Effort-based reinforcement processing and functional connectivity underlying amotivation in medicated patients with depression and schizophrenia

Il Ho Park, Boung Chul Lee, Jae Jin Kim, Joong Il Kim, Min Seung Koo

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41 Citations (Scopus)


Amotivation is a common phenotype of major depressive disorder and schizophrenia, which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted an fMRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value, as well as resting-state functional connectivities within the meso–striatal–prefrontal pathway. We found that integrated reward and effort values of low effort-positive reinforcement and high effort-negative reinforcement were behaviorally anticipated and represented in the putamen and medial orbitofrontal cortex activities. Patients with schizophrenia and depression did not show anticipation-related and work-related reaction time reductions, respectively. Greater amotivation severity correlated with smaller work-related putamen activity changes according to reward type in schizophrenia and effort level in depression. Patients with schizophrenia showed feedback-related putamen hyperactivity of low effort compared with healthy controls and depressed patients. The strength of medial orbitofrontal-striatal functional connectivity predicted work-related reaction time reduction of high effort negative reinforcement in healthy controls and amotivation severity in both patients with schizophrenia and those with depression. Patients with depression showed deficient medial orbitofrontal-striatal functional connectivity compared with healthy controls and patients with schizophrenia. These results indicate that amotivation in depression and schizophrenia involves different pathophysiology in the prefrontal-striatal circuitry.

Original languageEnglish
Pages (from-to)4370-4380
Number of pages11
JournalJournal of Neuroscience
Issue number16
Publication statusPublished - 2017 Apr 19

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Korean government (Ministry of Education, Culture, Sports, Science and Technology Grant NRF-2012R1A1A1010199). We thank Yongtak Jin and Deokman Kim for help with clinical data collection, Ju-Yeol

Publisher Copyright:
Copyright © 2017 the Authors.

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)


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