title: Frontal P3 event-related potential is related to brain glutamine/glutamate ratio measured in vivo.
abstract: BACKGROUND
  The auditory P3 event-related potential (ERP) is thought to index cognitive processing relevant to attention and working memory processes. Drug challenge studies suggest that glutamate neurotransmission plays an important role in modulating P3 ERP. However, while direct links between glutamate activity and P3 ERP response in humans are suspected, mechanistic details remain largely unknown. We investigated here the relationships between P3 ERP and indices of glutamatergic processing measured in vivo with proton magnetic resonance spectroscopy ((1)H MRS). We hypothesized that a higher index of glutamatergic processing (glutamine/glutamate ratio; abbreviated Gln/Glu) in the anterior cingulate (ACC) and in the parietal-occipital (POC) cortices would associate with larger frontal P3a and parietal P3b amplitudes, respectively.
  
  
  METHODS
  Frontal P3a (Fz) and parietal P3b (Pz) were collected from 32 healthy participants who performed an auditory oddball task. Resting glutamate (Glu), glutamine (Gln), and Gln/Glu (an index of glutamatergic processing) measures were obtained on a 4T MR scanner using J-resolved MR spectroscopy. Linear regression and partial correlations were used for statistical analysis.
  
  
  RESULTS
  Significant positive correlations were found between frontal P3a amplitude and ACC Gln/Glu ratio (partial R=0.57; P=0.001) and between frontal P3a amplitude and ACC Gln concentration (partial R=0.43; P=0.02). Relationships between parietal P3b and the glutamate indices in the POC were not significant.
  
  
  CONCLUSIONS
  These results indicate a specific connection between an index of glutamate neurotransmitter function in ACC and frontal P3 ERP, providing a novel insight into the neurochemistry underlying scalp recorded EEG response. Abnormalities in glutamate neurotransmission have been observed in schizophrenia and other psychiatric conditions and may underlie illness related deficits of P3 ERP.
authors: Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA 02452, USA; Psychosis Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA 02452, USA. Electronic address: mhall@mclean.harvard.edu.
authors: Mei-Hua
authors: MH
authors: Hall
authors: McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02452, USA.
authors: J Eric
authors: JE
authors: Jensen
authors: Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA 02452, USA; McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02452, USA.
authors: Fei
authors: F
authors: Du
authors: Psychiatric Genetics Program in Mood and Anxiety Disorders, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Jordan W
authors: JW
authors: Smoller
authors: Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA 02452, USA.
authors: Lauren
authors: L
authors: O'Connor
authors: VA Boston Healthcare System and Harvard Medical School, Boston, MA 02130, USA.
authors: Kevin M
authors: KM
authors: Spencer
authors: Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA 02452, USA.
authors: Dost
authors: D
authors: Öngür
mesh_terms: D000328:Adult; D018913:Event-Related Potentials, P300 / Q000502:physiology*; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055815:Young Adult
chemical_list: D005973:Glutamine; D018698:Glutamic Acid
keywords: Event-related potential; Glutamate; Magnetic resonance spectroscopy (MRS); P3