Altered Oscillatory Dynamics in People with HIV and Methamphetamine Use Disorder

艾滋病毒和甲基苯丙胺使用障碍患者的振荡动力学改变

• 批准号: 10590607
• 负责人: Mikki Schantell
• 金额: $ 1.71万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-09 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10590607
• 关键词: Acceleration; Address; Adherence; Adult; Area; Attention; Behavior; Behavioral; Brain; Brain Mapping; Brain region; CD4 Positive T Lymphocytes; Cell Count; Clinical; Cognition; Cognitive; Cognitive deficits; Complex; Contracts; Decision Making; Disease Progression; Dorsal; Dropout; Exhibits; Fellowship; Functional disorder; General Population; Goals; HIV; HIV Infections; HIV-associated cognitive impairment; HIV/AIDS; Human; Impaired cognition; Individual; International; Libido; Life Expectancy; Literature; Magnetoencephalography; Manuscripts; Maps; Mentors; Methamphetamine; Methamphetamine use disorder; Modeling; National Institute of Drug Abuse; Needle Sharing; Neurologic; Neurophysiology - biologic function; Neurosciences; Outcome; Paper; Participant; Peer Review; Performance; Persons; Play; Postbaccalaureate; Process; Public Health; Research; Risk; Role; Science; Scientist; Stimulus; Substance Use Disorder; System; Time; Training; United States; Unsafe Sex; Viral; Virus Replication; Visual attention; Work; addiction; antiretroviral therapy; attentional control; blood-brain barrier disruption; brain dysfunction; cognitive control; cognitive function; cognitive neuroscience; comorbidity; conflict resolution; craving; doctoral student; experience; imaging modality; immune activation; innovation; interest; medication compliance; methamphetamine effect; methamphetamine use; millisecond; neural; neuroAIDS; neuroimaging; premature; response; sexual risk taking; stimulus processing; substance use; sustained attention; temporal measurement; vigilance

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.

项目摘要/摘要 现在，病毒抑制艾滋病毒（PWH）的人的预期寿命接近一般人群，但是 他们患认知障碍的风险仍然相对于血清神经个体而显着升高。 甲基苯丙胺使用障碍（METH）是PWH中明显更普遍的另一种状况，并且 甲基苯丙胺也与认知障碍有关。具体而言，艾滋病毒和甲基苯丙胺似乎都有阴性 对与注意力和认知控制相关的过程的影响，包括决策，持续 注意并抑制任务无关的刺激。该领域的人类神经影像学研究表明 PWH和患有甲基苯丙胺的人在大脑网络中暴露了效率低下的神经加工，引起了人们的注意和 认知控制（例如，额叶，显着性）。但是，有额外的文学作品，特别是 关注HIV和METH对认知和脑功能障碍的协同作用。确定整体 艾滋病毒和甲基苯丙胺的影响至关重要，因为已经显示了注意力和认知控制网络的畸变 对临床结果产生负面影响，包括PWH中的药物依从性较差，更多 强烈的甲基苯丙胺渴望和适应不良的决策。 美国国家药物滥用研究所（NIDA）最近发出了特殊利益的通知（NOT-DA-21-030）引用 PWH和一种合并症的药物使用障碍，例如Meth“经常加剧或加速…… 认知/行为相对于非用户定义”，“涉及整个大脑建模或 考虑复杂系统的考虑可能会阐明[这些] 拟议的奖学金申请将在该领域提供高级培训，并启动A 通过一项动态神经影像学研究直接解决此呼叫的项目，该研究利用了最新发现 确定甲基苯丙胺和艾滋病毒对吸引注意力和网络的协同作用 具有和没有甲基匹配的匹配性血清负格的实际抑制PWH的认知控制功能障碍 控件（即四组）。 AIM 1将量化甲基对PWH对性能的不利协同影响 以及具有关注和认知控制的神经振荡动力学，而AIM 2将决定是否确定 METH突显了在病毒抑制的PWH中观察到的绝对升高的赞助皮质活性 与人口统计匹配的血清神经对照相比。申请人是承诺的二年级博士 研究神经科学的学生已经直接通过第一章手稿来脱颖而出 与拟议的工作有关 通过广泛的后洞研究经验的论文。在拟议的奖学金中，她将 由托尼·威尔逊（Tony Wilson）博士指导，托尼·威尔逊（Tony Wilson）是人类神经影像，艾滋病毒和物质的国际知名专家 使用 - 她将接受成瘾科学，神经活动和临床认知神经科学方面的高级培训。