title: Elevated functional connectivity along a corticostriatal loop and the mechanism of auditory/verbal hallucinations in patients with schizophrenia.
abstract: BACKGROUND
  Higher levels of inter-region functional coordination can facilitate emergence of neural activity as conscious percepts. We consequently tested the hypothesis that auditory/verbal hallucinations (AVHs) arise from elevated functional coordination within a speech processing network.
  
  
  METHODS
  Functional coordination was indexed with functional connectivity (FC) computed from functional magnetic resonance imaging data. Thirty-two patients with schizophrenia reporting AVHs, 24 similarly diagnosed patients without hallucinations, and 23 healthy control subjects were studied. FC was seeded from a bilateral Wernicke's region delineated according to activation detected during AVHs in a prior study.
  
  
  RESULTS
  Wernicke's-seeded FC with Brodmann area 45/46 of the left inferior frontal gyrus (IFG) was significantly greater for hallucinating patients compared with nonhallucinating patients but not compared with healthy control subjects. In contrast, Wernicke's-seeded FC with a large subcortical region that included the thalamus, midbrain, and putamen was significantly greater for the combined patient group compared with healthy control subjects after false discovery rate correction, but not when comparing the two patient groups. Within that subcortical domain, the putamen demonstrated significantly greater FC relative to a secondary left IFG seed region when hallucinators were compared with nonhallucinating patients. A follow-up analysis found that FC summed along a loop linking the Wernicke's and IFG seed regions and the putamen was robustly greater for hallucinating patients compared with nonhallucinating patients and healthy control subjects.
  
  
  CONCLUSIONS
  These findings suggest that higher levels of functional coordination intrinsic to a corticostriatal loop comprise a causal factor leading to AVHs in schizophrenia.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, Yale-New Haven Psychiatric Hospital, 184 Liberty Street LV108, New Haven, CT 06519, USA. ralph.hoffman@yale.edu
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Hoffman
authors.forename: Thomas
authors.initials: T
authors.lastname: Fernandez
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Michelle
authors.initials: M
authors.lastname: Hampson
mesh_terms: D000328:Adult; D000465:Algorithms; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D006212:Hallucinations / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D017072:Neostriatum / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000502:physiology*; D009483:Neuropsychological Tests; D011699:Putamen / Q000473:pathology / Q000503:physiopathology; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012959:Socioeconomic Factors; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D014705:Verbal Behavior / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents