Cognitive flexibility and reward motivation in adolescent cannabis use: An investigation of neurobehavioral mechanisms and intrinsic resting state connectivity.

7.项目总结： 在青春期开始使用大麻(CU)与认知方面的实质性后果有关 拒绝上瘾。虽然CU可能会扰乱青少年大脑发育的正常过程，但相对较少 已知青少年CU如何扰乱调节认知灵活性(适应变化)的回路 奖惩)和内在静息状态功能连接(RSFC)，并影响奖赏 动机(以目标为导向的行为赢得强化的数量)。这些领域都没有得到充分的研究 与成人CU相关的领域但对这些过程的不断了解可能解释为什么青春期发病的CU 与功能障碍和更高的问题物质使用率有关。托马斯医生的长期 职业目标是成为一名识别风险和影响的生物行为机制的独立研究人员 对青少年药物使用情况进行监测，以改进识别方法，以便有针对性地预防和治疗。这个 在这个为期4年的以患者为导向的职业指导奖中，将检验的中心假设是CU在上下文中 青春期大脑发育与额叶纹状体改变和认知灵活性受损有关 动机，以及内在的RSFC，这将随着铜暴露的变化而变化。中心方法论是使用 14-17岁参与CU的青少年的症状、电路和行为数据，以及典型的 发育对照青少年(n=40)。这款NIDA K23的职业发展目标 申请是为了获得以下方面的实践指导：(A)青少年CU的现象学和评估，(B) 使用功能磁共振成像测量青少年CU潜在的大脑/行为变化，以及(C)高级统计 通过学习计算精神病学模型，从这些数据中进行更高水平的推断的方法。这个 本K23的研究目标是：(1)识别认知灵活性的大脑/行为机制，并 (2)定义奖励动机中的行为改变；(3)使用 先进的统计方法，包括特定的计算模型，以整合神经和行为 在认知灵活性任务中对决策的贡献以及如何决定决策 CU青少年和对照青少年的成分有所不同。布朗大学是一个丰富的科学环境 由于导师在青少年物质使用、神经科学和 先进的统计方法和充足的资源来执行托马斯博士的培训计划- 关于导师、讲习班、课程(例如，神经解剖学)和职业发展(会议 演示文稿、出版物)。这个项目意义重大，因为它解决了人们对 认知灵活性、奖励动机和RSFC是迈向基于促进机制的第一步(A) 从常规慢性尿道炎发展为成瘾的预测因素，以及(B)青少年慢性尿道炎的治疗。这 Project在使用功能磁共振成像来探索相对较少研究的认知灵活性和 计算精神病学分析在有无CU青少年中的奖励动机。

7. PROJECT SUMMARY: 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) and intrinsic resting state functional connectivity (RSFC), and impacts reward motivation (the amount of goal-directed behavior to earn reinforcement). 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 4-year patient-oriented mentored career award is that CU in the context of adolescent brain development is linked to frontostriatal alterations and impaired cognitive flexibility, reward motivation, and intrinsic RSFC that will vary as a function of CU exposure. The central methodology is to use symptom, circuit, and behavioral data in 14-17 year old adolescents who are engaged in CU and also typically- developing control adolescents (n=40 of each). The career development objectives of this NIDA K23 application are to gain hands-on mentorship in (a) phenomenology and assessment of adolescent CU, (b) the use of fMRI to measure brain/behavior alterations underlying adolescent CU, and (c) advanced statistical methods for greater level of inference from these data, by learning a computational psychiatry model. The research objectives of this K23 are to: (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 a specific computational model, to integrate the neural and behavioral contributions to decision-making during a cognitive flexibility task and determine how decision-making components vary for CU adolescents and control adolescents. Brown University is a rich scientific environment to conduct this research due to the expertise of mentors in adolescent substance use, neuroscience, and advanced statistical methods with ample resources to carry out Dr. Thomas’s training plan consisting of hands- on mentorship, workshops, coursework (e.g., neuroanatomy), and professional development (conference presentations, 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 from regular CU to 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 and reward motivation among adolescents with and without CU using computational psychiatry analyses.