Lange, G, Steffener, J, Cook, D B et al. · NeuroImage · 2005 · DOI
This study used brain imaging to see what happens when people with ME/CFS listen to complex spoken information. Researchers found that people with ME/CFS could understand the information just as well as healthy people, but their brains had to work much harder to do it—using more brain regions and requiring greater effort. This provides scientific proof that the thinking and concentration difficulties ME/CFS patients report are real and visible on brain scans.
This study bridges subjective patient reports and objective biology by demonstrating that cognitive complaints in ME/CFS have measurable neurobiological correlates. It validates patients' experiences of cognitive difficulty and suggests that the brain must recruit additional resources to maintain normal performance, which may contribute to post-exertional malaise and fatigue.
This study does not prove that increased brain activation causes fatigue or that it is pathological rather than compensatory. It also does not establish whether this activation pattern is a primary disease mechanism or a secondary response to underlying physiological dysfunction. The cross-sectional design cannot determine causality or how activation patterns change over time.
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
Lange, G, Steffener, J, Cook, D B, Bly, B M, Christodoulou, C, Liu, W-C, et al. (2005). Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory.. NeuroImage. https://doi.org/10.1016/j.neuroimage.2005.02.011
BibTeX
@article{mecfsatlas-lange-2005-objective-evidence,
author = {Lange, G and Steffener, J and Cook, D B and Bly, B M and Christodoulou, C and Liu, W-C and Deluca, J and Natelson, B H},
title = {Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory.},
journal = {NeuroImage},
year = {2005},
doi = {10.1016/j.neuroimage.2005.02.011},
note = {PubMed: 15907308},
url = {https://www.mecfsatlas.com/evidence/lange-2005-objective-evidence},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/lange-2005-objective-evidence
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