Brain Sciences

22 pages, 894 KB

Open AccessArticle

Association Between Upper Respiratory Tract Infections and Parkinson’s Disease in Korean Populations: A Nested Case–Control Study Using a National Health Screening Cohort

by Hyuntaek Rim, Hyo Geun Choi, Jee Hye Wee, Joo Hyun Park, Mi Jung Kwon, Ho Suk Kang, Hoang Nguyen, In Bok Chang, Joon Ho Song and Ji Hee Kim

Brain Sci. 2025, 15(9), 939; https://doi.org/10.3390/brainsci15090939 (registering DOI) - 28 Aug 2025

Abstract

Background: Although several epidemiological studies have suggested a potential association between infections and Parkinson’s disease (PD), relatively few have specifically examined the relationship between upper respiratory tract infections (URIs) and PD, apart from coronavirus disease 2019 (COVID-19). Objectives: We investigated whether a history [...] Read more.

Background: Although several epidemiological studies have suggested a potential association between infections and Parkinson’s disease (PD), relatively few have specifically examined the relationship between upper respiratory tract infections (URIs) and PD, apart from coronavirus disease 2019 (COVID-19). Objectives: We investigated whether a history of URI was associated with the diagnosis of PD among Korean individuals aged ≥40 years, using data from the Korean National Health Insurance Service–Health Screening Cohort. Methods: A total of 5844 patients newly diagnosed with PD were identified and matched with 23,376 control participants at a 1:4 ratio based on age, sex, income, and geographical region. Conditional logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for PD, adjusting for potential confounders including smoking, alcohol consumption, body mass index, blood pressure, comorbidity scores, blood glucose, and serum cholesterol levels. Results: Overall, no significant association was found between a history of URI and PD when considering a two-year exposure window. However, in the one-year window analysis, individuals with a history of URI had a modestly reduced odds of PD (≥1, ≥2, or ≥3 episodes: (adjusted OR: 0.93, 95% CI: 0.88–0.97, aOR: 0.91, 95% CI: 0.87–0.96 and aOR: 0.92, 95% CI: 0.87–0.98, respectively). Subgroup analyses revealed that the inverse association was more pronounced among women, older adults (≥65 years), and those with higher comorbidity scores. No clear dose–response trend was observed across increasing frequencies of URI diagnoses. Conclusions: Our findings suggest that the apparent protective association between recent URI history and PD is unlikely to be causal and may instead reflect confounding by medication use or reverse causation related to the prodromal phase of PD. These results should therefore be interpreted with caution and regarded as hypothesis-generating. Further prospective studies incorporating detailed prescription data and long-term follow-up are warranted to clarify the role of infections and anti-inflammatory medications in the pathogenesis of PD. Full article

(This article belongs to the Special Issue Clinical Research on Parkinson’s Disease: Opportunities and Challenges (2nd Edition))

14 pages, 3848 KB

Open AccessArticle

Ictal MEG-EEG Study to Localize the Onset of Generalized Seizures: To See Beyond What Meets the Eye

by Valentina Gumenyuk, Oleg Korzyukov, Noam Peled, Patrick Landazuri, Olga Taraschenko, Sheridan M. Parker, Darya Frank and Spriha Pavuluri

Brain Sci. 2025, 15(9), 938; https://doi.org/10.3390/brainsci15090938 (registering DOI) - 28 Aug 2025

Abstract

Introduction: Patients with generalized epilepsy are rarely referred for advanced diagnostics like magnetoencephalography (MEG). This is due to the assumption that generalized seizures cannot be localized noninvasively. Methods: We present simultaneous MEG (306 channels) and EEG (64 channels) data from seven patients with [...] Read more.

Introduction: Patients with generalized epilepsy are rarely referred for advanced diagnostics like magnetoencephalography (MEG). This is due to the assumption that generalized seizures cannot be localized noninvasively. Methods: We present simultaneous MEG (306 channels) and EEG (64 channels) data from seven patients with drug-resistant generalized epilepsy. Three patients experienced typical generalized seizures during their MEG clinical evaluation. In total, 38 epileptiform events (three seizures, 35 interictal discharges) were analyzed using two software platforms and three localization methods: equivalent current dipole (ECD), sLORETA (via SWARM), and dynamic statistical parametric mapping (dSPM). Individual head models were created from each patient’s MRI. Results: MEG successfully localized seizure onset zones, showing distinct hypersynchronous discharges on all sensors as well as alternately during interictal discharges. Localization was consistent across methods and generalized events within subjects, revealing cortical sources in all cases, with rapid propagation (27–60 ms) across networks. Conclusions: This study demonstrates that MEG can meaningfully localize both seizures and interictal discharges in generalized epilepsy. This supports a broader use for MEG beyond focal epilepsy. Incorporating MEG in drug-resistant cases including generalized epilepsies may improve diagnosis and guide treatments including non-surgical options. Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

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11 pages, 227 KB

Open AccessArticle

Hematological Inflammatory Markers Across Neurodevelopmental Disorders: Preliminary Findings of an Observational Retrospective Study

by Raffaele Garotti, Maria Pia Riccio, Chiara Staffa, Mariangela Pezone and Carmela Bravaccio

Brain Sci. 2025, 15(9), 937; https://doi.org/10.3390/brainsci15090937 (registering DOI) - 28 Aug 2025

Abstract

Background/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this [...] Read more.

Background/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this retrospective observational study, we gathered data on 135 medication-free individuals aged 6 to 17 years: 90 with NDDs (34 with autism spectrum disorder (ASD), 29 with attention-deficit/hyperactivity disorder, 14 with intellectual disability, and 13 with tic disorder) and 45 typically developed controls. The variables analyzed were compared using analysis of variance including Bonferroni posthoc testing for pairwise comparisons Significance was defined as p < 0.05. Results: The analysis of variance revealed statistical significance for all evaluated CBC parameters, as well as for the lymphocyte-to-monocyte ratio. Notably, subjects with ASD exhibited increased values of neutrophils, lymphocytes, monocytes, and eosinophils compared to both typically developing subjects and other NDDs. The lymphocyte-to-monocyte ratio was found to be lower in the tic disorder group compared to typically developing subjects. The elevated lymphocyte and monocyte levels in ASD subjects might reflect chronic low-grade inflammation. Conclusions: Consistent with the evidence in literature, statistically significant differences between the NDD group and typically developed subjects in the CBC parameters were found. The principal limitations of this investigation are the restricted sample size and the exclusion of specific NDD subtypes. Future research is needed to evaluate CBC parameters and inflammatory indices in a broader spectrum of NDDs to better understand the immunoinflammatory response specific to each disorder. Full article

(This article belongs to the Special Issue From Neurodevelopment to Mental Health: New Insight on Psychiatric Disorders Among Children, Adolescents and Young Adults)

16 pages, 481 KB

Open AccessReview

Resident Training in Minimally Invasive Spine Surgery: A Scoping Review

by Michael C. Oblich, James G. Lyman, Rishi Jain, Dillan Prasad, Sharbel Romanos, Nader Dahdaleh, Najib E. El Tecle and Christopher S. Ahuja

Brain Sci. 2025, 15(9), 936; https://doi.org/10.3390/brainsci15090936 - 28 Aug 2025

Abstract

Background/Objectives: Minimally invasive spine surgery (MISS) is complex and requires proficiency with a variety of technological and robotic modalities. Acquiring these skills is a long and involved process, often with a steep learning curve. This paper seeks to characterize the state of [...] Read more.

Background/Objectives: Minimally invasive spine surgery (MISS) is complex and requires proficiency with a variety of technological and robotic modalities. Acquiring these skills is a long and involved process, often with a steep learning curve. This paper seeks to characterize the state of MISS training in neurosurgical and orthopedic residency programs, focusing on their effectiveness at minimizing substantial learning curves in the field, as well as highlighting potential areas for future growth. Methods: We conducted a scoping review of the PubMed, Scopus, and Embase databases utilizing the PRISMA extension for scoping reviews. Results: Of the 100 studies initially identified, 16 were included in our final analysis. MISS training types could be broadly grouped into four categories: virtual simulation (including AR and VR), physical models, hybrid didactic and simulation, and mentored training. Training with these modalities led to improvements in resident performance across multiple different MISS techniques, including percutaneous pedicle screw fixation, MIS dural repair, MIS-TLIF, MIS-LLIF, MIS-ULBD, microscopic discectomy/disk herniation repair, percutaneous needle placement, and surgical navigation. Specific improvements included reduced error rate, operation time, and fluoroscopy exposure, as well as increased procedural knowledge, accuracy, and confidence. Conclusions: The incorporation of MISS training modalities in spine surgery residency leads to increases in simulated performance and could serve as a means of overcoming significant learning curves in the field. Full article

(This article belongs to the Special Issue Neurosurgery: Minimally Invasive Surgery in Brain and Spine)

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27 pages, 1956 KB

Open AccessReview

Implications of Indolethylamine N-Methyltransferase (INMT) in Health and Disease: Biological Functions, Disease Associations, Inhibitors, and Analytical Approaches

by Seif Abouheif, Ahmed Awad and Christopher R. McCurdy

Brain Sci. 2025, 15(9), 935; https://doi.org/10.3390/brainsci15090935 - 28 Aug 2025

Abstract

Indolethylamine N-methyltransferase (INMT) is a Class 1 methyltransferase responsible for N-methylation of various endogenous and exogenous compounds, including tryptamine, serotonin, and dopamine. This review aims to provide a comprehensive overview of the biological and therapeutic relevance of INMT, emphasizing the human isoform (hINMT), [...] Read more.

Indolethylamine N-methyltransferase (INMT) is a Class 1 methyltransferase responsible for N-methylation of various endogenous and exogenous compounds, including tryptamine, serotonin, and dopamine. This review aims to provide a comprehensive overview of the biological and therapeutic relevance of INMT, emphasizing the human isoform (hINMT), highlighting its structural characteristics, disease association, and recent advances in analytical strategies. Dysregulation of INMT activity has been linked to a range of pathological conditions, including neuropsychiatric disorders, neurodegeneration, and several forms of cancer. These associations are addressed by integrating current findings across disease pathophysiology, enzyme inhibition, and analytical methodologies, including both radiolabeled and non-radiolabeled in vitro assays, for measuring INMT activity. We further explored the chemical diversity of INMT inhibitors, both natural and synthetic, and highlighted key compounds with therapeutic relevance. Additionally, recent commercial assays for quantifying INMT activity are emphasized. By integrating emerging evidence from structural biology and disease pathology with inhibitor profiling and analytical technologies, this review highlights the underexplored therapeutic potential of targeting INMT and underscores its value as a promising target for drug development and therapeutic applications. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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14 pages, 268 KB

Open AccessReview

Beyond the Eye: Glaucoma and the Brain

by Marco Zeppieri, Federico Visalli, Mutali Musa, Alessandro Avitabile, Rosa Giglio, Daniele Tognetto, Caterina Gagliano, Fabiana D’Esposito and Francesco Cappellani

Brain Sci. 2025, 15(9), 934; https://doi.org/10.3390/brainsci15090934 - 28 Aug 2025

Abstract

Glaucoma is traditionally classified as an ocular disease characterized by progressive retinal ganglion cell (RGC) loss and optic nerve damage. However, emerging evidence suggests that its pathophysiology may extend beyond the eye, involving trans-synaptic neurodegeneration along the visual pathway and structural changes within [...] Read more.

Glaucoma is traditionally classified as an ocular disease characterized by progressive retinal ganglion cell (RGC) loss and optic nerve damage. However, emerging evidence suggests that its pathophysiology may extend beyond the eye, involving trans-synaptic neurodegeneration along the visual pathway and structural changes within central brain regions, including the lateral geniculate nucleus and visual cortex. In this narrative review, we have used the phrase ‘brain involvement’ to underscore central changes that accompany or follow retinal ganglion cell loss; we have not intended to redefine glaucoma as a primary cerebral disorder. Neuroimaging studies and neurocognitive assessments in adult glaucoma patients, primarily older individuals with primary open-angle glaucoma reveal that glaucoma patients may exhibit alterations in brain connectivity and cortical thinning, aligning it more closely with neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. This evolving neurocentric perspective raises important questions regarding shared mechanisms—such as mitochondrial dysfunction, chronic inflammation, and impaired axonal transport—that may link glaucomatous optic neuropathy to central nervous system (CNS) pathology. These insights open promising therapeutic avenues, including the repurposing of neuroprotective and neuroregenerative agents, targeting not only intraocular pressure (IOP) but also broader CNS pathways. Furthermore, neuroimaging biomarkers and brain-targeted interventions may play a future role in diagnosis, prognosis, and individualized treatment. This review synthesizes current evidence supporting glaucoma as a CNS disease, explores the mechanistic overlap with neurodegeneration, and discusses the potential clinical implications of glaucoma within a neuro-ophthalmologic paradigm. Full article

(This article belongs to the Special Issue A Window to the Brain: Research in Neuro-Ophthalmology—Focus on The Retina)

26 pages, 1897 KB

Open AccessArticle

Deep Learning Method Based on Multivariate Variational Mode Decomposition for Classification of Epileptic Signals

by Shang Zhang, Guangda Liu, Shiqing Sun and Jing Cai

Brain Sci. 2025, 15(9), 933; https://doi.org/10.3390/brainsci15090933 - 27 Aug 2025

Abstract

Background/Objectives: Epilepsy is a neurological disorder that severely impacts patients’ quality of life. In clinical practice, specific pharmacological and surgical interventions are tailored to distinct seizure types. The identification of the epileptogenic zone enables the implementation of surgical procedures and neuromodulation therapies. [...] Read more.

Background/Objectives: Epilepsy is a neurological disorder that severely impacts patients’ quality of life. In clinical practice, specific pharmacological and surgical interventions are tailored to distinct seizure types. The identification of the epileptogenic zone enables the implementation of surgical procedures and neuromodulation therapies. Consequently, accurate classification of seizure types and precise determination of focal epileptic signals are critical to provide clinicians with essential diagnostic insights for optimizing therapeutic strategies. Traditional machine learning approaches are constrained in their efficacy due to limited capability in autonomously extracting features. Methods: This study proposes a novel deep learning framework integrating temporal and spatial information extraction to address this limitation. Multivariate variational mode decomposition (MVMD) is employed to maintain inter-channel mode alignment during the decomposition of multi-channel epileptic signals, ensuring the synchronization of time–frequency characteristics across channels and effectively mitigating mode mixing and mode mismatch issues. Results: The Bern–Barcelona database is employed to classify focal epileptic signals, with the proposed framework achieving an accuracy of 98.85%, a sensitivity of 98.75%, and a specificity of 98.95%. For multi-class seizure type classification, the TUSZ database is utilized. Subject-dependent experiments yield an accuracy of 96.17% with a weighted F1-score of 0.962. Meanwhile, subject-independent experiments attain an accuracy of 87.97% and a weighted F1-score of 0.884. Conclusions: The proposed framework effectively integrates temporal and spatial domain information derived from multi-channel epileptic signals, thereby significantly enhancing the algorithm’s classification performance. The performance on unseen patients demonstrates robust generalization capability, indicating the potential clinical applicability in assisting neurologists with epileptic signal classification. Full article

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

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16 pages, 538 KB

Open AccessArticle

Clinical Relevance of Peripheral Interleukins in Drug-Naive First-Episode Psychosis: Symptom-Specific Associations from the PANSS Dimensions

by Iva Binic, Jovana Petrovic, Olivera Zikic, Suzana Tosic Golubovic, Vladimir Djordjevic, Marko Stevanovic, Dane Krtinic and Marija Andjelkovic Apostolovic

Brain Sci. 2025, 15(9), 932; https://doi.org/10.3390/brainsci15090932 - 27 Aug 2025

Abstract

Background/Objectives: Emerging evidence suggests a role of immune–inflammatory mechanisms in the pathophysiology of schizophrenia, particularly in the early stages of the illness. Cytokines, as key mediators of inflammation, may affect brain function and clinical presentation. Drug-naive patients with first-episode psychosis (FEDN) offer [...] Read more.

Background/Objectives: Emerging evidence suggests a role of immune–inflammatory mechanisms in the pathophysiology of schizophrenia, particularly in the early stages of the illness. Cytokines, as key mediators of inflammation, may affect brain function and clinical presentation. Drug-naive patients with first-episode psychosis (FEDN) offer a unique opportunity to investigate these associations free from confounding pharmacological effects. Methods: This study included 38 patients with drug-naive first episode psychosis and 22 age- and sex-matched healthy controls. Serum concentrations of IL-1β, IL-2, IL-6, and IL-10 were measured using ELISA. Clinical symptoms were assessed using the PANSS scale. Statistical analyses included Mann–Whitney U tests, Spearman’s correlations, and ROC curve analysis. Results: Significantly elevated serum levels of IL-1β, IL-2, and IL-10 were observed in the FEDN group compared to the controls (p < 0.01), while IL-6 levels did not differ significantly. IL-2 exhibited the highest discriminatory power in differentiating the patients from the controls (AUC = 0.917; 95% CI: 0.759–1000.0; p < 0.001). IL-1β levels positively correlated with negative and general psychopathology symptoms, including hostility and grandiosity. IL-10 was associated with volitional disturbance and overall PANSS severity. Conclusions: Our findings underscore the relevance of immune dysregulation in the early stages of psychosis and highlight the potential of specific cytokines, particularly IL-2 and IL-1β, as peripheral biomarkers. Their diagnostic utility and correlation with symptom dimensions suggest a promising role in the development of precision psychiatry approaches, including early detection strategies and individualised therapeutic targeting. Longitudinal studies are needed to validate these findings and to assess their prognostic significance. Full article

(This article belongs to the Section Neuropsychiatry)

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28 pages, 4981 KB

Open AccessArticle

Neurodetector: EEG-Based Cognitive Assessment Using Event-Related Potentials as a Virtual Switch

by Ryohei P. Hasegawa and Shinya Watanabe

Brain Sci. 2025, 15(9), 931; https://doi.org/10.3390/brainsci15090931 - 27 Aug 2025

Abstract

Background/Objectives: Motor decline in older adults can hinder cognitive assessments. To address this, we developed a brain–computer interface (BCI) using electroencephalography (EEG) and event-related potentials (ERPs) as a motor-independent EEG Switch. ERPs reflect attention-related neural activity and may serve as biomarkers for cognitive [...] Read more.

Background/Objectives: Motor decline in older adults can hinder cognitive assessments. To address this, we developed a brain–computer interface (BCI) using electroencephalography (EEG) and event-related potentials (ERPs) as a motor-independent EEG Switch. ERPs reflect attention-related neural activity and may serve as biomarkers for cognitive function. This study evaluated the feasibility of using ERP-based task success rates as indicators of cognitive abilities. The main goal of this article is the development and baseline evaluation of the Neurodetector system (incorporating the EEG Switch) as a motor-independent tool for cognitive assessment in healthy adults. Methods: We created a system called Neurodetector, which measures cognitive function through the ability to perform tasks using a virtual one-button EEG Switch. EEG data were collected from 40 healthy adults, mainly under 60 years of age, during three cognitive tasks of increasing difficulty. Results: The participants controlled the EEG Switch above chance level across all tasks. Success rates correlated with task difficulty and showed individual differences, suggesting that cognitive ability influences performance. In addition, we compared the pattern-matching method for ERP decoding with the conventional peak-based approaches. The pattern-matching method yielded a consistently higher accuracy and was more sensitive to task complexity and individual variability. Conclusions: These results support the potential of the EEG Switch as a reliable, non-motor-dependent cognitive assessment tool. The system is especially useful for populations with limited motor control, such as the elderly or individuals with physical disabilities. While Mild Cognitive Impairment (MCI) is an important future target for application, the present study involved only healthy adult participants. Future research should examine the sources of individual differences and validate EEG switches in clinical contexts, including clinical trials involving MCI and dementia patients. Our findings lay the groundwork for a novel and accessible approach for cognitive evaluation using neurophysiological data. Full article

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

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15 pages, 350 KB

Open AccessArticle

Personal Values and Psychological Well-Being Among Emerging Adults: The Mediating Role of Meaning in Life

by Marianna Chmiel and Zdzisław Kroplewski

Brain Sci. 2025, 15(9), 930; https://doi.org/10.3390/brainsci15090930 - 27 Aug 2025

Abstract

Background/Objectives: Emerging adulthood involves identity exploration, instability, and a sense of being “in-between” adolescence and full adulthood. This study examined whether growth-oriented values (openness to change and self-transcendence) are associated with psychological well-being among emerging adults, and whether meaning in life (presence and [...] Read more.

Background/Objectives: Emerging adulthood involves identity exploration, instability, and a sense of being “in-between” adolescence and full adulthood. This study examined whether growth-oriented values (openness to change and self-transcendence) are associated with psychological well-being among emerging adults, and whether meaning in life (presence and search) is related to these variables. Methods: The study included 200 participants (M = 21.90, SD = 2.48). The following measures were used: the Psychological Well-Being Scales, the Meaning in Life Questionnaire, and the Portrait Values Questionnaire. Correlation and multiple regression analyses were conducted. Results: All key variables (psychological well-being, presence of meaning, search for meaning, openness to change, and self-transcendence) were significantly positively correlated (r = 0.27–0.74, p < 0.01). The presence of meaning explained the associations between both openness to change (β = 0.22, 95% CI [0.50, 1.26]) and self-transcendence (β = 0.20, 95% CI [0.36, 0.91]) with psychological well-being, whereas the search for meaning was not a significant intervening variable in either model. Conclusions: These findings highlight the relevance of growth-oriented values and the presence of meaning in understanding psychological well-being among emerging adults. Longitudinal research is needed to clarify the directionality of these relationships. Full article

(This article belongs to the Special Issue Focus on Mental Health and Mental Illness in Adolescents)

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15 pages, 877 KB

Open AccessReview

A Call for Conceptual Clarity: “Emotion” as an Umbrella Term Did Not Work—Let’s Narrow It Down

by Peter Walla, Angelika Wolman and Georg Northoff

Brain Sci. 2025, 15(9), 929; https://doi.org/10.3390/brainsci15090929 - 27 Aug 2025

Abstract

To cut a long story short, the term “emotion” is predominantly employed as a comprehensive designation, encompassing phenomena such as feelings, affective processing, experiences, expressions, and, on occasion, cognitive processes. This has given rise to a plethora of schools of thought that diverge [...] Read more.

To cut a long story short, the term “emotion” is predominantly employed as a comprehensive designation, encompassing phenomena such as feelings, affective processing, experiences, expressions, and, on occasion, cognitive processes. This has given rise to a plethora of schools of thought that diverge in their inclusion of these phenomena, not to mention the discordance regarding what emotions belong to the so-called set of discrete emotions in the first place. This is a problem, because clear and operational definitions are paramount for ensuring the comparability of research findings across studies and also across different disciplines. In response to this disagreement, it is here proposed to simplify the definition of the term “emotion”, instead of using it as an umbrella term overarching an unclear set of multiple phenomena, which is exactly what left all of us uncertain about the question what an emotion actually is. From an etymological perspective, the simplest suggestion is to understand an emotion as behavior (from the Latin verb ‘emovere’, meaning to move out, and thus the noun ‘emotion’ meaning out-movement). This suggests that an emotion should not be understood as something felt, nor as a physiological reaction, or anything including cognition. Instead, emotions should be understood as behavioral outputs (not as information processing), with their connection to feelings being that they convey them. Consider fear, which should not be classified as an emotion, it should be understood as a feeling (fear is felt). The specific body posture, facial expression, and other behavioral manifestations resulting from muscle contractions should be classified as emotions with their purpose being to communicate the felt fear to conspecifics. The underlying causative basis for all that exists is affective processing (i.e., neural activity), and it provides evaluative information to support decision-making. The essence of this model is that if affective processing responds above a certain threshold, chemicals are released, which leads to a feeling (e.g., felt fear) if the respective organism is capable of conscious experience. Finally, the communication of these feelings to conspecifics is happening by emotion-behavior (i.e., emotions). In summary, affective processing guides behavior, and emotions communicate feelings. This perspective significantly simplifies the concept of an emotion and will prevent interchangeable use of emotion-related terms. Last but not least, according to the current model, emotions can also be produced voluntarily in order to feign a certain feeling, which is performed in various social settings. Applications of this model to various fields, including clinical psychology, show how beneficial it is. Full article

(This article belongs to the Special Issue Defining Emotion: A Collection of Current Models)

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18 pages, 671 KB

Open AccessSystematic Review

Peripheral BDNF Levels in Individuals at Ultra-High Risk for Psychosis: A Systematic Review

by Omar Contreras, Carla Rivera, Carolina Villaseca, Francisco Mas, Benjamín Cartes, Rolando Castillo-Passi and Rodrigo R. Nieto

Brain Sci. 2025, 15(9), 928; https://doi.org/10.3390/brainsci15090928 - 27 Aug 2025

Abstract

Background/Objectives: Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for neurogenesis and synaptic plasticity, and alterations in its peripheral levels have been associated with schizophrenia and other psychotic disorders. However, findings on peripheral BDNF levels in individuals at ultra-high risk (UHR) for [...] Read more.

Background/Objectives: Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for neurogenesis and synaptic plasticity, and alterations in its peripheral levels have been associated with schizophrenia and other psychotic disorders. However, findings on peripheral BDNF levels in individuals at ultra-high risk (UHR) for psychosis have been inconsistent. This review synthesizes current evidence comparing peripheral BDNF levels in UHR populations with those in healthy controls (HCs), first-episode psychosis (FEP), and chronic schizophrenia (CS), focusing on BDNF’s potential relevance as a biomarker of psychosis risk and subsequent clinical course. Methods: A systematic search of PubMed, Scopus, and Web of Science identified studies reporting baseline peripheral BDNF levels in UHR individuals compared with HC, FEP, or CS. Of 755 records retrieved, 608 unique titles/abstracts were screened, 49 full texts reviewed, and 8 studies included. Two reviewers independently screened, extracted data, and assessed risk of bias. Given marked clinical and methodological variability, results were synthesized narratively. Results: Eight studies met eligibility criteria and were synthesized across three analytical categories: (1) UHR vs. HC; (2) UHR vs. FEP or CS; and (3) longitudinal outcomes. Findings were inconsistent; some studies reported lower BDNF in UHR relative to comparison groups, whereas others found no differences or higher levels, often influenced by clinical or methodological factors. Longitudinal analyses did not reveal consistent prognostic value, and heterogeneity precluded meta-analysis. Conclusions: Findings across studies were inconsistent and limited by small samples, as well as by methodological heterogeneity. While current evidence does not support its prognostic use, peripheral BDNF may still hold potential as part of a biomarker framework if evaluated in larger, standardized, and rigorously controlled studies. Full article

(This article belongs to the Special Issue Prediction and Prevention of Psychotic Disorders)

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20 pages, 1308 KB

Open AccessReview

Decoding Encoded Cravings: Epigenetic Drivers of Addiction

by Tousif Ahmed Hediyal, Omar Shukri, Elizabeth Stone, Amin Foroughi, Thangavel Samikkannu and Gurudutt Pendyala

Brain Sci. 2025, 15(9), 927; https://doi.org/10.3390/brainsci15090927 - 27 Aug 2025

Abstract

Drug abuse is a chronic, relapsing disorder marked by compulsive drug-seeking behavior and profound neurobiological consequences. Each year, millions of individuals face serious social and legal repercussions due to addiction. This review synthesizes findings from both preclinical and clinical studies to examine how [...] Read more.

Drug abuse is a chronic, relapsing disorder marked by compulsive drug-seeking behavior and profound neurobiological consequences. Each year, millions of individuals face serious social and legal repercussions due to addiction. This review synthesizes findings from both preclinical and clinical studies to examine how chronic exposure to substances such as alcohol, cocaine, methamphetamine, and opioids affects the central nervous system. Specifically, it explores the epigenetic modifications induced by these substances, including DNA methylation, histone modifications, and noncoding RNA regulation. The literature was selected using a thematic approach, emphasizing substance-specific mechanisms and their effects on gene expression, synaptic plasticity, and the brain’s reward circuitry. Emerging evidence links these epigenetic changes to long-term behavioral adaptations and even transgenerational inheritance. This review underscores the complex molecular pathways contributing to addiction, vulnerability, and relapse, offering insights into potential therapeutic targets. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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4 pages, 162 KB

Open AccessEditorial

Multidisciplinary Innovation in Neurosurgery and Neuroscience: Advancing Frontiers in Diagnosis, Therapy, and Neurological Rehabilitation

by Delia Cannizzaro, Roberto Stefini, Kenan Arnautovic and Franco Servadei

Brain Sci. 2025, 15(9), 926; https://doi.org/10.3390/brainsci15090926 - 27 Aug 2025

Abstract

In recent years, neurosurgery and clinical neuroscience have undergone a profound transformation, driven by an increasingly interdisciplinary approach that integrates technological innovation, the refinement of therapeutic protocols, and novel rehabilitative paradigms [...] Full article

(This article belongs to the Special Issue Advanced Clinical Technologies in Treating Neurosurgical Diseases)

14 pages, 1878 KB

Open AccessSystematic Review

Diffusion Tensor Tractography Studies for Causes of Dysphagia After Stroke: A Systematic Review

by Woo-Hyuk Jang, Seon-Hee Lee and Sang-Hyeok Lee

Brain Sci. 2025, 15(9), 925; https://doi.org/10.3390/brainsci15090925 - 27 Aug 2025

Abstract

Background/Objectives: This systematic review aimed to investigate the causes of dysphagia after stroke through diffusion tensor tractography (DTT) studies. Methods: This review used databases such as Google Scholar, PubMed, and ScienceDirect. Keywords related to stroke, dysphagia, and diffusion tensor tractography were [...] Read more.

Background/Objectives: This systematic review aimed to investigate the causes of dysphagia after stroke through diffusion tensor tractography (DTT) studies. Methods: This review used databases such as Google Scholar, PubMed, and ScienceDirect. Keywords related to stroke, dysphagia, and diffusion tensor tractography were utilized. Seven studies were selected and analyzed. Results: The analysis identified that damage to the corticobulbar tract (CBT) was the most frequently reported cause of dysphagia. Additionally, some studies suggested that damage to the vestibulospinal tract (VST) and the core vestibular pathway (CVP) contributed to dysphagia. Moreover, a significant negative correlation was found between dysphagia severity and key DTT-derived metrics, such as lower fractional anisotropy (FA) and tract volume (TV), indicating that reduced FA and TV values are associated with more severe dysphagia symptoms. Conclusions: DTT provides valuable insights into the neural mechanisms underlying dysphagia after stroke. Identifying the affected tracts can help diagnose dysphagia more accurately and develop targeted rehabilitation strategies. Full article

(This article belongs to the Special Issue Management of Acute Stroke)

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16 pages, 488 KB

Open AccessArticle

Plasma Neurofilament Light Chain in Patients Affected by Alzheimer’s Disease with Different Rate of Progression: A Retrospective Study on an ADNI Cohort

by Giuseppe Virga, Bruno Di Marco, Valeria Blandino and Tommaso Piccoli

Brain Sci. 2025, 15(9), 924; https://doi.org/10.3390/brainsci15090924 - 27 Aug 2025

Abstract

Background: Alzheimer’s disease (AD) shows highly variable progression rates among individuals. Plasma neurofilament light chain (NfL) has emerged as a potential biomarker of neurodegeneration. Objectives: this study aimed to evaluate the predictive value of plasma NfL in estimating the rate of clinical progression [...] Read more.

Background: Alzheimer’s disease (AD) shows highly variable progression rates among individuals. Plasma neurofilament light chain (NfL) has emerged as a potential biomarker of neurodegeneration. Objectives: this study aimed to evaluate the predictive value of plasma NfL in estimating the rate of clinical progression (RoP) in AD. Methods: we retrospectively analyzed 87 AD patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We stratified patients into two groups based on the median RoP, which was calculated from longitudinal Mini-Mental State Examination (MMSE) score evaluations: slow decliners (SD) and fast decliners (FD). We then compared plasma NfL levels between the two groups and examined their relationship with the progression rate. Results: patients with faster decline rates had higher levels of NfL. Logistic regression (LR) analysis revealed a strong correlation between plasma NfL levels and disease progression rates. Furthermore, a multivariate model incorporating Aβ42 levels improved predictive accuracy. Conclusions: these findings suggest that plasma NfL could serve as a valuable biomarker for monitoring the progression of Alzheimer’s disease, identifying patients at greater risk of rapid decline, and optimizing therapeutic strategies and clinical management. Future studies on larger cohorts will be essential to confirm and further explore these observations. Full article

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

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8 pages, 1153 KB

Open AccessPerspective

Dopamine D2 Receptors and Its Downstream Signaling in Compulsive Eating

by Caden Leung and Kabirullah Lutfy

Brain Sci. 2025, 15(9), 923; https://doi.org/10.3390/brainsci15090923 - 27 Aug 2025

Abstract

Obesity has become a major public health crisis and serves as an underlying condition for other chronic metabolic diseases. The dysregulation of the inhibitory and regulatory mechanisms of the mesolimbic dopamine system, particularly dopamine D2 receptors (D2Rs), plays a critical role in driving [...] Read more.

Obesity has become a major public health crisis and serves as an underlying condition for other chronic metabolic diseases. The dysregulation of the inhibitory and regulatory mechanisms of the mesolimbic dopamine system, particularly dopamine D2 receptors (D2Rs), plays a critical role in driving excessive food consumption and compulsive eating habits. Based on the current literature, chronic consumption of high-fat foods elicits hedonic sensations and has the potential to downregulate and desensitize D2Rs, impairing their signaling and inhibitory action. This impairment thereby alters the downstream signaling of the D2Rs, involving the inhibition of adenylyl cyclase and the associated cascade. Although individual components of this proposed pathway have been studied, a comprehensive synthesis has not been established. This review aims to explore the relationship between D2R downregulation and desensitization and their effects on the downstream signaling cascade. We hypothesize that alterations in this pathway may lead to the dysregulation of the expression of orexigenic and anorexigenic neuropeptides, contributing to binge-eating behaviors. Full article

(This article belongs to the Section Neuropharmacology and Neuropathology)

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10 pages, 597 KB

Open AccessBrief Report

Unlocking Creative Movement with Inertial Technology

by Eva Sánchez Martz, Alejandro Romero-Hernandez, Beatriz Calvo-Merino and Santiago Fernández González

Brain Sci. 2025, 15(9), 922; https://doi.org/10.3390/brainsci15090922 - 26 Aug 2025

Abstract

Background: This study examined the influence of creative thinking, shaped by different forms of episodic mental representations, on human movement. The primary objective was to investigate how creativity, elicited through distinct cognitive stimuli, affects movement variability. Methods: Twenty-four professional dancers developed two original [...] Read more.

Background: This study examined the influence of creative thinking, shaped by different forms of episodic mental representations, on human movement. The primary objective was to investigate how creativity, elicited through distinct cognitive stimuli, affects movement variability. Methods: Twenty-four professional dancers developed two original dance phrases, each inspired by either a visual or a narrative mental representation. Movement data were collected via inertial sensor technology and subsequently analysed to determine differences in motor expression. Results: The results indicated that movements performed under narrative representation conditions exhibited significantly increased risk-taking behaviour, greater movement amplitude, and a higher overall movement volume compared to those guided by visual stimuli. Conclusions: These findings underscore the role of creativity in modulating both the expressive and physical dimensions of human movement. Moreover, this research demonstrates the potential of inertial sensor technology not only to capture kinematic patterns but also to provide insight into the deeper layers of human artistic and cognitive processes. Full article

(This article belongs to the Special Issue New Insights into Movement Generation: Sensorimotor Processes)

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15 pages, 6096 KB

Open AccessCase Report

Causes of Death in Anti-IgLON5 Disease: A Novel Case Report and Systematic Literature Review

by Tina Howischer, Lukas Gattermeyer-Kell, Stephanie Hirschbichler, Thomas Seifert-Held, Jan Hinrich Bräsen, Petra Katschnig-Winter, Mariella Kögl, Sebastian Franthal, Christian Enzinger, Romana Höftberger and Petra Schwingenschuh

Brain Sci. 2025, 15(9), 921; https://doi.org/10.3390/brainsci15090921 - 26 Aug 2025

Abstract

Background/Objectives: Anti-IgLON5 disease is a neurological disorder characterized by the presence of autoantibodies directed against the neuronal cell adhesion protein IgLON5. Pathophysiology involves both autoimmune inflammation and neurodegenerative processes. The most common causes of death are sudden death, central hypoventilation, dysphagia, and aspiration. [...] Read more.

Background/Objectives: Anti-IgLON5 disease is a neurological disorder characterized by the presence of autoantibodies directed against the neuronal cell adhesion protein IgLON5. Pathophysiology involves both autoimmune inflammation and neurodegenerative processes. The most common causes of death are sudden death, central hypoventilation, dysphagia, and aspiration. However, the high rate of largely unclear sudden deaths calls for further research in this area. Methods: We performed a systematic search of the literature on causes of death in anti-IgLON5 disease following the PRISMA guidelines. In addition, we present a new case that was followed up in our clinic until death. Results: Of 258 publications with anti-IgLON5 disease, 21 publications comprising 61 cases that reported the causes of death were included in the analysis. The most common cause of death was death due to complications at 36.1%, followed by sudden death, accounting for 32.8% of the cases. Other causes include respiratory, cardiac, and unknown causes. The patient presented here as a case report was also diagnosed with cardiac amyloidosis and died from a cardiac cause of sudden death. Conclusions: Sudden death in anti-IgLON5 disease is one of the most common causes of death in the literature. A progressive neurodegenerative process in the brain stem causing central hypoventilation is generally assumed as a major causative factor. The case reported here had concomitant cardiac amyloidosis, which may raise the question as to whether unrecognized cardiac causes, which are not routinely screened for in this population, might represent another cause of sudden death, which would have important therapeutic implications. Full article

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