DESCRIPTION (provided by applicant): This proposal is for a K23 Mentored Patient Oriented Research Career Development Award that will prepare the candidate for a successful independent career in translational neurocognitive research. The candidate and his mentors at UT Southwestern Medical Center (UTSW) and Columbia University/New York State Psychiatric Institute (CU/NYSPI) designed a Staged Mentored and Arranged Transition (SMART) career development pathway to enable him to become a proficient, independent investigator working at the intersection of neurocognitive function, mood disorders, and neurostimulation interventions. This unique research niche will allow the candidate to leverage the expertise of his preceptors while establishing his individual identity as an independent investigator. The SMART pathway forms a collaborative network of expert mentors and advisors (Drs. Mustafa M. Husain, Sarah H. Lisanby, C. Munro Cullum, Herb Terrace, Ira Bernstein, George Alexopoulos, and Harold A. Pincus). The career development plan is comprised of scholarly didactics and seminars, expert preceptorship, hands-on experience at UTSW and CU/NYSPI, as well as tangible productivity including peer-reviewed manuscripts and grant applications. Unique to the candidate's career path is the pre- planned shift in primary appointment from UTSW to CU/NYSPI during this award period. This will facilitate his transitional goals as well as smooth his transition to independent status. The goal of his research project is to develop and conduct Translational Research Evaluating Neurocognitive Memory Processes (TREC-MP). The use of model animals to study neurocognitive functions has been employed extensively in basic science methodologies. However, the resulting applications for clinical human use have been limited. TREC-MP is a translational project that examines the psychometric properties in humans of experimental computerized neurocognitive measures developed for nonhuman primates undergoing electroconvulsive shock and magnetic seizure therapy. This incremental research study is designed to optimize the experimental neurocognitive battery in a healthy human cohort, then to determine the effects of depression on test performance, and finally to determine the neurocognitive performance of depressed subjects undergoing electroconvulsive therapy (ECT). The cognitive impact of ECT is well recognized and of considerable clinical significance, but what is less well understood is the complex interaction between depression and ECT on cognitive component processes. As such, newer methods of cognitive assessment are needed to elucidate similar and divergent cognitive processes across species, and identify underlying cognitive component processes of memory impairment in patients receiving ECT. As exemplified in recent NIMH translational neurocognitive research and clinical initiatives, one useful strategy would be the development of comparative nonhuman primate and human neurocognitive measures for specific neurocognitive domains and component processes. The application of a specific neurocognitive battery, predicated on basic science neurocognitive research with nonhuman primates provides a powerful method for understanding the cognitive component processes of memory deficits, thereby permitting the future development of targeted treatment interventions and useful clinical neurocognitive measures. [The aims of this project are: 1) Develop and validate experimental neurocognitive measures for use with healthy human participants, 2) Determine effects of depression on performance on experimental neurocognitive measures, and 3) Determine effects of ECT on performance on experimental neurocognitive measures.] Analyses will be conducted with both classical test and item response theory statistics. This project is scientifically innovative and important because it will provide a platform for the candidate to conduct translational neurocognitive research to help him understand the etiology of memory impairment and ultimately design appropriate clinical neurocognitive measures and interventions. The candidate's SMART pathway and TREC-MP project set the stage for his individualized and systematic development as an independent translational neurocognitive scientist.

Project Narrative Impaired cognitive functions associated with psychiatric treatments of severe depression contribute to poor functional outcomes. The objective of this career development award is for the candidate to become a proficient translational neurocognitive scientist. The long-term goal is for this translational neurocognitive research to provide a clearer understanding of the cognitive component processes that underscore cognitive functional impairments in order to develop psychometrically sound neurocognitive outcome measures and targeted treatment interventions.