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，而且包括大脑、心脏、肝脏、皮肤和肾脏在内的其他几个器官也可能受到影响。反过来，新冠肺炎会引起非常广泛的症状，包括神经系统症状，其中一些症状在疾病发作几个月后仍然存在。尤其令人感兴趣的是它对大脑的影响。为此，成像被用于研究COVID对大脑的影响，结果表明，许多人的脑组织受到广泛的损害，这种损害的程度通常(但不总是)与呼吸道症状的严重程度有关。导致大脑损伤的机制也还不清楚。重要的是，几乎所有以前使用神经成像来研究COVID对大脑的影响的研究都使用了解剖图像，即它们侧重于大脑结构。然而，研究COVID对脑功能的潜在影响也是非常重要的，并产生了巨大的潜力来补充解剖学研究。在这种背景下，这项拟议工作的主要目的是使用神经成像来研究COVID幸存者的脑功能。我们将收集静息状态(即受试者只需躺在扫描仪中)以及吸入温和二氧化碳丸剂和受控呼吸期间的功能磁共振成像(FMRI)数据，届时受试者将被指示以特定的节奏呼吸并屏息。这将使我们有机会直接评估发生在大脑特定区域的呼吸刺激的处理是否受到冠状病毒感染的影响。我们还将收集所有受试者的解剖图像，并评估COVID对大脑功能和结构的影响是否相互关联。拟议中的工作将极大地提高我们对COVID引起的广泛症状的了解，重点放在它对大脑功能组织及其呼吸控制中心的潜在影响上。反过来，这将有助于实现更好的、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.