Hippocampal Memory Circuits in Delusions

This study will investigate dentate gyrus (DG) and hippocampal CA3 sub field function, using the pattern separation paradigm, as reflected by the difference in brain activation in response to same-as-previously- seen (OLD) vs. similar-to-previously-seen (SIM) objects in first episode psychosis (FEP) subjects before and after anti psychotic treatment and in matched healthy controls (HC). The current study uses three novel high-resolution task-based and post-encoding resting fMRI measures to probe hippocampal circuitry in delusions. It will also study CA1 function, using a sequential associative mismatch paradigm, as reflected by activation of CA1 in response to mismatching information compared to memory of that stimulus in FEP subjects before and after antipsychotic treatment and in matched HC. Finally, this study will evaluate plasticity of hippocampal intrinsic functional connectivity (IFC) in response to memory consolidation, using an encoding-plasticity paradigm, in FEP subjects before and after anti psychotic treatment and in matched HC. For each of the three imaging projects, a total of 50 FEP subjects and 50 matched healthy controls (HC) will be studied; hence, 300 subjects will be studied over 5 years. Within each paradigm, medication-naive FEP subjects will be studied at baseline and 8 weeks after starting anti psychotic medication. HC participants will be studied at baseline and 8 weeks later but will not receive any treatment.