title: Common and differential pathophysiological features accompany comparable cognitive impairments in medication-free patients with schizophrenia and in healthy aging subjects.
abstract: BACKGROUND
  Dysfunction of the dorsolateral prefrontal cortex (DLPFC) and parahippocampal region along with poor working memory are common neurophysiological and behavioral features associated with schizophrenia and normal aging. It is, however, unknown whether the associated patterns of neural activation differ between these two groups when their cognitive performance is closely matched in a pairwise manner. The authors sought to pinpoint common and differential pathophysiological features that accompany comparable working memory impairments in schizophrenia and healthy aging.
  
  
  METHODS
  Fifty-three subjects were scanned with oxygen-15 water positron emission tomography regional cerebral blood flow measurements during working memory. Seventeen medication-free patients with schizophrenia were individually matched for working memory performance with 17 healthy aging subjects. Brain activation of the two index groups were compared with each other and with 19 young healthy individuals.
  
  
  RESULTS
  Patients with schizophrenia showed right DLPFC hypoactivation, both when compared with age-matched control subjects and after direct comparison with working memory performance-matched elderly subjects. Moreover, both groups with working memory deficits shared an inability to suppress parahippocampal and anterior medial prefrontal cortex activation.
  
  
  CONCLUSIONS
  These results provide new insights into the mechanisms by which impaired working memory performance can arise by showing that both common (parahippocampal/anterior medial PFC) and differential (DLPFC) pathophysiological features accompany similar cognitive impairments. The aging data also demonstrate that poor performance is not necessarily accompanied by the DLPFC hypofunction that was seen in schizophrenia. Finally, these results more closely link the DLPFC functional abnormalities in schizophrenia to the pathophysiology of the disorder rather than to poor performance per se.
authors.affiliation: Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Intramural Research Program, Bethesda, Maryland, USA. dreher@isc.cnrs.fr
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dreher
authors.forename: Paul
authors.initials: P
authors.lastname: Koch
authors.forename: Philip
authors.initials: P
authors.lastname: Kohn
authors.forename: Jose
authors.initials: J
authors.lastname: Apud
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: Karen Faith
authors.initials: KF
authors.lastname: Berman
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000503:physiopathology*