Trial Report The presence of attentional and interpretation biases in patients with severe MS-related fatigue (also ME/CFS), 2024, Knoop, Moss-Morris et al

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The presence of attentional and interpretation biases in patients with severe MS-related fatigue


Marieke de Gier, Joukje M Oosterman, Alicia Hughes, Rona Moss-Morris, Colette Hirsch, Heleen Beckerman, Vincent de Groot, Hans Knoop

Abstract

Objective:

Severe fatigue is a prevalent and disabling symptom in Multiple Sclerosis (MS). This study tested if a fatigue and physical activity-related attentional bias (AB), and a somatic interpretation bias (IB) is present in severely fatigued patients with MS, compared to healthy controls and patients with chronic fatigue syndrome (CFS/ME).

Method:

Severely fatigued patients with MS or CFS/ME and healthy controls completed a Visual Probe Task (VPT) assessing fatigue and physical activity-related AB, and an IB task that assesses the tendency to interpret ambiguous information in either a somatically threatening way or in a more neutral manner. The VPT was completed by 38 MS patients, 44 CFS/ME patients, and 46 healthy controls, the IB task by respectively 156, 40 and 46 participants.

Results:

ANOVA showed no statistical significant group differences in a fatigue-related AB or physical activity-related AB (omnibus test of interaction between topic*condition: F2,125 = 1.87; p = .159). Both patient groups showed a tendency to interpret ambiguous information in a somatically threatening way compared to healthy controls (F1,2 = 27.61, p < .001). This IB was significantly stronger in MS patients compared to ME/CFS patients. IB was significantly correlated with cognitive responses to symptoms in MS patients.

Conclusion:

MS patients tend to interpret ambiguous information in a somatically threatening way. This may feed into unhelpful ways of dealing with symptoms, possibly contributing to perpetuation of severe fatigue in MS.

Keywords: attentional bias, interpretation bias, fatigue, multiple sclerosis
Original language English
Number of pages 33
Journal British Journal of Health Psychology
Publication status Published - 26 Mar 2024

 
Brought to you by the Journal of Health Psychology, Kings College London. (in press)
I think this could be a good paper to look at, I suspect the investigators were disappointed that the chronic fatigue people did not look as different from healthy controls as the MS people did.

Chronic, severe fatigue is a highly prevalent (75-90%) and burdensome symptom in MS


In a cognitive behavioural model of MS-related fatigue, Van Kessel and Moss-Morris proposed that whereas disease-specific factors, such as neurodegeneration and inflammation, may initially trigger fatigue, cognitive and behavioural factors, e.g. viewing fatigue as uncontrollable or a sign of bodily damage, symptom-focussing or all-or-nothing behaviour, play a role in maintaining fatigue (van Kessel & Moss-Morris, 2006). Cognitive behavioural therapy (CBT) addressing these factors has been found effective in decreasing fatigue severity in MS patients (de Gier, Beckerman, et al., 2023; Moss-Morris et al., 2019; van den Akker et al., 2017).

In the cognitive model of persistent physical symptoms, automatic attentional and cognitive processes, such as selectively attending to somatic information and habitually interpreting physical sensations as health-threatening, have been proposed to play a role in perpetuating fatigue (Deary, Chalder, & Sharpe, 2007; Van den Bergh et al., 2017).

Whilst pain is intrinsically salient, it is likely that for someone with a chronic condition who experiences ongoing and debilitating fatigue, fatigue itself becomes salient and threatening.
Oh, for goodness sake, look at that bias. They allow that pain is salient (definition of salient - noticeable, important). But the authors are suggesting that fatigue only becomes salient when someone has a chronic condition and has debilitating fatigue. What rubbish - fatigue in anyone is salient, because the body is sending a signal 'take note, you need a rest'. It's sort of tautological - the sensation of fatigue only exists when it is noticed, in the same way that pain only exists when it is noticed.
 
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There are two parts to the study: Attention bias and interpretation bias. First, the attention bias:

Attention bias
Several studies in ME/CFS, which is defined by severe and debilitating fatigue with no known underlying pathology, found people with ME/CFS to have a tendency to direct attention towards fatigue-related stimuli, when compared to healthy individuals (Hughes et al., 2016; Hughes et al., 2017; Hughes et al., 2018). This AB in CFS patients is thought to reflect a strategy to continually monitor threats in the environment, in this case bodily signals, as opposed to an initial orientation or hypervigilance to threat which is found in patients with anxiety disorders (Hughes et al., 2016; Hughes et al., 2017). These CFS studies focused on biased attention towards illness-related stimuli, however, an AB may also serve as an avoidance of threatening stimuli, in which case the attention is involuntarily directed away from the stimulus.

Some evidence has been found for an AB away from physical activity- related stimuli in ME/CFS patients (van Heck, 2019). Fear-avoidance (avoiding activity out of fear for fatigue) is considered a perpetuating factor in chronic fatigue, and its reduction was found to be a mediator in the effect of CBT on fatigue severity in ME/CFS (Chalder et al., 2015) and across chronic medical conditions (de Gier, Picariello, et al., 2023).
Ugh. They really really don't get it, do they.

A Visual Probe Task (VPT)
The parameters and stimuli of the VPT were based on the VPT developed by Hughes et al. (2017) consisting of 24 pairs of fatigue-related (e.g. exhausted, headache, weak) and neutral words. These word pairs were translated and used in a replication study in a Dutch CFS sample (Hughes et al., 2018). In the present study, these were combined with 24 pairs of physical activity-related (e.g. running, cycling, lifting) and neutral words as used in the study of Van Heck et al. (2019).

Each trial started with a fixation cross in the centre of the screen (500 ms), followed by 2 words (one fatigue-related or physical activity-related and the other word was neutral), one word was presented above and the other below the fixation point. After 500 ms the words disappeared, and an arrow appeared at the central location of one of the words. Participants were instructed to press “c” on the laptop keyboard when the arrow pointed to the left, and “m” when the arrow pointed to the right, as quickly and accurately as possible. In total, the task consisted of 384 trials of 48 unique word-pairs. The duration of the total task was 15 to 20 minutes.
...
Individual AB scores were obtained by calculating the difference between the mean reaction times (in ms) to probes replacing the fatigue- or physical activity-related words and the probes replacing the neutral stimuli. AB scores were calculated separately for both word categories (fatigue-related versus physical activity-related). Positive values reflect an AB towards the threatening stimulus, indicating potential hypervigilance, and negative values reflect a tendency to direct attention away from threatening stimuli (avoidance).
24 pairs of fatigue-related words + neutral words; 24 pairs of activity-related words + neutral words. A pair of words appears on the screen, like this

Tired
+
Custard

And then the words disappear
and there is something like this:

<-
+

So, in that case, you are supposed to press c because the arrow points left, as opposed to m when the arrow points right. And the time it takes you to press the c or m is supposed to be related to how actively you were drawn to or away from the fatigue word or the activity word.

So, another example might be

Parsnip
+
somersaulting

followed by

->
+


The idea is that the attention of people with chronic fatigue is drawn towards the fatigue words (indicating hypervigilence) and away from the activity words (indicating fear avoidance), and so they will be looking or not looking at the place where the words were, and that will affect how quickly they respond to the arrow that appears where one word was.

I find it hard to believe that anyone thinks this exercise says anything about whether someone pays too much attention to the fatigue signals their body sends them. It seems laughable. They wrap it all up in fancy words - attentional behaviour and visual probe. But, it seems as scientific as a horoscope.

Here's the discussion about the lack of difference between people with ME/CFS and MS:
We found no evidence to support the previously found AB in ME/CFS patients (Hughes et al., 2017; Hughes et al., 2018). This was despite the ME/CFS patients being recruited from the same treatment centre, and having met the same inclusion criteria as the ME/CFS patients in the study of Hughes et al (2018). The large variance in reaction times, however, possibly reflects the heterogeneity of the attention bias in the ME/CFS group, which may be a factor in explaining the lack of effects. The inconsistency of AB findings between studies may also reflect the low test-re-test reliability of the dot-probe paradigm (Dear et al., 2011) indicating that the bias can vary over time, though research clearly shows that at a group level the bias exists. Further investigation and replication is warranted and may lead to more insight in the role and clinical relevance of AB in chronic fatigue.
But, but, the authors cry, we know those ME/CFS people really do have attentional bias. The authors even admit that maybe their test isn't that great, because it isn't picking up the abnormality the they know is there.

As for the MS people:
No evidence was found for a fatigue-related or physical activity-related attention bias in patients with MS.
Yep, they didn't look different to the healthy controls either.

Some more hand-wringing rationalisation:
No indication of an attentional avoidance of physical activity-related stimuli was found in MS or ME/CFS patients. This could imply that physical activity-related stimuli are less intrinsically threatening in the context of severe fatigue. Fatigue is less likely to occur as immediate as pain during physical activity, and is less intrinsically threatening compared to pain. Although fear-avoidance has been found to play an important role in the perpetuation of fatigue, this may be more likely the result of a top-down cognitive process, based on illness representations, than an unintentional bottom-up AB, explaining why no AB for physical activity-related information was found in the current study.
Make of that what you will. Something about maybe physical activity isn't that scary for people with fatigue as the consequence comes later and fatigue isn't that bad. And something about a top-down cognitive process being at work, rather than a rapid bottom-up process - which they presumably think is not cognitive. Maybe we have to have more time to realise that we are afraid of running. They don't seem to know what is going on, but, despite the lack of evidence from their study, they just know that fear-avoidance perpetuates fatigue.

There is more avoidance going on with the authors refusing to face up to the fact that their prejudices are baseless than there is in both the ME/CFS and MS cohorts combined.


Patients gave written consent for using these data for the present study.
I wonder if patients really understood how the data was going to be used.
 
From the quotes Hutan on which commented above
Attention bias

"Several studies in ME/CFS, which is defined by severe and debilitating fatigue with no known underlying pathology, found people with ME/CFS to have a tendency to direct attention towards fatigue-related stimuli, when compared to healthy individuals (Hughes et al., 2016; Hughes et al., 2017; Hughes et al., 2018). This AB in CFS patients is thought to reflect a strategy to continually monitor threats in the environment, in this case bodily signals, as opposed to an initial orientation or hypervigilance to threat which is found in patients with anxiety disorders (Hughes et al., 2016; Hughes et al., 2017)."

That's cool -- refer to "several studies" but all by the same principal investigator and by co-authors which are now authors of the presented trial [*]

I would suggest instead: "A team of health psychologists of which most happen to be also authors of this trial report repeatedly reported to have found..."

Brought to you by the Journal of Health Psychology, Kings College London.

by the British Journal of Health Psychology


---
[*] The references:

Hughes, A., Hirsch, C., Chalder, T., & Moss-Morris, R. (2016). Attentional and interpretive bias
towards illness-related information in chronic fatigue syndrome: A systematic review. Br J
Health Psychol, 21(4), 741-763. https://doi.org/10.1111/bjhp.12207

Hughes, A. M., Chalder, T., Hirsch, C. R., & Moss-Morris, R. (2017). An attention and interpretation
bias for illness-specific information in chronic fatigue syndrome. Psychol Med, 47(5), 853-
865. https://doi.org/10.1017/s0033291716002890

Hughes, A. M., Hirsch, C. R., Nikolaus, S., Chalder, T., Knoop, H., & Moss-Morris, R. (2018). Cross-
Cultural Study of Information Processing Biases in Chronic Fatigue Syndrome: Comparison of
Dutch and UK Chronic Fatigue Patients. Int J Behav Med, 25(1), 49-54.
https://doi.org/10.1007/s12529-017-9682-z

(And Hughes is also co-author of this trial report)
 
It's high time these people were stopped from playing silly psychological games with sick people, and, worse, drawing unwarranted conclusions from them. It's harmful, insulting and not good science.
Yep it’s one thing if it were a student paying other students but the amount of effort for severe MS patients to have been dragged in for this makes me think there is a major ethical issue that isn’t unique to ME and needs us to get on board other charities to form a charter of acceptability and if it’s due to lack of adjustments so they understand the ‘potential harm’ spell it to them that if you get sick people in it needs to be more worthwhile and adjusted so it isn’t taking advantage of their fragility physically to get results or vulnerability to impose coercion etc

I don’t have the words for this the design it is such utter unjustifiable nonsense with no understanding of any literature to have done it this way that it’s embarrassing they have jobs in institutions calling themselves academic
 
Same old laughable rubbish that actually makes the Stanford Prison Experiment look tame and wise by comparison. None of this even makes sense.

They present their BPS stuff as holistic, but then go on pretending like a few millisecond more or less pressing a button when presented arbitrary words can be used to interpret an entire person's life experience. And they are willing to interpret anything.

But they still get money for it. And will keep on getting more money for it. Because the lack of results is irrelevant, continuing to ask the questions is all that matters, as it keeps their lies influential. No different than some opinion-havers writing dozens and dozens of editorials about the same topic, how some group of people is ruining society and other nonsense. They're the "just asking questions" crowd. Questions that don't need to be asked.
 
Several studies in ME/CFS, which is defined by severe and debilitating fatigue with no known underlying pathology, found people with ME/CFS to have a tendency to direct attention towards fatigue-related stimuli, when compared to healthy individuals

People with diabetes have a tendency to direct attention towards glucose-containing foods, when compared to healthy controls.
 
There are two parts to the study: Attention bias and interpretation bias. First, the attention bias:

Attention bias

Ugh. They really really don't get it, do they.

A Visual Probe Task (VPT)

24 pairs of fatigue-related words + neutral words; 24 pairs of activity-related words + neutral words. A pair of words appears on the screen, like this

Tired
+
Custard

And then the words disappear
and there is something like this:

<-
+

So, in that case, you are supposed to press c because the arrow points left, as opposed to m when the arrow points right. And the time it takes you to press the c or m is supposed to be related to how actively you were drawn to or away from the fatigue word or the activity word.

So, another example might be

Parsnip
+
somersaulting

followed by

->
+


The idea is that the attention of people with chronic fatigue is drawn towards the fatigue words (indicating hypervigilence) and away from the activity words (indicating fear avoidance), and so they will be looking or not looking at the place where the words were, and that will affect how quickly they respond to the arrow that appears where one word was.

I find it hard to believe that anyone thinks this exercise says anything about whether someone pays too much attention to the fatigue signals their body sends them. It seems laughable. They wrap it all up in fancy words - attentional behaviour and visual probe. But, it seems as scientific as a horoscope.

Here's the discussion about the lack of difference between people with ME/CFS and MS:

But, but, the authors cry, we know those ME/CFS people really do have attentional bias. The authors even admit that maybe their test isn't that great, because it isn't picking up the abnormality the they know is there.

As for the MS people:

Yep, they didn't look different to the healthy controls either.

Some more hand-wringing rationalisation:

Make of that what you will. Something about maybe physical activity isn't that scary for people with fatigue as the consequence comes later and fatigue isn't that bad. And something about a top-down cognitive process being at work, rather than a rapid bottom-up process - which they presumably think is not cognitive. Maybe we have to have more time to realise that we are afraid of running. They don't seem to know what is going on, but, despite the lack of evidence from their study, they just know that fear-avoidance perpetuates fatigue.

There is more avoidance going on with the authors refusing to face up to the fact that their prejudices are baseless than there is in both the ME/CFS and MS cohorts combined.



I wonder if patients really understood how the data was going to be used.
So no knowledge of peripheral.vision issues and the effect of fatigue on eyesight ( there have been studies on this ) .
Not even trying

ETA spelling
 
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So no knowledge of peripheral.vision issues and the effect of fatigue on eyesight ( there have been studies on this ) .
Bot even trying
Well, they do comment on reaction times obliquely, and the reaction times are reported in Table 2. For me, that would be one big and real result of the study.
Mean reaction time of the ME/CFS group was about 628 ms, regardless of what they were reacting to in the Attention bias game. Mean reaction time of the MS group was about 670. Mean reaction time of the healthy controls was about 528.

They found a measurable difference in reaction times between groups, and that is completely glossed over.

The way the game was set up, those peripheral vision issues and effect of fatigue on eyesight didn't matter, because mean reaction in and of itself, didn't matter. It was just the comparison between neutral words and the words supposedly triggering hypervigilance or avoidance.

(They also mention that they had a problem with their healthy controls,, with abnormally high rates of missed responses. They chucked out a substantial percentage of their healthy control data out because of this.)
 
People with diabetes have a tendency to direct attention towards glucose-containing foods, when compared to healthy controls.
That one utterly makes sense guven I assume when first diagnosed reading ingredients lists for those terms is important. And given they are small print and lots of items often in said list you’d be training yourself to actively spot those words?

there is a reason they put allergens in bold now to make it easier
 
People with everything to lose if the rest of the world learns how dodgy they are tend to try diverting the world's attention away from how dodgy they are.
It’s appalling isn’t it to imagine these people deliver thee assertions AT people and their ideas have created forced imposition of awful things based on their madness ie it sounds deluded, is deluded and silly but boy is the impact on those targeted not left at small by these people sadly
 
There are two parts to the study: Attention bias and interpretation bias.
Onto interpretation bias:
interpreting somatic sensations in a threatening way (IB)
According to Van den Bergh et al.’s model of symptom experience (2017), interpretations of bodily sensations are based on expectations based on past experiences. MS patients are likely to have had negative or threatening somatic experiences such as disease exacerbations, somatosensory deficits, pain, impaired balance or motor weakness, and the chances of experiencing this again are realistic in the context of MS. In a recent study, MS patients reported more damage beliefs compared to other patients with long-term conditions, such as myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS) and Type 1 Diabetes Mellitus (de Gier, Picariello, et al., 2023). When this prediction generalizes to more commonly occurring bodily sensations, such as fatigue, this may lead to an overestimation of threat, which maynegatively affect someone’s ability to cope with these symptoms.
In ME/CFS studies patients show a negative IB for ambiguous somatic/illness-related information (Hughes et al., 2016; Hughes et al., 2017). These negative, illness-related interpretations were found to be associated with unhelpful responses to fatigue such as catastrophic thinking styles, fear-avoidance and all-or-nothing behaviour (Hughes et al., 2017).
To date, however, it is unknown if similar information processing biases play a role in chronic fatigue in medical conditions such as MS. The goal of the present study was therefore to investigate if similar attentional and interpretation biases are present in severely fatigued patients with MS, as in patients with ME/CFS, compared to healthy controls.
The problematic information processing biases are taken as a given in ME/CFS, with the aim being to compare and contrast.


Implicit Interpretation bias task
The online IB task was based on the IB task developed by Hughes at al. (2017), which was already translated in Dutch (Hughes et al., 2018) and extended by 2 scenarios related to fear of disease progression1 (an example of a scenario can be found in supplement 2). The task was administered online and could be completed at home. During the first part of the task 12 day-to-day ambiguous situations that could be interpreted in either a neutral or a negative somatic manner were presented with a title for each. Participants had to imagine themselves in these situations, rate the “pleasantness” of the situation and answer a question about each scenario. After reading the 12 scenarios, the second part of the task presented the title of a scenario again followed by 4 different sentences to be rated in terms of how similar in meaning they were to the original scenario. Two were potential targets that represented interpretations of the original scenario, one positive and the other a somatically threatening interpretation. The other two sentences were foils (positive and negative) which were not plausible interpretations of the scenario.

Participants were asked to rate all 4 sentences on similarity to the original scenario from 1 (very different in meaning) to 4 (very similar in meaning). The four sentences were presented in random order varying between scenarios. Mean similarity ratings of the positive and somatic interpretations were calculated separately for the analyses. An IB index was obtained by subtracting the mean similarity rating of the positive (target) interpretations from the mean similarity rating of the somatic (target) interpretations. Higher index scores indicate a stronger tendency to interpret ambiguous somatic information in a threatening way.

Post-hoc comparisons between groups showed that both MS and ME/CFS patients endorsed somatic interpretations significantly more than healthy controls (mean difference = 0.66, 95% CI 0.48 to 0.84, Cohen’s d = 1.12 and 0.43, 95% CI 0.20 to 0.66, Cohen’s d = 0.46 respectively), but for MS patients this was an even stronger effect than for ME/CFS patients (mean difference = 0.24, 95% CI 0.05 to 0.42, Cohen’s d = 0.48).

To summarise, for each of 12 ambiguous scenarios, participants had to rate how similar 4 sentences were to the scenario. One sentence put a positive interpretation on the scenario, one a negative somatic interpretation. The other two sentences were not designed to not be plausible representations of the scenario.

Here are the results:

Mean (and SD) of interpretations of all groups

Similarity rating................................... ME/CFS (n=40).................MS (n=156)................Healthy controls (N=46)

Similarity rating of positive interpretation....2.85 (0.42)................ 2.82 (046) ...................2.96 (0.50)
Similarity rating of somatic interpretation.....2.23 (0.52)............... 2.47 (0.57) ...................1.81 (0.38)
Similarity rating of positive foil ...................1.35 (0.32) ...............1.39 (0.40) ...................1.42 (0.36)
Similarity rating of negative foil...................1.18 (0.18) ................1.26 (0.25) ..................1.22 (0.24)

Values of statistical significance for result comparisons are not reported. Also, I'm not sure about the size of the MS samples - there were two MS samples. Is it possible they recruited more people in order to find some sort of a result?

Anyway. All three groups were equally likely to think a positive interpretation of the scenario was reasonable.

Both disease groups were more likely than healthy controls to think that a negative somatic interpretation of the scenario was reasonable, with the multiple sclerosis people rating those interpretations as more similar than the ME/CFS people. I don't think the ME/CFS results on this were significantly different from the healthy controls.
It is completely understandable and reasonable for the disease groups to rate a negative somatic interpretation as possible - they have had vivid personal experience of bodies not working well. But the difference is quite small.

And, it's such a huge leap in logic from there to 'manufacturing feelings of fatigue out of non-harmful normal body sensations'.

It would be laughable if people weren't actually paying attention to these investigators, and paying them to provide CBT sessions to cure people of their fatigue.
 
Informed consent:
Informed consent was obtained from all individual participants included in the study.

Welfare of animals
This article does not contain any studies with animals performed by any of the authors.

Conflict of Interests
The authors declare that they have no conflict of interest.
I do wonder about the informed consent - did participants really understand that the results would be used to try to label their fatigue as a product of attentional and interpretational biases?

I laughed about the comment about the welfare of animals. Because humans are animals and the authors have not considered the considerable harm that will flow from this study and its suggestion that people with MS can cure their fatigue by thinking differently about it.

And, as for the conflicts of interest, how can there not be a conflict of interest? The authors are in the business of providing CBT to fix false illness/symptom beliefs. And they did their best to find some false illness/symptom beliefs to fix.

That conflict of interest is plastered all over this study, including the way a lack of a difference between the ME/CFS participants and the healthy controls in so-called attentional and interpretational bias is minimised. Those findings for ME/CFS participants blow a giant hole in the basis for CBT to correct false-illness beliefs.

Conclusion

Patients with MS show a stronger tendency to interpret ambiguous somatic information in a somatically threatening ways compared to healthy controls, with MS patients showing an even stronger IB compared to ME/CFS patients. Although this IB is understandable considering the nature of MS, it may affect patients’ ability in dealing with daily fluctuation of symptoms such as fatigue, and contribute to the perpetuation of fatigue.

Future research may gain more insight in the way the IB relates to the fatigue severity in MS and if addressing this more explicitly during interventions for fatigue could potentially optimize treatment outcome.
 
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