Neurochemical and Functional Correlates of Memory in Emerging Adult Marijuana Users

 描述(申请人提供)：18-22岁的新兴成年人吸食大量大麻(MJ)的比率最高。在这个年龄段大量使用MJ与较差的社交、学习和职业功能有关。重要的是，这一时期的特点也是大脑持续成熟。重要的是，参与长期记忆的区域，如前额叶皮质和海马体，发育相对较晚，也有高密度的大麻素受体，这是MJ精神活性成分的主要靶标。因此，鉴于在典型的MJ使用高峰期，这些敏感的大脑区域和相应的认知过程仍在发育，因此研究大量使用MJ对这些区域的结构和功能的影响是至关重要的。最近的研究表明，青少年和新兴的成年重度MJ使用者表现出较差的记忆表现，以及在工作记忆和长期记忆任务中异常的功能磁共振成像(FMRI)大脑反应模式。然而，当结合其他成像方法进行检查时，这些功能磁共振反应模式可能会得到更好的理解。值得注意的是，磁共振波谱(MRS)可以测量反映细胞完整性和能量学的特定神经化学物质，因此可以为MJ使用者功能和认知异常的神经化学机制提供关键的洞察。为此，这项拟议的研究将整合MRS和功能磁共振成像，以更好地了解新兴成年MJ使用者记忆处理改变的神经生物学相关性。我们将在同一成像会议上评估fMRI和MRS，以表征两个已知与记忆有关的大脑区域的功能和神经化学，这两个区域被认为受到MJ大量使用的特别影响：背外侧前额叶皮质(DLPFC)和海马体。FMRI数据将在图形记忆任务的执行过程中收集，该任务在抽象视觉刺激的编码和随后的识别过程中确定大脑反应，并通常激活DLPFC和海马体。质子磁共振波谱数据将在右侧DLPFC和右侧海马区获得，以测量这些区域的大脑代谢物。这种对神经化学物质和与记忆相关的大脑反应的伴随测量将允许直接调查典型的最频繁使用MJ期间和持续大脑成熟期间神经元完整性和功能之间的关联。这项研究的结果将通过确定大量使用MJ的认知和神经生物学相关性，对公共健康具有重要意义，这可能会更好地为治疗和预防工作提供信息，并为研究治疗方案的神经生物学结果提供一个模型。总体而言，拟议的培训和研究计划将在多种神经成像技术的理论和实施方面提供特殊的培训和机会，并为今后开展旨在描绘物质使用的多方面神经认知影响的研究的独立研究铺平道路。

 DESCRIPTION (provided by applicant): Emerging adults ages 18-22 show the highest rates of heavy marijuana (MJ) use. Heavy MJ use during this age range is associated with poorer social, academic, and occupational functioning. Importantly, this period is also characterized by continued brain maturation. Importantly, regions involved in long-term memory, such as prefrontal cortex and hippocampus, develop relatively late and also have high densities of cannabinoid receptors, the primary targets for the psychoactive components of MJ. Thus, given that these sensitive brain regions and corresponding cognitive processes are still developing during the typical age of peak MJ use, it is critical to investigate the impact of heavy MJ use on the structure and function of these regions. Recent work suggests that adolescent and emerging adult heavy MJ users demonstrate poorer memory performance, as well as abnormal functional magnetic resonance imaging (fMRI) brain response patterns on working memory and long-term memory tasks. However, these fMRI response patterns may be better understood when examined in conjunction with additional imaging methods. Notably, magnetic resonance spectroscopy (MRS) can measure specific neurochemicals that reflect cellular integrity and energetics, and could therefore provide critical insight into the neurochemical mechanisms of functional and cognitive abnormalities in MJ users. To this end, the proposed study will integrate MRS and fMRI to better understand the neurobiological correlates of altered memory processing in emerging adult MJ users. We will assess both fMRI and MRS in the same imaging session in order to characterize the function and neurochemistry of two brain regions known to be involved in memory and thought to be particularly impacted by heavy MJ use: dorsolateral prefrontal cortex (DLPFC) and hippocampus. fMRI data will be collected during the performance of a Figural Memory task, which ascertains brain response during the encoding and subsequent recognition of abstract visual stimuli, and typically activates DLPFC and hippocampus. Proton MRS data will be acquired in the right DLPFC and right hippocampus to measure brain metabolites in these regions. This concomitant measurement of neurochemicals and memory-related brain response will allow the direct investigation of the associations between neuronal integrity and function during the period of typical heaviest MJ use and continued brain maturation. The results of this study will have significant relevance to public health by identifyig cognitive and neurobiological correlates of heavy MJ use, which may better inform treatment and prevention efforts, as well as provide a model for studying the neurobiological outcomes of treatment programs. Overall, the proposed training and research plan will provide exceptional training and opportunities in the theory and implementation of multiple neuroimaging techniques, as well as pave the way towards an independent research career conducting future studies aimed at delineating the multifaceted neurocognitive implications of substance use.