title: Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging.
abstract: BACKGROUND
  Functional neuroimaging experiments have implicated prefrontal cortex (PFC) in memory processes. Several studies of schizophrenic patients have shown failure of activation in the dorsolateral region of PFC (DLPFC). We used a graded memory challenge to characterize functional neuroanatomical differences between schizophrenic and control subjects. The graded manipulation of task demands enabled us to assess group differences in the context of normal and abnormal psychological task performance.
  
  
  METHODS
  Memory-related activity was assessed using positron emission tomography in schizophrenic patients and age-matched controls during performance of a graded memory task. Subjects underwent scanning while learning and recalling word lists of variable length.
  
  
  RESULTS
  We used a model that assessed linear and nonlinear effects of memory load. Nonlinear group differences in DLPFC activation were observed. Controls showed a steepening slope of DLPFC increase as task demands increased. By contrast, schizophrenic subjects showed initial DLPFC increases that fell away with increasing memory load. The DLPFC response in schizophrenic subjects was closely related to measured task performance. In addition, schizophrenic subjects failed to show task-related decreases in activity in the left superior temporal and inferior parietal gyrus.
  
  
  CONCLUSIONS
  Patients with schizophrenia showed a failure in DLPFC activation only in the face of diminished performance measures, suggesting that a full characterization of task-related changes in DLPFC activation must consider performance levels. However, striking failures of deactivation in superior temporal and inferior parietal regions were independent of task performance, possibly reflecting a core abnormality of the condition.
authors.affiliation: Wellcome Department of Cognitive Neurology, Institute of Neurology, London, England.
authors.forename: P C
authors.initials: PC
authors.lastname: Fletcher
authors.forename: P J
authors.initials: PJ
authors.lastname: McKenna
authors.forename: C D
authors.initials: CD
authors.lastname: Frith
authors.forename: P M
authors.initials: PM
authors.lastname: Grasby
authors.forename: K J
authors.initials: KJ
authors.lastname: Friston
authors.forename: R J
authors.initials: RJ
authors.lastname: Dolan
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000502:physiology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology; D012559:Schizophrenia / Q000175:diagnosis* / Q000503:physiopathology; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000502:physiology; D014055:Tomography, Emission-Computed; D014705:Verbal Behavior / Q000502:physiology; D014888:Wechsler Scales / Q000706:statistics & numerical data