Characterization of Reward Processing in Adolescent Marijuana Use

项目摘要/摘要 青春期是一个脆弱的发育阶段，青年的中枢神经会发生显著变化 系统。药物应激源，如滥用药物，可以对这些变化产生深远的影响。 在青春期。大麻(MJ)是青少年中使用最广泛的麻醉剂，仅次于酒精。一个 令人震惊的是，36%的高中生在过去的一年里使用过MJ，21%的高中生在过去的一个月里使用过MJ。当然了, 许多尝试MJ的青少年只在青春期这样做，几乎没有长期的经历 效果。尽管如此，相当一部分人确实遇到了问题，他们最初的MJ实验可能会 升级为极其不利的后果，包括成瘾和其他精神疾病。然而， 这种转变的确切神经生物学基础还不是很清楚，但被认为是相关的。 有奖赏功能障碍。在K01颁奖期间，候选人将从事一项创新的研究 在青少年MJ使用者中，考察初始MJ使用对奖励处理的影响，同时也接受 进行此类研究所需的基本培训。具体地说，该项目将检查神经机制 通过多模式神经成像支持青少年MJ使用者的奖赏功能障碍 (EEG)和功能磁共振成像(FMRI)]，并测试这些神经成像标记物 在12个月的随访中预测疾病症状的升级。嵌入在这个新项目中的是明确的 培训目标，将在著名的多学科指导团队的指导下实施 研究科学家。拟议的培训计划将培养以下方面的能力：(1)临床特征 青少年药物使用；(2)利用功能磁共振成像研究奖赏环路；(3)为临床提供先进的生物统计学 结果评估。在基线上，使用MJ的青少年和MJ天真控制的青少年将执行任务 分别用EEG和fMRI探测奖赏预期和奖赏加工的实现阶段。 参与者还将接受静息状态的fmri扫描，以精确描绘潜在的神经回路。 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。我们的目标是 研究奖赏功能障碍的基线神经影像标志物是否能预测药物使用的升级 症状学。重要的是，西奈山的伊坎医学院是一个理想的开展环境 儿童和青少年的神经成像研究，因为它拥有完整的儿科情绪和焦虑 障碍项目(P-MAP；负责人：加贝博士)进行面谈和行为测试，以及大脑 影像中心(BIC；负责人：戈尔茨坦博士)进行脑电和功能磁共振成像扫描。总的来说，拟议的研究和 培训目标将为候选人在青少年精神病理评估方面提供坚实的基础 和功能神经成像，有助于启动他的独立研究生涯，同时也显著 促进我们对青少年物质使用背后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.