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。项目摘要： 在青少年启动的大麻使用（CU）与认知的实质后果有关 拒绝成瘾。虽然CU可能会破坏青春期大脑发育的正常过程，但相对较少 了解青少年CU如何破坏介导认知灵活性的电路（适应变化 奖励和惩罚）以及内在的休息状态功能连接性（RSFC），并影响奖励 动机（目标指导的行为赚取加强的行为）。这些领域都被理解 相对于成人铜的领域却提高了对这些过程的知识，可以解释为什么青少年发作的Cu 与功能障碍和有问题的物质使用率有关。托马斯博士的长期 职业目标是成为一名独立研究人员，以识别风险和影响的生物行为机制 青春期药物使用以改善靶向预防和治疗的识别方法。这 在这个为期4年的以患者为导向的修订职业奖中进行检验的中心假设是CU在上下文中 青春期大脑发育与额叶的改变和认知灵活性受损，奖励有关 动机和内在的RSFC将随CU暴露的函数而变化。中心方法是使用 从事CU且通常 - 开发控制青少年（每个n = 40）。 NIDA K23的职业发展目标 应用是在（a）现象学和青少年铜评估中获得动手心态，（b） 使用fMRI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，从这些数据中提出更高的推理方法。这 该K23的研究目标是：（1）确定认知灵活性的大脑/行为机制 使用fMRI与CU关联的RSFC； （2）定义奖励动机的行为改变； （3）使用 高级统计方法，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，并确定决策 组件因CU青少年和控制青少年而变化。布朗大学是一个丰富的科学环境 由于导师的专业知识在青少年使用，神经科学和 具有丰富资源的高级统计方法，以执行托马斯博士的培训计划，包括动手 关于精神训练，讲习班，课程（例如神经解剖学）和专业发展（会议 演讲，出版物）。该项目很重要，因为解决有关的知识之死 认知灵活性，奖励动机和RSFC是促进基于机制的第一步（a） 预测从常规铜到成瘾的进展的指标，以及（b）青少年中Cu的治疗方法。这 项目使用fMRI来探讨认知灵活性和 使用计算精神病学分析的具有和不具有CU的青少年之间的动机。