title: Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations.
abstract: BACKGROUND
  Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS).
  
  
  METHODS
  Schizophrenia patients with (AH; n=12) and without hallucinations (NH; n=8) and healthy controls (HC; n=11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyri were defined anatomically.
  
  
  RESULTS
  The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4±6.1 mm (range: 2.7-36.1 mm) for Broca's area and 16.8±6.2 mm (range: 4.5-26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p=0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p=0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p=0.03) and negative (p=0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p=0.008).
  
  
  CONCLUSIONS
  This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci.
authors.affiliation: Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Homan
authors.affiliation: Unit for Magnetic Resonance Spectroscopy and Methodology, Department of Clinical Research and Institute of Diagnostic, Interventional and Pediatric Radiology, University of Bern, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Vermathen
authors.affiliation: Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Van Swam
authors.affiliation: Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Federspiel
authors.affiliation: Unit for Magnetic Resonance Spectroscopy and Methodology, Department of Clinical Research and Institute of Diagnostic, Interventional and Pediatric Radiology, University of Bern, Switzerland.
authors.forename: Chris
authors.initials: C
authors.lastname: Boesch
authors.affiliation: University Hospital of Psychiatry, University of Bern, Switzerland.
authors.forename: Werner
authors.initials: W
authors.lastname: Strik
authors.affiliation: Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Switzerland. Electronic address: dierks@puk.unibe.ch.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dierks
authors.affiliation: Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hubl
authors.affiliation: Unit for Magnetic Resonance Spectroscopy and Methodology, Department of Clinical Research and Institute of Diagnostic, Interventional and Pediatric Radiology, University of Bern, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Kreis
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods; D065711:Broca Area / Q000503:physiopathology*; D005260:Female; D006212:Hallucinations / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007802:Language; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D009415:Nerve Net / Q000503:physiopathology*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D012559:Schizophrenia / Q000150:complications / Q000503:physiopathology*; D065813:Wernicke Area / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: Auditory hallucinations; Language; Magnetic resonance spectroscopy; Myo-inositol; N-acetyl-aspartate; Schizophrenia