Disturbances in the neural circuitry underlying reward processing and decision making are likely to be associated with an increased risk common emotional and addictive disorders that have their origins in childhood and adolescence. These disorders include depression and alcohol and nicotine abuse and dependence. It has now become possible to use fMRI to investigate this neural circuitry, together with its developmental trajectory and relationship with critical key physiological events such as puberty. However, these studies are severely hampered by critical methodological limitations, including the presence of magnetic susceptibility effects resulting in signal loss in many key brain regions (ventral striatum, amygdala, orbital frontal cortex), as well as issues related to the cross registration of sub-cortical and orbital frontal brain regions to facilitate the analysis of within and between group comparisons. In the present application, our multidisciplinary group of investigators will tackle these technical limitations and develop and validate solutions designed to improve our ability to investigate this brain circuitry and its development in healthy as well disordered groups of children and adolescents. We will optimize a rapid event-related Reward Contingent Decision (RCD) paradigm for acquisition of data in children and adolescents. We will also develop a whole-brain data acquisition method for rapid event-related pediatric fMRI at 3T that is robust to susceptibility artifacts by combining 3D tailored RF pulse excitations with SENSE acquisitions. Finally, we shall develop a novel volumetric image, deformable registration algorithm especially for deep sub-cortical gray matter structures such as the amygdala and the basal ganglia, including nucleus accumbens. The long term goals of this research are to take maximal advantage of the opportunity provided by event- related fMRI to achieve a better understanding of the development of neurobehavioral systems of reward that influence decision-making and risk appraisal in adolescence, achieve a more mechanistic understanding of the emergence of sensation seeking, risk-taking, and reckless behavior during adolescent development, and to use these methodological advances in fMRI to provide a more powerful cognitive neuroscientific framework for our ongoing developmental and clinical investigations into emotional and substance-use problems emerging during adolescence.
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