Transcriptional signatures of cortical morphometric variability in temporal lobe epilepsy
Abstract Objective Widespread cognitive deficits in temporal lobe epilepsy (TLE) are associated with macroscale brain structural changes. However, the correlation between the changes in the cortical morphological similarity of the TLE and gene expression remains unclear. Methods Structural magnetic resonance imaging (MRI) was collected from 31 TLE patients and 35 healthy controls to construct an individual‐level Morphometric INverse Divergence (MIND) network. Changes in cortical morphological similarity attributable to TLE and their cognitive correlates were assessed. Using a public transcriptional dataset, we linked TLE‐related structural changes to specific gene expression and biological pathways. Results TLE patients exhibited macroscopic morphological changes in the posterior cingulate cortex and dorsolateral prefrontal cortex, which were associated with cognitive impairments such as processing speed and working memory. Notably, TLE‐related MIND changes were spatially correlated with the expression of epilepsy‐associated genes, which were predominantly enriched in biological processes including cellular regulation and synaptic transmission. Significance MIND reveals macroscopic morphometric abnormalities of TLE. The microscopic transcriptional patterns have facilitated the understanding of the molecular mechanisms underlying cortical susceptibility. Plain Language Summary TLE patients often have memory and thinking problems. This study used brain scans to show that TLE patients have structural changes in two brain regions, the posterior cingulate cortex and dorsolateral prefrontal cortex. These changes are linked to slower processing speed and poorer working memory. Importantly, the brain changes were spatially related to the activity of TLE susceptibility genes involved in cell regulation and signal transmission between neurons. This helps explain how microscopic gene patterns may contribute to large‐scale brain changes and cognitive difficulties in TLE.