outcomes were assessed using the Clinician-Administered PTSD Scale (CAPS-5) sleep item, PTSD Checklist (PCL-5) sleep item, and Patient Health Questionnaire (PHQ-9) sleep items at baseline, post-treatment, and 3-month follow-up. Treatment consisted of 15 sessions over 8 weeks. Results: At 3-months’ follow-up, 63.79% of participants demonstrated clinically meaningful reduction in sleep disturbances (≥1 point reduction in CAPS-5 Item 20). Sleep improvement showed a moderate correlation with overall PTSD symptom reduction (r = 0.484, p < 0.001) and a balanced improvement pattern (−15.1% early, −9.1% late). Sleep responders sustained improvement across multiple measures and showed significant increases in cognitive reappraisal (mean change: +2.57 ± 1.0, p = 0.006), while non-responders showed initial but un-sustained improvement in trauma-related dreams. Conclusions: Amyg-EFP-NF shows preliminary promise for treating PTSD-related sleep disturbances. Our exploratory analyses suggest distinct temporal patterns of sleep improvement and potential associations with enhanced cognitive reappraisal capacity that warrant rigorous investigation in future randomized controlled trials. Full article
(This article belongs to the Special Issue Brain Stimulation for Psychiatric Disorders: Emerging Evidence and New Perspectives—2nd Edition)
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Case Report
Spontaneous Intracranial Hypotension in a Patient with Systemic Lupus Erythematosus and End-Stage Renal Failure: A Case Report and a Literature Review
by Konstantinos Paterakis, Alexandros Brotis, Adamantios Kalogeras, Maria Karagianni, Theodosios Spiliotopoulos, Christina Arvaniti, Argiro Petsiti, Marianna Vlychou, Efthimios Dardiotis, Eleni Arnaoutoglou and Kostas N. Fountas
Brain Sci. 2025, 15(3), 296; https://doi.org/10.3390/brainsci15030296 - 12 Mar 2025
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Abstract
Background and Objectives: End-stage renal failure (ESRF) patients are at an increased risk of various neurological complications, particularly after hemodialysis. The current case report describes a rare presentation of spontaneous intracranial hypotension (SIH) in a patient with ESRF caused by systemic lupus [...] Read more.
Background and Objectives: End-stage renal failure (ESRF) patients are at an increased risk of various neurological complications, particularly after hemodialysis. The current case report describes a rare presentation of spontaneous intracranial hypotension (SIH) in a patient with ESRF caused by systemic lupus erythematosus (SLE). Methods: We present our case report. We also performed a systematic literature search in PubMed, Scopus, and Dimensions for the current literature review. Results: A total of 296 unique articles were identified, and their full text was retrieved. However, only one case report was relevant to our study and is summarized thereunder. The treatment approach involved high-dose intravenous steroids, surgical evacuation of the cranial subdural collections, and epidural blood patches to seal the presumed dural defect. Conclusions: This case report describes a rare presentation of SIH in a young patient with ESRF due to SLE. Diagnostic imaging revealed extensive subdural and epidural fluid collections in the brain and spinal cord, respectively, along with a few T2 FLAIR hyperintensities noted in the right thalamus, left cerebellar hemisphere, and right occipital gyrus that subsequently resolved. The treatment approach involved high-dose intravenous steroids, surgical evacuation of the cranial subdural collections, and epidural blood patches to seal the presumed dural defect. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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