BACKGROUND
Despite recent advances, the pathophysiology of functional neurological disorder (FND) remains incompletely understood. Structural neuroimaging studies have identified grey matter alterations in somatomotor, salience, limbic, and default mode network associated areas, although findings are inconsistent. Mega-analyses, which combine individual-level data across studies, can help clarify structural alterations.
METHODS
We conducted a mega-analysis of brain structural morphometrics derived from T1-weighed MRI scans from fifteen international research groups. After across-site harmonisation with ComBat, we compared 493 functional motor and seizure patients with 564 healthy controls. Euler numbers were included to account for head motion.
RESULTS
The FND cohort showed reduced cortical thickness in the bilateral superior frontal gyri (left d = 0.22, right d = 0.21) and sulci (d = 0.22 & 0.23), bilateral superior precentral sulcus (d = 0.22 & 0.26), right precentral gyrus (d = 0.25), right paracentral gyrus and sulcus (d = 0.23), right cuneus (d = 0.23), and right inferior opercular gyrus (d = 0.21); reduced left postcentral gyrus surface area (d = 0.25) and right hippocampal volume (d = 0.22). No regions were different in relative surface area. There were no associations between morphometrics and illness duration, or lifetime history of depression or anxiety. Differences between motor and seizure variants were not identified.
CONCLUSIONS
This large mega-analysis suggests subtle morphometric differences, particularly in prefrontal and motor regions. This may represent predisposing vulnerabilities, compensatory mechanisms, or FND-specific alterations. Improved neuropsychiatric characterisation of FND research cohorts will help further contextualise the biological relevance of structural alterations.
Matt Butler, M. Vignando, J. Allendorfer et al.· Biological Psychiatry· 0 citations
Abstract Individuals with autosomal dominant frontotemporal dementia (FTD) exhibit considerable variability in disease onset and progression. Both modifiable and non-modifiable factors—such as sex, educational attainment or geographic region of residence—may contribute to this heterogeneity, potentially through their influence on cognitive reserve. The aim of the present study was to investigate the role of cognitive reserve modulators within the Genetic Frontotemporal dementia Initiative (GENFI) cohort. To this end, we used functional MRI (i.e. spatial chronnectome measures) and neurodegenerative markers (i.e. plasma neurofilament light chains levels) to determine disease stage using a Discriminative Event-Based Model (DEBM). We then examined how potential modulators influence the relationship between disease stage and cognitive performance. We analysed a total of 711 participants, including 106 patients with genetic FTD, 325 presymptomatic mutation carriers and 280 non-carriers healthy controls. Female participants showed a weaker association between disease stage and cognitive performance compared to males (P < 0.001), with difference becoming progressively more pronounced across symptomatic stages. Educational attainment exhibited a similar effect: individuals with higher education demonstrated an attenuated association compared to those with secondary or primary schooling (P < 0.001), with differences already detectable at prodromal disease stages. The effect of geographical region of residence was associated with education levels, but appeared to have an indirect and less strong influence. In summary, sex and educational attainment significantly affect the development and maintenance of cognitive reserve in individuals with genetic FTD. These findings underscore the importance of identifying disease-modifying interventions since the presymptomatic stages of the disease.
E. Premi, Damiano Archetti, A. Redolfi et al.· Brain Communications· 0 citations