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

说明(申请人提供)：大麻(MJ)的使用仍然是青少年使用的最受欢迎的非法药物(1)。在成人中，MJ的使用与较差的抑制控制和情感处理有关(41-52)。这些过程的神经联系主要在额叶边缘区域(53、55、58、63、67、114)，这些区域继续发育到青春期(71-82、85-87)。青少年MJ使用者的额缘功能才刚刚开始被描述；长期使用MJ与执行功能低下(111-116)、女性前额叶皮质和杏仁核大脑结构异常(112、118、121、203)以及大脑对抑制性控制任务的异常反应(114)有关。尽管有证据表明情绪不佳(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异常的额叶边缘脑功能。体力活动和心肺健康已被证明对成年人的大脑功能有积极影响(143,155-164)。尽管在更年轻的样本中的发现是有希望的(169-179)，但很少有研究检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，目前尚不清楚体育活动或健身的程度是否可以缓解慢性MJ暴露对青少年额叶边缘脑功能的负面影响。我们的主要目的是1)描述MJ使用对额叶边缘脑功能和连接性的影响，2)确定体力活动或心肺健康的程度是否缓和了青少年正常对照组(n=50)和重度MJ使用者(n=50)的这些影响。这两组人都将平衡50%的高度活跃和50%的久坐不动的个人。体重指数、种族和性别将在不同群体之间保持平衡。青少年将接受为期三周的禁欲监测，在此期间将收集持续活动数据(通过加速计和日记)。然后，他们将进行最大摄氧量测试，以确定心肺(有氧)健康的程度。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)。具体地说，青少年将完成抑制控制和情感处理功能磁共振任务。在功能磁共振成像任务期间，将检查MJ使用、体力活动和健康以及额叶边缘功能和连接性之间的直接和间接关系。还将检查大脑结构和行为与额叶边缘功能的相关性。因此，该提案将更好地了解MJ对青少年额缘功能的影响，并将确定增加体力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善工具，以减少青少年反复使用MJ的负面后果。最终，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.