Altered Oscillatory Dynamics in People with HIV and Methamphetamine Use Disorder

项目摘要/摘要 病毒抑制的艾滋病毒携带者(PWH)现在的预期寿命接近普通人群，但 与血清阴性者相比，他们患认知障碍的风险仍然很高。 甲基苯丙胺使用障碍(甲基苯丙胺)是另一种在威斯康星医院更为普遍的疾病，以及 冰毒也与认知障碍有关。具体地说，艾滋病毒和冰毒似乎都有阴性 对包括决策在内的注意力和认知控制相关过程的持续影响 注意，抑制与任务无关的刺激。这一领域的人类神经成像研究表明， PWH和冰毒患者在大脑网络中表现出低效的神经处理，这些网络服务于注意力和 认知控制(例如，额顶叶、突显)。然而，现存的文献很少，特别是关于 关于艾滋病毒和冰毒对认知和脑功能障碍的协同作用。确定总体情况 艾滋病毒和冰毒的影响是至关重要的，因为已经显示出注意力和认知控制网络的异常 对临床结果有负面的下游影响，包括PWH的药物依从性较差，更多 对冰毒的强烈渴望，以及不适应的决策。 国家药物滥用研究所(NIDA)最近发布了一份特别关注通知(NOT-DA-21-030)，引用 慢性阻塞性肺疾病和冰毒等共病物质使用障碍通常会加剧或加速… 认知/行为缺陷“相对于非使用者，以及”涉及全脑建模或 对复杂系统的考虑可能会阐明[这些]背后的大脑网络层面的机制。 临床缺陷。“拟议的研究金申请将提供这一领域的高级培训，并发起 通过利用最新发现的动态神经成像研究直接解决这一呼叫的项目 确定冰毒和艾滋病毒对大脑区域和网络的协同作用，这些区域和网络服务于注意力和 在病毒抑制的PWH中使用和不使用冰毒以及匹配的血清阴性的认知控制功能障碍 对照组(即四组)。目标1将量化威尔斯亲王医院中冰毒对性能的不利协同影响 以及为注意力和认知控制服务的神经振荡动力学，而目标2将决定 甲氨蝶呤加重病毒抑制的PWH中观察到的异常升高的自发皮质活动 与人口统计学上匹配的血清阴性对照组相比。申请者是一个很有前途的二年级博士。 学习神经科学的学生，已经通过第一次撰写的手稿直接脱颖而出 与拟议的工作有关，两份第一次创作的手稿正在接受同行审查，以及大量的合著 论文具有广泛的毕业后研究经验。在提议的奖学金中，她将成为 由托尼·威尔逊博士指导，他是一位国际知名的人类神经成像、艾滋病毒和物质专家 她将接受成瘾科学、神经艾滋病毒和临床认知神经科学方面的高级培训。

Project Summary/Abstract Virally suppressed people with HIV (PWH) now have a life expectancy near that of the general population, yet their risk of developing cognitive impairment remains substantially elevated relative to seronegative individuals. Methamphetamine use disorder (METH) is another condition that is significantly more prevalent in PWH, and METH is also associated with cognitive impairment. Specifically, both HIV and METH appear to have a negative impact on the processes associated with attention and cognitive control, including decision-making, sustained attention, and inhibiting task irrelevant stimuli. Human neuroimaging studies in this area have shown that both PWH and people with METH exhibit inefficient neural processing within the brain networks serving attention and cognitive control (e.g., frontoparietal, salience). However, there is a dearth of extant literature, specifically with regard to the synergistic effects of HIV and METH on cognitive and brain dysfunction. Identifying the overall impact of HIV and METH is critical, as aberrations in attention and cognitive control networks have been shown to have negative downstream effects on clinical outcomes, including poorer medication adherence in PWH, more intense methamphetamine cravings, and maladaptive decision-making. The National Institute on Drug Abuse (NIDA) recently issued a Notice of Special Interest (NOT-DA-21-030) citing that PWH and a comorbid substance use disorder such as METH “often have exacerbated or accelerated … cognitive/behavior deficits” relative to nonusers, and that “approaches that involve whole brain modeling or consideration of complex systems are likely to illuminate brain network-level mechanisms underlying [these] clinical deficits.” The proposed fellowship application would provide advanced training in this area and initiate a project that directly addresses this call through a dynamic neuroimaging study that leverages recent discoveries to identify the synergistic effects of METH and HIV on the brain regions and networks that serve attention and cognitive control dysfunction in virally suppressed PWH with and without METH and matched seronegative controls (i.e., four groups). Aim 1 will quantify the adverse synergistic impact of METH in PWH on performance and the neural oscillatory dynamics serving attention and cognitive control, while Aim 2 will determine whether METH accentuates the abnormally elevated spontaneous cortical activity observed in virally suppressed PWH compared to demographically matched seronegative controls. The applicant is a promising second-year PhD student studying neuroscience who has already distinguished herself through a first-authored manuscript directly related to the proposed work, two first-authored manuscripts under peer review, and a high number of coauthored papers through extensive postbaccalaureate research experience. In the proposed fellowship, she will be mentored by Dr. Tony Wilson – an internationally known expert in human neuroimaging, HIV, and substance use – and she will receive advanced training in addiction science, neuroHIV, and clinical cognitive neuroscience.