Mapping the brain’s fatigue network: a transdiagnostic systematic review & meta-analysis on functional correlates of mental fatigue, 2025, Schumann

[Dolphin]

Quite a lot of the studies looked at are ME/CFS studies.

https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcaf315/8242808?searchresult=1

https://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcaf315/64149947/fcaf315.pdf

Journal Article Accepted manuscript

Mapping the brain’s fatigue network: a transdiagnostic systematic review and meta-analysis on functional correlates of mental fatigue​

Andy Schumann , Monica Di Giuliano , Steffen Schulz , Feliberto de la Cruz , Teresa Kreuder , Georg Seifert , Karl-Jürgen Bär
Author Notes
Brain Communications, fcaf315, https://doi.org/10.1093/braincomms/fcaf315
Published:

28 August 2025
Article history

Abstract​

Mental fatigue is a significant psychopathological symptom that has recently gained attention, particularly in chronic fatigue syndrome/myalgic encephalomyelitis and Post COVID-19 condition. However, fatigue is a clinically relevant symptom across a wide range of mental and neurological disorders.

To identify a transdiagnostic functional network associated with fatigue, we conducted an activation likelihood estimation meta-analysis of neuroimaging studies. The primary inclusion criterion was studies involving any medical condition where patients exhibited significantly higher levels of fatigue compared to healthy controls. A systematic literature review across three major scientific databases identified 46 eligible neuroimaging studies, including a total of 2,603 individuals.

The meta-analysis of these studies revealed a widespread cortical-subcortical network involving frontal, limbic, basal ganglia, and parietal structures. Three main clusters were highlighted: a frontal-striatal-limbic cluster, a frontal-cingulate cluster, and a parietal cluster, with regions implicated in cognitive, emotional, and somatosensory symptoms associated with mental fatigue. Quality analysis indicated a moderate risk of bias in the majority of the included studies.

Overall, our findings provide scientific evidence for a transdiagnostic mental fatigue network in the brain, with key nodes located in the lateral frontal cortex, cingulate cortex, insula, thalamus, precuneus, and caudate. These results support the theory of thalamic-striatal-cortical dysfunction, which may impair compensatory mechanisms related to mental fatigue. Additionally, abnormal activation of limbic and parietal regions may contribute to cognitive, emotional, and attentional impairments linked to fatigue.

Graphical Abstract
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[Snow Leopard]

Note that there are brain/behavioural responses to fatigue which is most likely what they are measuring - the patterns they observe aren't necessarily the cause or sensory mechanisms of mental fatigue.

 

[Jonathan Edwards]

Agreed, studies of this sort don't tell us where the problem lies at all.

Studies of this sort have been used in basic consciousness studies for some time but the pitfalls have largely been ignored. A rather nice study showed that although people thought a signal on an fMRI scan showed where you were experiencing the letter L, it turned out to be the area that lights up when you see what you are told to look for, whether it is L, P or a bagel.

It highlights the embarrassing fact that neuroscientists have no clue where in the brain anything is perceived and it what structural scale. They think they do, but invoking models that turn out to be physically impossible.