The impact of chronic cannabis use on neuromagnetic activity in persons living with HIV

摘要/项目摘要 本申请描述了研究计划和研究计划，导致博士学位的一部分，结合MD- 内布拉斯加大学医学中心博士课程。研究计划的中心目标是确定 与艾滋病毒感染有关的异常脑动力学在使用大麻的人中有何不同。艾滋病毒感染者 （PLWH）有发生神经系统共病的显著风险，如HIV相关的神经认知功能障碍。 手（Hand）此外，许多PLWH是慢性大麻使用者，这种使用本身被认为会改变 长期的大脑功能，并可能调节与艾滋病毒相关的神经变化。高级神经- 使用脑磁图（MEG）的成像研究已经确定了神经动力学的特定变化 然而，与HIV感染和HAND相关，尚不清楚这些动态是否在那些 长期使用大麻。因此，拟议的研究路线旨在通过使用MEG来解决这一知识差距 对一组长期使用大麻的PLWH进行成像，并将其与非使用者的PLWH进行比较， 没有艾滋病毒的慢性大麻使用者和未感染的对照组。所有参与者将接受神经- 将认知表现与神经测量相关联的心理测试。利用脑磁图，我们可以确定神经- 通过量化基于任务的和自发的神经网络， 振荡活动在三个认知范式，这是已知的，引发神经活动有关的视觉- 空间处理、选择性注意和言语工作记忆。这些任务中的每一项都被证明是 引起PLWH和未感染对照之间的神经振荡活动的差异。将对MEG数据进行成像 使用先进的波束形成方法来生成动态功能图，并将比较各组 使用方差分析，与艾滋病毒感染和慢性大麻使用的主题之间的因素。这不仅可以让 用于识别与艾滋病毒和大麻使用相关的神经变化，但也确定 艾滋病毒感染与大麻使用之间的相互作用。此外，酒精使用将作为一个因素进行检查， 有兴趣确定在我们的样本中增加酒精使用的影响。我们的具体目标是：（1）量化 与慢性大麻使用和艾滋病毒感染相关的神经动力学， 处理，注意力和工作记忆，并研究如何艾滋病毒相关的畸变在大麻用户的不同 通过研究大麻使用者和非使用者是否感染艾滋病毒，（2）确定相互作用 慢性大麻和酒精使用在PLWH的大脑和认知功能方面的差异。总之，我们 将利用脑磁图，先进的源重建方法，神经振荡分析，神经心理学， 测试描绘慢性大麻使用和艾滋病毒感染之间的神经生理学关系。的 研究计划的目的是通过纳入严格的培训，以支持这一研究计划，建立 导师谁是艾滋病毒和药物使用领域的领导者，其主要目标是发展和扩大 申请人的研究和临床技能，以产生一个成功的医生，科学家。

Abstract/Project Summary This application describes the research plan and program of study leading to a PhD as part of a combined MD- PhD Program at the University of Nebraska Medical Center. The central goal of the research plan is to identify how aberrant brain dynamics related to HIV infection differ in those who use cannabis. People living with HIV (PLWH) are at a significant risk for developing neurologic comorbidities such as HIV-associated neurocognitive disorder (HAND). Additionally, many PLWH are chronic cannabis users, and such use itself is thought to alter long-term brain function, and potentially modulate the neural changes associated with HIV. Advanced neuro- imaging studies using magnetoencephalography (MEG) have identified specific changes in the neural dynamics related to HIV infection and HAND, however, it is unknown whether these dynamics differ in those who chronically use cannabis. Thus, the proposed line of research aims to address this knowledge gap by using MEG imaging in a group of PLWH who are chronic cannabis users and comparing them to PLWH who are non-users, chronic cannabis users without HIV, and a non-user uninfected control group. All participants will undergo neuro- psychological testing to relate cognitive performance to neural measures. Using MEG, we will identify the neuro- physiological dynamics altered by HIV and cannabis use by quantifying task-based and spontaneous neural oscillatory activity during three cognitive paradigms, which are known to elicit neural activity related to visual- spatial processing, selective attention, and verbal working memory. Each of these tasks have been shown to elicit differences in neural oscillatory activity between PLWH and uninfected controls. MEG data will be imaged using an advanced beamforming approach to generate dynamic functional maps, and groups will be compared using ANOVAs, with between-subjects factors of HIV infection and chronic cannabis use. This will not only allow for the identification of neural changes associated with HIV and cannabis use independently, but also determine the interaction between HIV infection and cannabis use. Additionally, alcohol use will be examined as a factor of interest to determine the effect of increasing alcohol use within our sample. Our specific aims are: (1) To quantify the neural dynamics associated with chronic cannabis use and HIV-infection in regards to activity serving spatial processing, attention, and working memory, and examine how HIV-related aberrations differ in cannabis users by studying cannabis users and nonusers with and without HIV-infection., and (2) to determine the interaction between chronic cannabis and alcohol use in regards to brain and cognitive function in PLWH. In summary, we will utilize MEG, advanced source reconstruction methods, neural oscillatory analyses, and neuropsychological testing to delineate the neurophysiological relationship between chronic cannabis use and HIV infection. The program of study is designed to support this research plan by incorporating rigorous training by established mentors who are leaders in the fields of HIV and drug use, with the primary goal of developing and expanding the research and clinical skills of the applicant to produce a successful physician-scientist.