title: The roles of reward, default, and executive control networks in set-shifting impairments in schizophrenia.
abstract: Patients with schizophrenia (SZ) show deficits on tasks of rapid reinforcement learning, like probabilistic reversal learning (PRL), but the neural bases for those impairments are not known. Recent evidence of relatively intact sensitivity to negative outcomes in the ventral striatum (VS) in many SZ patients suggests that PRL deficits may be largely attributable to processes downstream from feedback processing, involving both the activation of executive control task regions and deactivation of default mode network (DMN) components. We analyzed data from 29 chronic SZ patients and 21 matched normal controls (NCs) performing a PRL task in an MRI scanner. Subjects were presented with eight pairs of fractal stimuli, for 50 trials each. For each pair, subjects learned to choose the more frequently-rewarded (better) stimulus. Each time a criterion was reached, the better stimulus became the worse one, and the worse became the better. Responses to feedback events were assessed through whole-brain and regions-of-interest (ROI) analyses in DMN. We also assessed correlations between BOLD signal contrasts and clinical measures in SZs. Relative to NCs, SZ patients showed comparable deactivation of VS in response to negative feedback, but reduced deactivation of DMN components including medial prefrontal cortex (mPFC). The magnitudes of patients' punishment-evoked deactivations in VS and ventromedial PFC correlated significantly with clinical ratings for avolition/anhedonia. These findings suggest that schizophrenia is associated with a reduced ability to deactivate components of default mode networks, following the presentation of informative feedback and that motivational deficits in SZ relate closely to feedback-evoked activity in reward circuit components. These results also confirm a role for ventrolateral and dorsomedial PFC in the execution of response-set shifts.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. jwaltz@mprc.umaryland.edu
authors.forename: James A
authors.initials: JA
authors.lastname: Waltz
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kasanova
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ross
authors.forename: Betty J
authors.initials: BJ
authors.lastname: Salmeron
authors.forename: Robert P
authors.initials: RP
authors.lastname: McMahon
authors.forename: James M
authors.initials: JM
authors.lastname: Gold
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002908:Chronic Disease; D056344:Executive Function; D005246:Feedback; D017709:Fractals; D006801:Humans; D007858:Learning; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011336:Probability; D012565:Schizophrenic Psychology