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

Cell Reports (Jun 2024)

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

Affiliations

Praveen Suthaharan: 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
Summer L. Thompson: Department of Psychiatry, Yale University, New Haven, CT, USA
Rosa A. Rossi-Goldthorpe: Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA
Peter H. Rudebeck: Icahn School of Medicine at Mount Sinai, New York, NY, USA
Mark E. Walton: Department of Experimental Psychology, Oxford University, Oxford, UK
Subhojit Chakraborty: 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
Maryann P. Noonan: Department of Experimental Psychology, Oxford University, Oxford, UK; Department of Psychology, University of York, York, UK
Vincent D. Costa: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA
Elisabeth A. Murray: Laboratory of Neuropsychology, NIMH, Bethesda, MD, USA
Christoph D. Mathys: Interacting Minds Centre, Aarhus University, Aarhus, Denmark; Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland
Stephanie M. Groman: 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
Anna S. Mitchell: Department of Experimental Psychology, Oxford University, Oxford, UK; School of Psychology, Speech, and Hearing, University of Canterbury, Christchurch, New Zealand
Jane R. Taylor: 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
Philip R. Corlett: 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; Corresponding author
Steve W.C. Chang: 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; Corresponding author

Journal volume & issue: Vol. 43, no. 6
p. 114355

Abstract

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Summary: 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.

CP: Neuroscience

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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