Multimodal Imaging of NeuroHIV Dynamics (MIND): An Omaha-Pittsburgh Consortium

NeuroHIV 动力学 (MIND) 的多模态成像：奥马哈-匹兹堡联盟

• 批准号: 9919644
• 负责人: JAMES T. BECKER
• 金额: $ 94.17万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9919644
• 关键词: AIDS dementia; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adult; Affect; Architecture; Area; Attention; Behavioral; Brain; Brain Mapping; Brain region; Chronic; Code; Cognition Disorders; Cognitive; Cognitive Science; Collection; Complication; Custom; Data; Data Analyses; Databases; Development; Disease; Economics; Electrophysiology (science); Etiology; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Goals; HIV; HIV Infections; HIV-associated cognitive impairment; HIV-associated neurocognitive disorder; Human; Image; Impaired cognition; Impairment; Individual; Knowledge; Life Expectancy; Literature; Magnetic Resonance Imaging; Magnetoencephalography; Maps; Measures; Mediator of activation protein; Medical History; Medical center; Memory impairment; Methods; Modality; Monitor; Motor; Motor Cortex; Multimodal Imaging; National NeuroAids Tissue Consortium; Nature; Nebraska; Neurobiology; Neurologic; Neurons; Neuropsychological Tests; Parietal Lobe; Participant; Patients; Penetration; Performance; Persons; Physiological; Physiology; Play; Prevalence; Publishing; Quality of life; Request for Applications; Request for Proposals; Research; Research Domain Criteria; Resources; Rest; Risk; Role; Sampling; Short-Term Memory; Source; Structure; Targeted Research; Techniques; Terminal Disease; The Multicenter AIDS Cohort Study; Thick; Time Series Analysis; Unemployment; Universities; Viral; Visual Perception; Visual attention; Western World; Work; antiretroviral therapy; cognitive control; cognitive function; cognitive system; cognitive task; comorbidity; gamma-Aminobutyric Acid; hemodynamics; imaging approach; imaging modality; imaging study; innovation; instrumentation; interest; lifestyle factors; magnetic resonance spectroscopic imaging; medication compliance; motor disorder; multimodality; neural circuit; neuroAIDS; neuroimaging; neuromechanism; neuronal circuitry; novel; receptor; relating to nervous system; response

Project Summary/Abstract HIV-infected adults in the western world have a life expectancy near that of the general population, but are at a significantly elevated risk of developing cognitive impairments. Such impairments are the most common neurological complication of HIV disease, with prevalence estimates ranging from 35-70% of all HIV-infected individuals. Research targeting such comorbidities has been identified as a top priority by the Office of AIDS Research (NOT-OD-15-137). While the mechanisms underlying these deficits are not well understood, numerous human neuroimaging studies have examined the brain areas that may be involved, and overall these studies have been largely successful in identifying the critical hubs and networks. However, many questions remain regarding basic circuit dysfunction within these brain regions, and consequently there is a clear and common need to further investigate the neural dynamics and connectivity, as well as other key physiological parameters that may underlie the development and progression of HIV-related cognitive dysfunction. This proposal responds to RFA-MH-18-610, which requests proposals that “advance knowledge of the etiology of mild to moderate forms of HIV-related cognitive dysfunction by clarifying the role played by altered neuronal circuits, receptors, and networks,” using “novel neuro-electrophysiological and neuroimaging techniques.” The Multimodal Imaging of NeuroHIV Dynamics (MIND) Consortium responds to this call with an innovative, large- scale multimodal neuroimaging study that uses the latest breakthroughs in instrumentation and data analyses to identify the pathophysiology of neuroHIV in virally-suppressed adults. Specifically, the consortium will use advanced magnetoencephalographic (MEG) imaging to quantify the region- and circuit-level neural dynamics serving cognitive processing, 3-Tesla MRI and multimodal parcellation methods to map areal brain architecture, functional MRI (fMRI) for hemodynamics and intrinsic networks, and 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to quantify GABA levels in multi-voxel slabs of interest identified by the functional modalities. The investigative team includes a unique combination of experts in MEG, MRI/fMRI, MRSI, and cognitive psychology from the University of Nebraska and University of Pittsburgh Medical Centers (UNMC/UPMC). In addition, this consortium will harness existing resources such as the Multicenter AIDS Cohort Study (MACS) database and the National NeuroAIDS Tissue Consortium (NNTC) and, consistent with the RFA, will follow the Research Domain Criteria (RDoC) framework to define cognitive constructs. The consortium’s overarching hypothesis is that HIV-infected adults will exhibit aberrations in local inhibitory circuits, and that these deficits will alter gamma oscillations and thereby impair neuronal coding and interregional functional connectivity in the theta range. Such gamma deficits would provide robust explanatory power for the breadth of pathophysiological findings in the existent literature, and the MIND study is uniquely powered to investigate the underlying sources of these deficits, which are likely multifactorial (e.g., medical history, lifestyle factors, CNS viral penetration).

项目摘要/摘要 西方世界的艾滋病毒感染的成年人的预期寿命接近一般人群，但处于 显着增加了患认知障碍的风险。这种障碍是最常见的 HIV疾病的神经系统并发症，患病率估计为所有感染HIV的35-70％ 个人。艾滋病办公室已将针对此类合并症的研究确定为重中之重 研究（NOT-OD-15-137）。尽管这些缺陷的基础机制尚不清楚，但 许多人类神经影像学研究都检查了可能涉及的大脑区域，总体而 研究在很大程度上成功地识别了关键的枢纽和网络。但是，很多问题 在这些大脑区域内的基本电路功能障碍仍然存在，因此有一个清晰的和 进一步研究神经动力学和连通性以及其他关键生理的共同需求 可能是与HIV相关认知功能障碍的发展和进展的参数。 该提案对RFA-MH-18-610的回应，该提议要求“提高对病因的了解 通过改变神经元所起的作用，与中度至中度形式的HIV相关认知功能障碍 电路，接收器和网络，“使用“新型神经电子生理和神经影像学技术”。这 神经hiv动力学的多模式成像（思维）财团对此呼吁的响应具有创新的大型 - 比例多模式神经影像学研究，该研究使用仪器和数据分析中的最新突破 鉴定病毒抑制成年人中神经HIV的病理生理学。具体而言，财团将使用 先进的磁志学（MEG）成像，以量化区域和电路级神经动力学 提供认知处理，3-TESLA MRI和多模式拟合方法来绘制面积大脑结构， 用于血液动力学和内在网络的功能性MRI（fMRI）以及7-TESLA磁共振光谱 成像（MRSI）以量化由功能方式鉴定的有趣的多素板中的GABA水平。 调查团队包括MEG，MRI/fMRI，MRSI和认知的独特组合 内布拉斯加州大学和匹兹堡大学医学中心（UNMC/UPMC）的心理学。在 此外，该财团将利用现有的资源，例如多中心艾滋病队列研究（MAC） 数据库和国家神经辅助组织（NNTC），与RFA一致，将遵循 研究领域标准（RDOC）框架定义认知构建体。财团的总体 假设是，感染HIV的成年人将在局部抑制回路中表现出畸变，并且这些缺陷 将改变γ振荡，从而损害神经元编码和区域间功能连接性 theta范围。这样的伽玛定义将为病理生理的广度提供强大的拔出能力 现有文献中的发现和思维研究是为了调查潜在来源的独特动力 在这些缺陷中，可能是多因素（例如病史，生活方式因素，CNS病毒渗透）。