Brain Functional Connectivity Mapping of Behavioral Flexibility in Rhesus Monkeys.

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), which 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 fMRI. A self-pacing ASST was administered to three cohorts of rhesus monkeys (total n = 35, 18 female). Increased performance over 30 consecutive sessions segregated the monkeys into two populations, termed High Performers (HP, n = 17) and Low Performers (LP, n = 17), with one anomaly. Compared with LPs, HPs had higher rates of improving performance over sessions and completed the 8 sets/sessions 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. A whole-brain independent components analysis of resting-state fMRI under isoflurane identified four strong networks. Of these, a dual regression analysis revealed that a designated "executive control network," differed between HPs and LPs. Specific areas of connectivity in the rhesus executive control network, 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.