title: Contribution of substantia nigra glutamate to prediction error signals in schizophrenia: a combined magnetic resonance spectroscopy/functional imaging study.
abstract: BACKGROUND
  Because dopamine neurons signal a mismatch between expected and actual reward called prediction error (PE), aberrant PE signals in schizophrenia have been attributed to known dopaminergic abnormalities. However, dysfunction ofN-methyl-D-aspartate receptors on cortical γ-aminobutyric acid neurons, as hypothesized in schizophrenia, could lead to excess glutamate release in the substantia nigra (SN) and affect reward processing.
  
  
  OBJECTIVE
  The aim of this study was to investigate the contribution of SN glutamate to PE signals in healthy controls (HC) and patients with schizophrenia (SZ).
  
  
  METHODS
  We recruited 22 medicated SZ and 19 HC. We obtained (1) functional magnetic resonance imaging during a probabilistic monetary reward task to assess PE-related blood oxygen level-dependent (BOLD) signal and (2) magnetic resonance spectroscopy to measure Glx (glutamate+glutamine) in the SN. To identify group differences in regions where the BOLD signal varies as a function of PE, we analyzed PEs generated during the task as parametric modulators of reward delivery. Finally, we examined the correlation of PE-related BOLD signal and SN Glx in each group.
  
  
  RESULTS
  Relative to HC, PE-related BOLD signals in SZ were significantly different in the midbrain/SN and ventral striatum. In SZ, SN Glx was significantly elevated. In HC, but not in SZ, PE-related BOLD signal in SN was positively correlated with SN Glx.
  
  
  CONCLUSIONS
  These results suggest a role of glutamate in the neural coding of PE in controls. They indicate that glutamatergic dysfunction might contribute to abnormal PE coding in schizophrenia, suggesting the use of glutamate-targeted approaches to improve these deficits.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: White
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Nina V
authors.initials: NV
authors.lastname: Kraguljac
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, USA.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Reid
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Lahti