# Investigating the neural correlates of fatigue in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome(ME/CFS)

> **NIH NIH F30** · HOWARD UNIVERSITY · 2020 · $50,520

## Abstract

PROJECT SUMMARY/ABSTRACT
Unrelenting pathological fatigue is a common symptom across a wide range of diseases and is the prominent
feature of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS). Despite its near ubiquitous
reporting, little is known about the neurobiology of fatigue. ME/CFS diagnoses presents a definitive medical
challenge. Misdiagnoses are common due to lack of biomarkers, reliance on a subjective phemonological criteria
and symptom overlap with depression. Individuals with ME/CFS also present with complaints of executive
dysfunction. Although cross sectional fMRI studies have reported unique changes in resting state and task
evoked brain activity, findings are not specific and show overlap with depression. A striking clinical feature of
ME/CFS is the response to exercise, known as post-exertional malaise (PEM). PEM is recognized as the
incremental increase in fatigue severity and executive dysfunction following acute exercise. In contrast, patients
with depression report a decrease in symptom burden. Despite this known divergent response, studies trying to
illuminate predictive biomarkers or the causative association between exercise and changes in functional brain
activity have not been adequately attempted. To address this gap, we developed and subsequently tested the
utility of a novel and longitudinal 3-day fMRI-exercise paradigm on Gulf War Illness (GWI); a disorder with
tremendous overlap of symptoms. Published findings and preliminary evidence from our GWI studies suggest
our paradigm may be effective in revealing the neurobiology of fatigue in ME/CFS. This proposal aims to harness
the unique combination of fMRI and exercise to elucidate neural correlates of fatigue in ME/CFS. The proposal
has three aims. The first aim is to characterize exercise associated decrements in fatigue by modeling changes
in functional connectivity within the Default Mode Network. The second aim is designed to demonstrate the
consequence of exercise on the causal interactions between higher level cognitive neural systems by effective
connectivity analysis. The third aim will leverage machine learning algorithms to predict ME/CFS status from
baseline task-free resting state fMRI. Findings would provide strong evidence of pathophysiological mechanisms
that maintain the chronicity of fatigue in ME/CFS. Furthermore, the importance of an accurate and detailed
description of the neurobiological constructs of fatigue will be a critical step in developing reliable diagnostic tests
and potential therapeutic targets. Outcomes from this proposal would suggest an alternative paradigm for
studying the neurobiology of fatigue in a broad number of pathological states and potential detection of this
almost universal symptom complaint in a clinical setting.

## Key facts

- **NIH application ID:** 9963415
- **Project number:** 5F30NS103563-04
- **Recipient organization:** HOWARD UNIVERSITY
- **Principal Investigator:** Rakib Rayhan
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-07-31 → 2021-07-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963415

## Citation

> US National Institutes of Health, RePORTER application 9963415, Investigating the neural correlates of fatigue in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome(ME/CFS) (5F30NS103563-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9963415. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*