MRS/fMRI Investigations of Adolescent Cannabis Use

描述（由申请人提供）：我们拟议研究的总体目标是通过应用一组互补的磁共振技术来检查大麻对吸食大麻的青少年和健康不使用大麻的青少年的额叶系统发育及其功能的影响。（MR）技术和神经心理学评估。我们以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，我们发现大麻使用的早期发作和较差的神经心理学表现之间存在关联，以及在成年人停止使用大麻后不久，前扣带回和背外侧前额叶皮质的运动和记忆功能测量中出现异常皮质激活。因此，我们建议在两个青少年队列中研究大麻使用开始年龄的影响：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。将两组与年龄匹配的非吸烟青少年进行比较。虽然已经积累了大量证据表明大麻使用和额叶执行功能改变之间的关联，但很难研究和记录与大麻相关的人类大脑功能变化，特别是在青春期。在这项提案中，我们将利用高空间分辨率和增加的信号噪声提供的互补高场MR技术来调查化学和功能的影响，大麻使用额叶脑区域，已知在青春期进行成熟的细化。具体而言，本研究将纳入局灶性功能MR BOLD技术使用认知和情感的挑战范例在3特斯拉，和单体素GABA光谱的扣带回在4特斯拉，与神经心理学措施的执行功能，以解决这个问题是否发展额叶脑区更容易受到非法药物的使用时，有一个早期与晚期发作的大麻使用。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的抑制性处理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.