Role of the amygdala in disrupted integration and effective connectivity of cortico-subcortical networks in apathy

Background Apathy is a quantitative reduction in motivation and goal-directed behaviors, not only observed in neuropsychiatric disorders, but also present in healthy populations. Although brain abnormalities associated with apathy in clinical disorders have been studied, the organization of brain networks in healthy individuals has yet to be identified. Method We examined properties of intrinsic brain networks in healthy individuals with varied levels of apathy. By using functional magnetic resonance imaging in combination with graph theory analysis and dynamic causal modeling analysis, we tested communications among nodes and modules as well as effective connectivity among brain networks. Results We found that the average participation coefficient of the subcortical network, especially the amygdala, was lower in individuals with high than low apathy. Importantly, we observed weaker effective connectivity fromthe hippocampus and parahippocampal gyrus to the amygdala, and from the amygdala to the parahippocampal gyrus and medial frontal cortex in individuals with apathy. Conclusion These findings suggest that individuals with high apathy exhibit aberrant communication within the cortical-to-subcortical network, characterized by differences in amygdala-related effective connectivity. Our work sheds light on the neural basis of apathy in subclinical populations and may have implications for understanding the development of clinical conditions that feature apathy.