Characterization of Reward Processing in Adolescent Marijuana Use

项目总结/摘要 青春期是一个脆弱的发展阶段，在这个阶段，青少年的中枢神经系统发生了重大变化， 系统药物压力，如滥用药物，可以对这些变化产生深远的影响 在青春期。海洛因（MJ）是青少年中使用最广泛的麻醉剂，仅次于酒精。一 令人吃惊的是，36%的高中毕业生报告说在过去一年中使用了MJ，21%的人在过去一个月中使用了MJ。当然，我想， 许多尝试MJ的青少年只在青春期这样做，并且很少或没有长期的经验。 方面的影响.尽管如此，一个显着的少数经验的问题，他们最初的MJ实验， 升级到极端不利的结果，包括成瘾和其他精神疾病。但 这种转变的确切神经生物学基础尚不清楚，但被认为与 奖励功能障碍在K 01奖期间，候选人将追求创新的研究路线 研究初始MJ使用对青少年MJ使用者奖励处理的影响，同时也接受 进行此类研究需要进行必要的培训。具体来说，该项目将研究神经机制 通过多模式神经成像[脑电图]支持青少年MJ使用者的奖励功能障碍 (EEG)和功能性磁共振成像（fMRI）]，并测试这些神经成像标记物是否 预测12个月随访时疾病病理学的升级。在这个新颖的项目中， 培训目标，将在一个多学科指导小组的指导下实施， 研究科学家。拟议的培训计划将培养以下方面的能力：（1） 青少年物质使用;（2）利用功能磁共振成像研究奖励回路;（3）临床研究的先进生物统计学 成果评估。在基线时，使用MJ的青少年和MJ初治的对照青少年将执行任务 分别用脑电图和功能磁共振成像来探测奖赏处理的奖赏预期和获得阶段。 参与者还将接受静息状态功能磁共振成像扫描，以精确描绘潜在的神经元回路。 奖励处理最后，参与者将在基线后12个月返回进行临床随访。目标是 研究奖赏功能障碍的基线神经影像学标志物是否可预测物质使用的升级 医学。重要的是，西奈山伊坎医学院是进行 儿童和青少年的神经影像学研究，因为它拥有设备齐全的儿科情绪和焦虑 疾病计划（P-MAP;主任：Gabbay博士）进行访谈和行为测试，以及大脑 成像中心（BIC;主任：Goldstein博士）进行EEG和fMRI扫描。总体而言，拟议的研究和 培训目标将为候选人提供青少年精神病理学评估的坚实基础 和功能性神经成像，促进了他的独立研究生涯，同时也显着 推进我们对青少年物质使用的神经认知机制的理解。

PROJECT SUMMARY/ABSTRACT Adolescence is a vulnerable developmental stage where significant changes occur in a youth’s central nervous system. Pharmacological stressors, such as drugs of abuse, can have a profound impact on these changes during adolescence. Marijuana (MJ), second to alcohol, is the most widely used intoxicant in adolescents. A staggering 36% high-school seniors reported using MJ in the past year and 21% in the past month. Of course, many adolescents who experiment with MJ only do so during adolescence and experience little to no long-term effects. Nonetheless, a significant minority does experience problems and their initial MJ experimentation can escalate to extremely adverse outcomes including addiction and other psychiatric conditions. However, the precise neurobiological underpinnings of such transition is not well-understood, but are posited to be associated with reward dysfunction. During the K01 award period, the Candidate will pursue an innovative line of research examining the impact of initial MJ use on reward processing in adolescent MJ users, while also receiving essential training required to conduct such research. Specifically, the project will examine neural mechanisms underpinning reward dysfunction in adolescent MJ users via multimodal neuroimaging [electroencephalography (EEG) and a functional magnetic resonance imaging (fMRI)], and test whether these neuroimaging markers predict escalation of disease symptomology at 12-month follow-up. Embedded within this novel project are clear training aims, which will be implemented with guidance from a multidisciplinary mentoring team of renowned research scientists. The proposed training plan will develop competency in (1) clinical characterization of adolescent substance use; (2) utilization of fMRI to study reward circuity; and (3) advance biostatistics for clinical outcome assessment. At baseline, MJ-using adolescents and MJ-naïve control adolescents will perform tasks that probe reward anticipation and attainment stages of reward processing, separately with EEG and fMRI. Participants will also undergo a resting-state fMRI scan for precise delineation of the neuronal circuitry underlying reward processing. Lastly, participants will return 12 months after baseline for a clinical follow-up. The goal is to investigate whether baseline neuroimaging markers of reward dysfunction predict escalation in substance use symptomatology. Importantly, Icahn School of Medicine at Mount Sinai is an ideal environment to conduct neuroimaging research with children and adolescents, as it boasts fully-equipped Pediatric Mood and Anxiety Disorders Program (P-MAP; Chief: Dr. Gabbay) to conduct interviews and behavioral testing, and the Brain Imaging Center (BIC; Chief: Dr. Goldstein) for EEG and fMRI scanning. Collectively, the proposed research and training goals will provide the Candidate with a strong foundation in adolescent psychopathological assessment and functional neuroimaging, facilitate in launching his independent research career, while also significantly advancing our understanding of neurocognitive mechanisms underlying adolescent substance use.