Bipolar disorder (BPD) in a major source of morbidity and mortality for adults in America, with more than $24 billion spent annually; however, far less is known about BPD in children and adolescents. Emerging data shows that BPD children are impaired in reversal learning. This process requires behavioral adaptation to changing stimulus-reward contingencies and engages the ventral prefrontal cortex (vPFC), ventral striatum, and amygdala. My long-term goal is to understand how brain/behavior interactions, central to emotion regulation, differentiate normal from psychiatrically ill children, in order to develop more effective diagnostic and treatment strategies. The study of reversal learning will facilitate my efforts in this respect. ? ? The objectives of this application are to (1) acquire training in fMRI methods and experimental design, (2) identify neurological correlates of impaired reversal learning in pediatric BPD, and (3) develop an R01 application based on this work. My central hypothesis is that BPD children have specific impairments in reversal learning due to dysfunction in a neural circuit encompassing the vPFC, ventral striatum, and amygdala. To test this hypothesis, I will: (1) use fMRI to identify substrates of reversal learning in normal children; (2) determine functional neuroanatomical and behavioral differences in BPD children during reversal learning; (3) evaluate the specificity of reversal learning deficits in psychiatric controls. I will use the """"""""response reversal"""""""" task developed by our group to evaluate reversal learning with 3 Tesla fMRI and behavioral data. This will be among the first studies to link behavioral dysfunction to brain abnormalities in children with strictly defined BPD. From these studies, I expect to determine that BPD children have selective alterations in fronto-temporal structures during reversal learning. ? ? The proposed work will positively impact child mental health advancing our knowledge of the underlying brain/behavior abnormalities mediating BPD in children and adolescents. In turn, greater pathophysiological understanding of pediatric BPD will move the field of pediatric BPD beyond symptom-based diagnosis, potentially allowing more accurate or earlier diagnosis, thus reducing the morbidity and mortality in children and adolescents suffering from this debilitating disorder. ? ? ? ? ?
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