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

Praveen Suthaharan; Summer L Thompson; Rosa A Rossi-Goldthorpe; Peter H Rudebeck; Mark E Walton; Subhojit Chakraborty; Maryann P Noonan; Vincent D Costa; Elisabeth A Murray; Christoph D Mathys; Stephanie M Groman; Anna S Mitchell; Jane R Taylor; Philip R Corlett; Steve W C Chang

doi:10.1016/j.celrep.2024.114355

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

Cell Rep. 2024 Jun 25;43(6):114355. doi: 10.1016/j.celrep.2024.114355. Epub 2024 Jun 13.

Authors

Affiliations

¹ Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA; Kavli Institute for Neuroscience, Yale University, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA.
² Department of Psychiatry, Yale University, New Haven, CT, USA.
³ Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA.
⁴ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ Department of Experimental Psychology, Oxford University, Oxford, UK.
⁶ Department of Experimental Psychology, Oxford University, Oxford, UK; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 9EL, UK.
⁷ Department of Experimental Psychology, Oxford University, Oxford, UK; Department of Psychology, University of York, York, UK.
⁸ Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
⁹ Laboratory of Neuropsychology, NIMH, Bethesda, MD, USA.
¹⁰ Interacting Minds Centre, Aarhus University, Aarhus, Denmark; Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland.
¹¹ Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA.
¹² Department of Experimental Psychology, Oxford University, Oxford, UK; School of Psychology, Speech, and Hearing, University of Canterbury, Christchurch, New Zealand.
¹³ Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Psychology, Yale University, New Haven, CT, USA; Wu Tsai Institute, Yale University, New Haven, CT, USA; Department of Neuroscience, Yale University, New Haven, CT, USA.
¹⁴ Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA; Kavli Institute for Neuroscience, Yale University, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Psychology, Yale University, New Haven, CT, USA; Wu Tsai Institute, Yale University, New Haven, CT, USA. Electronic address: philip.corlett@yale.edu.
¹⁵ Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA; Kavli Institute for Neuroscience, Yale University, New Haven, CT, USA; Department of Psychology, Yale University, New Haven, CT, USA; Wu Tsai Institute, Yale University, New Haven, CT, USA; Department of Neuroscience, Yale University, New Haven, CT, USA. Electronic address: steve.chang@yale.edu.

Abstract

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.

Keywords: CP: Neuroscience; belief updating; lesion; mediodorsal thalamus; monkeys; orbitofrontal cortex; paranoia; probabilistic reversal learning task.

MeSH terms

Animals
Culture
Female
Humans
Macaca mulatta
Male
Paranoid Disorders
Prefrontal Cortex* / pathology
Reward
Thalamus / pathology

Abstract

MeSH terms

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