Our research primarily focuses on neuroimaging in schizophrenia conducted in collaboration with the Nathan Kline Insititute, Brookhaven National Laboratory, and the NYU School of Medicine's Department of Radiology. In previous functional studies of schizophrenia using positron emission tomography (PET), we concentrated on cerebral metabolic patterns of glucose utilization that distinguish schizophrnic patients from normal subjects, and in differentiating schizophrenic subtypes. For example, we and others found a reduction in frontal lobe metabolism in schizophrenia patients as compared to normal subjects and that this pattern of metabolic hypofrontally correlated with the severity of "negative" symptoms. We also utilized PET in clinical pharmacologic studies, in which, for example, we studied the cerebral metabolic response to acute amphetamine challenge and subchronic haleoperidol treatment in schizophrenic patients, as well as characterized dopamine receptor occupancy related to neuroleptic treatment and clinical response.

Our structural studies in schizophrenia derive from a data base of high-resolution 3D TI- and T2- weighted images which we acquired throughtout the entire brain in over 100 schizophrenic patients and normal control subjects. These studies were conducted at the New York Department of Veterans Affairs Medical Center magnetic resonance imaging (MRI) facility. Data analysis included volumetric and alternative analysis, including shape analysis and image averaging (co-registration) techniques. Results suggest two separate pathological processes underlying the pathophysiology of negative symptoms of schizophrenia wherein frontal lobe dysfunction and associated cognitive deficits may derive, in part, from a "dysconnection" of frontal pathways.

In ongoing and future work, we plan to further pursue these questions and hypotheses with functional MRI studies of cognitive processes in negative and non-negative syndrome schizophrenic patients.