Large-Scale Internetwork Functional Connectivity Mediates the Relationship between Serum Triglyceride and Working Memory in Young Adulthood.

Previous research has demonstrated that serum lipid profile is associated with cognitive function as well as brain structure and function in middle-aged, elderly, and clinical populations. However, the nature and extent of lipids-brain-cognition relationships in young adulthood are largely unknown. In this study, 157 healthy young adults underwent resting-state functional MRI scans. Functional connectivity between and within 14 functional networks were calculated using independent component analysis. Peripheral venous blood samples were collected to measure serum lipids. Working memory was assessed using a 3-back task. Linear regression, correlation, and mediation analyses were conducted to test for potential associations between serum lipids, inter- and intranetwork functional connectivity, and working memory performance. We found that higher serum triglyceride (TG) level was correlated with stronger connectivity between left frontoparietal and ventral attention networks, between right frontoparietal and dorsal attention networks, between right frontoparietal and dorsal sensorimotor networks, between right frontoparietal and lateral visual networks, and between salience (SN) and ventral sensorimotor (vSMN) networks, as well as lower connectivity between posterior default mode and left frontoparietal networks, between left frontoparietal and medial visual networks, and between ventral attention and dorsal sensorimotor networks. In addition, higher SN-vSMN connectivity was related to lower 3-back accuracy. More importantly, the relationship between serum TG and 3-back accuracy was mediated by SN-vSMN connectivity. Our findings not only may expand existing knowledge regarding serum lipids-brain-cognition relations from the perspective of large-scale functional network organization but also may inform a translational conceptualization of how to improve cognitive function through regulating serum lipids.