MRS/fMRI Investigations of Adolescent Cannabis Use

描述(申请人提供)：我们建议的研究的总体目标是通过应用一套互补的磁共振(MR)技术和神经心理学评估来研究大麻对吸食大麻的青少年和健康的不使用大麻的青少年额叶系统及其功能的影响。我们先前的研究已经确定了健康青少年在认知、形态测量和功能磁共振成像(FMRI)方面的年龄相关差异。此外，我们还发现，在成人停止使用大麻后不久，在运动和记忆功能方面，早期开始使用大麻与较差的神经心理表现以及前扣带回和额叶背侧皮质异常激活之间存在关联。因此，我们建议在两个青少年队列中研究开始使用大麻的年龄的影响：1)14岁的队列，报告至少100次使用大麻；2)18岁的队列，报告相同数量的大麻使用，但直到16岁生日后才开始吸烟。这两组人将与年龄匹配的不吸烟青少年进行比较。尽管已有大量证据表明吸食大麻与额叶执行功能改变之间存在关联，但很难研究和记录与大麻相关的人脑功能变化，尤其是在青春期。在这项提议中，我们将利用互补的高场磁共振技术提供的高空间分辨率和更高的信噪比来研究大麻使用对额叶大脑区域的化学和功能影响，已知这些区域在青春期经历了成熟的精炼。具体地说，这项研究将在3特斯拉使用认知和情感挑战范式的焦点功能MR BOLD技术，以及在4特斯拉使用扣带回的单体素GABA波谱，与执行功能的神经心理学测量相结合，以解决以下问题：当大麻开始使用的时间早或晚时，大脑额叶发育区域是否更容易受到非法药物使用的影响。我们相信，这些对大脑功能的补充测量将为滥用大麻的青少年抑制加工和决策的神经机制提供新的见解，这对早期干预和补救具有意义。

DESCRIPTION (provided by applicant): The overall aim of our proposed study is to examine the effects of marijuana on the development of frontal lobe systems and their function in marijuana-smoking adolescents and healthy non-using adolescents by applying a complementary set of magnetic resonance (MR) techniques and neuropsychological assessments. Our previous investigations have identified age-related differences in cognition, morphometry and functional magnetic resonance imaging (fMRI) in healthy adolescents. Furthermore, we have found an association between early onset of marijuana use and poorer neuropsychological performance, as well as abnormal cortical activation in the anterior cingulate and dorsal lateral prefrontal cortex on measures of motor and memory function shortly after cessation of marijuana use in adults. We therefore propose to examine the effects of age of onset of marijuana use in two adolescent cohorts: 1) a 14 year old cohort who report a minimum of 100 episodes of using marijuana; and 2) an 18 year old cohort who report the same amount of marijuana usage, but who did not begin smoking until after their 16th birthday. Both groups will be compared to age matched non-smoking adolescents. Although significant evidence has accumulated indicating an association between marijuana use and altered frontal-executive function, it has been difficult to study and document functional human brain changes associated with marijuana, particularly during adolescence. In this proposal, we will take advantage of the high spatial resolution and increased signal to noise offered by complementary high field MR techniques to investigate chemical and functional effects of marijuana use in frontal brain regions that are known to undergo maturational refinements during adolescence. Specifically, this study will incorporate focal functional MR BOLD techniques using cognitive and affective challenge paradigms at 3 Tesla, and single voxel GABA spectroscopy of the cingulate at 4 Tesla, with neuropsychological measures of executive function, in order to address the question of whether developing frontal brain regions are more vulnerable to illicit drug use when there is an early versus late onset of marijuana use. We believe these complimentary measures of brain function will provide new insights into the neural mechanisms of inhibitory processing and decision- making in adolescents who abuse marijuana, which has implications for early intervention and remediation.