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

项目摘要 尽管广泛使用抗逆转录病毒联合疗法（cART），但近一半的HIV+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 结果。大脑结构和功能的改变始终与HIV相关的神经认知功能相关。 疾病（手），但艾滋病毒引起神经网络改变的机制， 相关的认知功能没有很好地表征。使用避孕套， 在HIV+人群中，可能会增加HAND的风险。我们的初步工作表明，同时发生 吸食大麻和艾滋病病毒感染加剧了主要神经网络的功能障碍，包括白色物质 异常和功能激活模式的解耦。利用强大的基础 我们的多学科小组对吸毒成瘾和艾滋病毒/艾滋病的神经行为研究， 研究将应用连接组学分析，以实现以下目标：（1）检查独立和 艾滋病毒和大麻对大脑结构和功能组织的相互作用;（2）调查 大脑组织中网络水平的破坏与认知障碍之间的纵向关系; 以及（3）使用机器深度学习算法来开发用于HAND诊断的个性化预测模型 以及基于多模态图特征的严重性。采用交叉滞后面板设计，200名成年人按 HIV和大麻状态（4组）将在基线和1年时进行多模式MRI和认知测试 后中心假设是大麻的使用会加剧大脑结构和功能的破坏 组织的表达和发展的手。我们的提案直接响应RFA-18- 610，其中强调有必要研究“滥用药物和艾滋病毒 感染通过改变神经网络介导相互作用损害CNS功能。这项研究使用了 团队科学方法，以解决艾滋病指定资金的高度优先主题，包括神经病学 并发症[NOT-15-137]。在良好的前提和可靠的初步数据的基础上， 该项目具有很强的潜力，以确定适当的神经生物标志物，可能有助于诊断， 监测慢性物质使用障碍患者的HAND，并作为新的临床目标 干预措施。此外，我们的分类模型有望提供一个可推广的框架 适用于个体患者，以定制治疗方法。

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.