Brain Sciences最新文献

{"title":"Interpretable Disorder Signatures: Probing Neural Latent Spaces for Schizophrenia, Alzheimer's, and Autism Stratification.","authors":"Zafar Iqbal, Md Mahfuzur Rahman, Qasim Zia, Pavel Popov, Zening Fu, Vince D Calhoun, Sergey Plis","doi":"10.3390/brainsci15090954","DOIUrl":"10.3390/brainsci15090954","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to develop and validate an interpretable deep learning framework that leverages self-supervised time reversal (TR) pretraining to identify consistent, biologically plausible functional network biomarkers across multiple neurological and psychiatric disorders.</p><p><strong>Methods: </strong>We pretrained a hierarchical LSTM model using a TR pretext task on the Human Connectome Project (HCP) dataset. The pretrained weights were transferred to downstream classification tasks on five clinical datasets (FBIRN, BSNIP, ADNI, OASIS, and ABIDE) spanning schizophrenia, Alzheimer's disease, and autism spectrum disorder. After fine-tuning, we extracted latent features and employed a logistic regression probing analysis to decode class-specific functional network contributions. Models trained from scratch without pretraining served as a baseline. Statistical tests (one-sample and two-sample <i>t</i>-tests) were performed on the latent features to assess their discriminative power and consistency.</p><p><strong>Results: </strong>TR pretraining consistently improved classification performance in four out of five datasets, with AUC gains of up to 5.3%, particularly in data-scarce settings. Probing analyses revealed biologically meaningful and consistent patterns: schizophrenia was associated with reduced auditory network activity, Alzheimer's with disrupted default mode and cerebellar networks, and autism with sensorimotor anomalies. TR-pretrained models produced more statistically significant latent features and demonstrated higher consistency across datasets (e.g., Pearson correlation = 0.9003 for schizophrenia probing vs. -0.67 for non-pretrained). In contrast, non-pretrained models showed unstable performance and inconsistent feature importance.</p><p><strong>Conclusions: </strong>Time Reversal pretraining enhances both the performance and interpretability of deep learning models for fMRI classification. By enabling more stable and biologically plausible representations, TR pretraining supports clinically relevant insights into disorder-specific network disruptions. This study demonstrates the utility of interpretable self-supervised models in neuroimaging, offering a promising step toward transparent and trustworthy AI applications in psychiatry.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12469018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Abnormalities Induced by High Glucose in Mixed Glial Cultures Are Maintained, Although Glucose Returns to Normal Levels.","authors":"Brandon Isai Herrera Solis, Frida Guerrero-Padilla, Elvia Mera Jiménez, Juan Manuel Vega López, María de Jesús Perea-Flores, Octavio Rodríguez-Cortés, Martha Edith Macías Pérez, Maricarmen Hernández-Rodríguez","doi":"10.3390/brainsci15090952","DOIUrl":"10.3390/brainsci15090952","url":null,"abstract":"<p><p><b>Background:</b> Metabolic memory refers to the long-term adverse effects of short-term disturbances in glucose metabolism. Recent evidence indicates that hyperglycemia-induced metabolic memory contributes to sustained cellular damage even after glycemic control, driven by increased production of reactive oxygen species (ROS), activation of inflammatory pathways, and accumulation of advanced glycation end products (AGEs). Although well characterized in endothelial and smooth muscle cells, this phenomenon may also occur in other cell types, including glial cells. <b>Objective:</b> This study aimed to evaluate the persistence of high-glucose (HG)-induced alterations after returning to normal glucose (NG) conditions in primary mixed glial cell (MGC) cultures. <b>Methods:</b> Primary MGCs were obtained from neonatal Wistar rat pups and cultured under three conditions for 21 days: NG (5.5 mM glucose), HG (25 mM glucose), and HG-NG (14 days in HG followed by 7 days in NG). Cell proliferation, apoptosis, ROS production, lipid peroxidation, mitochondrial activity, TNF-α, IL-6, and AGE formation were assessed. <b>Results:</b> MGCs cultured under HG and HG-NG conditions exhibited reduced proliferation without increased apoptosis. Both HG and HG-NG conditions promoted ROS overproduction accompanied by reduced mitochondrial activity, whereas only HG increased lipid peroxidation. Notably, TNF-α and AGE levels were elevated in both HG and HG-NG conditions, while IL-6 production decreased exclusively in HG-NG. <b>Conclusions:</b> These findings demonstrate the persistence of deleterious effects induced by HG in MGCs, even after restoration to NG conditions.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Entropy and Complexity in QEEG Reveal Visual Processing Signatures in Autism: A Neurofeedback-Oriented and Clinical Differentiation Study.","authors":"Aleksandar Tenev, Silvana Markovska-Simoska, Andreas Müller, Igor Mishkovski","doi":"10.3390/brainsci15090951","DOIUrl":"10.3390/brainsci15090951","url":null,"abstract":"<p><p>(1) Background: Quantitative EEG (QEEG) offers potential for identifying objective neurophysiological biomarkers in psychiatric disorders and guiding neurofeedback interventions. This study examined whether three nonlinear QEEG metrics-Lempel-Ziv Complexity, Tsallis Entropy, and Renyi Entropy-can distinguish children with autism spectrum disorder (ASD) from typically developing (TD) peers, and assessed their relevance for neurofeedback targeting. (2) Methods: EEG recordings from 19 scalp channels were analyzed in children with ASD and TD. The three nonlinear metrics were computed for each channel. Group differences were evaluated statistically, while machine learning classifiers assessed discriminative performance. Dimensionality reduction with t-distributed Stochastic Neighbor Embedding (t-SNE) was applied to visualize clustering. (3) Results: All metrics showed significant group differences across multiple channels. Machine learning classifiers achieved >90% accuracy, demonstrating robust discriminative power. t-SNE revealed distinct ASD and TD clustering, with nonlinear separability in specific channels. Visual processing-related channels were prominent contributors to both classifier predictions and t-SNE cluster boundaries. (4) Conclusions: Nonlinear QEEG metrics, particularly from visual processing regions, differentiate ASD from TD with high accuracy and may serve as objective biomarkers for neurofeedback. Combining complexity and entropy measures with machine learning and visualization techniques offers a relevant framework for ASD diagnosis and personalized intervention planning.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gray and White Matter Networks Predict Mindfulness and Mind Wandering Traits: A Data Fusion Machine Learning Approach.","authors":"Minah Chang, Sara Sorella, Cristiano Crescentini, Alessandro Grecucci","doi":"10.3390/brainsci15090953","DOIUrl":"10.3390/brainsci15090953","url":null,"abstract":"<p><strong>Background: </strong>Mindfulness and mind wandering are cognitive traits central to attentional control and psychological well-being, yet their neural underpinnings are yet to be elucidated. This study aimed to identify structural brain networks comprising gray matter (GM) and white matter (WM) that predict individual differences in mindfulness and distinct mind wandering tendencies (deliberate and spontaneous).</p><p><strong>Methods: </strong>Using structural MRI data and self-report measures from 76 participants, we applied an unsupervised data-fusion machine learning technique (parallel independent component analysis) to identify GM and WM networks associated with mindfulness and mind wandering traits.</p><p><strong>Results: </strong>Our analysis revealed several distinct brain networks linked to these cognitive constructs. Specifically, one GM network involving subcortical regions, including the caudate and thalamus, positively predicted mindfulness and deliberate mind wandering, while negatively influencing spontaneous mind wandering through the mediating role of the mindfulness facet \"acting with awareness.\" In addition, two separate WM networks, predominantly involving frontoparietal and temporal regions, were directly associated with reduced spontaneous mind wandering.</p><p><strong>Conclusions: </strong>These findings advance our current knowledge by demonstrating that specific GM and WM structures are involved in mindfulness and different forms of mind wandering. Our results also show that the \"acting with awareness\" facet has a mediating effect on spontaneous mind wandering, which provides supporting evidence for attentional and executive control models. These new insights into the neuroanatomical correlates of mindfulness and mind wandering have implications for ongoing research in the growing topic of mindfulness and mind wandering, mindfulness-based interventions, and other clinical applications.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Feasibility of a Telematic Version of Parkinson's Disease-Cognitive Rating Scale (PD-CRS).","authors":"Elisa Pini, Fulvio Pepe, Michelle Ingiardi, Veronica Laini, Nicoletta Ciccarelli, Eugenio Magni","doi":"10.3390/brainsci15090948","DOIUrl":"10.3390/brainsci15090948","url":null,"abstract":"<p><strong>Background/objectives: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder frequently associated with cognitive impairment. In the context of increasing interest in remote healthcare solutions, particularly after the COVID-19 pandemic, this preliminary study aimed to evaluate the feasibility of an online version of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), a first-level neuropsychological screening tool for mild cognitive impairment (MCI) in individuals with PD.</p><p><strong>Methods: </strong>Seventy-nine patients with idiopathic PD were recruited between October 2020 and February 2024. A telematic version of the PD-CRS was administered via video call using adapted materials (e.g., slide-based instructions and webcam-mediated tasks). Both patients and examiners completed a Visual Analogue Scale (VAS) to rate perceived difficulty. Descriptive statistics and non-parametric tests were used to analyze data.</p><p><strong>Results: </strong>Difficulty ratings were low for both patients (mean VAS = 1.60, SD = 0.88) and the examiner (mean VAS = 1.43, SD = 0.61), with no significant difference (<i>p</i> = 0.176). No demographic or clinical variable predicted difficulty.</p><p><strong>Conclusions: </strong>These findings support the feasibility and usability of an online version of PD-CRS. This approach may facilitate wider access to cognitive screening for PD patients, particularly those with mobility limitations or living in underserved areas.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conducting Performance-Assisted Resections in the Right Temporo-Insular Cortex: A Real-Time Neuropsychological Testing (RTNT) Protocol.","authors":"Barbara Tomasino, Ilaria Guarracino, Tamara Ius, Miran Skrap","doi":"10.3390/brainsci15090949","DOIUrl":"10.3390/brainsci15090949","url":null,"abstract":"<p><strong>Background/objectives: </strong>There is increasing interest within cognitive neuro-surgery in preserving domains not traditionally assessed during awake surgery. The study aims at proposing a specific protocol to assist surgical resection in right temporal areas. Patients were not evaluated during direct cortical stimulation; instead, assessments occurred during the resection itself. The real-time neuropsychological testing (RTNT) protocol employed tasks evaluating visuospatial and social cognition, administered repeatedly throughout the resection using varied items.</p><p><strong>Methods: </strong>A consecutive series of 24 patients (median age 44) performed RTNT. The aim of RTNT is to maintain high accuracy through resection. Lesions in the right temporal cortex and the subcortical white matter beneath can cause deficits; accordingly, not all of our patients had pre-surgery performance within the normal range. In this case, the aim of RTNT is to maintain the not perfect pre-surgery level.</p><p><strong>Results: </strong>We found a statistically significant between-tasks difference in the patients' median values (across RTNT runs), in their minimum score reached during resection, and in the delta between performance at the last vs. the first RTNT run. The tasks that varied belonged to visual-spatial attention (landmark task), face processing (recognition of famous faces), and social cognition (theory of mind). The outcome was measured by pre- vs. post-surgery neuropsychological score comparison. The number of patients scoring below the normal range did not significantly differ between post- vs. pre-intervention.</p><p><strong>Conclusions: </strong>Results demonstrated the feasibility of implementing a continuous monitoring protocol during the resection phase, and the potential of the selected tasks to assess visuospatial and social functions associated with the non-dominant (right) hemisphere.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating <i>PRDM8</i> DNA Methylation in Peripheral Tissues in Borderline Personality Disorder: Association with Symptom Severity but Not Adverse Childhood Experiences.","authors":"Annika Bender, Laila Bertele, Mirac Nur Musaoglu, Sarah Pasche, Susanne Edelmann, Vanessa Nieratschker","doi":"10.3390/brainsci15090950","DOIUrl":"10.3390/brainsci15090950","url":null,"abstract":"<p><strong>Background: </strong>Borderline Personality Disorder (BPD) is a complex psychiatric condition with multifactorial origins, with a high proportion of patients reporting early trauma. Stressors such as adverse childhood experiences (ACEs) can shape the epigenetic landscape including DNA methylation (DNAm) and act on gene expression. DNAm is increasingly being investigated as a molecular link between environmental exposures such as ACE and psychiatric outcomes. Differential DNAm of the gene PR domain zinc finger protein 8 (<i>PRDM8</i>), a histone methyltransferase, has recently been reported to be sensitive to early life trauma. Its role in BPD, especially in the context of ACE, remains to be elucidated.</p><p><strong>Methods: </strong>This study investigated DNAm patterns of <i>PRDM8</i> in peripheral blood and saliva obtained from BPD patients undergoing Dialectic Behavioral Therapy (DBT) compared to healthy control (HC) participants. Associations with ACE and BPD symptom severity were assessed, and therapy-related changes in DNAm were examined.</p><p><strong>Results: </strong>At baseline, BPD patients demonstrated significant hypomethylation of <i>PRDM8</i> in blood relative to the HC group. Following DBT, a nominally significant increase in DNAm was observed, aligning with inversely correlated symptom severity. No significant differences in saliva were detected. ACE was not associated with <i>PRDM8</i> DNAm.</p><p><strong>Conclusions: </strong>Our findings suggest that <i>PRDM8</i> DNAm might be associated with BPD and therapeutic intervention but not with ACE. Together with prior research, the results underscore the importance of future investigation of gene-environment interactions and the functional significance of <i>PRDM8</i> regulation in the pathophysiology of BPD.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems of Care for Treating Severe Acquired Brain Injury: Comparing the United States to Italy.","authors":"Nicholas J Cioe, Rita Formisano, Gregory O'Shanick, Juliet Haarbauer-Krupa, Valentina Bandiera, Elisa Berardi, Vincenzo Vinicola, Umberto Bivona","doi":"10.3390/brainsci15090943","DOIUrl":"10.3390/brainsci15090943","url":null,"abstract":"<p><p>Acquired Brain Injury (ABI) is now widely regarded as a chronic condition but this change in conceptualization has not yet been realized in the way rehabilitation and care are offered and funded in the United States. Similarly, it is widely accepted that an optimized ABI system includes integration across the phases of care and recovery that considers the bio-psycho-socio-ecological (BPSE) dimensions beyond the injury itself. Despite the importance of BPSE factors informing care, typical post-injury care and management remain focused on acute presentation and the biological nature of the injury and there still exists relevant inter-country differences for disorders of consciousness (DoC) neurorehabilitation after severe ABI. This collaboration with Italian colleagues explores and compares the types and locations of rehabilitative services offered in a Post-Coma Unit of neurorehabilitation center in Italy (namely, Santa Lucia Foundation IRCCS in Rome) and in the United States following a \"severe\" ABI (sABI). This narrative seeks to describe the degree to which both systems utilize a BPSE informed approach to care.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Nuclei in the Regulation of Sexual Behavior, Peripheral Nerves Related to Reproduction, and Their Alterations in Neurodegenerative Diseases: A Brief Review.","authors":"María de la Paz Palacios-Arellano, Jessica Natalia Landa-García, Edson David García-Martínez, Jorge Manzo-Denes, Gonzalo Emiliano Aranda-Abreu, Fausto Rojas-Durán, Deissy Herrera-Covarrubias, María Rebeca Toledo-Cárdenas, Genaro Alfonso Coria-Ávila, Jorge Manuel Suárez-Medellín, César Antonio Pérez-Estudillo, María Elena Hernández-Aguilar","doi":"10.3390/brainsci15090942","DOIUrl":"10.3390/brainsci15090942","url":null,"abstract":"<p><p>Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. This process culminates with ejaculation and the deposition of semen into the uterine tract with the aim of achieving fertilization. The brain plays a fundamental role in both generating motivation and executing male sexual behavior. Meanwhile, the spinal cord, through the autonomic nervous system and the pelvic ganglion, transmits information to the reproductive organs, including the testes. Currently, there is extensive evidence demonstrating the involvement of various brain structures in the regulation of sexual behavior, as well as specific regions of the spinal cord involved in the control of ejaculation. For instance, the medial preoptic area (MPOA) has been shown to regulate the secretion of pituitary hormones, which in turn modulate the function of reproductive organs. Among these, testosterone production is particularly notable, as this hormone not only directly affects reproductive organs but also exerts a modulatory role on brain nuclei responsible for sexual behavior. Although there is a reciprocal regulation between the nervous and endocrine systems, it is important to note that the execution of sexual behavior also impacts peripheral structures, such as the major pelvic ganglion (MPG) and the testis, preparing the organism for reproduction. The purpose of this mini-review is to provide an overview of the main brain nuclei involved in the regulation of sexual behavior, as well as the spinal cord regions implicated in reproduction. Finally, we discuss how these structures may alter their function in the context of neurodegenerative diseases, aiming to introduce readers to this field of study.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging of Cerebral Iron as an Emerging Marker for Brain Aging, Neurodegeneration, and Cerebrovascular Diseases.","authors":"Chi-Heng Zhou, Yi-Cheng Zhu","doi":"10.3390/brainsci15090944","DOIUrl":"10.3390/brainsci15090944","url":null,"abstract":"<p><p>Iron is critical for brain development, metabolism, and function; however, dysregulated iron disposition contributes to neurological diseases. Many neuroimaging techniques have enabled detection of iron susceptibility, and quantitative susceptibility mapping (QSM) offers a sensitive magnetic resonance imaging (MRI) technique for quantifying brain iron. To elucidate the functional role of cerebral iron and clarify the utility of QSM in establishing iron as a potential biomarker, this review synthesizes cellular and regional behaviours of iron from physiological aging to disease conditions, with a focus on neurodegeneration such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), as well as cerebral small vessel disease (CSVD) as cerebrovascular manifestation. Distinct patterns of iron distribution in deep gray matter and selective cortical regions are associated with motor and cognitive impairment, while the interaction between iron, vascular integrity, and glial function further stresses its pathological relevance. QSM of iron may, thereby, serve as a marker to monitor iron-related disease progression and facilitate intervention. Temporal dynamics of iron in brain pathology remain underexplored, and we emphasized the need for longitudinal mapping and multi-modality biomarker integration. Establishing iron as a clinically relevant imaging biomarker requires continued investigation into its topographical, molecular, and functional correlates across aging and disease trajectories.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}