Advance-CTR

Advance-CTR Mentored Research Awards (2018)

"Cognitive Flexibility and Reward Motivation in Adolescent Cannabis Use: An Investigation of Neurobehavioral Mechanisms and Intrinsic Resting State Connectivity"

Cannabis use (CU) initiated in adolescence is associated with substantial consequences, from cognitive decline to addiction. While CU may disrupt normal processes of adolescent brain development, relatively little is known about how adolescent CU disrupts circuits mediating cognitive flexibility (adaptation to changing rewards and punishments), reward motivation (the amount of goal-directed behavior to earn reinforcement), and intrinsic resting state functional connectivity (RSFC). These domains are all understudied areas relative to adult CU, yet advancing knowledge of these processes may explain why adolescent-onset CU is linked to functional impairments and higher rates of problematic substance use. Dr. Thomas’s long-term career goal is to become an independent researcher identifying bio-behavioral mechanisms of risks and effects of adolescent drug use in order to improve identification methods for targeted prevention and treatment. The central hypothesis to be tested in this mentored career award is that CU in the context of adolescent brain development results in fronto-striatal alterations and impaired cognitive flexibility, reward motivation, and intrinsic RSFC that will vary as a function of overall CU exposure. The central methodology of this pilot project is to use symptom, circuit, and behavioral data in 14-15 year olds who are engaged in CU and also typically-developing controls (n=10 of each). The career development objectives of this translational mentored career award application are to gain hands-on mentorship in (a) the use of fMRI to provide a comprehensive understanding of brain/behavior alterations in adolescent CU, (b) phenomenology and assessment of adolescent CU, and (c) advanced statistical methods for greater level of inference from these data. The research objectives of this project are: (1) to identify the brain/behavior mechanisms of cognitive flexibility and RSFC associated with CU using fMRI; (2) to define behavioral alterations in reward motivation; (3) to use advanced statistical methods, including one computational psychiatry model, to integrate fMRI data associated with cognitive flexibility and RSFC, behavioral data for reward motivation, and symptom-level data about CU and psychopathology. Brown University is a rich scientific environment to conduct this research due to the expertise of mentors in neuroscience, adolescent substance use, and advanced statistical methods, including computational psychiatry methods, with ample resources to carry out Dr. Thomas’s training plan consisting of coursework, hands-on mentorship, workshops, and professional development (conference presentation, publications). This project is significant because addressing the dearth of knowledge about cognitive flexibility, reward motivation, and RSFC is the first step towards facilitating mechanism-based (a) predictors of progression to cannabis addiction and (b) treatments for CU among adolescents. This project is innovative in its use of fMRI to probe the relatively understudied domains of cognitive flexibility, reward motivation, and RSFC among adolescents with and without CU using a salient computational psychiatry model.