Dissociative contributions of the anterior cingulate cortex to apathy and depression: Topological evidence from resting-state functional MRI

Apathy is defined as a mental state characterized by a lack of goal-directed behavior. However, the underlying mechanisms of apathy remain to be fully understood. Apathy shares certain symptoms with depression and both these affective disorders are known to be associated with dysfunctions of the frontal cortex-basal ganglia circuits. It is expected that clarifying differences in neural mechanisms between the two conditions would lead to an improved understanding of apathy. The present study was designed to investigate whether apathy and depression depend on different network properties of the frontal cortex-basal ganglia circuits, by using resting state fMRI. Resting-state fMRI measurement and neuropsychological testing were conducted on middle-aged and older adults (N=392). Based on graph theory, we estimated nodal efficiency (functional integration), local efficiency (functional segregation), and betweenness centrality. We conducted multiple regression analyses for the network parameters using age, sex, apathy, and depression as predictors. Interestingly, results indicated that the anterior cingulate cortex showed lower nodal efficiency, local efficiency, and betweenness centrality in apathy, whereas in depression, it showed higher nodal efficiency and betweenness centrality. The anterior cingulate cortex constitutes the so-called “salience network”, which detects salient experiences. Our results indicate that apathy is characterized by decreased salience-related processing in the anterior cingulate cortex, whereas depression is characterized by increased salience-related processing.