Published June 13, 2024 | Version v1
Journal article Open

Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia

Description

Beliefs—attitudes toward some state of the environment—guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14). Computational analyses indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models, these results have implications for understanding paranoia.

Data availability

Monkey behavioral data presented in this paper will be available upon request. Human behavioral data from the single-reversal PRL task and the multi-reversal with contingency shift PRL task data are publically available. The analysis scripts for this paper can be found at https://github.com/psuthaharan/belief-update-monkeys.

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Additional details

Identifiers

DOI
10.1016/j.celrep.2024.114355
Other
oai:uchicago.tind.io:12735

Funding

NIMH
R01MH12887
NIMH
R21MH120799-01
NIMH
R01MH128190
NIMH
R01MH120081

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Anesthesia and Critical Care