Neural correlates of executive dysfunction in schizophrenia: failure to modulate brain activity with task demands

In schizophrenia, executive functions are impaired and are associated with altered activation of prefrontal areas. We used H2[15]O PET to examine patients with schizophrenia and matched controls on a random number generation (RNG) task and a control counting (COUNT) task. To assess the effects of increasing task demand, both tasks were performed at three different rates (intervals 1, 2 or 3 s). Both groups showed a significant increase in the nonrandomness of responses at faster rates of RNG. Despite similar performances, patients but not controls showed higher activation of the right dorsolateral prefrontal cortex (DLPFC) and atypically reduced activation of the right anterior cingulate gyrus and the right medial frontal gyrus in RNG compared with COUNT, whereas only for controls, activation of the left DLPFC was increased and activation of the right superior temporal gyrus and the right superior frontal gyrus was reduced in the same comparison. Whereas for the controls several cortical areas including the bilateral superior temporal gyrus and the bilateral DLPFC, together with the right cerebellum, showed significant changes in regional cerebral blood flow with faster or slower rates, patients with schizophrenia showed rate-dependent changes only in the left cerebellum. In conclusion, the patients' failure to modulate cortical activation with changing demands of rate, particularly in prefrontal areas and in the cerebellum, and even when performance is similar to that in healthy controls, is a characteristic of their abnormal pattern of executive processing.