An advanced functional MRI study of frontostriatal injury in adults with HIV

成人 HIV 感染者额纹状体损伤的高级功能 MRI 研究

• 批准号: 10450246
• 负责人: Xiong Jiang
• 金额: $ 58.57万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450246
• 关键词: Adult; Affect; African American; Alcohol abuse; Anterior; Attention; Behavior; Behavioral; Behavioral Paradigm; Biological Markers; Brain Diseases; Brain imaging; Brain region; Cognitive; Corpus striatum structure; Cross-Sectional Studies; Data; Development; Diagnosis; Experimental Designs; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; HIV; HIV-associated neurocognitive disorder; High Prevalence; Hippocampus (Brain); Impairment; Individual; Injury; Learning; Link; Literature; Longitudinal Studies; Machine Learning; Magnetic Resonance Imaging; Measures; Mediating; Memory; Meta-Analysis; Modality; Motor; Neurocognitive; Neurocognitive Deficit; Neurons; Pattern; Performance; Play; Prefrontal Cortex; Prevalence; Process; Recording of previous events; Research; Resistance; Role; Severities; Short-Term Memory; Signal Transduction; Structure; Substance abuse problem; Surrogate Markers; Techniques; Testing; Thalamic structure; Therapeutic Effect; Variant; antiretroviral therapy; base; behavior test; cerebral atrophy; cingulate cortex; clinically relevant; cognitive function; cognitive neuroscience; comorbidity; design; effective therapy; executive function; flexibility; improved; innovation; male; mild neurocognitive impairment; mitochondrial dysfunction; nerve injury; neuroAIDS; neuromechanism; novel; pressure; relating to nervous system; success; tool; treatment response; virology

PROJECT SUMMARY/ABSTRACT In the era of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders, or HAND, remains high in people with HIV (PWH); as a result, there is increasing pressure to identify neural targets for effective therapies. However, to develop effective HAND treatments, there is a strong need for the development of sensitive behavioral tests that can quickly screen and effectively identify probable neurocognitive impairment in PWH and biomarkers that can accurately determine HAND status and evaluate therapeutic effects. This 5-year cross-sectional and longitudinal study is theoretically driven and specifically designed to tackle these challenges. Neural injury to the frontostriatal circuits (plus hippocampus, thalamus, and other associated regions) has long been recognized as a key component in HAND; however, the association between frontostriatal injury and HAND status remains to be elucidated. Recent findings suggest that injury to different key regions in the frontostriatal circuits may play differential roles in HAND status: frontal injury is more prevalent in PWH, but striatal injury better predicts HAND status. This suggests that an accurate assessment of neural injury at different frontostriatal regions (plus other key regions such as hippocampus and thalamus) may have the potential to serve as a biomarker to assist with HAND diagnosis and characterization. To test this hypothesis, we will investigate frontostriatal injury in PWH using two behavioral paradigms that are known to involve distinct frontostriatal regions, along with two advanced functional MRI (fMRI) techniques, fMRI- adaptation (fMRI-A) and multivariate pattern analysis (MVPA). Compared to conventional fMRI techniques, fMRI-A and MVPA techniques can better estimate neural tuning/selectivity that can be directly related to behavioral performance. Briefly, we hypothesize that frontostriatal injury – a central component in HAND – is highly prevalent in PWH and can be assessed behaviorally via two behavioral paradigms (Aim 1), and neurally via fMRI-A & MVPA (Aim 2). The integration of behavioral and fMRI data will help to assess the degree of neural injury at different frontostriatal and associated regions, which in turn may serve as a biomarker for HAND status (Aim 3). The probable impact of common comorbidities (e.g., history of substance and alcohol abuse, etc.) will also be investigated. In summary, this proposal is theoretically driven and highly innovative, with a strong promise for future clinically relevant development. The feasibility of the proposed research is supported by a strong foundation in cognitive neuroscience and neuroHIV, strong preliminary data, and an established research team. The success of this proposed project may help to develop sensitive behavioral tests that can effectively detect mild neurocognitive impairment in PWH, and a biomarker that can assist in determining HAND status/severity.

项目摘要/摘要 在联合抗逆转录病毒治疗(CART)的时代，艾滋病毒相关神经认知的流行 疾病，或手，在艾滋病毒携带者中仍然很高；因此，有越来越大的压力来 确定有效治疗的神经靶点。然而，要开发有效的手部治疗方法，有很强的 需要开发能够快速筛选和有效识别的敏感行为测试 PWH和生物标志物中可能的神经认知损害可以准确地确定手的状态和 评估治疗效果。这项为期5年的横断面和纵向研究是理论上推动的， 专门为应对这些挑战而设计的。 额纹状体环路(加上海马体、丘脑和其他相关区域)的神经损伤 长期以来一直被认为是手部的关键组成部分；然而，额纹状体损伤和 手的状态还有待阐明。最近的研究结果表明，大脑中不同关键区域的损伤 额纹状体环路在手部状态中可能扮演不同的角色：额部损伤在PWH中更常见，但 纹状体损伤能更好地预测手部状况。这表明，对神经损伤的准确评估 不同的额纹状体区域(加上其他关键区域，如海马体和丘脑)可能有 作为生物标记物辅助手部诊断和表征的可能性。为了测试这一点 假设，我们将使用两种已知的行为范式来研究PWH患者的额纹状体损伤 涉及不同的额纹状体区域，以及两种先进的功能磁共振成像(FMRI)技术，fMRI- 适应(fMRI-A)和多变量模式分析(MVPA)。与传统的fMRI技术相比， FMRI-A和MVPA技术可以更好地估计神经调节/选择性，这可以直接与 行为表现。简而言之，我们假设额纹状体损伤--手头的一个中心组成部分--是 在PWH中非常普遍，可以通过两种行为范式(目标1)来评估行为 通过fMRI-A和MVPA进行神经治疗(目标2)。行为和功能磁共振数据的整合将有助于评估 不同额纹状体及相关区域的神经损伤程度，这反过来可能是 手部状态的生物标志物(目标3)。常见合并症(如物质史)可能产生的影响 和酗酒等)也将接受调查。 总之，这一建议是理论驱动的，具有很高的创新性，在未来的临床上具有很强的前景。 相关发展。这项研究的可行性得到了坚实的认知基础的支持。 神经科学和神经艾滋病毒，强大的初步数据，以及成熟的研究团队。这件事的成功 拟议的项目可能有助于开发敏感的行为测试，可以有效地检测轻微的神经认知 PWH的损害，以及有助于确定手的状态/严重程度的生物标记物。