Brain functional connectivity mapping of behavioral flexibility in rhesus monkeys

Abstract

The predisposition to engage in autonomous habitual behaviors has been associated with behavioral disorders such as obsessive-compulsive disorder and addiction. Attentional set-shifting tasks (ASSTs), that incorporate changes governing the association of discriminative stimuli with contingent reinforcement, are commonly used to measure underlying processes of cognitive/behavioral flexibility. The purpose of this study was to identify primate brain networks that mediate trait-like deficits in ASST performance using resting state functional magnetic resonance imaging (rsfMRI). A self-pacing ASST was administered to 3 cohorts of rhesus monkeys (total n=35, 18 female). Increased performance over 30 consecutive sessions segregated the monkeys into 2 populations, termed High Performers (HP, n=17) and Low Performers (LP, n=17), with one anomaly. Compared to LPs, HPs had higher rates of improving performance over sessions and completed the 8 sets/session with fewer errors. LP monkeys, on the other hand, spent most of each session in the first set and often did not acquire the first reversal (Set 2). A whole-brain independent components analysis of rsfMRI under isoflurane identified 4 strong networks. Of these, a dual regression analysis revealed that a designated “executive control network” (ECN), differed between HPs and LPs. Specific areas of connectivity in the rhesus ECN, including frontal cortices (ventrolateral, ventromedial and orbital) and the dorsal striatum (caudate, putamen) correlated with perseverative errors and response latency. Overall, the results identify trait-like characteristics of behavioral flexibility that are associated with correlated brain activity involving specific nuclei of frontostriatal networks.

SIGNIFICANCE STATEMENT

Resting state functional connectivity MRI in rhesus monkeys identified specific nuclei in frontostriatal circuitry that were associated with population differences in perseverative and impulsive aspects of cognitive flexibility.