Prefrontal-amygdala interactions in social learning

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DESCRIPTION (provided by applicant): This is an application for a competitive revision to my current 'parent' R01 (MH080716) in response to Notice Number: NOT-OD-10-032, titled "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications (R01, R03, R15, R21, R21/R33, and R37) through the NIH Basic Behavioral and Social Science Opportunity Network (OppNet)." The parent R01 is progressing soundly in its aim to elucidate functional interactions between the prefrontal cortex and the amygdala while subjects learn about the social value of other individuals and their facial expressions. This work has significant implications for understanding how functional interactions between the prefrontal cortex and amygdala support social learning in psychiatrically healthy subjects. These data inform our understanding of how these systems might go awry in emotional disorders such as depression and anxiety. A question not addressed by the original application is how structural connections between the amygdala and prefrontal cortex might predict or vary with individual differences in social learning, and specifically in outcome measures such as anxiety. While conducting some of the proposed work of the parent R01 during years 1 and 2, we routinely add a scan that measures the structural integrity of white matter tracts (i.e., diffusion tensor imaging (DTI)]. We just published an exciting finding identifying a prefrontal-amygdala white matter tract, the integrity of which predicted subjects' anxiety levels (Kim et al., J Neurosci, 2009). The present application aims to expand upon this finding to determine if the particular structural pathway we identified is dependent on the functional task we used (i.e., passive viewing of fearful facial expressions). Here we propose additional tasks that require a greater degree of regulation on the part of subjects to determine if such regulatory tasks will be associated with the structural integrity of a similar pathway or separable pathways. We plan to fund 40% of a staff scientist (physicist) position with a specialization in DTI, as well as add one full-time Research Assistant position. These personnel will work with the PI (Whalen) and graduate student (Kim) (both funded under the parent R01) for a one-year period to carry out the proposed experiments. PUBLIC HEALTH RELEVANCE: An area of the brain called the amygdala is particularly responsive to the facial expressions of others and has been shown to exhibit exaggerated reactivity to the facial expression of fear in subjects with anxiety disorders. This may, in part, underlie the symptoms of increased vigilance and hyper-reactivity to potential threat that plague individuals with anxiety disorders. The studies proposed here will further our understanding of how structural differences in amygdala-prefrontal connectivity predict vulnerability to anxiety disorders.