Prefrontal function and schizophrenic symptoms

Neuroimaging and neuropsychological studies suggest that schizophrenia is a brain disease preferentially impairing frontal lobe function. Many of the cognitive and symptomatic abnormalities found in patients with schizophrenia resemble those found in patients with primary frontal lobe disease. Both groups of patients demonstrate abnormalities of behavior regulation that present as deactivation or disinhibition syndromes. Both groups also have striking cognitive deficits that are most apparent on tasks such as the Wisconsin Card Sort (WCS) that involve the switching of set and the integration of feedback in response planning. Regional cerebral blood flow studies demonstrate that patients with schizophrenia fail to normally activate prefrontal cortex during their performance of the WCS, providing convergent validity for the behavioral findings. This failure to activate dorsolateral prefrontal cortex may relate to ventricular enlargement and dopaminergic hypofunction. The latter finding is important because evidence from primate studies indicates that prefrontal cognitive performance is critically dependent upon the mesocortical dopamine system. Moreover, frontal lobe function may relate to limbic and striatal dopamine activity modulation. Thus, frontal dopamine dysfunction provides a model for the positive and negative symptoms of schizophrenia. Cognitive models of executive control processes allow for a differentiated approach to the nature of negative symptoms.