Effect of Bariatric Surgery in Pediatric Obesity on Brain and Cognition

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 DESCRIPTION (provided by applicant): The purpose of this exploratory proposal is to examine effects of bariatric surgery, specifically vertical sleeve gastrectomy, on functional and structural neural and cognitive function in adolescents aged 14-21 years. While obese adults face serious risk of poor health outcomes (cardiovascular, metabolic, musculoskeletal, respiratory, cancer), obese children bear the added burden of poor academic and psychosocial functioning, setting them on maladaptive developmental trajectories resulting in high social and economic costs to the person and the nation. Adolescence is a critical period for maturation of executive and motivational functioning, and severe obesity during this period puts youth at far greater risk for poor physical and psychological outcomes. Bariatric surgery as a treatment option is increasingly being adopted, with proven weight loss (13%-68% excess weight loss in 3-12 months post-surgery in our cohort) and improved metabolic and cardiovascular health. Whether cognitive and brain health also improve is an open question. The proposal will address this gap by taking advantage of the opportunity presented by adolescents who are already undergoing bariatric surgery at Children's National Medical Center. The proposal focuses on three areas of function known to be affected in pediatric obesity: executive function that depends on prefrontal cortes, long-term memory that depends on hippocampus and surrounding regions (medial temporal lobe), and reward function associated with ventral striatum. Aim 1 will test the hypothesis that executive function, verbal and visual memory, and reward sensitivity will improve following surgery. Aim 2 will test the hypothesis that functional activation and connectivity of prefrontal, medial temporal lobe, and ventral striatal regions will improve following surgery, using functional magnetic resonance imaging (fMRI). Lastly, Aim 3 will explore whether the magnitude of weight-loss induced change in metabolic indices (e.g., insulin resistance) mediates association between changes in neural correlates and cognitive function. Fifty adolescents who are candidates for surgery will undergo testing twice, 25 at a minimum of one month before surgery and then again 4 months after surgery, and 25 who have had their surgery delayed for insurance or other reasons who will be tested twice 4-5 months apart; in addition a non-obese control group of 25 adolescents matched for age and gender will also be tested twice at the same intervals. While Aim 1 and 2 seek initial evidence for impact of rapid weight loss on brain and cognitive function, Aim 3 will generate hypotheses about potential metabolic sources of functional neural effects of weight loss to be tested in future work. These findings will further understanding of the influence of the gut on brain and cognition at a critica time in development, by providing neurocognitive markers sensitive to metabolic health that can be used to test mechanistic hypotheses in future work.