FMRI measurements of prediction error and MRS measurements of midbrain glutamte in schizophrenia and healthy controls

Abstract

22 stable, medicated SZ and 19 matched HC completed a probabilistic monetary reward task, modeled after Rolls, McCabe, Redoute4. In this study we performed a magnetic resonance spectroscopy (MRS) study of the SN and a functional MRI (fMRI) study during performance of a PE task in patients with schizophrenia (SZ) and controls (HC). We hypothesized that in SZ (1) an abnormal relationship exists between blood-oxygen-level dependent (BOLD) signal during PE in the SN and ventral striatum, (2) glutamate + glutamine (Glx) levels are elevated in the SN, and (3) the relationship between PE and Glx is different between SZ and HC. It has been proposed that in schizophrenia hypofunction of N-methyl-D-aspartate (NMDA) receptors on γ-aminobutyric acid (GABA) inhibitory neurons could lead to excess glutamate (Glu) release. Because the substantia nigra (SN) receives Glu projections from cortical areas, increased cortical Glu transmission could therefore affect the SN and lead to altered dopaminergic (DA) transmission – a phenomenon well documented in schizophrenia1. Reward learning tasks are known to modulate the DA system2. Reward prediction errors (PE) occur when reward outcomes differ from what is predicted and DA neurons change their firing rates in response to reward PE3. INTRODUCTION