Role of cannabis on HIV-related cognitive impairment: a brain connectomics study

项目摘要 尽管广泛使用联合抗逆转录病毒疗法(CART)，但近一半的艾滋病毒+美国人将 经历HIV相关的神经系统合并症，对日常功能和临床产生负面影响 结果。大脑结构和功能的改变一直与HIV相关的神经认知有关 紊乱(手)，但艾滋病毒引起神经网络和 相关的认知功能没有得到很好的描述。大麻使用，这是不成比例的普遍 在HIV+人群中，可能会增加手部疾病的风险。我们的初步工作表明， 吸食大麻和艾滋病毒感染加剧了包括白质在内的主要神经网络的功能障碍 功能激活模式的异常和解偶。利用……的强大基础 我们的多学科团队对药物成瘾和艾滋病毒/艾滋病的神经行为研究，建议 研究将应用关联分析来实现以下目标：(1)考察独立和 HIV和大麻对大脑结构和功能组织的交互作用；(2)调查 脑组织网络水平紊乱与认知障碍的纵向关系； (3)使用机器深度学习算法开发手部诊断的个性化预测模型 以及基于多模图特征的严重性。使用交叉滞后面板设计，200名成年人按 艾滋病毒和大麻状况(4组)将在基线和1年进行多模式磁共振成像和认知测试 后来。中心假设是大麻的使用会加剧大脑的结构和功能紊乱。 作为手语表达和发展的基础的组织。我们的建议直接回应了RFA-18- 610，其中强调需要研究“滥用药物和艾滋病毒的根本机制” 感染通过改变的神经元网络相互作用，损害中枢神经系统的功能。这项研究使用了一个 团队科学方法，解决艾滋病指定资助的高优先主题，包括神经学 并发症[非-15-137]。建立在健全的前提和稳健的初步数据基础上，这一创新 项目有很强的潜力确定适当的神经生物标记物，可能有助于诊断和 监测慢性物质使用障碍患者的手并作为新的临床靶点 干预措施。此外，我们的分类模型有望提供一个可概括的框架 适用于个别患者量身定做治疗方法。

Project Summary Despite widespread use of combination antiretroviral therapy (cART), nearly half of HIV+ Americans will experience HIV-related neurological comorbidities that negatively impact daily functioning and clinical outcomes. Alterations in brain structure and function are consistently linked to HIV-associated neurocognitive disorders (HAND), but the mechanisms through which HIV causes alterations in neural networks and associated cognitive function are not well characterized. Marijuana use, which is disproportionately prevalent among HIV+ persons, may increase the risk of HAND. Our preliminary work suggests that co-occurring marijuana use and HIV infection intensifies dysfunction in major neural networks, including white matter abnormalities and decoupling of functional activation patterns. Capitalizing on a strong foundation of neurobehavioral research on drug addiction and HIV/AIDS by our multidisciplinary team, the proposed research will apply connectomic analyses to achieve the following aims: (1) examine the independent and interactive effects of HIV and marijuana on structural and functional organization of the brain; (2) investigate the longitudinal relationship between network-level disruptions in brain organization and cognitive impairment; and (3) use machine deep learning algorithms to develop individualized prediction models for HAND diagnosis and severity based on multimodal graph features. Using a cross-lagged panel design, 200 adults stratified by HIV and marijuana status (4 groups) will have multimodal MRIs and cognitive testing at baseline and 1 year later. The central hypothesis is that marijuana use will exacerbate structural and functional disruptions in brain organization that underlie the expression and progression of HAND. Our proposal responds directly to RFA-18- 610, which highlights the need for studies on “the underlying mechanisms whereby drugs of abuse and HIV infection interact to impair CNS functions mediated through altered neuronal networks.” This research uses a team science approach to address high priority topics for AIDS-designated funding, including neurological complications [NOT-15-137]. Building upon a sound premise and robust preliminary data, this innovative project has strong potential to identify appropriate neural biomarkers that may aid in the diagnosis and monitoring of HAND in persons with chronic substance use disorders and serve as targets for novel clinical interventions. In addition, our classification models are expected to provide a generalizable framework applicable to individual patients for tailoring of treatment approaches.