The ultimate goal of this proposal is to facilitate the transition of Dr.Yuji Takahashi into an independent and successful faculty member in the field of cognitive neuroscience research. Dr.Takahashi has been a postdoctoral fellow for 2.5 years under the auspices of the Long-Term Fellowship of the Human Frontier Science Program at University of Maryland School of Medicine. He has completed several studies devoted to understanding the neural mechanisms in cognitive function, the effects of non-contingent cocaine exposure on this function and neural encoding in an odor-guided decision-making task in rats. The career development plan in this proposal will allow Dr.Takahashi to develop new technical skills and several professional skills under the mentorship of Dr. Geoffrey Schoenbaum, that will enable him to research his goal, and, in particular, to complete successfully for funding as an independent investigator. The research project under this proposal is designed to test the hypothesis, arising from works of Dr.Schoenbaum's lab and Dr.Takahashi's preliminary work (described in Preliminary Studies in the proposal), that neural activity in orbitofrontal cortex (OFC) encodes outcome expectancies and that these signals are critical not only for guiding behavior but also for adjusting associative representations in the face of unexpected outcomes. This is one of the important orbitofrontal function underlying cognitive flexibility. The first Specific Aim in mentored phase will directly test this hypothesis and also examine the interaction between the OFC and brain regions downstream of OFC such as ventral tegmental area using a task which designed specifically examine this function. In the independent phase, Dr.Takahashi will expand his research area to the nucleus accumbens (NAC), which receives major input from OFC and VTA and also sends efferent to dopamine neurons in VTA. Based on these anatomical findings, NAC has been implicated as a """"""""limbic-motor interface """"""""though which motivationally significant information guides behavior. According to this, behavioral and electrophysiological studies have suggested that interactions among these brain regions are important for flexible goal-directed behavior. The second Specific Aim will test the role of NAC and also the role of interactions among NAC, OFC and VTA for flexible control of behavior in the face of unexpected outcomes.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Career Transition Award (K99)
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Special Emphasis Panel (ZMH1-ERB-L (01))
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Desmond, Nancy L
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University of Maryland Baltimore
Anatomy/Cell Biology
Schools of Medicine
United States
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Bond, Gary R; Drake, Robert E; Campbell, Kikuko (2016) Effectiveness of individual placement and support supported employment for young adults. Early Interv Psychiatry 10:300-7
Takahashi, Yuji K; Chang, Chun Yun; Lucantonio, Federica et al. (2013) Neural estimates of imagined outcomes in the orbitofrontal cortex drive behavior and learning. Neuron 80:507-18
Iglesias, Sandra; Mathys, Christoph; Brodersen, Kay H et al. (2013) Hierarchical prediction errors in midbrain and basal forebrain during sensory learning. Neuron 80:519-30
Singh, Teghpal; McDannald, Michael A; Takahashi, Yuji K et al. (2011) The role of the nucleus accumbens in knowing when to respond. Learn Mem 18:85-7
Takahashi, Yuji K; Roesch, Matthew R; Wilson, Robert C et al. (2011) Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex. Nat Neurosci 14:1590-7