Resting State Functional Connectivity of the Lateral and Medial Hypothalamus in Cocaine Dependence: An Exploratory Study

The role of dopamine in cocaine misuse has been extensively documented for the mesocorticolimbic circuit. Preclinical work from earlier lesion studies to recent multidisciplinary investigations has suggested that the hypothalamus is critically involved in motivated behavior, with the lateral and medial hypothalamus each involved in waking/feeding and resting/satiety. However, little is known of hypothalamus function and dysfunction in cocaine misuse. Here, we examined resting state functional connectivity of the lateral and medial hypothalamus in 70 individuals with cocaine dependence (CD) and 70 age as well as gender matched healthy controls (HC). Image pre-processing and analyses followed published work. Compared to HC, CD showed increased lateral hypothalamic connectivity with dorsolateral prefrontal cortex and decreased functional connectivity with the ventral precuneus. CD showed increased medial hypothalamic connectivity with the inferior parietal lobule and decreased connectivity with the ventromedial prefrontal cortex, temporal gyrus, fusiform gyrus, and ventral striatum. Further, at trend level significance, the connectivity strength between lateral hypothalamus and dorsolateral prefrontal cortex was positively correlated with total amount of cocaine use in the past month (p = 0.004, r = 0.35) and the connectivity strength between medial hypothalamus and ventral striatum was negatively correlated with cocaine craving as assessed by the Tiffany Cocaine Craving Questionnaire (p = 0.008, r = −0.33). Together, the findings demonstrated altered resting state functional connectivity of the hypothalamus and may provide new insight on circuit level deficits in cocaine dependence.