The major goal of this project is to analyze the neurocognitive components of working memory deficits in schizophrenia. The three proposed studies are designed to specify parameters of the prefrontal working memory systems and to characterize their possible links to the expression of the symptoms of schizophrenia. The investigator's global hypothesis is that an inability to regulate behavior by prefrontal working memory systems may demarcate cardinal features of schizophrenia. Growing evidence supports this view but the role of working memory in clinical symptoms is unclear, because of the functional heterogeneity of the frontal lobes, multiplicIty of the working memory systems and diffuse definitions of symptoms. The roles of the dorsolateral prefrontal and ventral/orbitofrontal systems in schizophrenia will be probed, using a series of specific experiments designed to assess dissociation and integration of the multiple working memory systems. Spatial working memory is mediated by a neural circuitry including the dorsolateral prefrontal cortex, whereas visual (nonspatial) and olfactory working memory systems are associated with the integrity of the ventral/orbitofrontal system. There are 3 studies, consisting of 3 experiments each. Study 1 is focused on examining spatial, visual (nonspatial) and olfactory working memory systems separately in schizophrenia patients in order to determine which systems are consistently impaired independent of fluctuating symptoms versus which systems are linked to the symptoms. Young siblings of schizophrenia patients will be tested to see if they show similar patterns of deficit. Study 2 is concerned with determining how these anatomically and psychologically separable working memory systems are dissociated, coordinated or inhibited to guide action by a control mechanism (the """"""""central executive""""""""). In Study 3, the integrity of the connections between orbitofrontal and dorsolateral prefrontal systems will be examined by inspecting the roles of affect, arousal and reward on working memory. Ultimately, all the components of working memory and subdivisions of frontal systems must be integrated in an organism with intact personality and self-regulating behaviors. The key to understanding cognitive deficits and symptoms of schizophrenia may be found in the patterns of dissociation and integration of these multiple systems, in response to specific task demands. In summary, this project will enable the investigator to further identity and elucidate neurocognitive components of schizophrenia and thus contribute towards our understanding of the complex interplay between cortical functions, cognitive deficits and clinical syndromes in men and women with schizophrenia.
