Background: Working memory (WM) deficits are well known in schizophrenia and have been associated with abnormal activation patterns of the prefrontal cortex (PFC) during cognitive performance. The magnitude and particularly the direction of the PFC activation -- i.e., increased (hyperfrontality) or decreased (hypofrontality) -- in schizophrenia, as well as its pathophysiological implications, remain controversial. Working memory is supported by a distributed neural network, whose main components are the PFC and the posterior parietal (PPC) cortices. Monkey studies indicate that, during WM performance, PFC functional lesions may be compensated by the PPC if task demands center mainly on anticipating responses, but not if they center on remembering cues. We hypothesized that a primarily dysfunctional PFC in schizophrenia might show hypofrontality or hyperfrontality as a result, respectively, of efficient or inefficient PPC compensation, as dictated by task demands. To test our proposition, we biased the demands of WM tasks toward anticipating responses or remembering cues and measured its impact on the PFC-PPC functional balance in a group of schizophrenic patients and one of normal control subjects.
Methods: We used functional magnetic resonance imaging to measure correlates of neuronal activity in the PFC and PPC of schizophrenic patients and control subjects performing WM tasks that either demanded information retention or allowed for response anticipation.
Results: When compared to control subjects, schizophrenic patients exhibited decreased PFC activation and increased PPC activation during anticipatory WM performance, and increased PFC activation during mnemonic WM performance.
Conclusions: In schizophrenia, a PFC dysfunction results in hypo- or hyperfrontality as a function of whether other alternate areas of a PFC-PPC network for WM are available and efficacious in supporting specific task demands.