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Principal Investigator: Agostina Casamento Moran
Organization: HUGO W. MOSER RES INST KENNEDY KRIEGER
Fiscal Year: 2024
Award: $99,113
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY
Fatigue is one of the most common and debilitating symptoms in neurological, psychiatric, and other chronic
illnesses; however, it remains poorly understood and undertreated. Post-acute sequelae of SARS-CoV-2
infection (PASC) is a novel syndrome characterized by a range of symptoms present four or more weeks after
the acute phase of COVID-19. Among these symptoms, severe fatigue is the most common and debilitating.
Critical hurdles to understanding and treating fatigue include its multidimensional nature and the lack of
quantitative methods to characterize it. In this MOSAIC K99/R00 application, I propose to use a novel `fatigue
paradigm' that leverages neuromuscular, neuroeconomic, and computational methods to objectively investigate
the neurobiological mechanisms of three features of fatigue in healthy individuals and individuals with PASC:
feeling of weariness (how weary one feels), sense of effort (how one perceives a previously exerted force), and
willingness to exert effort (an individual's decision to engage in effortful actions). My central hypothesis is that
fatigue is comprised of at least three separable features, which represent distinct psychophysiological aspects,
have unique neural correlates, and are differentially affected by PASC.
The experiments proposed for the K99 Phase, which will be executed in Dr. Vikram Chib's Neuroeconomic
Laboratory in the Kennedy Krieger Institute and Department of Biomedical Engineering at Johns Hopkins, will
identify the brain network(s) encoding the features of fatigue in healthy individuals (Aim 1) and investigate how
fatigue manifests in individuals with PASC (Aim 2). Through these projects, and the guidance of my mentoring
team (Drs. Vikram Chib, Karen Quigley, Laura Malone, and Martin Lindquist), I will acquire complementary
expertise in neuroimaging, psychophysiology, and computational and translational neuroscience. In the R00
Phase, I propose to merge my expertise in neuromuscular physiology and motor control with my newly acquired
skills to identify the brain network(s) encoding fatigue in PASC (Aim 3). This Phase will be executed in my own
laboratory upon securing an independent faculty position.
The current epidemiological significance of fatigue and PASC makes this proposal especially timely and
important, as it will significantly advance our understanding of fatigue and contribute to the NIH's RECOVER
initiative. Further, the proposed research and training plans will allow me to accomplish my long-term career goal
of becoming an independent investigator who will distinguish the neurobiological mechanisms of fatigue in
different illnesses and develop targeted clinical interventions.
Terms: <Affect><Affective><Age><Behavioral><Biofeedback><Biomedical Engineering><Brain><Brain Nervous System><COVID-19><COVID-19 infection><COVID-19 virus infection><COVID19 infection><CV-19><Chronic Disease><Chronic Illness><Clinical><Computing Methodologies><Coronavirus Infectious Disease 2019><Data><Decision Making><Development Plans><Dimensions><Economic Burden><Encephalon><Epidemiology><Exhibits><Faculty><Fatigue><Feeling><Foundations><Future><Goals><Health><Health Care Systems><Healthcare Systems><Individual><Intervention><Intervention Strategies><Investigators><Isometric Exercise><Isometrics><Laboratories><Lack of Energy><Learning><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mentors><Methods><Muscle><Muscle Tissue><Muscle-Setting Exercise><NIH><NMR Imaging><NMR Tomography><National Institutes of Health><Nature><Neurologic><Neurological><Nuclear Magnetic Resonance Imaging><PASC><Participant><Patient Self-Report><Phase><Physiologic Psychology><Physiological Psychology><Physiology><Position><Positioning Attribute><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><Psychophysiological><Psychophysiology><Race><Races><Research><Research Personnel><Researchers><SARS-CoV-2 infection><SARS-CoV2 infection><Secure><Self-Report><Severe acute respiratory syndrome coronavirus 2 infection><Static Exercise><Symptoms><Syndrome><Techniques><Training><United States><United States National Institutes of Health><Zeugmatography><acute COVID-19><acute SARS-CoV-2 infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><ages><bio-engineered><bio-engineers><bioengineering><biological engineering><career><career development><chronic COVID-19 sequelae><chronic disorder><common symptom><computational methodology><computational methods><computational neuroscience><computer based method><computer methods><computing method><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease-19><coronavirus infectious disease-19><debilitating symptom><epidemiologic><epidemiological><experiment><experimental research><experimental study><experiments><feelings><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><interventional strategy><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><motor control><muscular><neural correlate><neural imaging><neuro-imaging><neurobiological mechanism><neuroeconomics><neuroimaging><neurological imaging><neuromuscular><novel><physiopsychology><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><prevent><preventing><psycho-physiological><racial><racial background><racial origin><response><sex><skill acquisition><skill development><skills><translational neuroscience><willingness>