Schillings, M L, Kalkman, J S, van der Werf, S P et al. · Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2004 · DOI
This study compared how the brains and muscles of ME/CFS patients and healthy people control muscle strength during a sustained squeeze test. Researchers found that ME/CFS patients had weaker voluntary control from their brain to their muscles at the start of the task, even though their muscles themselves were less fatigued afterward. This suggests that in ME/CFS, the problem may originate from reduced brain-to-muscle signaling rather than muscle weakness itself.
This study provides objective neurophysiological evidence that reduced brain-to-muscle signaling contributes to exercise limitation in ME/CFS, moving beyond subjective symptom reporting. Understanding this central mechanism could help validate ME/CFS as a physiological condition and guide development of targeted interventions based on the underlying cause rather than symptoms alone.
This study does not prove that central activation failure is the only cause of exercise intolerance in ME/CFS, nor does it establish the specific neurological or biochemical mechanisms responsible for the impaired signaling. The cross-sectional design cannot determine whether reduced central activation is a primary disease feature or a secondary adaptation, and results are limited to a single muscle group in female participants only.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Schillings, M L, Kalkman, J S, van der Werf, S P, van Engelen, B G M, Bleijenberg, G, & Zwarts, M J (2004). Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome.. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. https://doi.org/10.1016/j.clinph.2004.06.007
BibTeX
@article{mecfsatlas-schillings-2004-diminished-central,
author = {Schillings, M L and Kalkman, J S and van der Werf, S P and van Engelen, B G M and Bleijenberg, G and Zwarts, M J},
title = {Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
year = {2004},
doi = {10.1016/j.clinph.2004.06.007},
note = {PubMed: 15465441},
url = {https://www.mecfsatlas.com/evidence/schillings-2004-diminished-central},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/schillings-2004-diminished-central
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