Cognitive impairment and associated neurobehavioral dysfunction in post-COVID syndrome, 2025, Schmidt et al

Cognitive impairment and associated neurobehavioral dysfunction in post-COVID syndrome

Laura Marie Schmidt, Carsten Klingner, Insa Petersen, Annika Volkmer, Minne Schreiber, Alexander Schmidt, Philipp Reuken, Bianca Besteher, Christian Geis, Markus Ullsperger, Kathrin Finke, Eva Maria Martin, Sven Rupprecht, Stefan Brodoehl, Franziska Wagner

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Highlights
· Post-COVID patients show significantly slower reaction times on cognitive tasks.
· Slower reaction times in post-COVID patients are associated with brain hypoarousal.
· Increased reward influence over time: The effect of rewarding cues on task performance increases significantly over time for post-COVID patients.
· fMRI scans reveal delayed activation in the left frontal gyrus and increased task-positive network activity during cognitive tasks.

Abstract
There is a high prevalence of neuropsychiatric sequelae in post-COVID syndrome, most commonly chronic fatigue, the mechanisms of which remain poorly understood. As altered function of the reward system has been suggested as a causal factor, we aimed to distinguish whether reward processing or task-unspecific cognitive operations are impaired in post-COVID syndrome.

Our cohort study included 24 patients diagnosed with post-COVID syndrome and 24 demographically matched healthy controls. Questionnaire assessment of neuropsychiatric symptoms and socio-demographic variables, the Monetary Incentive Delay Task during an fMRI scan, and pupillary measurements were performed.

In addition to clinical neuropsychiatric symptoms, participants in the post-COVID group demonstrated significantly slower task performance compared to healthy controls, although the function of behavioral reward circuits appeared unimpaired. However, the influence of rewarding cues on post-COVID patients increased significantly over time during task performance, correlating with temporally delayed activation of the left frontal gyrus and increased activity in task-unspecific brain regions in post-COVID patients. Furthermore, slower reaction times on the task were associated with a lower pupil diameter and a higher pupillary unrest index.

This study proposes that post-COVID syndrome is a process that may not affect reward processing, but leads to neural hypoarousal and temporally altered brain activity in frontal and task-unspecific brain regions.

Link (Psychiatry Research) [Paywall]

 

Fatigue as a result of faulty reward processing? Sounds a lot the «effort preference». And of course they found that reward processing wasn’t impacted. Which means that they have to discard the hypothesis.

 

So they expected to find PCS patients were less reward-motivated (because of our "anhedonia" causing us to imagine that we're fatigued, innit)

but they actually found the opposite?

 

@Eleanor I’m not sure I agree with their hypothesis. Because why would your performance decline over time because you’re less motivated by rewards? Wouldn’t it make more sense to see a general lower performance overall?

Unless they believe that people automatically stop putting in effort over time, and they need rewards to keep going? But at that point, it can be questioned if the rewards are high enough?

From the study:

This is from the user manual of the MID-T, and the example uses very low rewards.

I also wonder if it was only the effect of the rewarding cues that increased, or if they observed the same effect with the other cues as well. Because that might indicate an overall learning effect - that people with brainfog need some time to get going.

After all, the PC performed worse in general.

 

Oh. Yes. Hypothesis totes discarded. For they are scientists, and scientists totes discard their debunked hypotheses.



Although, it's not as if this is a valid way of testing this. Not that we can see the details, but it's not possible to differentiate fatigue from lack of motivation, and they can simply be a matter of perspective. Just like paralysis can be framed as giving up on the motivation to walk, if one has the motivation to frame it this way.

Best they can do is ask. Usually in the hands of psychs it would involve very odd questions that are interpreted even more oddly. And they can simply discard results if they disagree with them.

Basically the simple choice of looking yet again for this ridiculous gotcha says everything about the intent of this study. They're just doing a very expensive version of trying to catch someone who is paralyzed by continuously looking away and back very quickly in a "HAHA! Gotcha moving! Oh, nevermind." "HAHA! Gotcha moving! Oh, nevermind." "HAHA! Gotcha moving! Oh, nevermind." "HAHA! Gotcha moving! Oh, nevermind."

 

I wonder what it says that this is basically identical to the EEfRT junk, but they don't mention it, and it's not in the references. Maybe they're unaware, but this is the same test with the same intent and conditions that make it invalid.

Also very insulting and infantilizing. As if a dollar is something that should motivate an adult suffering from chronic illness, like we're clapping seals begging for a fish. I hate how they look down on us so smugly while pushing out the most mediocre effort humans can put together.

 

Yeah, it’s the same issue all over again, especially the refusal to consider alternative explanations and interpretations of the tests.

 

Good point.

The whole thing is probably pretty tenuous anyway given the infant nature of the art of trying to interpret psychological states from fMRI, and perhaps especially so in the context of other people's findings on cerebral blood flow.

 

Maybe they caught cognitive PEM on fMRI camera without knowing?

 

Just would like to make people aware that this is an Elsevier journal so you can request patient access:

(Maybe we could add the link to the opening posts of threads on research articles published by Elsevier?)

 

The most disturbing thing about the EEfRT episode was when the creators of the test, who explicitly said it should not be used in a similar context, found nothing wrong with that, most likely because they don't believe in ME/CFS, or at best just don't understand how it meets their criteria for not being valid in this case. It just sealed the deal for just how much this is not a problem with individuals but with systems that are simply not functioning correctly. How as long as the systems are malfunctioning, most individuals will simply fail because it's the only acceptable way of doing things.

It just reminds me exactly of the worst politics out there, where some people will completely flip their approval of one thing or another, usually because their chosen leader has changed their tune, even to the point of rejecting things they have claimed as deep core personal values for most of their lives. It's the exact same problem.

 

I think it’s just an extremely pervasive problem in psychological testing. I once did a a very similar “test” for ADHD where letters flashed on the screen and you had to press a key on the right ones.

The idea was that people with ADHD would get bored a lot faster and their reaction time/accuracy would be a lot worse.

They told me I couldn’t have ADHD because my reaction time in the later part of the test was even better than average. Which was because the test had the exact same mechanism as a mini-game l had been playing a lot recently in a popular video game.

Funnily enough, the fact that I would spend hours and hours on games and completely lose track of time, to the point of forgetting to eat or drink, was a piece of evidence of ADHD hyperfixation for the competent psychiatrist who eventually diagnosed me.

 

I’m glad you eventually found a competent psychiatrist!

I had a similar experience with my neuropsychiatric evaluation after I got ME/CFS from covid. I did a load of tests, and many of them were very similar to things I like doing anyways. I don’t think those make me any smarter, just good at solving and optimising silly games.