Molecular mechanisms underlying the neural correlates of working memory.

Background: Working memory (WM), a core component of executive functions, relies on a dedicated brain system that maintains and stores information in the short term. While extensive neuroimaging research has identified a distributed set of neural substrates relevant to WM, their underlying molecular mechanisms remain enigmatic. This study investigated the neural correlates of WM as well as their underlying molecular mechanisms.

Results: Our voxel-wise analyses of resting-state functional MRI data from 502 healthy young adults showed that better WM performance (higher accuracy and shorter reaction time of the 3-back task) was associated with lower functional connectivity density (FCD) in the left inferior temporal gyrus and higher FCD in the left anterior cingulate cortex. A combination of transcriptome-neuroimaging spatial correlation and the ensemble-based gene category enrichment analysis revealed that the identified neural correlates of WM were associated with expression of diverse gene categories involving important cortical components and their biological processes as well as sodium channels. Cross-region spatial correlation analyses demonstrated significant associations between the neural correlates of WM and a range of neurotransmitters including dopamine, glutamate, serotonin, and acetylcholine.

Conclusions: These findings may help to shed light on the molecular mechanisms underlying the neural correlates of WM.