Use of EEfRT in the NIH study: Deep phenotyping of PI-ME/CFS, 2024, Walitt et al

@EndME I know you've read a bunch of EEfRT papers at this point, have any of these studies asserted that EEfRT is meant to measure "effort preference"? As far as I can tell, Wallit seems to have invented the construct as they make no reference to any studies that actually use the term "effort preference". In fact, the only study Wallit ever cites when discussing effort preference is Treadway 2009, which never uses the term.

If there isn't any evidence that other reserachers have used EEfRT to measure "effort preference" (and it certainly wasn't what Treadway designed it to measure), then I think that's an important critique to highlight in conjunction with the 65% completion of hard task issue.

I agree with what others have said that at this point, it's probably better to not focus on the exclusion of HV F since they'll always have some plausible deniability there (at least for the letter to the editor).

 

That's an odd framing. This strategy doesn't artificially increase payouts, it effectively increases payouts. It's just bad game design if they do that.

 

@Karen Kirke any chance you could share the SF-36 data file with me or let me know how I could request a copy? Is my understanding correct that it wasn't included with the Wallit 2024 data so you had to request it separately?

~EDIT: Never mind, I found your post about how to request access, thanks! ~

I think @bobbler raises a good point and I'd like to run an analysis to see if the there's a relationship between SF-36 and ability to complete the hard task on EEfRT (i.e. was ability here correlated with self-reported disability)

 

Just sharing this message today from Koroshetz, for visibility, when I had asked for paper amendment of ‘effort preference’ term (mods I left in both channels but feel free to edit or delete where you see fit).

“Understand the anxiety but it’s very important that the community understands the finding.

To simplify how the brain works I could say that the brain circuits are constantly estimating the difference between the effort required and the reward to be gained from executing an action. This applies to all behaviors, even to what I am typing now. This is easier to understand in estimating the degree of force you need to exert to pick something up something, but even the more automatic behaviors like whether we are “hungry” enough to eat. So the finding is very important. In the persons with ME/CFS the circuits that do this estimation of effort are malfunctioning. They even see an abnormality in brain activation related to this finding. They see alterations in dopamine metabolites (potentially related to the reward signals). And they speculate that it is abnormalities in the immune system that are driving the abnormality.

So this has nothing to do with “psychological”, this is a real abnormal finding in how our neural systems are supposed to work.

Planning a hybrid workshop to explain the findings to the subjects and the general community soon.”

 

They might be, but even if they weren't, we still wouldn't be able to do it.

Jaysus. How many different ways do we need to say this?

 

Also if any advise a reply / rebuttal / follow-up back let me know any thoughts (there are several other leaders CC’ed in the thread, ie Nath, Marrazzo, etc.). Otherwise I’m unsure what to really say back.

 

Feels oddly like damage control.

 

Hmm interesting, I've as a very lay non-expert, questions on a few issues here.

Could you point me to what you specifically said when you asked for this?

Apologies as this is just a bit of a riffing/brainstorming thoughts. It seems another case of having to 'get to the bottom of' what is being talked about here, as if understanding the EEfRT wasn't enough of an odyssey. I probably also need to look at the grip strength stuff they've combined in too (and that thread), but there is also the papers where they've combined the two trying to claim '5 ways of looking at effort' or something.

Firstly the response seems to have side-stepped the 'operationalisation of wanting' focus of the EEfRT and be trying to focus (clue being in 'force') on the grip-strength side of things. Whilst then mixing in bits about reward that they didn't measure in the grip test (only in the EEfRT test) and that they failed to contextualise properly (as evidenced by the completion rate findings)?

If we are going to have to go down this road with unpicking it getting mixed in with these terms with the grip-strength stuff...

I can't remember the exact name of the module back then but the closest now seems to be something like neuropsychology of action/movement.

Anyway even in that undergraduate module the thing that was clear is that 'how the brain works' is that it has both forward and backward processing when executing an action. Examples used were indeed people who perhaps had a stroke or a disease where their balance was off or they were reaching to the left of the actual object, said people then get information going back to the brain that they'd 'missed the object' from eg what their hand felt or didn't feel when it went to grip, as well of course 'sight' seeing the vase smash to the ground.

Isn't it that backward processing that probably means the mirror-trick works for phantom limb syndrome? : Mirror Therapy for Phantom Limb Pain | NEJM

EDIT: I feel compelled here to note that the mirror (in those it does help) can only fix 'the pains' and doesn't, of course, solve the missing leg - a metaphor/misunderstanding that I can't help but think of re: certain areas vs ME/CFS.

ANd we all know hunger is about leptin and grellin. Again forward and backward information as you eat something and feel full-up and satisfied or don't appropriately. Problems with either of these can cause issues. But you can also have eg an IBD that means you aren't absorbing things or there are digestion issues in other ways and so on that would be likely to produce some sort of feedback into the loop?
EDIT: but I'm not sure what that one 'has got to do with the price of eggs' [ What does that have to do with the price of eggs - Idioms by The Free Dictionary ] here at all?

Anyway as your body gets used to disability that information will impute into the calculations too. Sorry this isn't strictly right, but as it popped into my head for a moment as levity I thought I'd say it: I've got a picture in my head of when you get a puppy that grows really fast into being a pretty huge dog and still thinks it can curl up on the small lap of a person. Who is swamped under them. When I think of their 'mismatch' stuff.

Anyway
None of the tasks used were a 'one-off reach for the vase', or 'put it down on x marks the spot' so that backwards loop is even more relevant in their examples used than their forward one. And I'm not sure if it was a forward processing issue that you would have seen a downward curve rather than too low a force right off the bat? That backwards loop will of course be the one that is communicating the fatiguability information and I'm not convinced they've managed to nail the inference that information 'must be wrong' or that the effort calculation has somehow got the wrong multipliers in there or something.

And a grip strength test is less about holding a vase and then dropping it because your brain didn't calculate how hard you need to grip it, and more like eg how long can you hold the hot saucepan handle? the feedback sensations related to fatiguing/fatiguability, and a test where something heavy isn't going to drop on your foot, or something smash as part of the calculations of the 'pros vs cons' (and in the case of those two scenarios, how long you've got to put it down somewhere calculation for action)?

Anyway eventually your 'automatic' function (if your conscious one also doesn't) should if it is working right release your grip from that hot saucepan handle when it begins to burn the hand too badly. Even if you are just cm from getting to the sink. There is a lot less of a downside of loosening a grip on a grip-test where people are just looking at what you can do than hot water going down your legs

So, apologies if lots of other people are more up with understanding this but I'm trying to put together the pieces of info that they did measure and what they mean as a bit of a jigsaw puzzle of this mismatch thing


It's all very well trying to minimise out disability (which seems to be one issue with the completion stuff for EEfRT) and use a tone inferring you are doing it 'because the reader must be unable to understand' but that clearly isn't why they are saying things that are incorrect.

The dopamine note is interesting, but is that being interpreted in the 'psych-neuro' sense rather than being seen potentially as a 'downstream' given that there are lots of conditions where dopamine is affected and of course said conditions (like Parkinsons) have specific motor issues.

 

I wrote to Koroshetz:

“I am writing today with concern on the recent NIH ME/CFS publication. I’m asking that the term “effort preference” be removed from the paper immediately, so that it is not framed as a cause of ME/CFS. As a person living with this disease, I hope you will sincerely consider this ask.”

 

Thanks for confirming.

 

No, I wasn't intending to claim that, just that in ME the response can be much more prolonged.

I don't think it really matters to the argument that these are the 'flu signals' and not the 'pacing signals' that would determine effort preference.

 

PS Please don't take any of my trying to work out what to make of this as suggestions on what to reply, or indeed that it should involve any kind of rebuttal (I'm just trying to work out in the first place what they are trying to suggest in what they've said).

I'm just trying to think myself up to speed on the issue itself, then there is the question about what is the sensible or strategic thing to do - I hope that doesn't come across as insensitive as I know that leaves you holding the 'hot potato' so to speak?

I think the angle/question of those who are noting it might be damage control etc is just as important on the conversation about that one

 

I'm sure @EndME has probably got more useful pointers here, but thought in the mean time I'd point you towards these two papers which is the closest I've found to it starting to be used in the 'effort sense':

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms | Schizophrenia Bulletin | Oxford Academic (oup.com)
Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 2—External Validity and Correlates | Schizophrenia Bulletin | Oxford Academic (oup.com)

It's interesting that they have both EEfRT and grip-strength (along with 3 other tests) in the tests they've chosen - and reading this struck me I wondered whether this is what Walitt was gesturing towards?

 

@andrewkq
I've noticed that Treadway is a co-author on the first one, but doesn't appear to be on the second one (which looks at external validity etc). I don't know what the likelihood is of there being history of commentary from someone who is a co-author of any kind (as they wouldn't be a peer-reviewer, but might reply to comments or there be other conversations) or how one might seek it if they had fuller access to databases of those kinds of things. Or whether on the second where he isn't a co-author it is worth looking for comments from said paper from him there?

 

This looks to me like complete bullshit. What finding? What meaningful result?
Estimating reward does not come in to falling on the floor feeling sick.

There may be a difference in brain activation but who is to say it is an 'abnormality'?

If abnormalities in the immune system are driving it maybe it is a normally functioning response. You don't plan to feel ill. You may plan to try to feel less ill.

 

Their evidence for this is we just made it up.

 

What is Koroshetz role here? Is he just a figurehead cum cheerleader for the study?

Is he seriously asking patients to believe this?

 

We understand the findings perfectly well. The issue is that we disagree with their weaponizing of pseudoscience to string together a theory that has no basis in reality. I honestly don't know how I would respond to this, it feels very condescending.

 

And for the sub-group who made the same choices, but couldn't complete the clicks on said hard tasks, then still continued to choose them ?