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

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Craniocervical dystonia (CCD) is recognized as a network disorder impacting multiple brain regions.
• The molecular underpinnings of these functional brain changes in CCD remain largely unexplored.

Purpose of the Study:

• To investigate the molecular changes associated with the functional brain architecture in CCD.
• To identify gene expression patterns linked to imaging-defined functional alterations in CCD.

Main Methods:

• Utilized resting-state functional magnetic resonance imaging (rs-fMRI) on 146 CCD patients and 137 healthy controls (HCs).
• Analyzed differences in amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo).
• Integrated transcriptomic data from the Allen Human Brain Atlas with rs-fMRI findings using partial least squares regression.

Main Results:

• Identified significant functional alterations in CCD patients within specific brain regions, including the occipital and postcentral gyri.
• Found positive associations between functional alterations and 1763 genes, enriched in synaptic signaling and neuronal systems.
• Observed negative associations with 2318 genes, enriched in monoatomic cation transport, DNA damage response, and neurodevelopment, including known dystonia risk genes.

Conclusions:

• This research elucidates a genetic pathological mechanism contributing to brain functional changes observed in CCD.
• The findings provide a molecular basis for understanding CCD and may inform future therapeutic strategies.