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

青少年大麻使用的认知灵活性和奖励动机：神经行为机制和内在静息态连接的调查。

• 批准号: 10595079
• 负责人: Sarah Ann Thomas
• 金额: $ 19.68万
• 依托单位: EMMA PENDLETON BRADLEY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10595079
• 关键词: 17 year old; Acceleration; Address; Adolescence; Adolescent; Adolescent marijuana use; Adult; Affect; Age; Area; Award; Behavior; Behavioral; Behavioral Mechanisms; Behavioral Model; Biological; Brain; Brain region; Cannabinoids; Cannabis; Chronic; Cognitive; Computer Models; Corpus striatum structure; Data; Data Analyses; Decision Making; Development; Diffusion; Drug usage; Education; Educational workshop; Environment; Etiology; Exhibits; Failure; Functional Magnetic Resonance Imaging; Goals; Impaired cognition; Impairment; Individual; Intervention; Investigation; Knowledge; Learning; Link; Magnetic Resonance Imaging; Measures; Mediating; Mentors; Mentorship; Methodology; Methods; Modeling; Motivation; National Institute of Drug Abuse; Neuroanatomy; Neurosciences; Occupational; Outcome; Pathway interactions; Pharmacotherapy; Prefrontal Cortex; Prevention; Process; Psychiatry; Psychological reinforcement; Public Health; Publications; Punishment; Research; Research Personnel; Research Project Grants; Resources; Rest; Reversal Learning; Rewards; Risk; Scientist; Statistical Methods; Statistical Models; Stimulus; Strategic Planning; Symptoms; Testing; Training; Universities; Visit; Work; addiction; adolescent brain development; adolescent drug use; adolescent substance use; adverse outcome; biobehavior; brain based; career; career development; cognitive control; design; flexibility; functional disability; high school; improved; innovation; longitudinal design; maladaptive behavior; marijuana use; marijuana user; neglect; neural; neural circuit; neural recruitment; neurobehavioral; neuroimaging; non-drug; novel; patient oriented; phenomenological models; receptor; research and development; response; skills; substance use; success; symposium; treatment response

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.

7. 项目概要： 青春期开始使用大麻（CU）与认知方面的重大后果相关 虽然 CU 可能会破坏青少年大脑发育的正常过程，但影响相对较小。 众所周知，青少年 CU 如何扰乱介导认知灵活性的回路（适应不断变化的环境） 奖励和惩罚）和内在静息状态功能连接（RSFC），并影响奖励 动机（获得强化的目标导向行为的数量）。这些领域都没有得到充分研究。 与成人 CU 相关的领域，但提高对这些过程的了解可能可以解释为什么青少年发生 CU 与功能障碍和托马斯博士长期滥用药物有关。 职业目标是成为一名独立研究人员，识别风险和影响的生物行为机制 青少年吸毒情况的调查，以完善识别方法，进行有针对性的预防和治疗。 在这个为期 4 年的以患者为导向的指导职业奖中要测试的中心假设是 CU 在这种背景下 青少年大脑发育的影响与额纹状体的改变和认知灵活性、奖励受损有关 动机和内在 RSFC 将随着 CU 暴露的函数而变化 核心方法是使用。 参与 CU 的 14-17 岁青少年的症状、回路和行为数据，并且通常- 发展控制青少年（每人 n = 40）。 NIDA K23 的职业发展目标。 应用程序的目的是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来测量青少年 CU 的大脑/行为改变，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。 该 K23 的研究目标是：（1）确定认知灵活性和行为的大脑/行为机制 RSFC 使用 fMRI 与 CU 相关联；(2) 定义奖励动机的行为改变；(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 认知灵活性任务期间对决策的贡献，并确定决策如何进行 科罗拉多大学青少年和对照青少年的组成部分有所不同 布朗大学拥有丰富的科学环境。 由于导师在青少年物质使用、神经科学和 先进的统计方法和样本资源来执行托马斯博士的培训计划，包括动手 关于指导、研讨会、课程作业（例如神经解剖学）和专业发展（会议 该项目意义重大，因为它涉及有关知识的深度。 认知灵活性、奖励动机和 RSFC 是促进基于机制的第一步 (a) 从常规 CU 进展为成瘾的预测因素，以及 (b) 青少年 CU 的治疗。 该项目的创新之处在于使用功能磁共振成像来探索认知灵活性和认知灵活性等相对未被充分研究的领域。 使用计算精神病学分析对患有和不患有 CU 的青少年进行奖励动机。