Decreased functional connectivity in [LC] patients with high neuroinflammatory activity, 2026, Visser, Appelman, Knoop, van Vugt+

[SNT Gatchaman]

Decreased functional connectivity in post-COVID syndrome patients with high neuroinflammatory activity

Spoiler: Authors

Denise Visser; Leo Pieperhoff; Luigi Lorenzini; Sandeep Sv Golla; Sander Cj Verfaillie; Anouk Verveen; Elsmarieke van de Giessen; Marijke E den Hollander; Janneke Horn; Caroline M van Heugten; Menno D de Jong; Cees C van den Wijngaard; Tessa van der Maaden; Maria Prins; Patrick Schober; Robert C Schuit; Michael Kassiou; Albert D Windhorst; Brent Appelman; Michele van Vugt; Bart Nm van Berckel; Hans Knoop; Alle Meije Wink; Ronald Boellaard; Frederik Barkhof; Nelleke Tolboom

INTRODUCTION
Previous research suggests some post-COVID patients with neurocognitive complaints (NCC) show neuroinflammation. Like in inflammatory diseases, this may affect network connectivity. This study aimed to compare resting-state functional connectivity in individuals with and without i) neuroinflammation and ii) persistent post-COVID NCC.

METHODS
Forty-five participants (mean age 49±9 years, 60% female) who had a SARS-CoV-2 infection 27±9 months earlier completed neurocognitive assessment (Checklist-Individual-Strength), 60-minute dynamic [18F]DPA-714 PET scan with arterial sampling for neuroinflammation, and 3T MRI scan for resting-state functional connectivity. Twenty resting-state networks (RSNs) were identified using independent component analysis. Group differences in within-RSN connectivity were analyzed using general linear models. Differences in subcortico-cortical between-RSN connectivity—between brainstem or thalamus and cortical RSNs—were assessed using interaction models.

RESULTS
Ten participants (22%) showed neuroinflammation on [18F]DPA-714 PET, and 31 (69%) reported persistent NCC. Lower within-RSN connectivity was observed in the visual-peripheral (Nvoxels=3151, PFWE<0.05, tmean=1.77 and tmax=3.34) and dorsal-attention networks (Nvoxels=29, PFWE<0.05, tmean=1.59 and tmax=3.66) in those with neuroinflammation, and in the visual-peripheral (Nvoxels=721, PFWE<0.05, tmean=1.89 and tmax=3.45) and default mode networks (Nvoxels=123, PFWE<0.05, tmean=2.24 and tmax=4.68) in those with NCC. A significant interaction effect showed reduced functional connectivity in a large, bilateral cerebellar cluster (Nvoxels=2648, PFWE<0.05, tmean=2.31 and tmax=3.84) with increasing global [18F]DPA-714 binding in participants with NCC. Lastly, thalamic-somatomotor and brainstem-control network connectivity (between-RSN) was altered in both individuals with persistent NCC and those with neuroinflammation, with thalamic-somatomotor changes mainly driven by NCC and brainstem-control changes by neuroinflammation.

CONCLUSION
Our results suggest that neuroinflammation in individuals with persistent NCC after SARS-CoV-2 infection is linked to altered functional connectivity in RSNs central to higher-order cognitive functions.

HIGHLIGHTS
• Lower within- and between-network connectivity on MRI in post-COVID individuals

• Lower connectivity in patients with high neuroinflammatory activity on PET

• Lower connectivity in individuals with post-COVID neurocognitive complaints

• Lower thalamic-somatomotor connectivity is driven by neurocognitive complaints

• Lower brainstem-control connectivity is driven by neuroinflammatory activity

Web | DOI | NeuroImage | Open Access

 

[Eleanor]

What are they identifying as 'neuroinflammation' and 'neuroinflammatory activity'? (I've tried looking at the paper but too foggy.)

 

[rvallee]

I can't do otherwise than reflexively dismiss studies involving Knoop, but I'm really puzzled at the idea that if there is neuroinflammation, why would changes in functional connectivity be relevant, rather than the neuroinflammation? Maybe as far as understanding what is happening there are applications, but when it involves people like Knoop the goal is not to understand but to market their product.

It's not as if anyone knows what to do about functional connectivity, what it is, or what it involves. Of course that's the product here, CBT and "mind-body" stuff is what they claim to do, but no one seems to have any real clue about what any of it actually means. What does higher/lower functional connectivity even means? This all seems to be a modern analogue to "chemical imbalance" to me.

 

[Liie]

I can't do otherwise than reflexively dismiss studies involving Knoop

Same. It makes me think about what the hidden motivation could be.

Does he want to attach his name to biomed articles just so he can claim before patient groups that he also does biomed research? Or is this study created so he can claim something like "stress causes neuro-inflammation, so patients need CBT for stress".

Or maybe he really have interests in many different things.

For forum members who don't know about Knoop, he is a psychologist and psychosomatist who is famous for (among other things) hiding actigraphy null results.

 

[Grigor]

Just for context about Knoop. This study was as far as I'm aware conducted right at the beginning of the pandemic. People weren't really aware of who Knoop was. Knoop wanted to test if his patients from the ReCOVer trial would objectively improve.

Thus far I've not seen any data or hint that they did. Otherwise he would probably be screaming it from the rooftop.

Anyways, I don't think these researchers have any special love for Knoop.