Recent findings from cognitive neuroscience have substantially shaped our understanding of the functional architecture of human cognition and its neural underpinnings. Furthermore, a wide range of new non- invasive behavioral and imaging tools have become available to investigate the neural basis of cognition and its impairment in clinical populations. The most rapid possible progress toward understanding and treating impaired cognition in schizophrenia requires the application of the most current and tools and constructs to this effort. The purpose of this R24 Developmental Translational Center for Integrative Behavioral Science is to build collaborations between some of the world's experts on the neuroscience of attention, memory, language and emotional processing, processes that are impaired in schizophrenia, senior schizophrenia researchers who focus their careers on these problems, and junior investigators and trainees who will benefit greatly from the interdisciplinary training provided by the Center. Over the course of the Award we will develop a Translational Research Center in which both forward and backward translation will occur. The development of a cohesive Center structure to support the design and execution of a set of studies that will test the overarching hypothesis that specific deficits in cognitive control functions normally supported by specific elements of the prefrontal cortex (PFC) are associated with specific deficits in attention, memory, language and emotional processing in schizophrenia. Further, it is predicted that these specific cognitive deficits and associated alterations in prefrontal function are associated with disorganization and negative symptoms, but not positive symptoms. To test this hypothesis we will pursue four Specific Aims, using state of the art behavioral, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) methodologies in a single group of early schizophrenia patients.
These Aims will test four specific hypotheses linked to the overall Center hypothesis. 1) Schizophrenia patients will show a deficit in the cognitive control processes that activate appropriate stimulus-response mappings and suppress competing stimulus-response mappings. 2) Schizophrenia patients will exhibit a specific deficit in dorsolateral PFC dependant cognitive control processes supporting relational processing in working memory and relational encoding into long term memory. 3) Schizophrenia patients have a deficit in the cognitive control processes that suppress contextually inappropriate information during language comprehension. 4) Schizophrenia patients have a specific deficit in maintaining an emotional response following the offset of an emotional stimulus. Successful completion of this work will enable us to develop an interdisciplinary collaborative research group that will generate a series of translational RO1's to conduct innovative translational research focused on understanding cognitive and neural mechanisms underlying impaired cognition in schizophrenia. ? ? ?
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