Glial activation and metabolite contributions to 'brain fog' post-acute sequelae of COVID-19 (PASC)

胶质细胞激活和代谢物对 COVID-19 急性后遗症“脑雾”的贡献（PASC）

• 批准号: 10741681
• 负责人: Michael B VanElzakker
• 金额: $ 25.05万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10741681
• 关键词: 21 year old; Anatomy; Anterior; Applications Grants; Attention; Autoantibodies; Behavioral; Bilateral; Biological Markers; Blood; Blood Vessels; Blood specimen; Brain; COVID-19 pandemic; Cerebrovascular system; Chemicals; Choline; Chronic Fatigue Syndrome; Coagulation Process; Consensus; Creatine; Data; Data Correlations; Functional Magnetic Resonance Imaging; Future; Home; Image; Impairment; Individual; Inflammation; Inflammatory; International; Left; Link; MRI Scans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Modality; Neurologic; Parietal Lobe; Participant; Patient Self-Report; Performance; Positron-Emission Tomography; Post-Acute Sequelae of SARS-CoV-2 Infection; Prefrontal Cortex; Publications; Reporting; SARS-CoV-2 infection; Saliva; Scanning; Severities; Source; Symptoms; Syndrome; Techniques; Testing; Time; Visit; World Health Organization; behavioral response; blood oxygen level dependent; brain fog; case control; cognitive control; cognitive task; coronavirus disease; distraction; executive function; glial activation; interest; microbiome; neural; neuroimaging; radioligand; recruit; response; saliva sample; sleep quality; systemic inflammatory response; uptake; wearable device

Project summary The COVID-19 pandemic has left potentially millions of individuals with ongoing symptoms months after initial infection by SARS-CoV-2, a syndrome called post-acute sequalae of COVID-19, or PASC. A common and often-debilitating core symptom of PASC is colloquially known as "brain fog," which involves disruption in cognitive control or the ability to maintain focus and attention especially in the presence of distraction. Our project is based in the fact that the key cognitive control hub, the anterior midcingulate cortex (aMCC), is also uniquely sensitive to systemic inflammation, which several studies have reported in PASC. By using dual MR-PET neuroimaging during a cognitive control task, we will operationalize and objectively measure the brain fog symptom, and test the potential contribution of microglial activation and metabolite concentrations to this symptom. The multi-source interference task (MSIT) is a well-validated cognitive control task that reliably activates the aMCC when administered during fMRI. We will recruit 11 individuals with World Health Organization defined PASC who also fulfill at least one criterion from each cluster of the myalgic encephalomyelitis International Consensus Criteria, and 11 COVID-recovered healthy matched controls. All participants will complete the MSIT task during MRI-PET (magnetic resonance imaging - positron emission tomography) neuroimaging. Functional MRI will be conducted during performance of the MSIT task. We expect the fMRI blood oxygen level-dependent (BOLD) response to be larger and more intense in PASC than control aMCC. At an individual level, we will locate the voxel within aMCC that is most activated (peak voxel) during MSIT, and we will use this region of interest (ROI) to extract data from the other neuroimaging modalities acquired by the MR-PET scanner. Using the [11C]PBR28 radioligand, we expect to find increased microglial activation within the aMCC ROI in PASC versus controls. Furthermore, using a whole-brain magnetic resonance spectroscopy (MRS) sequence, we expect to find increased concentration of inflammation-linked chemical metabolites within that same ROI. By using these complimentary techniques, we will create an objective measure of brain fog, and will create a more detailed mechanistic understanding of its cause.

项目概要 COVID-19 大流行已导致数百万人在几个月后仍出现持续症状 最初感染 SARS-CoV-2，这是一种称为 COVID-19 急性后遗症（PASC）的综合征。一个常见的 PASC 经常使人衰弱的核心症状通俗地称为“脑雾”，涉及破坏 认知控制或保持注意力的能力，尤其是在分心的情况下。 我们的项目基于以下事实：关键的认知控制中枢，前中扣带皮层 (aMCC)， 对全身性炎症也具有独特的敏感性，多项研究已在 PASC 中报道了这一点。通过使用 在认知控制任务期间使用双 MR-PET 神经影像，我们将操作并客观地测量 脑雾症状，并测试小胶质细胞激活和代谢物的潜在贡献 浓度到这种症状。多源干扰任务（MSIT）是一种经过充分验证的认知任务 在功能磁共振成像期间执行时，可靠地激活 aMCC 的控制任务。我们将招聘11人 世界卫生组织定义的 PASC 还满足每个集群中至少一项标准 肌痛性脑脊髓炎国际共识标准，以及 11 名康复的健康匹配的新冠肺炎患者 控制。所有参与者将在 MRI-PET（磁共振成像 - 正电子发射断层扫描）神经影像。功能性 MRI 将在表演期间进行 MSIT 任务。我们预计 fMRI 血氧水平依赖性 (BOLD) 反应会更大、更多 PASC 中的强度比对照 aMCC 中的强度。在个体层面上，我们将在 aMCC 中找到最重要的体素。 在 MSIT 期间激活（峰值体素），我们将使用该感兴趣区域 (ROI) 从 MR-PET 扫描仪采集的其他神经影像模式。使用 [11C]PBR28 放射性配体，我们 预计与对照组相比，PASC 中 aMCC ROI 内的小胶质细胞激活有所增加。此外， 使用全脑磁共振波谱（MRS）序列，我们期望发现增加 同一 ROI 内与炎症相关的化学代谢物的浓度。通过使用这些 补充技术，我们将创建脑雾的客观测量，并将创建更详细的 对其原因的机械理解。