Methamphetamine and HIV status modulate the neural dynamics underlying executive dysfunction and emotion dysregulation

甲基苯丙胺和艾滋病毒状态调节执行功能障碍和情绪失调的神经动力学

• 批准号: 10762904
• 负责人: Mikki Schantell
• 金额: $ 5.35万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762904
• 关键词: Acceleration; Address; Adherence; Adult; Anterior; Area; Attention; Award; Behavior; Brain; Brain Mapping; Brain region; CD4 Positive T Lymphocytes; Cell Count; Clinical; Cognition; Cognitive; Collaborations; Complex; Conflict (Psychology); Consequences of HIV; Contracts; Data; Decision Making; Disease Progression; Dorsal; Dropout; Emotional; Enrollment; Equation; Executive Dysfunction; Exhibits; Functional disorder; Future; General Population; Goals; HIV; HIV Infections; HIV-associated cognitive impairment; Human; Impaired cognition; Individual; Intervention; Libido; Life Expectancy; Literature; Magnetoencephalography; Maintenance; Manuscripts; Maps; Mentors; Methamphetamine; Methamphetamine dependence; Methamphetamine use disorder; Methods; Modeling; Monitor; National Institute of Drug Abuse; Needle Sharing; Neurophysiology - biologic function; Outcome; Overdose; Paper; Pathway interactions; Persons; Pharmaceutical Preparations; Postbaccalaureate; Prefrontal Cortex; Process; Research; Risk; Role; Science; Stimulus; Substance Use Disorder; System; Techniques; Time; Training; United States; Unsafe Sex; Update; Viral; Virus Replication; Work; addiction; blood-brain barrier disruption; career; cingulate cortex; cognitive control; cognitive neuroscience; comorbidity; comparison control; conflict resolution; craving; direct application; emotion dysregulation; emotion regulation; executive function; experience; immune activation; innovation; interest; medication compliance; methamphetamine effect; methamphetamine use; millisecond; neural; neural circuit; neuroAIDS; neuroimaging; neurophysiology; neuroregulation; novel; personalized intervention; pharmacologic; pre-doctoral; premature; response; sexual risk taking; 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 cognitive control and emotion regulation, 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 cognitive control and emotion regulation (e.g., frontoparietal, salience). However, there is a dearth of extant literature, specifically regarding the synergistic effects of HIV and METH on executive and emotional dysfunction. Identifying the overall impact of HIV and METH is critical, as aberrations in 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 application 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 executive dysfunction and emotion dysregulation. We will enroll PWH and seronegative controls with and without METH. Aim 1 (awarded F31 project) will quantify the impact of METH on HIV-related aberrations in the neural oscillatory dynamics serving executive dysfunction. Aim 2 (proposed herein) will identify how HIV and METH independently and synergistically contribute to the altered oscillatory dynamics underlying emotion dysregulation, while Aim 3 will elucidate the bidirectional pathways whereby HIV and METH modify the neural systems governing emotion regulation and executive function, leading to accentuated breakdowns in both domains. The applicant is a NIDA-supported F31 predoctoral fellow studying cognitive neuroscience who has already distinguished herself through four first-authored manuscripts directly related to the proposed work, and numerous coauthored papers through extensive collaboration, mentoring, and postbaccalaureate research experience. The work proposed in this application will complete the applicant’s dissertation, as part of her training for a career in addiction science in neuroHIV, which will provide critical direction for her future work identifying novel targets for interventions to reduce suffering in PWH and comorbid methamphetamine addiction.

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 对与认知控制和情绪调节相关的过程的影响，包括决策， 持续关注，抑制任务无关的刺激。该领域的人类神经影像学研究已显示 PWH和有甲基苯丙胺的人在大脑网络中揭示了效率低下的神经加工 认知控制和情绪调节（例如，额叶，显着性）。但是，有多余的死亡 文学，特别是关于艾滋病毒和甲基苯丙胺对行政和情绪功能障碍的协同作用的文献。 确定艾滋病毒和甲基甲基的整体影响至关重要，因为认知控制网络的畸变已经存在 证明对临床结果有负面影响，包括较差的药物依从性 PWH，更激烈的甲基苯丙胺渴望和不良适应性决策。 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] 临床缺陷。”提出的应用程序通过动态神经影像学研究直接解决了此调用 这利用了最近的发现来确定甲基苯和艾滋病毒对大脑区域的协同作用以及 服务执行功能障碍和情绪失调的网络。我们将注册PWH和血清调子 带有和没有甲基苯丙胺的控制。 AIM 1（授予F31项目）将量化甲基酸碱对HIV相关的影响 为执行功能障碍的神经振荡动力学的畸变。 AIM 2（在此处提议）将确定 HIV和METH如何独立和协同促进振荡动力学的改变 情绪失调，而AIM 3将阐明双向途径，艾滋病毒和甲基苯丙胺改变了 控制情绪调节和执行功能的神经系统，导致两者的突出崩溃 域。申请人是NIDA支持的F31前研究者，研究认知神经科学 已经通过与拟议作品直接相关的四个成文作的手稿与众不同，并且 通过广泛的合作，心理和后肠龙研究通过大量合着的论文。 经验。作为培训的一部分，本申请中提出的工作将完成申请的论文 对于神经hiv的成瘾科学职业，这将为她未来的工作提供关键的方向 干预措施减少PWH和合并甲基苯丙胺成瘾的新目标。