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Area of Science:

  • Neuroscience
  • Genomics
  • Medical Imaging

Background:

  • Multiple Sclerosis (MS) is characterized by functional network abnormalities linked to accumulating structural damage.
  • The biological basis and spatial distribution of these MS-related functional network abnormalities remain unclear.
  • Investigating the interplay between gene expression and brain network alterations is crucial for understanding MS pathophysiology.

Purpose of the Study:

  • To investigate the associations between MS-related functional network abnormalities and physiological gene expression.
  • To identify specific genes and biological pathways correlating with altered brain network topography in MS patients.
  • To explore differences in gene expression and network alterations across MS subtypes and cognitive statuses.

Main Methods:

  • Utilized resting-state functional MRI (fMRI) to generate degree centrality maps in 558 MS patients and 214 healthy controls (HC).
  • Correlated functional network centrality abnormalities with gene expression data from the Allen Human Brain Atlas (AHBA).
  • Performed pathway enrichment analysis on significantly associated genes using the Multimodal Environment for Neuroimaging and Genomic Analysis.

Main Results:

  • MS patients exhibited altered centrality in the default-mode network (DMN) and salience network/cerebellum compared to HC, associated with immune and cytokine-related genes.
  • Progressive MS showed increased centrality in DMN and cerebellum, linked to epigenetic and mitochondrial genes, versus relapsing-remitting MS.
  • Cognitively impaired MS patients displayed higher centrality in DMN and mesial temporal lobe, negatively correlated with DNASE1 and CP gene expression.

Conclusions:

  • Physiological regional gene expression spatially correlates with functional network alterations observed in multiple sclerosis.
  • Biological factors, including inflammation, immune response, epigenetic, and mitochondrial functions, may influence regional vulnerability or resilience in MS.
  • Specific gene expression patterns are associated with cognitive impairment in MS, potentially implicating DNA degradation and iron homeostasis.