Impact of Marijuana Exposure on Brain Maturation

描述(由申请人提供)：这是根据PA-06-001编写的申请的第二个修订版。它描述了一个系统的5年培训计划，通过使用磁共振成像(MRI)技术，包括结构MRI、磁共振波谱(MRS)和扩散张量成像(DTI)，非侵入性地测量大脑结构和化学物质，在大麻滥用的神经成像方面启动独立的研究生涯。这项计划将允许这位神经学家候选人启动技术复杂的研究，以了解青少年中的大麻滥用及其作为“入门”毒品的潜在作用。这一目标将通过严格的培训计划来实现，整合适合候选人目标和经验的教学和研究部分。夏威夷大学(UH)提供了理想的培训环境：UH拥有全新的最先进的3Tesla研究专用磁共振扫描仪；该项目的导师以应用这些尖端技术研究药物成瘾机制而闻名。在他们的监督下，候选人将评估经常使用大麻的青少年以及年龄和性别匹配的未接触大麻的受试者，使用体内MRI、MRS和DTI来测量大脑结构和化学，以及认知能力和皮质醇水平的次要测量。我们假设：1)在吸食大麻的受试者中，灰质体积相对于白质体积的比例会更低。2)多个地区的谷氨酸和肌醇(神经胶质标记物)浓度将降低。3)皮质醇的增加和认知能力的下降将与大脑结构和化学成分的变化相关。这一奖项将为PI提供受保护的时间，使其成功成为一名独立调查员，致力于研究大脑在关键的青春期对大麻暴露的反应，当时大脑仍处于成熟阶段。

DESCRIPTION (provided by applicant): This is a second revision of an application written in response to PA-06-001. It describes a systematic 5- year training plan to launch an independent research career in neuroimaging of marijuana abuse through the use of magnetic resonance imaging (MRI) techniques, including structural MRI, magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) to non-invasively measure brain structure and chemistry. This plan will allow the candidate, a neuroscientist, to initiate technologically sophisticated research of relevance to understanding marijuana abuse in adolescents and its potential role as a "gateway" drug. This goal will be achieved through a rigorous training plan, integrating didactic and research components tailored to the candidate's goals and experience. The University of Hawaii (UH) provides an ideal training environment: UH is home to a brand new state-of-the-art 3 Tesla research dedicated MR scanner; and the mentors of this project are renowned for the application of these cutting-edge technologies to study mechanisms of drug addiction. Under their supervision, the candidate will evaluate adolescents with regular marijuana use and age and gender matched non-marijuana exposed subjects, using in vivo MRI, MRS, & DTI to measure of brain structure and chemistry, as well as secondary measures of cognitive abilities and cortisol levels. We hypothesize: 1) The proportion of gray matter volume relative to white matter volume will be lower in marijuana exposed subjects. 2) Multiple regions will have decreased glutamate and myo-inositol (glial marker) concentrations. 3) Increased cortisol and poorer cognitive performance will correlate with changes in brain structure and chemistry. This award would provide the PI with protected time to successfully become an independent investigator dedicated to the study of the brain's response to marijuana exposure during the critical adolescent years when the brain is still maturing.