fMRI Investigation of Active Maintenance in Schizophrenia

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DESCRIPTION (provided by applicant): A distinguishing feature of human behavior is our ability to titrate our responses to stimuli and events with reference to contextual and contingent information. Thus, we are freed from simple reflexes and the idiosyncrasies of our immediate environment. The dorsalateral prefrontal (DLPFC), owing to its abundant connections with cortical sensory areas, is uniquely situated, to facilitate cognitive control over sensory inputs and higher order processing of these inputs. Human and animal studies have demonstrated the crucial involvement of the DLPFC in cognitive control. However, the specific mechanism by which cognitive control is exerted, remains to be elucidated. The emergence of powerful neuroimaging techniques have led to new insights into the functional architecture of the DLPFC, building on and complementing results obtained from animal, as well as, human studies using other techniques. The study of DLPFC function and its modulation of "bottom up" processes has profound clinical implications. The dysfunction of the DLPFC can lead to devastating conditions, as documented by lesion patients. The pathophysiology of schizophrenia likely involves many brain regions and cognitive processes. However, several lines of evidence point to the centrality of of the DLPFC dysfunction in the elaboration of many of its symptoms. Analogous to the discovery of schizophrenia genes, the mapping of the neural correlates of altered cognitive processes in schizophrenia is an important first step in the process of discovering new treatments for this illness. I propose a parallel series of studies, first, in healthy adults, to elucidate the precise neural mechanisms involved in DLPFC modulation of sensory inputs in the service of higher order cognitive processes. I will then study these processes in a group of schizophrenics to document dysfunction of the DLPFC. I plan to conduct these studies employing sophisticated neuroimaging and analytical techniques to examine the dynamic interactions of the DLPFC with the visual system.