Connectivity between Salience and Default Mode Networks and subcortical nodes distinguishes between two classes of ME/CFS 2022 Su et al

Abstract

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with unknown pathophysiology. Functional MRI (fMRI) studies in ME/CFS have reported disparate connectivities for the brain salience (SA) and default mode (DMN) networks.

In this study, we acquired resting state and task fMRI with an advanced scanner for improved subject numbers: 24 healthy controls (HC) and 42 ME/CFS patients, 18 meeting International Consensus Criteria (ICC) and 24 meeting Fukuda criteria. We evaluated mean FC between SA and DMN network hub, and subcortical regions known to be involved in ME/CFS. We tested the hypothesis that ME/CFS connectivity differed from HC and the ICC and Fukuda classes are distinguished by different connectivities with HC for different pairs of SA, DMN or subcortical hubs. During resting state fMRI only two connections differed from HC, both for Fukuda ME/CFS and both with an SA hub. During task fMRI 10 ME/CFS connections differed from HC, 5 for ICC and 5 for Fukuda. None were common to both classes. Eight of the 10 different connections involved an SA hub, six of 10 were weaker in ME/CFS, 4 stronger. SA connections to the hippocampus and brainstem reticular activation system (RAS) differed from and were stronger than HC. The SA mediates the relative activity of the DMN and executive networks and imbalance will have functional consequences. The RAS and hippocampus modulate cortical activation. Different regulatory connections are consistent with the impaired cognitive performance and sleep-wake cycle of ME/CFS. Different neuropathology is involved in ICC and Fukuda classes.

Paywall, https://www.liebertpub.com/doi/10.1089/brain.2022.0049

 

Is this study a sort of follow up to the 2021 study discussed here? Same team, similar numbers of participants.

The 2021 study appeared to say that Fukuda and ICC brains look different on diffusion tensor imaging. We were all a bit confused in that thread as to what was really being shown.

Whereas the 2022 study is an fMRI one but this time the abstract couldn't be more clear: "Different neuropathology is involved in ICC and Fukuda classes". That's a bold statement. And important if correct.

Unfortunately we only have the abstract for now. If I understand correctly there are 3 groups being compared, 24 healthy controls, 24 pwME meeting Fukuda only, and 18 pwME meeting ICC.

During resting state fMRI there were differences between HC and Fukuda (from which I conclude there was no difference between HC and ICC in the resting state).

During task fMRI there were again differences between HC and Fukuda but this time there were also differences between HC and ICC. Notably they were different differences.

So that would support the claim that "different neuropathology is involved in ICC and Fukuda classes". However, the cohorts are small and we don't know how strong the differences were. Nor do they tell us how they classified Fukuda vs ICC.

We tend to think of ICC as a sort of Fukuda Plus, i.e. if you meet ICC you very likely also meet the less strict Fukuda. But their findings here suggest an either/or situation instead.

The one criterion that's obligatory for Fukuda but not for ICC is unrelenting fatigue. So are we looking here at the underpinnings of a subgroup that's constantly fatigued (Fukuda) versus a subgroup that's only fatigued as part of PEM (ICC)? That could explain why at rest only the Fukuda group showed any differences compared to HC, i.e. those differences could relate to fatigue.Though iIt doesn't explain why the task fMRI differences are completely different, you'd think at least some of the ones showing in Fukuda would also show in ICC.

Need to see more than the abstract.

 

Note that a more rigorous study in mild traumatic brain injury — which has had similar findings previously reported — showed no difference in resting state functional connectivity, after corrections.

A Comprehensive and Broad Approach to Resting-State Functional Connectivity in Adult Patients with Mild Traumatic Brain Injury (2024, American Journal of Neuroradiology)