Investigation of the effects of COVID-19 on the functional resting-state and respiratory-related organization of the brain using multimodal neuroimaging

自一年前COVID大流行爆发以来，很明显，该病毒的影响不仅限于呼吸系统，还可能影响其他几个器官，包括大脑、心脏、肝脏、皮肤和肾脏。反过来，COVID-19会引起非常广泛的症状，包括神经系统症状，其中一些症状在发病后持续数月。特别有趣的是它对大脑的影响。为此，影像学已被用于研究COVID对大脑的影响，结果表明，许多人的脑组织遭受了广泛的损伤，这种损伤的程度通常（但不总是）与呼吸道症状的严重程度有关。导致脑损伤的机制也尚不清楚。重要的是，之前几乎所有使用神经成像来研究COVID对大脑影响的研究都使用了解剖学图像，即它们专注于大脑结构。然而，研究COVID对脑功能的潜在影响也非常重要，并为补充解剖学研究提供了巨大的潜力。在这种情况下，拟议工作的主要目的是使用神经成像来研究COVID幸存者的大脑功能。我们将收集静息状态（即受试者只是躺在扫描仪中）以及吸入轻度二氧化碳和控制呼吸期间的功能磁共振成像（fMRI）数据，当受试者被指示以特定的节奏呼吸并屏住呼吸时。这将使我们有机会直接评估大脑特定区域对呼吸刺激的处理是否受到COVID的影响。我们还将收集所有受试者的解剖图像，评估COVID对脑功能和结构的影响是否相互关联。拟议的工作将极大地增强我们对COVID引起的广泛症状的认识，重点关注其对大脑功能组织及其呼吸控制中心的潜在影响。反过来，这将有助于更好的，个性化的短期和长期治疗。

Since the outbreak of the COVID pandemic a year ago, it has become evident that the effects of the virus are not limited to the respiratory system and that several other organs, including the brain, heart, liver, skin and kidneys can be affected. In turn, COVID-19 causes a very wide range of symptoms, including neurological symptoms with some of these symptoms persisting several months after disease onset. Of particular interest are its effects on the brain. To this end, imaging has been used to study the effects of COVID on the brain and the results have suggested that many individuals suffer widespread damage in their brain tissue and that the extent of this damage is usually (but not always) related to the severity of the respiratory symptoms. The mechanisms that cause brain damage are also not understood yet. Importantly, almost all previous studies that have used neuroimaging to study the effects of COVID on the brain have used anatomical images, i.e. they have focused on brain structure. However, investigating the potential effects of COVID on brain function is also of great importance and yields significant potential for complementing anatomical studies. In this context, the main aim of the proposed work is to use neuroimaging to study brain function in COVID survivors. We will collect functional magnetic resonance imaging (fMRI) data both during the resting-state (i.e. subjects will just lie in the scanner), as well as during inhalation of mild carbon dioxide boluses and controlled breathing, when subjects will be instructed to breath at a specific rhythm and hold their breath. This will give us the opportunity to directly assess whether the processing of respiratory stimuli which take place in specific areas of the brain is affected by COVID. We will also collect anatomical images from all subjects and assess whether COVID effects on brain function and structure are related to each other. The proposed work will greatly enhance our knowledge on the wide range of symptoms caused by COVID, focusing on its potential effects on the functional organization of the brain and its respiratory control centers. In turn, this will contribute towards better, individualized short-term and long-term therapies.