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.

项目概要/摘要 病毒受到抑制的艾滋病毒感染者 (PWH) 现在的预期寿命接近普通人群，但 与血清阴性个体相比，他们发生认知障碍的风险仍然相对较高。 甲基苯丙胺使用障碍 (METH) 是另一种在艾滋病毒感染者中更为普遍的病症，并且 METH 还与认知障碍有关，具体来说，HIV 和 METH 似乎都具有负面影响。 对与认知控制和情绪调节相关的过程的影响，包括决策， 持续注意力，并抑制与任务无关的刺激这一领域的人类神经影像学研究表明。 感染者和冰毒患者的大脑网络中都表现出低效的神经处理能力 认知控制和情绪调节（例如，额顶叶、显着性）。 文献，特别是关于艾滋病毒和冰毒对执行和情绪功能障碍的协同作用。 识别艾滋病毒和冰毒的总体影响至关重要，因为认知控制网络的畸变已经 研究显示对临床结果有负面的下游影响，包括药物依从性较差 艾滋病毒感染者、对甲基苯丙胺更强烈的渴望以及适应不良的决策。 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)，援引 艾滋病毒感染者和诸如冰毒之类的共病物质使用障碍“常常加剧或加速...... 相对于非用户的认知/行为缺陷”，以及“涉及全脑建模或 对复杂系统的考虑可能会阐明[这些]背后的大脑网络级机制 所提出的应用程序通过动态神经影像研究直接解决了这一问题。 利用最近的发现来确定冰毒和艾滋病毒对大脑区域的协同作用， 我们将招募 PWH 和血清阴性患者。 使用和不使用 METH 的控制措施 目标 1（授予 F31 项目）将量化 METH 对 HIV 相关的影响。 目标 2（本文提出）将识别导致执行功能障碍的神经振荡动力学畸变。 HIV 和 METH 如何独立和协同地影响潜在振荡动力学的改变 情绪失调，而目标 3 将阐明 HIV 和 METH 改变情绪的双向途径 控制情绪调节和执行功能的神经系统，导致两者的严重崩溃 申请人是 NIDA 支持的 F31 博士前研究员，研究认知神经科学，拥有 已经通过与拟议工作直接相关的四篇第一作者手稿而脱颖而出，并且 通过广泛的合作、指导和学士后研究，共同撰写了许多论文 本申请中提出的工作将完成申请人的论文，作为她培训的一部分。 从事神经艾滋病毒成瘾科学的职业生涯，这将为她未来的工作提供关键方向 减少感染者痛苦和共病甲基苯丙胺成瘾的干预措施的新目标。