030-22 – Atypical large-scale functional networks in newly diagnosed focal epilepsy shows brain-wide patterns of gene expression implicated in epilepsy

Neuroimaging research is providing insights into newly diagnosed focal epilepsy (NDfE) as a disorder of brain connectivity linked to functional impairments which may have an identifiable genetic component. We used gradient-based analysis of resting-sate-fMRI data to identify connectome alterations in patients with NDfE (n = 27) compared to age and sex-matched controls (n = 36). Using a brain-wide gene expression dataset, gene combinations associated with altered brain regions were then entered into an enrichment analysis. We found an increased differentiation of connectivity profiles between unimodal and transmodal networks in NDfE, which was particularly pronounced in patients with persistent seizures at 12-months follow-up (n=10). Differences corresponded to gradient score reductions in a visual network and increases in limbic and default mode systems which subserve higher-level cognition. Cortical difference maps were spatially correlated with regional expression of a weighted gene combination. These genes were enriched for disease and ontology terms and pathways associated with epilepsy and seizure susceptibility. Large-scale functional hierarchy may be altered in focal epilepsy from diagnosis and correlate with response to treatment. Combining functional neuroimaging and transcriptional data may provide a mechanistic insight into how gene processes may drive alterations in brain function mediating the genetic risk of epilepsy.