The infamous intramural National Institutes of Health (NIH) paper on post-infectious Myalgic Encephalomyelitis (ME), a disease affecting many millions worldwide, purports to define the ME phenotype based on a cohort of 17 ME patients. With this study, NIH continues its obstinate false portrayal of ME as a disease characterized mainly by fatigue. However, the agency put a new spin on its decades-old fatigue narrative. Using the Effort Expenditure for Rewards Task (EEfRT) in a 15-patient sub-set, the investigators reframed fatigue as “unfavorable preference” to exert effort or an “unfavorable” “Effort Preference”—which they say is the decision to avoid the harder task—to be a “defining feature” of ME. According to NIH, this Effort Preference outcome was the study’s “primary objective.” The agency, in essence, pathologized pacing and branded ME with a new and highly prejudicial malingerers’ label.
The Effort Preference claim is an endorsement and expansion of the work of Dr. Simon Wessely, the knighted potentate of the biopsychosocial brigade, which disparages the disease and its patients. According to Wessely, ME is a disorder of the perception of effort, which is identical with NIH’s characterization of Effort Preference. NIH used Wessely’s body of work as a blueprint for the NIH intramural study.
I have analyzed the EEfRT data and have found some serious issues. I will show that the investigators arrived at their false Effort Preference claim by failing to control for a number of confounding factors, for example by not excluding those patients who were demonstrably too sick to validly participate in the EEfRT as well as by misinterpreting and/or misrepresenting the effort data in a number of ways. Furthermore, the effort testing actually demonstrated that ME patients performed better on the EEfRT than the control group based on the reported data, something the authors obscured by failing to include the relevant analyses and disregarding the fact that patients employed a more effective optimization strategy on EEfRT testing than controls did, disproving the Effort Preference assertion. The study is a textbook case of the breathtaking power of statistics in the hands of researchers inclined to reverse-engineer their desired outcome. There is also a serious issue with the integrity of the data, some of which has clearly been falsely recorded, rendering the entire EEfRT data set unreliable.
These and the many other issues I will discuss are a manifestation of the deeply entrenched institutional NIH bias against ME that pervades the agency.
I would like to ask for your indulgence in reading this article because it is long and quite technical in parts, which is why I have split it into four parts. The first part explains that the Effort Preference claim—exactly—mirrors Wessely’s claims about ME. In other parts, I will share my analysis of the EEfRT data, discuss the various confounding factors invalidating the EEfRT results, explain the historically exclusive use of the EEfRT in the field of psychology and the unprecedented nature of NIH’s coining of the gravely prejudicial term Effort Preference to redefine a disease, refute NIH’s attempts to justify their Effort Preference claim, demonstrate the low quality of the intramural paper, and discuss how NIH’s institutional bias has gotten us here through their unconscionable staffing.
I promise that staying with the article is worth it. It is not every day that NIH researchers are shown, without a doubt, to have repeatedly misrepresented their findings in blatant fashion.
Effort Preference as a Defining Feature of ME
The investigators used, as the basis for their Effort Preference claim, the results of the button-pressing test of the modified (from its original design) EEfRT, a behavioral measure of reward-based motivation and effort-based decision-making that analyzes choices of hard as opposed to easy tasks in the context of the EEfRT.
According to the NIH study authors, Effort Preference is
“how much effort a person subjectively wants to exert”
and
“the decision to avoid the harder task.”
The alleged Effort Preference finding is emphasized in the paper’s abstract and conclusion over any other findings by being mentioned first and by being described as a “defining feature.”
In contrast, other findings (for example, alterations of gene expression profiles and sex differences) were mentioned later in the abstract and/or conclusion and presented as “consistent with,” not as “defining.” The study’s outcome also pointed to chronic antigen stimulation of an infectious pathogen, but those findings were downplayed as merely “suggested.” In other words, findings other than Effort Preference were given less weight. In total, Effort Preference was mentioned 26 times in the paper. By highlighting and amplifying the Effort Preference claim, the authors are signaling that it is the most important result of their study.
Here is how the authors explained their Effort Preference claim during the May 2, 2024 NIH Symposium on the intramural study: There is a valuation network in the brain that computes the cost-to-benefit ratio of effort and rewards, which impacts how effort feels. The process by which the valuation network determines the effort-reward ratio is called effort discounting. The authors claim that the EEfRT results are a behavioral sign for impaired effort discounting in ME patients. NIH named that impairment an “altered Effort Preference.” It manifests, according to NIH, in a discrepancy of how much ME patients think they can exert and how much they can, in fact, exert.
In other words, the allegedly altered Effort Preference in patients manifests in a dysfunctional perception of effort and/or rewards resulting in a misperception of patients’ capacity to exert. This, NIH claims, leads to deconditioning and functional disability. That is the main outcome of the intramural paper.
In addition, the investigators claim that only controls—but not ME patients—showed signs of peripheral muscular fatigue and neuromuscular fatigue.
Note that the abstract refers to ME as a “disorder” in blunt contravention of the 2011 expert Myalgic Encephalomyelitis: International Consensus Criteria (ME:ICC) and the 2015 NIH-funded clinical definition by the Institute of Medicine (IOM) (now National Academy of Medicine). It is also untrue that there are no disease-modifying treatments. There are a number of treatments that improve ME symptoms, including the immune-modulator and antiviral Ampligen, which is extremely effective in a sizable group of properly identified ME patients. What would have been accurate to say is that the FDA has been derelict in its duty to approve Ampligen, which has been in FDA-approved trials for decades, and other clearly effective therapeutics for ME. Of course, the claim that the patient-selection process was rigorous is self-serving and false as well as has been discussed many times and is addressed further in Parts 3 and 4 of this article. Finally, NIH just had to throw in the trope that ME is poorly understood, conflating their refusal to accept the findings of many thousands of peer-reviewed, published papers by ME researchers documenting the biomedical abnormalities of the disease with a lack of understanding of the disease. The abstract set the tone for the rest of the paper.
The Staffing of this Study Guaranteed Harmful Results
Given the staffing of this study, its alleged findings were guaranteed to be extremely prejudicial and harmful for ME patients.
Saligan’s Promotion of GET to Cure Catastrophizing in ME. Dr. Leorey Saligan, co-author of the intramural paper co-authored, while at NIH, a literature review on Chronic Fatigue Syndrome (or what he calls “chronic fatigue”) and catastrophizing, “Association of catastropizing and fatigue: A systematic review,” which promotes cognitive-behavioral therapy for ME patients. Advocates had protested Saligan’s involvement with the intramural study to no avail. See this excerpt from the catastrophizing paper:
“Catastrophizing was defined in these three studies as a belief that fatigue can cause negative outcomes such as dying. … Individuals with CFS grouped as high catastrophizers reported significantly greater fatigue severity than the non-catastrophizers. Although the high catastrophizers and non-catastrophizers experienced the same number of CFS-related symptoms, the high catastrophizers reported significantly greater disruption of fatigue with their activities of daily living than the non-catastrophizers. … One study investigated the effect of [mindfulness-based cognitive therapy] on fatigue by specifically targeting catastrophizing. Both fatigue and catastrophic thinking of CFS patients decreased immediately, at two and six months after [mindfulness-based cognitive therapy]. This result indicated that catastrophizing may serve as a behavioral marker that can be a target for fatigue reduction intervention like [mindfulness-based cognitive therapy]. Two of the three articles reviewed in this section showed small to moderate associations of catastrophizing on fatigue severity, and one showed a large association of catastrophizing on momentary fatigue and fatigue recall discrepancy.”
Walitt does not believe that ME is a medical entity. Dr. Brian Walitt, who designed and ran the study, is an acolyte of the biopsychosocial school. If you are not familiar with Walitt’s work, I recommend reading his Fibromyalgia papers. His views on Fibromyalgia mirror his views on ME because, in his opinion, the only difference between the two is which symptoms a patient predominantly complains about. He claims that if that is pain, the patient has Fibromyalgia, and if that is fatigue, the patient has ME.
This is perfectly aligned with Wessely’s view:
“The distinction between fibromyalgia and CFS is largely arbitrary and both overlap with affective disorder.”
That is, of course, false. Yes, there is symptom overlap between ME and Fibromyalgia, but the two also differ in meaningful ways and are separate medical entities. For example, Fibromyalgia patients experience symptom relief with exercise whereas ME patients are harmed by exercise. The paper “Culture, science and the changing nature of fibromyalgia” is a good place to start familiarizing yourself with Walitt’s beliefs. In it, Walitt opined that Fibromyalgia—and, therefore, ME— is a psychocultural construct (i.e., “shaped primarily by psychological factors and societal influences”) and a somatic symptom disorder that is associated with psychological illness (including major psychopathologies). Walitt asserts that patients gravitate toward Fibromyalgia or ME diagnoses because they are more desirable diagnoses than a psych diagnosis as they are more socially acceptable.
Below are two Walitt clips. In the first one, he talks about the relief of physicians once he educates them—”say[s] his message”—about no longer having to pretend that Fibromyalgia patients suffer from any abnormalities. In the second clip, Walitt claims that any and all life experience is psychosomatic.
The two clips above are from an interview Walitt gave in 2015. If you have not seen it yet, I encourage you to watch the ten-minute interview in its entirety; it will leave no doubt where the NIH study would inevitably lead under Walitt’s direction. In Walitt’s opinion, Fibromyalgia and ME are created by the mind and are normal ways of experiencing life as opposed to medical entities, so the fact that NIH saddled patients with the assertion that they overestimate effort and/or underestimate rewards should have come as no surprise to anybody. Walitt was unequivocal in this interview with respect to his opinion that Fibromyalgia, and, therefore, ME, is a disorder of subjective perception. NIH’s formalizing of Walitt’s views in the study that he ran by blaming a dysfunctional perception of effort and/or rewards was the predetermined outcome of the NIH study.
Since the 2015 interview, Walitt has come a long way in learning to be less obvious with his propaganda and more sophisticated with euphemisms in order to conceal his long-held psych beliefs behind more palatable and scientific-sounding verbiage, but Walitt’s convictions obviously have not changed. It is hard to fathom that somebody like Walitt has a place at NIH, but he is far from the only one there with such extremist views.
You can read more about Walitt here (my analysis of his 2015 interview) and here (my initial analysis of the intramural study).
Right out of Wessely’s Playbook
It is crucial to understand that the authors of the NIH study, with its Effort Preference claim, have been emphatically endorsing, amplifying, and building on the narrative of the biopsychosocial origins of ME propagated by Wessely, Wessely comrades, Dr. Michael Sharpe and Dr. Peter White, and other followers of the biopsychosocial school of ME, which falsely claims that patients can recover by adjusting dysfunctional beliefs and behaviors and reversing deconditioning. This has manifested in various references by NIH over time, directly and indirectly citing and accepting as factually correct the work of Wessely et al.
For example, take a look at the following slide frequently used by Dr. Avindra Nath, principal investigator of the intramural study:
The slide cites two studies. The first one cites Wessely and White. The second one is co-authored by Wessely; it is cited in the intramural NIH paper.
and
“Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study”
Most importantly, the Effort Preference claim clearly and unabashedly continues and expands on the work of Wessely et al. according to whom ME is a “general disorder of perception” and of “misperception” of “the sense of effort.” Below is a quote by Wessely in the “Chronic Fatigue Syndrome” chapter of Encyclopedia of Stress (Wessely, Simon; Cleare, Anthony J. (2000). “Chronic fatigue syndrome“. In Fink, George (editor). Encyclopedia of Stress. Academic Press. pp. 460–467. ISBN 9780080569772.).
“One theme that emerges from the literature of all the fatigue syndromes is the possibility of a general disorder of perception, perhaps of both symptoms and disability. At the heart of this misperception lies the sense of effort. Chronic fatigue syndrome patients clearly experience increased effort in everyday physical and mental tasks, reflected in a sense of painful muscle exertion and painful cognitive processing. This increased effort is the [sic] not the result of increased neuromuscular or metabolic demands (a Victorian concept), nor does it result in any substantial decline in actual muscle or cognitive performance. The result is a mismatch between patients’ evaluation of their physical and mental functioning and the external evidence of any consistent deficits. The basis of this disorder of effort must remain speculative, particularly since the perception of effort is a complex topic. It is possible that it is because the sufferer needs to devote more attention, even energy, to processes that the rest of us find automatic, be it muscular exertion or mental concentration.
“From this fundamental problem flow other problems identified in CFS, such as increased symptom monitoring, decreased tolerance, increased anxiety, and so on. These are not unique to CFS and have been described in fibromyalgia and irritable bowel syndrome. Thus some centrally mediated disorder of perception of information may underlie the experience of fatigue syndromes and explain the widespread discrepancies between the intensity of symptoms and disability and objective testing of a number of different parameters, both physiological and neuropsychological.” [emphasis added]
Below is the corresponding screenshot from the book:
This Wessely quote is practically a summary of the NIH study’s main claim, an altered Effort Preference in ME. Both Wessely and NIH agree in their assertion that ME is a centrally mediated disorder; see the screenshot of NIH’s conclusion above as well as the following quote from the NIH paper:
“Considering all the data together, PI-ME/CFS appears to be a centrally mediated disorder.”
Moreover, NIH’s absurd failure to find POTS, Neurally Mediated Hypotension, decreased Natural Killer Cell function, neurocognitive dysfunction, muscle fatigue, sleep abnormalities, lymph node enlargement, ventilatory function abnormalities, abnormalities on brain imaging, brain injury as well as other very common findings—does that sound like NIH studied properly diagnosed ME patients?— jibes with Wessely’s false claim that there is no “substantial decline in actual muscle or cognitive performance” and no “external evidence of any consistent deficits,” allegedly resulting in “widespread discrepancies between the intensity of symptoms and disability and objective testing.”
Walitt’s and Saligan’s clairvoyant prediction. In NIH’s press release accompanying the publication of the paper, Walitt is quoted as follows:
“… fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform.”
That is NIH’s characterization of Effort Preference. Walitt’s message is unmistakable: patients only think that they are impaired. This statement mirrors, to a T, Wessely’s claim:
“The result is a mismatch between patients’ evaluation of their physical and mental functioning and the external evidence of any consistent deficits”
It also tracks with how Walitt and Saligan characterized ME in a 2016 NIH chemobrain paper he and Saligan co-authored:
“The discordance between the severity of subjective experience and that of objective impairment is the hallmark of somatoform illnesses, such as fibromyalgia and chronic fatigue syndrome.”
Being a rheumatologist and nurse scientist respectively, who likely had not heard of the EEfRT at the time of the chemobrain paper, it is quite extraordinary that Walitt and Saligan predicted in 2016 precisely what the 2024 NIH study that Walitt would end up designing and running, and particularly the EEfRT testing, would find. The very thing that the NIH authors claim defines ME—Effort Preference or what Walitt calls “a mismatch between what someone thinks they can achieve and what their bodies perform”—is what Walitt and Saligan characterized as “the hallmark of somatoform illnesses, such as … chronic fatigue syndrome” in 2016 and what Wessely claims is at the heart of ME.
The table below illustrates just how closely the NIH study tracks Wessely’s effort claim; NIH is 100% aligned with Wessely:
Effort Preference claim was the main goal of the intramural study. Showing “the existence of EEfRT performance difference” between ME patients and controls was the “primary objective” of the intramural study, according to a comment by NIH in the Peer Review File. In other words, confirming Wessely’s claim was what the NIH investigators had set out to do.
In Part 2, I will share my analysis of the EEfRT data and of NIH’s misrepresentation of the data that was required to make their Effort Preference claim.