Introduction: The amygdala has been shown to play a role in nicotine dependence by mediating reward and impulsivity. Here we demonstrate the structural connectivity of the amygdala to a broader brain reward network using probabilistic tractography. We hypothesized that amygdala connectivity with other reward-related structures correlates with impulsivity and nicotine dependence.
Methods: Diffusion and structural MRI was obtained from 197 randomly selected healthy subjects from the human connectome project dataset. Probabilistic tractography (using FSL) was performed between the amygdala and the brainstem, dorsolateral prefrontal cortex (DLPFC), hippocampus, insula, NAc, OFC, and rostral anterior cingulate cortex (rACC) (Figure 1). Seed masks were generated using automated segmentation (FreeSurfer software). Statistical maps of amygdala connectivity were generated. Impulsivity was determined using the area under the curve (AUC) on a temporal discounting monetary task. Tobacco dependence (low vs. high difficulty quitting) was assessed using DSM-based behavioral questionnaires.
Results: Structural connectivity of the amygdala to the specified structures was spatially segregated (Figure 2). The amygdala showed highest connectivity with the hippocampus, OFC and brainstem (p < 0.001) (Figure 3). There was a significant correlation between connectivity with the hippocampus, OFC, insula and rACC and impulsivity (p < 0.001 for hippocampus and OFC, p < 0.05 for insula and rACC). Higher connectivity with the hippocampus was associated with decreased impulsivity while higher connectivity with the OFC was associated with increased impulsivity (Figure 4). Subjects with greater nicotine dependence displayed significantly decreased hippocampal but increased brainstem and rACC connectivity (p < 0.05) (Figure 5).
Conclusions: The amygdala displays spatially segregated subregions with high connectivity with the hippocampus, OFC and brainstem. Connectivity with the hippocampus is correlated with low impulsivity and lower levels of nicotine dependence. On the other hand, connectivity with the OFC and rACC is correlated with higher impulsivity and higher nicotine dependence.
Patient Care: This work increases our understanding of the structural connectivity of the amygdala and its relationship to impulsivity and addiction. This data will help us to develop novel targeted neuromodulatory treatments for addiction to nicotine and other substances.
Learning Objectives: The learning objectives are to understand: 1) the use of diffusion tractography to estimate structural connectivity of the amygdala 2) how connectivity of the amygdala influences impulsivity and 3) the role of the amygdala in nicotine dependence.