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Investigating the neural underpinnings of Chronic Fatigue: A multi-modal approach, 2021, Rayhan (PhD thesis)

Discussion in 'ME/CFS research' started by Dolphin, Nov 4, 2021.

  1. Dolphin

    Dolphin Senior Member (Voting Rights)

    Messages:
    3,612
    Source: Howard University
    Date: April 16, 2021
    URL:
    https://www.proquest.com/openview/c0a823ec519e5e6acdd89c29ff4a4b2a/1


    Investigating the neural underpinnings of Chronic Fatigue:
    A multi-modal approach
    ----------------------------------------------------------
    Rakib U. Rayhan
    - Department of Physiology and Biophysics, Howard University,
    Washington DC, USA


    Abstract

    Unrelenting pathological fatigue is a common symptom across a wide range
    of diseases. Despite its near ubiquitous reporting, little is known
    about the neurobiology of fatigue. Absence of a clinical consensus
    definition, meaningful treatment options, and reliable methods that
    allow for the detection and study of fatigue further hamper our
    understanding. In the study of clinically relevant fatigue, its
    presentation is often secondary to a diagnosed illness such as Multiple
    Sclerosis (MS) or cancer.
    However, there are two illnesses where
    unrelenting fatigue is the primary feature: Gulf War Illness (GWI) and
    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Diagnoses
    are based on case definition criteria that solely relies on subjective
    symptoms and their duration. Lack of identified pathophysiological
    mechanisms, use of subjective criteria for diagnoses, and symptom
    overlap with psychiatric illnesses make ME/CFS and GWI debatable
    syndromes within the field of medicine. Despite the controversy, both
    share a very notable symptom that may further our understanding of
    fatigue. This cardinal complaint is known as post-exertional malaise
    (PEM) and is defined as an increase in the severity of fatigue and other
    symptoms from baseline following a physically demanding activity. Unlike
    other reported symptoms, PEM is associated with a distinct event that
    leads to a before and after clinical state. The causal nature of PEM
    presents an opportunity to study fatigue and worsening symptomatology in
    a controlled research setting. Previous attempts have been made to
    recapitulate PEM, but did not provide reproducible findings. To address
    those limitations, we developed a novel protocol that subsequently
    modeled PEM using a multi-day paradigm where an fMRI brain scan was
    taken before and after two fatiguing exercise stressors. Data presented
    provides sufficient proof-of-principle that the protocol successfully
    modeled PEM. Initial studies were completed in GWI subjects and showed
    disrupted cortical activity within Working Memory (WM) and Default Mode
    Network (DMN) cognitive domains. Follow-up studies in a larger cohort of
    ME/CFS subjects reproduced similar post-stressor alterations within the
    DMN and its underlying functional nodes. As a corollary, modalities
    assessing gray and white matter provided further evidence that central
    nervous dysfunction may underlie the chronic symptoms of these
    disorders. From a broader perspective, modeling PEM using the developed
    protocol may hold utility in studying chronic fatigue in other
    pathological states and for the first time provide accurate detection of
    this almost universal symptom in a clinical setting.

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    (c) 2021 Howard University
     

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