Molecular contextualization of the neural correlates of episodic memory

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BACKGROUND: Considerable neuroimaging effort has been dedicated to investigate the neural correlates of episodic memory, but the micro-scale molecular mechanisms that underlie the macro-scale neuroimaging correlates of episodic memory are still unclear. METHODS: Resting-state functional MRI data were obtained from a large cohort of 510 healthy young adults to calculate regional homogeneity (ReHo) to reflect spontaneous intrinsic brain activity. We then explored the relationship between California Verbal Learning Test-Ⅱ performance and ReHo across participants to delineate the neural substrates of episodic memory. Finally, we conducted the spatial relationship analyses between the neural correlates with gene expression and neurotransmitter atlases to further explore their potential genetic architecture and neurochemical underpinnings. RESULTS: Our analysis revealed a significant negative correlation between episodic memory and ReHo in the bilateral precuneus. Additional spatial correlation analyses revealed that the identified neural correlates of episodic memory were associated with expression of gene categories predominantly implicating signal transduction, immune system process, cellular metabolic process and anatomical structure development, as well as were linked to serotonin transporter. CONCLUSIONS: These findings may not only offer novel insights into the molecular substrates underlying the neural basis of episodic memory, but also help inform prevention and intervention strategies for individuals in at-risk and early phases of dementia.

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