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 largely overlap with brain regions related to the neural response to emotion and stress, the central autonomic network may mediate the autonomic response to negative emotional stimuli. We aimed to obtain evidence to determine whether neural connectivity of the central autonomic network 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 subjects with CUD and 23 control subjects 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 control group in nonimaging measures and brain activations but showed greater modulatory changes in left amygdala to hypothalamus EC (positively associated with Perceived Stress Scale score), right amygdala to bilateral fusiform gyri ECs (positively associated with Perceived Stress Scale score), and left ventrolateral prefrontal cortex to bilateral fusiform gyri ECs (negatively associated with Perceived Stress Scale score).

Conclusions: Left amygdala to hypothalamus EC and right amygdala to bilateral fusiform gyri ECs are possibly part of circuits underlying the risk of individuals with CUD to stress-related disorders. Correspondingly, left ventrolateral prefrontal cortex to bilateral fusiform gyri ECs are possibly part of circuits reflecting a protective mechanism.

Keywords: Cannabis use disorder; Central autonomic nervous system; DCM; Effective connectivity; Emotion; Stress.