DEFINING THE FOREBRAIN REWARD CIRCUITS IN ADULT VOLUNTEERS

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Substance use disorders (SUD) present such a national health problem in the U.S that several important government initiatives have targeted the public health impact of SUD (e.g., Healthy People 2010). Further, the NIDA has established prevention and early identification of addiction among adolescents as high priority areas. However, the insidious and early onset of substance use and the invasive nature of some of the methodologies (e.g., PET imaging) used to study adults have limited the investigation of child and adolescent populations at high risk for SUD. The development of the non-invasive functional magnetic resonance imaging (fMRI) provided the first opportunity to examine the prodromal characteristics of neural circuits prior to drug exposure. Recent fMRI studies that tested forebrain reward circuits in healthy adolescents have corroborated the large body of findings that implicate the nucleus accumbens (NAcc) and orbital frontal cortex, limbic forebrain structures, and the mesolimbic dopaminergic (DA) system that innervates both regions, in the hedonic response to a range of stimuli, including drugs of abuse. Adolescents had robust activation of ventral striatum (including the NAcc) and orbitofrontal cortex during reward-related tasks, with the former specifically associated with anticipating rewards and the latter with the processing of reward outcomes. Further, developmental trends in the reward-related activation of ventral striatum indicated less activation in adolescents than adults. These findings, together with evidence that low mesolimbic DA tone confers vulnerability to SUD, suggests that an early neurobiological marker of risk for SUD might be found in the ventral striatum and/or orbitofrontal cortex. Yet, limitations of the reward tasks that have been used in fMRI studies, including not adequately controlling for motor activity and complex response requirements, make them inappropriate for use with high-risk child populations. We designed the Anticipation, Conflict, and Reward (ACR) hybrid task as an event-related adaptation of the Monetary Incentive Delays (MID) task previously used in the study of healthy adolescents and young adults. A measure of conflict resolution was added to the reward anticipation and outcome components in the original task and the response requirements were simplified. Specifically, the simple reaction time (RT) task in the MID was replaced with a flanker task based on the Attention Network Task. Thus, the ACR provides three temporally distinct probes of reward anticipation, conflict resolution, and reward outcome. Further, the task also contains comparisons to identify cue- and conflict-related brain activation, and isolate this activation from that during reward anticipation and feedback. The ACR task will be used to test children with ADHD at high- versus low-risk for SUD in a recently funded K23 grant (K23 PA-00-003; P.I.: Ivanov) and a R21 proposal that is being prepared by the P.I. However, this new ACR task has not been piloted in any sample and therefore must be tested in the MRI scanner with healthy adults to ensure that the conditions from the MID task were not changed in the adaptation of the task, before they can be used with clinical populations and children. HYPOTHESES: (1) Cue-related motor preparation will produce robust, bilateral activation of the thalamus, as well as the inferior and superior parietal lobules (2) Conflict-related neural activity will be seen in the anterior cingulate gyrus and the anterior prefrontal cortex. (3) The ventral striatum will be activated by the anticipation of reward, but not by the anticipation of non-reward. (4) The processing of reward feedback or outcome will activate the orbitofrontal cortex, but non- reward feedback will not.