Developmental Brain Connectomes and Substance Use in Adolescence - PROJECT SUMMARY/ABSTRACT Adolescence is a unique neurodevelopmental period where bottom-up limbic processes are pronounced while top-down executive control is onboarded throughout this age range. This results in mismatch in neurodevelopment that favors subcortical network activity, rather than top-down inhibitory control networks. It is suggested this drives states that can outwardly appear impulsive and risk-taking, such as escalating substance use. Specific to this relationship is the deleterious effects of nicotine use on brain structure and function. Concerningly, nicotine and tobacco product usage are rising in prevalence rates among adolescents (i.e., during this unique neurodevelopmental period) and onset of these substances confer higher likelihood of increased use, development of substance use disorders, and later psychopathology. However, few studies have investigated the impact of nicotine exposure and use escalations on structural and functional brain networks in a prospective and longitudinal design. Let alone, utilizing advanced statistical approaches to combine structural and functional connectome data to fully investigate large-scale and unique network signatures of nicotine and tobacco product use. Moreover, given inherit sex differences in neurodevelopmental timing of both structural and functional brain outcomes, it stands to reason that sex differences may exist in how nicotine impacts these developmental trajectories. Despite this line of research, examinations of sex differences are limited and often skewed by sample distribution. Thus, this proposal seeks to investigate these questions in a large-scale and demographically diverse sample, prospectively, and prior to nicotine use initiation. This will be done through secondary data analysis leveraging the landmark NIH-funded Adolescent Brain Cognitive Development (ABCD) Study, following over 11,800 youth across 10 years. Functional and structural brain data will be utilized across the study period (5 time points), with a myriad of other biopsychosocial measures (including other exposures of nicotine: prenatal, secondhand, environment), in predicting network-based longitudinal trajectories (ages 9-18). This fellowship would provide Dr. Sullivan with an exceptional opportunity to build his skills within advanced longitudinal neuroimaging design, resting-state fMRI, diffusion tensor imaging, network-based statistics, all while building upon his foundation in substance use. A dedicated mentorship team of ABCD Study leaders and users of this data, with expertise in these domains, will ensure exceptional training. At the conclusion of this two-year fellowship, Dr. Sullivan will meet his goals of developing a diverse and high-quality skill set to carry into a K08 proposal and progress to an early career faculty status as a clinical research scientist with an expertise in substance use in neurodevelopmental contexts across cognitive, reward, and affective neurobiological domains. In addition, he will possess technical expertise of advanced longitudinal statistics, breadth of neuroimaging approaches, and leveraging large-scale “big data” to answer timely and impactful research questions across these areas.
