Functional hypofrontality and working memory dysfunction in schizophrenia.
OBJECTIVE
Hypofrontality is a common but not invariable finding in schizophrenia. Inconsistencies in the literature may reflect, in part, the fact that abnormal physiological responses in the prefrontal cortex are best identified under conditions that place well-specified functional demands on this region.


METHODS
The authors studied eight patients with schizophrenia and eight matched comparison subjects using [(15)O]H2O positron emission tomography and the "N-back" task, which activates the prefrontal cortex as a function of working memory load in normal subjects.


RESULTS
Under low-working-memory-load conditions, the accuracy of both groups in the N-back task was equal, but when the memory load increased, the patients' performance deteriorated more than did that of the comparison subjects. The regional cerebral blood flow response to increased working memory load was significantly reduced in the patients' right dorsolateral prefrontal cortex.


CONCLUSIONS
These results confirm the importance of using tasks that tap specific cognitive functions, linked to specific neural systems, in studies of brain-behavior relationships in schizophrenia. Hypofrontality is reliably demonstrated in schizophrenia during tasks that engage working memory functions of the prefrontal cortex.
Carter
C S
CS
Department of Psychiatry, University of Pittsburgh, Western Psychiatric Institute and Clinic, PA 15213, USA. cscarter+@pitt.edu
Perlstein
W
W
Ganguli
R
R
Brar
J
J
Mintun
M
M
Cohen
J D
JD
D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008568:Memory / Q000502:physiology*; D010104:Oxygen Radioisotopes; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D012039:Regional Blood Flow; D012559:Schizophrenia / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology; D012565:Schizophrenic Psychology; D014055:Tomography, Emission-Computed; D014867:Water
D010104:Oxygen Radioisotopes; D014867:Water