Distinct genetic signatures of cortical and subcortical regions associated with human memory

ABSTRACT

Despite the discovery of gene variants linked to memory performance, understanding the genetic basis of adult human memory remains a challenge. Here, we devised an unsupervised framework that relies on spatial correlations between human transcriptome data and functional neuroimaging maps to uncover the genetic signatures of memory in functionally-defined cortical and subcortical memory regions. Results were validated with animal literature and showed that our framework is highly effective in identifying memory-related processes and genes compared to a control cognitive function. Genes preferentially expressed in cortical memory regions are linked to memory-related processes such as immune and epigenetic regulation. Genes expressed in subcortical memory regions are associated with neurogenesis and glial cell differentiation. Genes expressed in both cortical and subcortical memory areas are involved in the regulation of transcription, synaptic plasticity and glutamate receptor signalling. Furthermore, distinct memory-associated genes such as PRKCD and CDK5 are linked to cortical and subcortical regions respectively. Thus, cortical and subcortical memory regions exhibit distinct genetic signatures that potentially reflect functional differences in health and disease, and nominates gene candidates for future experimental investigations.

SIGNIFICANCE STATEMENT The anatomical and functional aspects of human memory are well characterized, but its biological mechanisms are poorly understood. Here, to uncover genetic signatures associated with human memory function, we analyzed spatial correlations between micro-scale gene expression and macro-scale neuroimaging maps to derive memory-related biological processes and genes in an unsupervised manner. We found the gene signatures of cortical and subcortical memory to be largely distinct and are associated with memory. We identified less characterized memory-associated genes as well. Furthermore, our framework demonstrated effectiveness and precision in identifying gene signatures related to memory versus another function as a control. Overall, our work provides a human-centric approach to understanding the genetics of cognition, and identifies potential gene candidates for future experimental investigations.