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.

Background Extensive research has shown abnormal cerebral blood flow (CBF) in patients with major depressive disorder (MDD) that is a heritable disease. The objective of this study was to investigate the genetic mechanisms of CBF abnormalities in MDD. Methods To achieve a more thorough characterization of CBF changes in MDD, we performed a comprehensive neuroimaging meta-analysis of previous literature as well as examined group CBF differences in an independent sample of 133 MDD patients and 133 controls. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial association analyses were conducted to identify genes whose expression correlated with CBF changes in MDD, followed by a set of gene functional feature analyses. Results We found increased CBF in the reward circuitry and default-mode network and decreased CBF in the visual system in MDD patients. Moreover, these CBF changes were spatially associated with expression of 1532 genes, which were enriched for important molecular functions, biological processes, and cellular components of the cerebral cortex as well as several common mental disorders. Concurrently, these genes were specifically expressed in the brain tissue, in immune cells and neurons, and during nearly all developmental stages. Regarding behavioral relevance, these genes were associated with domains involving emotion and sensation. In addition, these genes could construct a protein-protein interaction network supported by 60 putative hub genes with functional significance. Conclusions Our findings suggest a cerebral perfusion redistribution in MDD, which may be a consequence of complex interactions of a wide range of genes with diverse functional features.