Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Neurosciences

Language

English (en)

Date of Award

Spring 3-10-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Deanna M Barch

Abstract

Anhedonia (a reduced experience of pleasure) and avolition (a reduction in goal-directed activity) are common features of schizophrenia that have substantial effects on functional outcome, but are poorly understood and treated. Here, we examine the potential contributions of three processes involved in the translation of reward information in the environment into goal-directed action among medicated individuals with schizophrenia. The first process, hedonics, or the enjoyment of pleasant experiences, was examined using an fMRI study of emotional experience in response to affective stimuli. Results were similar between patients and controls at a group level, but patients with greater anhedonia/avolition demonstrated reduced self-reports and brain activity in response to positive stimuli in ventral striatum and amygdala, regions associated with salience and reward. The second process we examined was reward prediction, which describes anticipatory responses to cues that predict reward. This process is thought to be mediated by the mesolimbic dopamine system, which shows evidence of dysregulation in schizophrenia. We examined reward prediction using a Pavlovian paradigm with monetary reward, using fMRI to examine brain responses during reward anticipation and receipt. Responses to reward receipt were largely intact in schizophrenia, while anticipation responses in ventral striatum, a major target of dopaminergic afferents, were reduced in those patients who were higher in anhedonia/avolition. The final process we examined was reinforcement learning, or the process by which positive and negative feedback influences trial-and-error choice behavior. Participants underwent fMRI during a reinforcement learning task with probabilistic feedback. Evidence from behavior and computational modeling suggested impairment in learning from positive feedback. However, neuroimaging data revealed largely intact striatal activation during both choice and feedback, a surprising result given the role of dopaminergic influence on corticostriatal circuits in mediating reinforcement learning. Instead, there was some evidence for reduced cortical responses to choice execution among patients, and to positive feedback among those patients higher in anhedonia/avolition. Together, these studies suggest that impairments in hedonics, reward prediction, and reinforcement learning may play a role in anhedonia/avolition in schizophrenia, but that these impairments are not sufficient causes of these symptoms; impairments in other higher-level cognitive processes are also likely to contribute.

DOI

https://doi.org/10.7936/K7MW2F6M

Comments

Permanent URL: http://dx.doi.org/10.7936/K7MW2F6M

Share

COinS