Ho Il Park, Boung Chul Lee, Jae-Jin Kim, Joong Il Kim and Min-Seung Koo
Journal of Neuroscience 10 March 2017, 2524-16; DOI: https://doi.org/10.1523/JNEUROSCI.2524-16.2017
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 a functional MRI 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 to 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 depression. Patients with depression showed deficient medial orbitofrontal-striatal functional connectivity compared to healthy controls and patients with schizophrenia. These results indicate that amotivations in depression and schizophrenia involve different pathophysiology in the prefrontal-striatal circuitry.