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)
基本信息
- 批准号:10741681
- 负责人:
- 金额:$ 25.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:21 year oldAnatomyAnteriorApplications GrantsAttentionAutoantibodiesBehavioralBilateralBiological MarkersBloodBlood VesselsBlood specimenBrainCOVID-19 pandemicCerebrovascular systemChemicalsCholineChronic Fatigue SyndromeCoagulation ProcessConsensusCreatineDataData CorrelationsFunctional Magnetic Resonance ImagingFutureHomeImageImpairmentIndividualInflammationInflammatoryInternationalLeftLinkMRI ScansMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMeasuresModalityNeurologicParietal LobeParticipantPatient Self-ReportPerformancePositron-Emission TomographyPost-Acute Sequelae of SARS-CoV-2 InfectionPrefrontal CortexPublicationsReportingSARS-CoV-2 infectionSalivaScanningSeveritiesSourceSymptomsSyndromeTechniquesTestingTimeVisitWorld Health Organizationbehavioral responseblood oxygen level dependentbrain fogcase controlcognitive controlcognitive taskcoronavirus diseasedistractionexecutive functionglial activationinterestmicrobiomeneuralneuroimagingradioligandrecruitresponsesaliva samplesleep qualitysystemic inflammatory responseuptakewearable device
项目摘要
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.
项目总结
新冠肺炎大流行可能让数以百万计的人在几个月后出现持续的症状
首次感染SARS-CoV-2,一种被称为新冠肺炎急性后后遗症的综合征,或PASC。一种常见的
而经常使人虚弱的PASC核心症状被俗称为“大脑迷雾”,涉及干扰。
在认知控制或保持注意力集中的能力上,尤指在分心的情况下。
我们的项目是基于这样一个事实,即关键的认知控制中枢,前中扣带皮质(AMCC),
对全身炎症也是唯一敏感的,几项研究已经在PASC上报道了这一点。通过使用
双MR-PET神经成像在认知控制任务中,我们将操作并客观测量
脑雾症状,并测试小胶质细胞激活和代谢物的潜在贡献
浓度对这种症状的影响。多源干扰任务(MSIT)是一种经过验证的认知任务
在功能磁共振成像期间给药时可靠地激活aMCC的控制任务。我们将招募11名个人
符合世界卫生组织定义的PASC,该PASC还满足每个集群的至少一项标准
肌痛性脑脊髓炎国际共识标准与11例COVID康复者匹配
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)神经成像。功能磁共振成像将在执行期间进行
MSIT任务。我们预计fMRI的血氧水平依赖(BOLD)反应将更大和更多
在PASC比对照MCC更强烈。在个人层面上,我们将在MCC中定位最
在MSIT期间被激活(峰值体素),我们将使用该感兴趣区域(ROI)从
MR-PET扫描仪获得的其他神经成像方式。使用[11C]PBR28放射性配体,我们
与对照组相比,预计在PASC患者的aMCC ROI中可以发现小胶质细胞活化增加。此外,
使用全脑磁共振波谱(MRS)序列,我们预计会发现
同一ROI内与炎症相关的化学代谢物的浓度。通过使用这些
免费赠送技术,我们将创造一个客观的测量大脑的雾,并将创造一个更详细的
对其原因的机械论理解。
项目成果
期刊论文数量(0)
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