TY - JOUR
T1 - Brain Functional Connectivity Mapping of Behavioral Flexibility in Rhesus Monkeys
AU - Grant, Kathleen A.
AU - Newman, Natali
AU - Lynn, Colton
AU - Davenport, Conor
AU - Gonzales, Steven
AU - Cuzon Carlson, Verginia C.
AU - Kroenke, Christopher D.
N1 - Funding Information:
Received Apr. 15, 2021; revised Apr. 21, 2022; accepted May 2, 2022. Author contributions: K.A.G. designed research; K.A.G., N.N., V.C.C.C., and C.D.K. edited the paper; K.A.G. wrote the paper; N.N., C.L., C.D., and C.D.K. performed research; S.G. contributed unpublished reagents/ analytic tools; C.D.K. analyzed data. This work was supported by National Institute on Alcohol Abuse and Alcoholism P60 AA010760, U01 AA013510, and U24 AA025473; and National Institutes of Health P51 OD011092. MRI instrumentation was supported by M.J. Murdock Charitable Trust. The authors declare no competing financial interests. Correspondence should be addressed to Kathleen A. Grant at grantka@ohsu.edu. https://doi.org/10.1523/JNEUROSCI.0816-21.2022 Copyright © 2022 the authors
Publisher Copyright:
Copyright © 2022 the authors
PY - 2022/6/15
Y1 - 2022/6/15
N2 - 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.
AB - 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.
KW - attentional set-shifting
KW - frontrostriatal circuits
KW - resting state networks
KW - rhesus monkey
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U2 - 10.1523/JNEUROSCI.0816-21.2022
DO - 10.1523/JNEUROSCI.0816-21.2022
M3 - Article
C2 - 35552233
AN - SCOPUS:85132452067
SN - 0270-6474
VL - 42
SP - 4867
EP - 4878
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 24
ER -