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

项目总结/摘要 在西方世界，感染艾滋病毒的成年人的预期寿命接近一般人口， 认知障碍的风险显著增加。这种损伤是最常见的 艾滋病毒疾病的神经系统并发症，患病率估计占所有艾滋病毒感染者的35-70% 个体艾滋病办公室已将针对此类合并症的研究确定为最优先事项 研究（NOT-OD-15-137）。虽然这些缺陷背后的机制还不清楚， 许多人类神经成像研究已经检查了可能涉及的大脑区域，总体而言， 这些研究在确定关键枢纽和网络方面基本上取得了成功。然而，许多问题 仍然关于这些大脑区域内的基本电路功能障碍，因此有一个明确的， 共同需要进一步研究神经动力学和连接，以及其他关键的生理 这些参数可能是HIV相关认知功能障碍发展和进展的基础。 本提案响应了RFA-MH-18-610，该提案要求提出“促进病因学知识 轻度至中度形式的艾滋病毒相关的认知功能障碍，通过阐明改变的神经元所起的作用， 电路，受体和网络，“使用”新的神经电生理和神经成像技术。的 神经HIV动力学多模态成像（MIND）联盟响应这一呼吁，推出了一个创新的大型- 大规模多模式神经成像研究，使用仪器和数据分析的最新突破 以确定病毒抑制成人中神经HIV的病理生理学。具体而言，该财团将利用 先进的脑磁图（MEG）成像，以量化区域和回路水平的神经动力学 提供认知处理、3特斯拉MRI和多模式分割方法，以绘制区域大脑结构， 用于血流动力学和内在网络的功能性MRI（fMRI），以及7特斯拉磁共振光谱 磁共振成像（MRSI）来量化由功能模态识别的感兴趣的多体素板中的GABA水平。 调查团队包括MEG，MRI/fMRI，MRSI和认知方面的专家 内布拉斯加大学和匹兹堡大学医学中心（UNMC/UPMC）的心理学。在 此外，该联盟将利用现有资源，如多中心艾滋病队列研究（MACS） 数据库和国家神经艾滋病组织联盟（NNTC），并与RFA一致，将遵循 研究领域标准（RDoC）框架来定义认知结构。该联盟的首要任务是 一种假设是，HIV感染的成年人将在局部抑制回路中表现出畸变，这些缺陷 将改变伽马振荡，从而损害神经元编码和区域间功能连接， θ范围这种伽马缺陷将为病理生理学的广度提供强有力的解释力。 现有文献中的发现，MIND研究是唯一能够调查潜在来源的研究。 这些缺陷，这可能是多因素的（例如，病史、生活方式因素、CNS病毒渗透）。

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).