Computational models of aberrant attribution of salience in schizophrenia and the effects of medication: An event related fMRI study

It has been known for decades that dopamine abnormalities are relevant to the pathophysiology of schizophrenia (mainly psychotic symptoms) and that blocking the dopamine system is associated with improvements in symptoms. How one gets from this neurochemi cal change to the expressed behavior abnormalities (i.e., psychosis, negative symptoms, cognitive deficits) is unclear. The main purpose of this proposal is to use a new computational framework that ties dopamine to reward and to combine it with event-re lated functional Magnetic Resonance Imaging (fMRI) to examine if and how aberrant attribution of salience/reward abnormalities manifest in patients with schizophrenia and how they change with treatment. We will compare drug-free patients with schizophren ia to appropriately matched normal controls to examine how reward learning is impaired in these patients. Further, we will follow these subjects longitudinally, with antipsychotic treatment, to examine how treatment alters symptoms and reward learning. T he study will use event-related fMRI with learning paradigms based on classical Pavlovian conditioning. Data from our team confirm the feasibility of this method. To study the effect of illness distinct from antipsychotics, drug-free first-episode patient s will be examined prior to beginning with antipsychotic treatment. These patients will then be treated with antipsychotics in a standardized fashion and after eight weeks of treatment patients will be tested again to examine how treatment has modified sy mptoms and reward signaling. Appropriately matched healthy control will also be included in the study. The study is based on a collaboration between the TOP study group in Oslo, and Prof. Shitij Kapur and the Brain Imaging Group at CAMH, Toronto, Canada.