Altered effective connectivity of central autonomic network in response to negative facial expression in adults with cannabis use disorder

Abstract Background Cannabis use is associated with an increased risk of stress-related adverse cardiovascular events. Because brain regions of the central autonomic network (CAN) largely overlap with brain regions related to the neural response to emotion and stress, the CAN may mediate the autonomic response to negative emotional stimuli. We aimed to obtain evidence whether neural connectivity of the CAN is altered in individuals with cannabis use disorder (CUD) when they are exposed to negative emotional stimuli. Methods Effective (directional) connectivity (EC) analysis using Dynamic Causal Modeling was applied to functional magnetic resonance imaging data acquired from 23 CUD subjects and 23 controls of the Human Connectome Project while they performed an emotional face-matching task with interleaving periods of negative-face (fearful/angry) and neutral-shape stimuli. The EC difference (modulatory change) was measured during the negative-face trials relative to the neutral-shape trials. Results The CUD group was similar to the controls in non-imaging measures and brain activations, but showed greater modulatory changes in the left amygdala to hypothalamus EC (positively associated with Perceived-Stress score), the right amygdala to bilateral fusiform gyri ECs (positively associated with Perceived-Stress score), and the left ventrolateral prefrontal cortex to bilateral fusiform gyri ECs (negatively associated with Perceived-Stress score). Conclusions The left amygdala to hypothalamus EC and the right amygdala to bilateral fusiform gyri ECs are possibly part of circuits underlying the risk of CUD individuals to stress-related disorders. Correspondingly, the left ventrolateral prefrontal cortex to bilateral fusiform gyri ECs are possibly part of circuits reflecting a protective mechanism.