Document text
Principal Investigator: Michael B VanElzakker
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2024
Award: $208,750
Funding agency: National Institute of Neurological Disorders and Stroke
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.
Terms: <21 year old><21 years of age><Anatomic Sites><Anatomic structures><Anatomy><Anterior><Applications Grants><Attention><Autoantibodies><Behavioral><Bilateral><Biological Markers><Blood><Blood Reticuloendothelial System><Blood Sample><Blood Vessels><Blood specimen><Brain><Brain Nervous System><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 virus infection><COVID-19 years><COVID19 infection><CV-19><Cerebrovascular system><Chemicals><Choline><Chronic Fatigue Disorder><Chronic Fatigue Syndrome><Chronic Fatigue and Immune Dysfunction Syndrome><Chronic Infectious Mononucleosis-Like Syndrome><Clotting><Coagulation><Coagulation Process><Consensus><Coronavirus Infectious Disease 2019><Creatine><Data><Data Correlations><Encephalon><Functional MRI><Functional Magnetic Resonance Imaging><Future><Grant Proposals><Home><Image><Impairment><Individual><Inflammation><Inflammatory><International><Left><Link><ME/CFS><MR Imaging><MR Spectroscopy><MR Tomography><MRI><MRI Scans><MRIs><Magnetic Resonance Imaging><Magnetic Resonance Imaging Scan><Magnetic Resonance Spectroscopy><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Modality><Myalgic Encephalomyelitis><NMR Imaging><NMR Tomography><Neurologic><Neurological><Nuclear Magnetic Resonance Imaging><PASC><PET><PET Scan><PET imaging><PETSCAN><PETT><Parietal Lobe><Participant><Patient Self-Report><Performance><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Postviral Fatigue Syndrome><Prefrontal Cortex><Publications><Rad.-PET><Reporting><Royal Free Disease><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV2 infection><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Saliva><Scanning><Scientific Publication><Self-Report><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severities><Source><Symptoms><Syndrome><Techniques><Testing><Time><Visit><World Health Organization><Zeugmatography><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><age 21><age 21 years><autoimmune antibody><autoreactive antibody><behavior response><behavioral response><bio-markers><biologic marker><biomarker><blood oxygen level dependent><blood oxygenation level dependent><blood vessels in the brain><brain blood vessels><brain fog><brain vasculature><case control><case-controlled><cerebral blood vessel><cerebral vasculature><cerebrovascular vessels><cerebrovasculature><chronic COVID-19 sequelae><cognitive control><cognitive task><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><distraction><executive control><executive function><fMRI><glial activation><glial cell activation><homes><imaging><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><interest><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><microbiome><neural><neural imaging><neuro-imaging><neuroimaging><neurological imaging><parietal cortex><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><post COVID-19 sequelae><post acute sequelae following COVID-19><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><quality of sleep><radioligand><recruit><response><saliva sample><salivary sample><self reactive antibody><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sleep quality><systemic inflammation><systemic inflammatory response><twenty-one year old><twenty-one years of age><uptake><vascular><wearable><wearable device><wearable electronics><wearable system><wearable technology><wearable tool><wearables>