Effects of adolescent alcohol exposure on functional brain connectivity

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ABSTRACT This is an application for a Mentored Research Scientist Development Award (K01) to support the career development of Dr. Margaret Broadwater as an independent academic research scientist. The candidate is an early stage investigator with a strong background in behavioral alcohol pharmacology studies and is relatively new to the field of magnetic resonance imaging (MRI). The applicant's career and research training will be overseen by a strong mentoring team and supported by strong institutional commitment to the candidate's career development. The training outlined in this proposal will allow the candidate to develop a successful, productive research laboratory that will be at the forefront of alcohol research using functional connectivity MRI (fcMRI) in rodents. In humans and rodents, functional connectivity can be assessed with MRI by correlating fluctuations in blood-oxygen-level-dependent (BOLD) signal, a surrogate marker of neural activity, between brain regions. The proposed studies will use this tool to examine the effects of adolescent alcohol exposure on brain. Alcohol use during adolescence is common and initiation of alcohol use at an early age is associated with development of later alcohol use disorders. Chronic alcohol use during adolescence may result in deficits of inhibitory, top-down control of the prefrontal cortex (PFC) on subcortical brain structures, possibly contributing to compulsive and inflexible behavior typically seen in addiction. Indeed, the prefrontal cortex (PFC) is particularly vulnerable to alcohol use during adolescence, the developmental period of cortical maturation; however, it is unknown how PFC connectivity to other brain regions may be affected by adolescent alcohol exposure. The overarching hypothesis of this proposal is that adolescent alcohol exposure will alter maturation of PFC connectivity, leading to persistent deficits in PFC functional connectivity and altered responding to acute alcohol challenge in adulthood. These results will be informative for ongoing research initiatives from the NIH assessing consequences of adolescent alcohol use in humans, and ultimately will aid in our understanding of potential mechanisms for addiction vulnerability to identify targets for therapeutic intervention and reversal.