Mega-analysis of Structural Brain Imaging in Functional Neurological Disorder.

Imaging biomarkers in functional neurological disorders

Abstract Recent advances in neuroimaging have significantly reshaped our understanding of functional neurological disorder (FND), shifting the focus from structural damage to dysfunctional brain networks. Building on Charcot's early intuition of a ‘functional lesion’, this review traces the evolution of neuroimaging research in FND, from its historical roots to current developments. We synthesize findings from structural and functional imaging studies, highlighting alterations in brain regions involved in motor control, self-agency and emotion regulation. Task-based fMRI studies have shown atypical activation in areas such as the supplementary motor area, dorsolateral prefrontal cortex and temporo-parietal junction, supporting the notion of impaired voluntary motor control. Additionally, changes in the amygdala and periaqueductal grey point to the role of emotional dysregulation. Structural imaging reveals grey and white matter alterations, while machine learning applied to resting-state connectivity shows promise for biomarker development. Emerging evidence also suggests that genetic and epigenetic factors—particularly within oxytocinergic and serotonergic systems—may contribute to individual vulnerability. We argue for a multi-modal approach integrating neuroimaging, genetics and computational methods to advance both the diagnosis and treatment of FND. This article is part of the discussion meeting issue ‘Digital healthcare for the management of functional neurological disorders’.

A systematic review of brain structural and functional alterations in pediatric mild traumatic brain injury

Introduction Pediatric mild traumatic brain injury (pmTBI) constitutes 70–90% of childhood traumatic brain injury cases. While magnetic resonance imaging (MRI) reveals subtle brain alterations, fragmented evidence across modalities limits understanding of long-term neurobiological consequences. Methods This systematic review synthesized 42 studies from MEDLINE/PubMed, Web of Science, Cochrane Library, and Scopus (inception to December 2025) employing structural MRI and functional MRI (fMRI). Methodological quality was assessed using a modified GRADE framework. Results White matter investigations (n = 18) suggested widespread microstructural alterations in limbic and commissural pathways-alongside reduced global network efficiency and disrupted hub connectivity in executive and salience networks. Gray matter studies (n = 9) identified regional cortical thinning in prefrontal and parietal regions, hippocampal atrophy persisting up to 1 year. Resting-state fMRI studies (n = 5) revealed diminished default mode network (DMN) integrity and elevated striatal spontaneous activity. Task-based fMRI studies (n = 10) demonstrated compensatory hyperactivation during working memory and inhibitory tasks-manifesting as enhanced preparatory activation but resource depletion during execution-alongside lower DMN deactivation and persistent cerebrovascular reactivity abnormalities extending to chronic phases. Discussion In sum, multimodal MRI provides evidence suggesting systematic structural and functional alterations in pmTBI encompassing white matter disruption, gray matter vulnerability, and network reorganization.

Macro-structural brainstem volumetry in generalized epilepsy: assessment of subcortical network involvement

Disrupted structural covariance network in presbycusis patients: evidence from a large sample mri-based morphometric study

Background Presbycusis is characterized by progressive age-related hearing loss and is often associated with cognitive decline and mental health disorders. Objective This study aimed to investigate gray matter volume (GMV) alterations and structural covariance network (SCN) reorganization in presbycusis patients via magnetic resonance imaging (MRI) and graph theory analysis. Methods A total of 129 presbycusis patients and 121 age-matched healthy controls (HCs) underwent neuropsychological assessments and high-resolution T1-weighted MRI. The voxel-based morphometry (VBM) method at the region of interest (ROI) level and the graph theory analysis method of the SCN based on GMV were used to study the impact of presbycusis on brain structure. Results Patients presented altered nodal topological properties in multiple brain regions, including the right insula, left hippocampus, bilateral superior frontal gyrus, and occipital cortices. Significant differences were observed in the characteristic path length (Lp) and normalized characteristic path length (λ) between the groups (p < 0.05). Cognitive assessments revealed impairments in executive function, memory, and visual-spatial abilities (p < 0.05). Conclusion Presbycusis is associated with GMV reduction and SCN reorganization across sensory, cognitive, and emotional brain networks. Compensatory neural mechanisms, such as enhanced visual processing, may alleviate the adverse impacts of auditory deprivation. These findings elucidate the neuroanatomical basis of cognitive decline in presbycusis and highlight the necessity of early clinical intervention.

Structural Connectivity Alterations Within Frontal Subregions in Parkinson's Disease: Implications for Motor Dysfunction.

RATIONALE AND OBJECTIVES Parkinson's disease (PD) is characterized by disrupted basal ganglia-thalamo-cortical connectivity, yet how frontal network topology relates to motor phenotype heterogeneity remains unclear. Conventional atlas-based approaches average out microscale organization within heterogeneous cortical areas. This study aimed to characterize fine-grained frontal subregional connectivity alterations in PD using high-resolution structural network analysis. MATERIALS AND METHODS Twenty-three patients with PD and 22 age- and sex-matched controls underwent diffusion tensor imaging and T1-weighted magnetic resonance imaging. Individual high-resolution frontal networks were constructed, and graph-theoretical metrics were computed for each frontal subregion to quantify connectivity patterns. Consensus Louvain clustering assessed modularity, and machine learning with SHapley Additive exPlanations interpretation performed individual classification. RESULTS Patients with PD exhibited heterogeneous topological alterations across multiple frontal subregions (corrected p < 0.05). The left rostral middle frontal gyrus (RMF.L) showed increased density and degree, whereas the lateral and medial orbitofrontal cortices showed decreases. RMF.L further exhibited a greater number of modules together with an altered modular organization. These topological alterations were significantly correlated with UPDRS-III motor scores. Topological features achieved a diagnostic accuracy of 91.69% for PD diagnosis and 91.90% for subtype differentiation, exceeding the performance of connectivity-based features. CONCLUSION Intraregional topological reorganization within the frontal lobe, most prominently in RMF.L, was associated with motor impairment in PD and may reflect maladaptive network remodeling. High-resolution network analysis may provide a sensitive framework for characterizing intraregional structural reorganization in PD and warrants further validation as an adjunctive imaging marker for disease stratification.

Substantia nigra iron-related alterations, white matter disruption, and functional network dysconnectivity in temporal lobe epilepsy: a multimodal neuroimaging study

The authors' multimodal findings suggest subregion- and laterality-specific alterations in the SN of patients with TLE, with patterns differing between RTLE and LTLE.