Graph Theoretic Analysis of Brain Networks in Cannabis Users

描述（由申请人提供）：大麻（CB）是美国使用最广泛的非法物质，CB滥用或依赖的终生流行率约为8.5%，任何使用率为32%。CB的主要精神活性成分是δ-9-四氢大麻酚（THC），它作为人脑中广泛分布的CB 1受体的配体。CB的使用与一系列认知缺陷有关，流行病学证据表明CB的使用是精神病的一个危险因素。动物研究表明，大麻对神经功能和可塑性具有普遍影响，特别是在发育过程中，这种影响在接触大麻后可能会持续存在。然而，人们对CB 1的使用如何影响人类大脑结构和功能的连接性，或者这种变化在停止使用后是否会持续存在的了解甚少。该项目将评估当前CB使用者、过去使用者（>一年禁欲）和健康青少年和无CB使用史的年轻人（每组N = 30）的功能和结构连接性以及网络特性。扩散张量成像和白色物质纤维束成像将用于量化全脑中的白色物质连接。将使用功能MRI评价静息连接。为了研究全脑网络的拓扑特性，将使用图论分析来测量全局和区域网络特性。初步数据表明，CB用户在全球网络组织的改变，这些异常与冲动性增加，增加模仿和言语功能受损。我们预测，CB的使用与网络组织的结构和功能的效率较差，特别是在高密度的CB 1受体的区域。据预测，目前的CB用户将显示出更大的变化，在连接比 禁欲用户，发病较早，更多的接触CB将预测更严重的连接障碍。在当前和以前的CB 1用户中，我们预测网络改变的严重程度将与CB使用相关的认知测量和人格特征相关。这种方法可能会导致深入了解CB使用如何影响人脑网络;停止使用后网络干扰是否恢复;以及网络改变与人格和认知功能的关系。更一般地说，由于药物滥用往往会引起大脑内动机和认知系统的广泛变化，本研究中开发的方法可能在研究药物使用的影响和对干预措施的反应方面具有广泛的应用。

DESCRIPTION (provided by applicant): Cannabis sativa (CB) is the most widely used illicit substance in the United States, with lifetime prevalence of CB abuse or dependence of about 8.5%, and of any use of 32%. The principal psychoactive ingredient of CB is delta-9-tetrahydrocannabinol (THC) which acts as a ligand for widely distributed CB1 receptors in the human brain. CB use is associated with a spectrum of cognitive deficits, and epidemiological evidence has accumulated that CB use is a risk factor for psychosis. Animal studies suggest that cannabis has pervasive effects on neural function and plasticity, especially during development, which can persist after the period of exposure. Nevertheless, there is little understanding of how CB1 use affects human brain structural and functional connectivity, or whether such changes persist after discontinuation of use. This project will evaluate functional and structural connectivity and network properties in current CB users, past users (> one year abstinence) and healthy adolescents and young adults with no history of CB use (N = 30 in each group). Diffusion tensor imaging and white matter fiber tractography will be used to quantify the white matter connectivity in the whole brain. Functional MRI will be used to evaluate resting connectivity. To investigate the topological properties of the whole-brain network, graph theoretic analysis will be used to measure global and regional network properties. Preliminary data indicated CB users have alterations in global network organization, and that these abnormalities are associated with increased impulsivity, increased schizotypy and impaired verbal function. We predict that CB use is associated with poorer efficiency in network organization for both structure and function, particularly in regions with high densities of CB1 receptors. It is predicted that current CB users will show greater alterations in connectivity than abstinent users, and that earlier onset and more exposures to CB will predict greater severity of connectivity disturbance. In current and former CB1 users, we predict that severity of network alterations will correlate with cognitive measures and personality traits associated with CB use. This approach may lead to insights into how CB use affects the human brain network; whether network disturbances recover after cessation of use; and the relationship of network alterations to personality and cognitive function. More generally, since drugs of abuse often cause widely distributed changes in motivational and cognitive systems within the brain, the methods developed in this study may have broad application in the study of the effects of drug use and response to interventions.