Imbalanced Brain Connectome: A Novel Link between Functional Somatic Disorders, Multiple Chemical Sensitivity, and Post-COVID patients

Haghshenas Bilehsavar, S.; Bonetti, L.; Gleesborg, C.; Juhl Lunde, S.; Ovesen, T.; Sigsgaard, T.; Vase, L.; L. Kringelbach, M.; Rosengaard, A.; Fink, P.; Moller, A.; Gormsen, L. K.

doi:10.1101/2025.10.22.683928

bioRxiv · 10.1101/2025.10.22.683928

Imbalanced Brain Connectome: A Novel Link between Functional Somatic Disorders, Multiple Chemical Sensitivity, and Post-COVID patients

Haghshenas Bilehsavar, S.·Bonetti, L.·Gleesborg, C.·Juhl Lunde, S.·Ovesen, T.·Sigsgaard, T.·Vase, L.·L. Kringelbach, M.·Rosengaard, A.·Fink, P.·Moller, A.·Gormsen, L. K.

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Abstract

This study aimed to investigate and assess shared patterns of structural brain connectivity across three clinical populations. Despite significant advancements in neuroimaging, structural connectivity alterations have been underexplored in functional somatic disorders (FSDs), multiple chemical sensitivity (MCS), and post-COVID-19 conditions (PC). Clinical observations suggest that olfactory symptoms may represent a missing link between these three patient groups. Using diffusion-weighted MRI and voxel-based probabilistic tractography, structural connectivity was analysed in 57 females (MCS: 16, FSD: 15, PC: 11, and 15 matched healthy controls). Independent-sample t-tests (with FDR correction) and permutation testing were applied to assess group-level differences, particularly in inter- and intra-hemispheric connectivity. A marked decrease in inter-hemispheric connectivity was observed in patients (70.9%) compared with controls (29.1%; p < 0.001). The finding was consistent across all diagnostic groups. These alterations remained stable following reanalysis and aggregation, reliably distinguishing patients from controls. No significant differences were found in intra-hemispheric connectivity across the patient groups. Additionally, out of 12 predefined interregional connections, ten showed significant alterations in at least one patient group. The findings reveal robust and consistent reduced inter-hemispheric connectivity in patients with MCS, FSD, and PC, highlighting a potentially shared neurobiological signature among the patient groups.

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Haghshenas Bilehsavar, S., Bonetti, L., Gleesborg, C., Juhl Lunde, S., Ovesen, T., Sigsgaard, T., Vase, L., L. Kringelbach, M., Rosengaard, A., Fink, P., Moller, A., Gormsen, L. K.. 2025-10-22. Imbalanced Brain Connectome: A Novel Link between Functional Somatic Disorders, Multiple Chemical Sensitivity, and Post-COVID patients. https://doi.org/10.1101/2025.10.22.683928

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