Modulation of task-related MEG activity by SCN2A sodium channel genotype

Authors

• AH Gerlich
• FW Carver
• T Holroyd
• D Dickinson
• KF Berman
• R Coppola

Abstract

SCN2A, a gene encoding the alpha-2 subunit of the voltage-gated type II sodium channel, mediates the conformational changes necessary for the formation of action potentials in the CNS. Additionally, studies show that variants in SCN2A alter nervous system function. Furthermore, there exists a disparity in general cognitive performance between carriers of the T allele (T/T or C/T) and those of the homozygous C allele (C/C), and this disparity differs in healthy controls from those with schizophrenia and their unaffected siblings. In Scult et al. (2015), correlation between fMRI activation in the dl-PFC and dACC was shown to significantly mediate cognitive ability with these disparities in healthy controls. Here we extend the investigation of genetic modulation with magnetoencephalography. MEG data was collected during both a resting state and working memory task. SCN2A SNP data was obtained from the NIMH Sibling Study (Dickinson et al. 2014). Using 30 carriers of the T allele (15 homozygous and 15 heterozygous) and 30 of the homozygous C allele, beamformer source localization was performed to identify significant brain regions varied by genotype and task. The source localization analysis showed significant differences by genotype for activity in the dl-PFC and dACC, supporting the findings from Scult et al. These regions may be implicated in differences in cognitive processing and/or intellectual functioning in healthy controls, as mediated by the conformational differences in the type II sodium channel. Further studies utilizing such imaging techniques may also support a similar correlation in affected populations (schizophrenia, autism spectrum, and neurodevelopmental disorders).

Scientific Focus Area: Neuroscience

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