The Neural Association Between Symptom and Cognition in Major Depressive Disorder: A Network Control Theory Study

Major depressive disorder (MDD) is characterized by intercorrelated clinical symptoms and cognitive deficits, whose neural mechanisms in relation to these disturbances remain unclear. To elucidate this, we applied the relatively new approach of Network Control Theory (NCT), which considers how network topology informs brain dynamics based on white matter connectivity data. We used the NCT parameter of average controllability (AC) to assess the potential control that brain network nodes have on brain-state transitions associated with clinical and cognitive symptoms in MDD. DTI and high-resolution T1-weighted anatomical imaging were performed on 170 MDD patients (mean age 31.6 years; 72 males, 98 females) and 137 healthy controls (HC; mean age 33.4 years; 64 males, 73 females). We used an NCT approach to compare AC between the groups. We then performed partial Spearman's rank correlation and moderation/mediation analyses for AC and cognition and clinical symptom scores. Compared with HC, MDD patients had lower AC in the left precuneus and superior parietal lobule and higher AC in the right precentral gyrus (preCG) and superior frontal gyrus (SFG), predominantly in the default-mode, somatomotor, and attention networks. In the HC group, AC of right preCG was positively associated with processing speed. While in the MDD group, AC of right SFG was negatively associated with memory function and also negatively moderated the association between memory and anxiety symptoms. The current study highlighted that the altered brain controllability may provide a novel understanding of the neural substrate underlying cognitive control in MDD. Disrupted control of right SFG during state transitions may partially explain the variable relationship between memory and anxiety symptoms in MDD.