Recent models of depression have outlined a relationship between limbic, emotion processing and salience brain regions in depression, with the hypothesis that fronto-parietal, executive control brain regions are unable to regulate these limbic regions. Yet, despite these theoretical claims, there remains a paucity of cognitive and emotion challenge studies during functional imaging to assess these proposed disrupted emotion-processing and executive-regulatory circuits in depression. Further, complicating depression research is the controversy surrounding the model of depression as unitary or heteromodal entities, with different clinical subtypes. The current proposal contrasts performance and activation during fMRI while subjects complete an emotion processing and an executive functioning task to determine brain circuits involved in these processes. In addition, type and severity of anxiety symptoms is further explored in the proposal using a dimensional approach. The principal investigator (PI), Scott Langenecker, Ph.D., has proposed to carry out this research in the context of continuing education activities directed towards developing expertise in statistical models, functional MRI physics, and depression subtypes. With the assistance of his mentor, Jon-Kar Zubieta, M.D., Ph.D., and his co-mentor, Doug Noll, Ph.D., Dr. Langenecker has assembled a broad range of researchers and statisticians to assist in this endeavor. This K award allows for a change in research direction, from functional imaging work in healthy aging, to address executive functioning and emotion regulation in depression. Expertise is necessary to fully exploit functional MRI to understand the neurophysiology of depression, including cognitive and emotional challenges. Mentorship and collaborative relationships are proposed with a number of exceptional researchers in depression and functional imaging. Short-term goals address expansion of the Pis knowledge base, while completing the proposed study. Long term goals address increasing diagnostic subtyping accuracy and reliability for depression, understanding the relationship between regulatory and experiential aspects of emotion in depression, and using these mechanisms to enhance treatment matching paradigms. Sufficient theoretical background, methodological rigor, and strong preliminary data support the hypotheses and aims of this project. An R01 proposal is planned for the end of year three of the proposed project, as a springboard to the development of the Pis independent research career. The University of Michigan Depression Center provides an outstanding medium for pursuing this study, with an exceptional cohort of depression researchers available to the PI and his assembled team. ? ? ?
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