Prefrontal-Limbic Circuitry Is Associated With Reward Sensitivity in Nonhuman Primates

Kwang-Hyun Hur; Steven L Meisler; Walid Yassin; Blaise B Frederick; Stephen J Kohut

doi:10.1016/j.biopsych.2024.02.1011

Prefrontal-Limbic Circuitry Is Associated With Reward Sensitivity in Nonhuman Primates

Biol Psychiatry. 2024 Mar 1:S0006-3223(24)01131-4. doi: 10.1016/j.biopsych.2024.02.1011. Online ahead of print.

Authors

Kwang-Hyun Hur¹, Steven L Meisler², Walid Yassin¹, Blaise B Frederick³, Stephen J Kohut⁴

Affiliations

¹ Behavioral Neuroimaging Laboratory, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
² Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, Massachusetts.
³ Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; McLean Imaging Center, McLean Hospital, Belmont, Massachusetts.
⁴ Behavioral Neuroimaging Laboratory, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; McLean Imaging Center, McLean Hospital, Belmont, Massachusetts. Electronic address: skohut@mclean.harvard.edu.

PMID: 38432521
DOI: 10.1016/j.biopsych.2024.02.1011

Abstract

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 that underlie it are not completely understood. Here, we sought to investigate the relationship between multimodal 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; 7 female, 5 male) 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). Animals were divided into high (n = 6) or low (n = 6) reward sensitivity groups based on essential value for 30% milk. Multimodal 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: Animals in the high sensitivity group had greater dorsolateral prefrontal cortex, centromedial amygdaloid complex, and middle cingulate cortex volumes than animals in the low sensitivity group. Furthermore, compared with monkeys in the low sensitivity group, high sensitivity monkeys had lower fractional anisotropy in the left dorsal cingulate bundle connecting the centromedial amygdaloid complex and middle cingulate cortex to the dorsolateral prefrontal cortex, and in the left superior longitudinal fasciculus 1 connecting the middle cingulate cortex to the dorsolateral prefrontal cortex.

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.

Keywords: Brain structure; Gray matter volume; Nonhuman primate; Prefrontal-limbic circuitry; Reward sensitivity; White matter microstructure.