Excessive eating and the health and social problems resulting from it are the most serious problems associated with PWS. Despite the seemingly uncontrollable aspect of food related issues for people with PWS, laboratory studies of food choice reveal orderly and consistent food preferences in this population. Further, food rewards have been used successfully to teach speech articulation and physical exercise participation in people with PWS. During the current funding period, there was no detrimental impact of using food rewards and food-related cues on learning by people with PWS as compared to a population of comparably obese people, despite observing that food had greater motivational value for them. In addition, obsessive-compulsive symptoms in PWS subjects were negatively related to their performance on a sequential learning task. These findings have led us to hypothesize that food-related behavior problems in PWS are more likely to be related to obsessive-compulsive symptoms associated with PWS rather than the inflated motivational value of food. In the proposed research, adolescents and adults with PWS, a control group matched for MA and CA, and children, adolescents and adults with obsessive-compulsive disorder (OCD) will be evaluated. First, we propose to test the hypothesis that obsessive-compulsive symptoms in people with PWS and in people with OCD stem from altered frontal cortical processes. We will test this by comparing performance by these subjects on laboratory learning tasks known to involve orbitofrontal systems (e.g. Object Alternation), and tasks involving other frontal regions (e.g., extradimensional shift). Second, we will test whether perseverative errors on these tests are exacerbated exclusively in the PWS group when food related cues and rewards are used in these procedures. We also propose to examine how the altering the predictability of rewards associated exclusively with specific cues affects memory performance by people with PWS and OCD. We will then use functional magnetic resonance imaging to compare orbital frontal cortex (OFC) activation in people with PWS, people with OCD and controls. The major goal of the proposed research is to understand mechanisms underlying learning problems and food- related behavior problems in people with PWS.
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