Spatial gene expression and functional network abnormalities in multiple sclerosis: exploring biological influence on brain functional reorganization
Description
This dataset refers to a study where 558 patients with multiple sclerosis (MS) and 214 healthy controls (HC) underwent neurological assessment and 3T MRI acquisition, including resting-state functional MRI (RS fMRI). In addition, 491 MS patients completed a comprehensive neuropsychological evaluation for cognitive status assessment. RS functional connectivity (FC) abnormalities were quantified using degree centrality analysis to characterize large-scale brain network reorganization associated with MS. Spatial patterns of functional abnormalities were then compared between HC and different MS phenotypes, including relapsing-remitting and progressive MS, as well as between cognitively preserved and cognitively impaired patients. To investigate the biological basis of RS FC, spatial correlations were performed between regional degree centrality abnormalities and the expression of 3634 MS-related genes derived from the Allen Human Brain Atlas (AHBA). Genes significantly associated with imaging-derived network alterations underwent pathway enrichment analysis. Compared to HC, MS patients showed increased degree centrality mainly in the default-mode network (DMN), associated with genes involved in inflammation resolution and immune regulation, and reduced centrality in salience network and cerebellar regions linked to cytokine-response genes. Progressive MS patients exhibited higher centrality in DMN and cerebellar areas than HC and relapsing-remitting MS patients, correlating with genes related to epigenetic and mitochondrial functions. Among MS patients, 144 (29.3%) were cognitively impaired and showed increased centrality in DMN and mesial temporal regions compared to cognitively preserved patients and HC. These abnormalities negatively correlated with DNASE1 and CP gene expression, implicated in DNA degradation, iron homeostasis, and neurodegeneration. Regional gene expression spatially correlated with MS-related functional network abnormalities.
Files
Categories
Funders
- European Union - Next Generation EU - NRRP M6C2 Investment 2.1Grant ID: PNRR-MAD-2022-12376530, CUP master C43C22001290007