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Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear.

ABSTRACT: Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here, we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented rats from learning to avoid a lever that was punished with a stimulus that coterminated with footshock. Our second experiment demonstrated that retrieval of punishment learning is also somewhat mOFC-dependent, as lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent rats from reacquiring the ability to avoid a punished lever when it was learned prior to lesions being administered. In both experiments, Pavlovian fear conditioning to the stimulus was intact for all animals. Together, these results reveal that the mOFC regulates punishment learning and retrieval in a manner that is separate from any role in Pavlovian fear conditioning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.

SUBMITTER: Ma C

PROVIDER: S-EPMC8152850 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Previous literature suggests that a balance between Pavlovian and instrumental decision-making systems is critical for optimal decision-making. Pavlovian bias (i.e., approach toward reward-predictive stimuli and avoid punishment-predictive stimuli) often contrasts with the instrumental response. Although recent neuroimaging studies have identified brain regions that may be related to Pavlovian bias, including the dorsolateral prefrontal cortex (dlPFC), it is unclear whether a causal relationship exists. Therefore, we investigated whether upregulation of the dlPFC using transcranial current direct stimulation (tDCS) would reduce Pavlovian bias. In this double-blind study, participants were assigned to the anodal or the sham group; they received stimulation over the right dlPFC for 3 successive days. On the last day, participants performed a reinforcement learning task known as the orthogonalized go/no-go task; this was used to assess each participant's degree of Pavlovian bias in reward and punishment domains. We used computational modeling and hierarchical Bayesian analysis to estimate model parameters reflecting latent cognitive processes, including Pavlovian bias, go bias, and choice randomness. Several computational models were compared; the model with separate Pavlovian bias parameters for reward and punishment domains demonstrated the best model fit. When using a behavioral index of Pavlovian bias, the anodal group showed significantly lower Pavlovian bias in the punishment domain, but not in the reward domain, compared with the sham group. In addition, computational modeling showed that Pavlovian bias parameter in the punishment domain was lower in the anodal group than in the sham group, which is consistent with the behavioral findings. The anodal group also showed a lower go bias and choice randomness, compared with the sham group. These findings suggest that anodal tDCS may lead to behavioral suppression or change in Pavlovian bias in the punishment domain, which will help to improve comprehension of the causal neural mechanism.

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Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear.

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