[18F]-FDG-PET Metabolic Differences in Mesial Temporal Lobe Epilepsy Correlate with Brain-Wide Gene Expression

Introduction: Mesial temporal lobe epilepsy (MTLE) has been shown to be associated with glucose metabolic abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain metabolic changes in MTLE and gene expression is unclear.

Methods: The cohort included individuals with MTLE (n=104) and age- and sex-matched healthy controls (n=100). Brain gene expressions were obtained from the ALLEN Human Brain Atlas (AHBA) (http://human.brain-map.org), a whole-brain transcriptomic dataset. We examine the link between brain-wide gene expression and glucose metabolic changes in individuals with MTLE, using Positron Emission Computed Tomography (PET) data from the independent cohorts and a publicly available transcriptomic dataset. Partial least squares (PLS) regression was used to determine the relationship between regional changes in metabolic similarity network (MSN) and transcriptional activity for all 10,027 genes.

Results: MSN analysis shows glucose metabolic differences in individuals with MTLE compared to control subjects. Using human brain gene expression data, we observe that the gene expression spatially correlates with metabolic similarity network differences (r=0.546, p<0.001). Analysis of signature genes suggests that OSBPL9 (r=0.389, p<0.001) and PHF24 (r=-0.399, p<0.001) gene expression account for most of the observed correlation with MTLE-specific MSN differences.

Conclusions: Our findings link MTLE-related MSN abnormalities and transcriptional data to advance our understanding of the relationship of molecular mechanisms to glucose metabolism changes in MTLE.

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