Reaction time deficits in a 3D virtual reality test in patients with ME/CFS, 2025, Ladek et al

forestglip

forestglip

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Reaction time deficits in a 3D virtual reality test in patients with ME/CFS
Anja-Maria Ladek; Marianna Lucio; Christian Y Mardin; Bettina Hohberger
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Purpose
Chronic Fatigue Syndrome (ME/CFS) is a debilitating post-infectious disorder affecting approximately 140,000–310,000 individuals in Germany, characterized by symptoms such as post-exertional malaise (PEM) and cognitive impairments.

Considering the neurotropic effects of various pathogens, this study hypothesized that reaction time (RT) in three-dimensional (3D) visual tasks would be significantly prolonged in ME/CFS patients compared to controls.

Methods
A total of 112 participants (56 ME/CFS patients and 56 controls) were recruited at the Department of Ophthalmology, Universität of Erlangen-Nürnberg. RT was assessed using a Virtual-Reality-Ocular-Test-System, presenting 3D stimuli at three disparity levels (275, 550, 1100) across 9 viewing directions. Participants completed three gaming repetitions (G1, G2, G3).

Mixed-effects models were used to evaluate group differences, with age and gender included as covariates. Pairwise contrasts were calculated to assess changes across repetitions. The study has been approved by the local ethics committee and performed in accordance with the tenets of the Declaration of Helsinki.

Results
Least square means (LS-Means) for RT in ME/CFS patients were significantly prolonged compared to controls at all disparity levels: 2333 ms vs. 1561 ms (disparity 275), 1625 ms vs. 1208 ms (disparity 550), and 1264 ms vs. 959 ms (disparity 1100), all p < 0.001. Age was a significant covariate (p<0.001), while gender showed no effect.

Both groups demonstrated improvements in RT over repetitions; however, controls exhibited greater improvements. The difference in RT between groups became more pronounced by G3 (p = 0.00021). ME/CFS patients consistently lagged behind controls, particularly in later gaming repetitions, potentially reflecting the impact of PEM.

Conclusions
ME/CFS patients exhibit prolonged RTs in a virtual 3D environment compared to controls, with their performance deteriorating further over time. This highlights the potential utility of virtual 3D vision testing as a diagnostic and functional assessment tool for ME/CFS, particularly in understanding cognitive and physical impairments associated with PEM.

This abstract was presented at the 2025 ARVO Annual Meeting, held in Salt Lake City, Utah, May 4-8, 2025.

Link [Investigative Ophthalmology & Visual Science] (Abstract only)
 
I think a reaction time deficit is the most consistent finding in all cognitive testing (I wrote a blog about this years ago, but don't have the energy to find that now). On the other hand, nobody I know with this illness is ever complained about reaction time being a significant problem, so who knows what it means.

Edit unfortunate Siri misquotes corrected, apologies
 
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forestglip said:
ME/CFS patients consistently lagged behind controls, particularly in later gaming repetitions, potentially reflecting the impact of PEM.

Conclusions
ME/CFS patients exhibit prolonged RTs in a virtual 3D environment compared to controls, with their performance deteriorating further over time. This highlights the potential utility of virtual 3D vision testing as a diagnostic and functional assessment tool for ME/CFS, particularly in understanding cognitive and physical impairments associated with PEM.
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How did they identify PEM?
 
Simon M said:
On the other hand, nobody I know with this illness is ever complained about reaction time being a significant problem, so who knows what it means.
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I have seen people with ME/CFS complaining about a difficulty with timed tasks, and avoiding them because they become stressful rather than than fun. I've seen comments like that made in relation to online gaming.

I had the impression that most people with ME/CFS noticed a (fluctuating) reduction of reaction speed.
 
Hutan said:
I have seen people with ME/CFS complaining about a difficulty with timed tasks, and avoiding them because they become stressful rather than than fun. I've seen comments like that made in relation to online gaming.

I had the impression that most people with ME/CFS noticed a (fluctuating) reduction of reaction speed.
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Yes, I can imagine it's a problem with online gaming, which is a pretty artificial situation.

I've never heard anyone with this illness mentioned reaction time as a problem general conversation or discussion about symptoms. Could you be more specific, I'm curious?
 
Simon M said:
I think a reaction time deficit is the most consistent finding in all cognitive testing (I wrote a blog about this years ago, but don't have the energy to find that now). On the other hand, nobody I know with this illness is ever complained about reaction time being a significant problem, so who knows what it means.
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Yeah, a good overall description of my cognitive limitations is that I can do most of the things I used to do, but much, much slower. In some cases a few times slower, at its worst easily 100x slower. Definitely not all, directly proportional to how much concentration it takes, but most things humans do on a daily basis are mostly autopilot stuff.

The lack of complaints about reaction time is probably just a matter of terminology. We don't think about reaction times on this order, of milliseconds and seconds, because the deficits are much more pronounced on bigger time scales. Taking weeks to fill in a simple form is much more problematic than being 1-2 seconds slower at some physical manipulation tasks or puzzle, so the short scale reaction time simply gets lost in the big picture.

So I think it's all covered in the slowed thinking that's reported, but lab testing is terribly ill-suited to work those out. Ironically, one problem is specifically that those tests utilize autopilot tasks, because they don't want us to think about things, but that's our main problems, so of course they won't find it. They're testing the wrong things, they're explicitly testing the only part that still somewhat works, slower, while ignoring the parts that don't, the higher order executive functioning, most of which many of us can't even do, so can't be meaningfully tested.
 
Same as @hotblack I notice that it gets worse with PEM, or just exhaustion from doing too much that hasn’t escalated to PEM yet. Definitely a noticeable increase in clumsiness and kitchen accidents. I don’t drive unless I feel very alert and haven’t had to do anything taxing during the day.
 
Simon M said:
I think a reaction time deficit is the most consistent finding in all cognitive testing (I wrote a blog about this years ago, but don't have the energy to find that now). On the other hand, nobody I know with this illness is ever complained about reaction time being a significant problem, so who knows what it means.

Edit unfortunate Siri misquotes corrected, apologies
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My impression is that slow reaction time may be more prevalent than the level of discussion about it suggests because unless you regularly do things where reaction time is critical, like driving or gaming, it’s not a major issue day to day, compared to all the other symptoms

We’ve discussed reaction speeds before, for example here
 
My reaction time is absolutely wayyyy slower than it was before.

But I’m severe to the point it’s not like I can do anything where reaction time matters anyways. But I have a constant sluggish feeling and feel like I live in slo-mo ever since being severe.
 
Simon M said:
is it possible that slow reaction times could have influence the finger tapping test in the Wallit "effort preference" experiment?

I don't know how big the effect size is for reaction time, but it could be an important factor with ME/CFS performed badly

@Karen Kirke
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I haven't looked at reaction times - I have a feeling someone ruled out an issue there early on, but I could be wrong. However, I have looked at button press rates, and I think there's something there. They were beyond the scope of our piece, but it is something that @andrewkq and the rest of us might be able to look into more.

I was really struck by how consistent the finding of a kind of generalised slowing is when looking at the literature. Hence our line:
Indeed, studies using several other measures point to motor speed impairments in ME/CFS (Majer et al., 2008; Michiels et al., 1996; Schrijvers et al., 2009), echoing patients' cognitive processing speed deficits (Lange et al., 2024; Sebaiti et al., 2022).
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