Association between functional alterations and specific transcriptional expression patterns in craniocervical dystonia.

PURPOSE: Craniocervical dystonia (CCD) is a large-scale network disorder that involves functional changes in multiple brain regions. However, the association between these functional changes and the underlying molecular mechanisms has not been explored.

OBJECTIVE

We aimed to characterize the molecular changes associated with the imaging-defined functional architecture of the brain in CCD.

METHODS

Resting-state functional magnetic resonance imaging (rs-fMRI) data were obtained from 146 patients with CCD and 137 healthy controls (HCs). Differences in the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were compared between groups. Transcriptomic data were obtained from the Allen Human Brain Atlas to identify the gene expression patterns underlying the affected functional architecture in CCD using partial least squares regression.

RESULTS

Compared to HCs, patients with CCD showed common functional alterations, mainly in the left middle occipital gyrus, right middle occipital gyrus, right calcarine, right precentral gyrus, and left postcentral gyrus. These functional alteration patterns were positively associated with 1763 genes (including five risk genes for dystonia) enriched for synaptic signaling, regulation of trans-synaptic signaling, and neuronal systems, while they were negatively associated with 2318 genes (including eight risk genes for dystonia), which were enriched for monoatomic cation transport, DNA damage response and neurodevelopment.

CONCLUSIONS

Our study reveals a genetic pathological mechanism explaining CCD-related brain functional changes.