title: Exploring the neural correlates of delusions of reference.
abstract: BACKGROUND
  Referential delusions are the most common symptom of schizophrenia and offer an opportunity to examine the neural correlates of delusions because they occur in discrete episodes that can be studied in the scanner. The cortical midline structures (CMS) and subcortical regions, including the amygdala and striatum, are linked with self-reference in healthy adults. Less is known about the neural substrates of altered self-reference in schizophrenia.
  
  
  METHODS
  In this study, patients with schizophrenia experiencing prominent referential delusions (n = 18) and healthy control subjects (n = 17) were presented with ambiguous sentences while in the magnetic resonance imaging scanner and asked to rate whether they felt the sentences had been written specifically about them. The sentences were either generic (nonpersonalized) or individually tailored personalized sentences, designed to induce referential ideation. We hypothesized that both groups would show activity in the CMS, limbic, and striatal regions and that induced referential ideation would be associated with greater activity in striatal areas in patients with schizophrenia.
  
  
  RESULTS
  A robust main effect of endorsement (endorsed vs. nonendorsed) was observed in the CMS, as well as subcortical regions, including the nucleus accumbens/ventral striatum, amygdala, insula, and midbrain dopamine regions. A group-by-endorsement interaction was seen in the medial prefrontal cortex, insula and nucleus accumbens/ventral striatum. Activity in insula and ventral striatum also correlated with the strength of the delusions of reference.
  
  
  CONCLUSIONS
  Referential ideation in persons with delusions is associated with heightened CMS, limbic and striatal activity and reduced differentiation between self- and non-self-relevant information.
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Menon
authors.forename: Taylor W
authors.initials: TW
authors.lastname: Schmitz
authors.forename: Adam K
authors.initials: AK
authors.lastname: Anderson
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff
authors.forename: Michele
authors.initials: M
authors.lastname: Korostil
authors.forename: David
authors.initials: D
authors.lastname: Mamo
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.forename: Jean
authors.initials: J
authors.lastname: Addington
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D003702:Delusions / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007389:Internal-External Control; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012559:Schizophrenia / Q000150:complications* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012649:Self Concept; D012938:Social Perception