Evidence of reward system dysfunction in youth at clinical high-risk for psychosis from two event-related fMRI paradigms

Zachary B. Millman, Keith Gallagher, Caroline Demro, Jason Schiffman, Gloria M. Reeves, James M. Gold, Pamela J. Rakhshan Rouhakhtar, John Fitzgerald, Nicole D. Andorko, Samantha Redman, Robert W. Buchanan, Laura M. Rowland, James A. Waltz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Abnormal reward processing is thought to play an important role in the development of psychosis, but relatively few studies have examined reward prediction errors, reinforcement learning (RL), and the reward circuitry that subserves these interconnected processes among individuals at clinical high-risk (CHR) for the disorder. Here, we present behavioral and functional neuroimaging results of two experimental tasks designed to measure overlapping aspects of reward processing among individuals at CHR (n = 22) and healthy controls (n = 19). We found no group differences in response times to positive, negative, or neutral outcome-signaling cues, and no significant differences in brain activation during reward anticipation or receipt. Youth at CHR, however, displayed clear RL impairments, as well as attenuated responses to rewards and blunted prediction error signals in the ventral striatum, dorsal anterior cingulate cortex (dACC), and ventromedial prefrontal cortex (vmPFC). Greater contrasts for cue valence (gain-loss) and outcome magnitude (large-small) in the vmPFC were associated with more severe negative symptoms, and deficits in dACC signaling during RL were associated with more depressive symptoms. Our results provide evidence for RL deficits and abnormal prediction error signaling in the brain's reward circuitry among individuals at CHR, while also suggesting that reward motivation may be relatively preserved at this stage in development. Longitudinal studies, medication-free participants, and comparison of neurobehavioral measures against both healthy and clinical controls are needed to better understand the role of reward system abnormalities in the development of psychosis.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalSchizophrenia Research
StatePublished - Dec 2020

Bibliographical note

Funding Information:
This work was funded by a grant from the Betty Huse Foundation (to J. Waltz), and by the National Institute of Mental Health (NIMH) Grants R01-MH112612 and R34-MH110506 , and the Maryland Department of Health and Mental Hygiene , Behavioral Health Administration through the Center for Excellence on Early Intervention for Serious Mental Illness (OPASS# 14-13717G/M00B4400241 ).

Publisher Copyright:
© 2019 Elsevier B.V.


  • Clinical high-risk
  • fMRI
  • Prediction error
  • Psychosis
  • Reinforcement learning
  • Reward processing


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