Prefrontal-Limbic Circuitry is Associated with Reward Sensitivity in Nonhuman Primates.

BACKGROUND: Abnormal reward sensitivity is a risk factor for psychiatric disorders, including eating disorders such as overeating and binge-eating disorder, but the brain structural mechanisms underlying it are not completely understood. Here, we sought to investigate the relationship between multi-modal whole-brain structural features and reward sensitivity in nonhuman primates.

METHODS: Reward sensitivity was evaluated through behavioral economic analysis in which monkeys (adult rhesus macaques, 5 males; 7 females) responded for sweetened-condensed milk (10,30,56%), Gatorade, or water using an operant procedure in which the response requirement increased incrementally across sessions (i.e., fixed ratio 1,3,10,etc.). Subjects were divided into high (N=6) or low (N=6) reward sensitivity groups based on essential value for 30% milk. Multi-modal magnetic resonance imaging was used to measure gray matter volume and white matter microstructure. Brain structural features were compared between groups and their correlations with reward sensitivity for various stimuli was investigated.

RESULTS: Subjects in the High Sensitivity group had greater dorsolateral prefrontal cortex (dlPFC), centromedial amygdaloid complex (CeMA), and middle cingulate cortex (MCC) volumes compared to subjects in the Low Sensitivity group. Further, High Sensitivity monkeys had lower fractional anisotropy in the left dorsal cingulate bundle connecting CeMA and MCC to the dlPFC, and left superior longitudinal fasciculus 1 connecting the MCC to the dlPFC, compared to monkeys in the Low Sensitivity group.

CONCLUSIONS: These results suggest that neuroanatomical variation in prefrontal-limbic circuitry is associated with reward sensitivity. These brain structural features may serve as predictive biomarkers for vulnerability to food-based and other reward-related disorders.