Effects of Physical Activity & Marijuana Use on Frontolimbic Functioning During A

描述（由申请人提供）：大麻（MJ）使用仍然是青少年中最流行的非法药物(1)。在成人中，MJ的使用与抑制控制和情感处理不良有关（41-52）。与这些过程相关的神经系统主要位于额叶边缘区（53,55,58,63,67,114），并继续发育至青春期（71- 82,85 -87）。青少年MJ使用者的额叶功能才刚刚开始被表征；长期使用MJ与执行功能差（111-116）、女性前额皮质和杏仁核脑结构异常（112,118,121,203）以及大脑对抑制控制任务的异常反应（114）有关。尽管有证据表明青少年情绪不佳（112），但尚不清楚青少年使用MJ是否会影响情感处理过程中的大脑功能。目前，还没有已知的治疗方法来改善青少年的异常额叶脑功能。体育活动和心肺健康都被证明对成年人的大脑功能有积极影响（143,155-164）。虽然在年轻样本中的发现很有希望（169-179），但很少有研究调查身体活动或心肺健康是否会影响健康青少年的神经认知功能。此外，目前尚不清楚身体活动或健康程度是否会调节慢性MJ暴露对青少年额叶脑功能的负面影响。我们的主要目的是：1)表征MJ使用对额叶脑功能和连通性的影响；2)确定身体活动或心肺健康的程度是否会缓和青少年正常对照（n=50）和重度MJ使用者（n=50）的这些影响。两组的比例都是平衡的，其中50%是高运动量的，50%是久坐不动的。身体质量指数、种族和性别将在各群体之间保持平衡。青少年将经历为期三周的监控禁欲期，在此期间将收集连续的活动数据（通过加速度计和日记）。然后，他们将进行VO2最大测试，以确定心肺（有氧）健康程度。最后，青少年将接受心理和神经心理测试（测量身体活动、营养、物质使用、情绪、个性、应对方式和认知功能），并接受结构和功能磁共振成像（fMRI）。具体来说，青少年将完成抑制控制和情感处理fMRI任务。在fMRI任务中，MJ使用、身体活动和健康、额叶功能和连通性之间的直接和间接关系将被检查。大脑结构和行为相关的额叶功能也将被检查。因此，该建议将更好地理解MJ使用对青少年额叶功能的影响，并将确定增加体育活动或健身是否会使这些负面影响正常化。这将导致设计低成本的改进工具，以减少青少年反复使用MJ的负面后果。最终，研究结果将有助于改善青少年吸毒者的预防策略和行为治疗。

DESCRIPTION (provided by applicant): Marijuana (MJ) use continues to be the most popular illicit drug used among adolescents (1). In adults, MJ use is associated with poor inhibitory control and affective processing (41-52). The neural correlates of these processes are primarily in frontolimbic regions (53, 55, 58, 63, 67, 114), which continue to develop into adolescence (71- 82, 85-87). Frontolimbic functioning in adolescent MJ users has only begun to be characterized; chronic use of MJ is associated with poor executive functioning (111-116), aberrant prefrontal cortex and amygdala brain structure in females (112,118,121,203) and abnormal brain response to an inhibitory control task (114). Despite evidence of poor mood (112), it is unknown whether adolescent MJ use impacts brain function during affective processing. Currently, there are no known treatments to ameliorate aberrant frontolimbic brain functioning in adolescents. Both physical activity and cardiorespiratory fitness have been shown to have positive effects on brain function in adults (143,155-164). Although the findings in younger samples are promising (169-179), few studies have examined whether physical activity or cardiorespiratory fitness affect neurocognitive functioning in healthy adolescents. Further, it is unknown whether extent of physical activity or fitness moderates the negative consequences of chronic MJ exposure on frontolimbic brain functioning in adolescents. Our primary aims are to 1) characterize the effects of MJ use on frontolimbic brain functioning and connectivity and 2) determine whether extent of physical activity or cardiorespiratory fitness moderate these effects in adolescent normal controls (n=50) and heavy MJ users (n=50). Both groups will be balanced for 50 percent highly active and 50 percent sedentary individuals. Body mass index, ethnicity and gender will be balanced across groups. Teens will undergo a three week monitored abstinence period during which continuous activity data (by accelerometer and diary) will be collected. They will then have VO2 maximum testing to establish extent of cardiorespiratory (aerobic) fitness. Finally, teens will be administered a psychological and neuropsychological battery (measuring physical activity, nutrition, substance use, mood, personality, coping styles, and cognitive functioning) and undergo structural and functional magnetic resonance imaging (fMRI). Specifically, teens will complete inhibitory control and affective processing fMRI tasks. The direct and indirect relationships between MJ use, physical activity and fitness, and frontolimbic functioning and connectivity during the fMRI tasks will be examined. Brain structure and behavioral correlates of frontolimbic functioning will also be examined. Thus, the proposal will provide a better understanding of consequences of MJ use on frontolimbic functioning in adolescents and will determine whether increased physical activity or fitness normalizes these negative effects. This will lead to the design of low-cost ameliorative tools in reducing negative consequences of repeated MJ use in teens. Ultimately, results will help improve prevention strategies and behavioral treatments for adolescent drug users. PUBLIC HEALTH RELEVANCE: The current study will characterize the effects of marijuana (MJ) on frontolimbic brain functioning in healthy teens. It will also determine whether physical activity or aerobic fitness normalizes the negative consequences of MJ use on brain function. These findings will lead to the development of viable low-cost addiction prevention or ameliorative tools in reducing negative consequences of repeated MJ use during adolescence.