Erin C Dowd1, Michael J Frank2, Anne Collins3, James M Gold4, Deanna M Barch5. 1. Division of Biology and Biomedical Sciences, Neuroscience Program, Washington University in St. Louis. 2. Department of Psychology, Brown University. 3. Department of Psychology, University of California at Berkeley. 4. Department of Psychiatry, Maryland Psychiatric Research Center. 5. Departments of Psychological & Brain Sciences, Psychiatry, and Radiology, Washington University in St. Louis.
Abstract
BACKGROUND: 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 examined whether alterations in reinforcement learning may contribute to these symptoms in schizophrenia by impairing the translation of reward information into goal-directed action. METHODS: 38 stable outpatients with schizophrenia or schizoaffective disorder and 37 healthy controls underwent fMRI during a probabilistic stimulus selection reinforcement learning task with dissociated choice- and feedback-related activation, followed by a behavioral transfer task allowing separate assessment of learning from positive versus negative outcomes. A Q-learning algorithm was used to examine functional activation relating to prediction error at the time of feedback and to expected value at the time of choice. RESULTS: Behavioral results suggested a reduction in learning from positive feedback in patients; however, this reduction was unrelated to anhedonia/avolition severity. On fMRI analysis, prediction error-related activation at the time of feedback was highly similar between patients and controls. During early learning, patients activated regions in the cognitive control network to a lesser extent than controls. Correlation analyses revealed reduced responses to positive feedback in dorsolateral prefrontal cortex and caudate among those patients higher in anhedonia/avolition. CONCLUSIONS: Together, these results suggest that anhedonia/avolition are as strongly related to cortical learning or higher-level processes involved in goal-directed behavior such as effort computation and planning as to striatally mediated learning mechanisms.
BACKGROUND: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 examined whether alterations in reinforcement learning may contribute to these symptoms in schizophrenia by impairing the translation of reward information into goal-directed action. METHODS: 38 stable outpatients with schizophrenia or schizoaffective disorder and 37 healthy controls underwent fMRI during a probabilistic stimulus selection reinforcement learning task with dissociated choice- and feedback-related activation, followed by a behavioral transfer task allowing separate assessment of learning from positive versus negative outcomes. A Q-learning algorithm was used to examine functional activation relating to prediction error at the time of feedback and to expected value at the time of choice. RESULTS: Behavioral results suggested a reduction in learning from positive feedback in patients; however, this reduction was unrelated to anhedonia/avolition severity. On fMRI analysis, prediction error-related activation at the time of feedback was highly similar between patients and controls. During early learning, patients activated regions in the cognitive control network to a lesser extent than controls. Correlation analyses revealed reduced responses to positive feedback in dorsolateral prefrontal cortex and caudate among those patients higher in anhedonia/avolition. CONCLUSIONS: Together, these results suggest that anhedonia/avolition are as strongly related to cortical learning or higher-level processes involved in goal-directed behavior such as effort computation and planning as to striatally mediated learning mechanisms.
Authors: Thomas W Weickert; Alejandro Terrazas; Llewellyn B Bigelow; James D Malley; Thomas Hyde; Michael F Egan; Daniel R Weinberger; Terry E Goldberg Journal: Learn Mem Date: 2002 Nov-Dec Impact factor: 2.460
Authors: Thomas W Weickert; Terry E Goldberg; Michael F Egan; Jose A Apud; Martijn Meeter; Catherine E Myers; Mark A Gluck; Daniel R Weinberger Journal: Biol Psychiatry Date: 2010-02-20 Impact factor: 13.382
Authors: Victoria B Gradin; Poornima Kumar; Gordon Waiter; Trevor Ahearn; Catriona Stickle; Marteen Milders; Ian Reid; Jeremy Hall; J Douglas Steele Journal: Brain Date: 2011-04-10 Impact factor: 13.501
Authors: Richard J Beninger; James Wasserman; Katherine Zanibbi; Danielle Charbonneau; Jennifer Mangels; Bruce V Beninger Journal: Schizophr Res Date: 2003-06-01 Impact factor: 4.939
Authors: Florian Schlagenhauf; Quentin J M Huys; Lorenz Deserno; Michael A Rapp; Anne Beck; Hans-Joachim Heinze; Ray Dolan; Andreas Heinz Journal: Neuroimage Date: 2013-11-27 Impact factor: 6.556
Authors: Matthias N Hartmann-Riemer; Steffen Aschenbrenner; Magdalena Bossert; Celina Westermann; Erich Seifritz; Philippe N Tobler; Matthias Weisbrod; Stefan Kaiser Journal: Sci Rep Date: 2017-01-10 Impact factor: 4.379
Authors: Henry W Chase; Polina Loriemi; Tobias Wensing; Simon B Eickhoff; Thomas Nickl-Jockschat Journal: Hum Brain Mapp Date: 2018-03-24 Impact factor: 5.038
Authors: John H Krystal; John D Murray; Adam M Chekroud; Philip R Corlett; Genevieve Yang; Xiao-Jing Wang; Alan Anticevic Journal: Schizophr Bull Date: 2017-05-01 Impact factor: 9.306
Authors: Anne G E Collins; Matthew A Albrecht; James A Waltz; James M Gold; Michael J Frank Journal: Biol Psychiatry Date: 2017-05-31 Impact factor: 13.382
Authors: Dennis Hernaus; Michael J Frank; Elliot C Brown; Jaime K Brown; James M Gold; James A Waltz Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2018-12-07