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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5553_Библиотеки_им_академика_М_И_Перельмана
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reinforcing the notion that this drug is not just another passing fad, but
a bona fide breakthrough in the field of fatigue management.
Analogously, the leaflet promoting Vibolin emphasizes how
effective management of fatigue is essential for enhancing individuals’
well-being and functional capacity. The advertisement targeted at
physicians is designed to captivate the attention and tap into the
desires and expectations of its primary audience, but also those of
patients. The fortifying stimulant deploys a combination of scientific
terminology and persuasive rhetorical tools. At its core, the
advertisement embodied the spirit of an era imbued with a relentless
pursuit of self-improvement, optimism, and modernity. An era in which
doctors are encouraged to advise patients to use pharmaceutical
technologies as much as automobile innovations to achieve self-
improvement targets and a sense of fulfillment. Emblazoned with the
Organon logo, by then considered a symbol of the quality of
European laboratories, Vibolin’s advertisement exuded credibility and
authority—one of the issues that interest groups, such as the
Pharma-Kampagne, had with this type of advertisement. Western
pharmaceutical companies were interested in expanding and
solidifying markets of consumers in nations across Africa, Asia, and
Latin America ( 1985). Organon’s emblem was intended to
complement the whimsical cartoon-styled imagery, adding a
reference to the pharmaceutical prowess of an innovation developed
in the Netherlands. A similar approach was likewise implemented in
the promotion of Festavital. Underneath the text and additional
information on Festal, enzymatic-digestive pills, the Hoechst logo in
the corner of the leaflet boasts “mas [sic] de 100 años de
experiencia” (more than one hundred years of experience).
The availability of Festavital, among others, purportedly expanded
the horizon of pharmaceutical possibilities for patients of all genders
and age groups. Taking vitamins, which had become quite common
since the 1950s, was not enough. Hoechst saw the need to develop
an enhanced supplement as a solution to those experiencing reduced
levels of energy and performance—one that could mitigate all the
various physiological, psychological, and environmental factors that
contributed to the onset and subsequent severity of fatigue.
Additions, such as pancreatic enzymes and lipotropic factors, are
presented as a more effective combination to tackle the multifaceted
nature of exhaustion, digestive disorders, and “desgaste prematuro”
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(premature wear and tear of the body). Skeptical of its efficacy,
eventually launched a campaign against the commercialization
of Festavital, and by proxy Hoechst, on the grounds that “there is no
medical justification for such an irrational mixture” ( 1985, n.p.).
The action sought to put pressure on Hoechst to explain why an
enhanced supplement was marketed as a medicine that was
allegedly effective for a series of conditions, without specifying one.
questioned how Festavital was approved in the first place. The
main premise of the campaign was to draw attention to the excessive
commercialization of vitamin supplements sold by European
laboratories in non-Western markets.
Eventually, the multivitamin formula disappeared from pharmacies
across the region, as well as Vibolin, although for different reasons.
Once anabolic steroids were further researched and it became clear
that they were not as safe or effective as advertised, they ceased to
be used for (over-the-counter) therapeutic purposes, except for
specific cases (i.e., oncology). As for Sostenon (Sustanon), it is still
used in modern medicine to treat confirmed testosterone deficiency.
An analysis of the advertisement material used to promote Vibolin,
Sostenon, and Festavital in Latin America in the 1960s unveils some
patterns of how illness is rendered visible. These include the use of
imagery that encapsulates how patients experience the conditions
they expect pharmaceuticals to mitigate or cure and how advertisers
craft a vision of one’s future self to the viewer through a combination
of claims in both plain terms and medical terminology, and the
inclusion of references to the context in which pharmaceutical
innovations emerge.
Despite its lack of directly perceptible traits, fatigue has been
imaged and thus rendered visible through changing practices of
medical visualization. Reviewing the use of visual references in the
1960s, advertisements of medicines prescribed to manage tiredness-
related physical symptoms, some patterns emerge. A gendered lens
is superimposed on the iconographical representation of fatigue since
these are pharmaceutical formulas targeting specific demographic
groups. Expectations in terms of performance, vitality, and vigor
inform the construction of an idealized, energized body that differs
strikingly from an energy-depleted one. Strength is a trait that men
apparently ought to exude, and pharmaceutical technologies are a
means to attain desired and desirable standards. In the case of
advertisement, the goal is to tap into the need of exhausted bodies
seeking restoration, implying that fatigue could be pharmaceutically
managed. The male body is used as a reference and target. Lack of
vitality is presented as an alteration of an ill-understood condition, yet
one that is curable thanks to scientific advances, according to the
reviewed promotional material. From this perspective, conclusively,
the visibility of fatigue is expressed through an amalgam of symptoms
that can be capturable through images and interpretable through
cultural references.
Case Study 2: Articulating the Neuropathophysiology of
through Functional Brain Maps
Conceptual Framework
Gonzalez Rodriguez’s case study showed how fatigue as a vaguely
defined sign of ill health was portrayed in pharmaceutical
advertisements in the 1960s in Latin America. The following case
study shifts the perspective to how , as a specific, albeit
contested, multisymptomatic disorder, has been experimentally
framed in present-day neuroimaging research with a global scope.
Importantly, this case study does not discuss how images mediate
existing medical knowledge to the broader public, nor does it
approach images “as instruments for [merely] visualizing information”
(Krämer 2022, 269, emphasis in original). Instead, images are
understood here as “tools for gaining, operating and exploring
information” (Krämer 2022, 269, emphasis in original). Accordingly,
this analysis examines how researchers deploy a particular cutting-
edge neuroimaging technology in specifically designed experimental
settings to produce empirical images that operate as active tools for
generating new medical insights into the underlying neurophysiology
of . It also foregrounds how the context-specific operations
involved in producing these images vary across different experiments
depending on the research questions posed about .
is a complex, chronic disease characterized by varied
symptoms that, besides persistent fatigue, include memory problems,
sleep abnormalities, and muscular pain, as well as the defining clinical
feature called post-exertional malaise () that encompasses the
exertion-induced worsening of all symptoms (Carruthers et al.
2011). Because of the absence of diagnostic laboratory tests,
unknown etiology, and lack of reliable treatments, is often
disparagingly equated with hysteria, malingering, or imaginary
psychosomatic complaints (Diedrich 2021; Friedman 2019). The view
that is entirely psychological or psychosocial causes, thus lacking
a biological basis, remains widespread even among medical
professionals (Froehlich et al. 2022). However, this view has been
contradicted by growing empirical research findings about the
patients’ multiple physiological anomalies in immune responses,
energy metabolism, and nervous system functioning (Rivera et al.
2019; Komaroff 2019). So far, the research findings have remained in
the domain of basic science, without applications in clinical practice.
Since 2004, a sustained strand of neurological research has
deployed a noninvasive neuroimaging technology called functional
magnetic resonance imaging (f) to study the neural basis of
patients’ elusive symptoms. Using f, researchers indirectly
measure neurophysiological correlates of brain activity in living human
subjects under controlled experimental conditions. In an f
experiment, participants are placed inside a specialized scanner and
instructed to perform a particular task (task-based f) or to rest
and think of nothing (resting-state f) while the scanner generates
imaging data. At the end of the measurement, researchers obtain
noisy f data that are illegible even to experts (Muhr 2022).
Researchers must submit these data to multiple stages of algorithmic
processing and statistical analysis to compute functional brain maps
(Huettel, Song, and McCarthy 2009), which they can then interpret,
thus making judgments about the experimental subjects’ brain activity
of interests and correlated cognitive functions.
In medical research, f data are often collected for a group of
patients with a particular disorder and a control group that typically
consists of healthy subjects. Depending on the type of data analysis
performed, the resulting group-level f maps can be divided into
activation and connectivity brain maps (Huettel, Song, and McCarthy
2009). Activation maps visualize how spatial patterns of statistically
significant local task-dependent neural activity of interest differ
between patients and control subjects at the group level. Connectivity
maps display the differences in the distribution of functional
connections across widespread brain regions and networks between
patients and control subjects.
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In f-based research on , scientists produce functional brain
maps aiming to link a particular experimentally isolated aspect of this
complex disorder to anatomically localizable dysfunctions of individual
brain areas or to disturbances in functional connectivity across distant
brain regions. Hence, in the research context, brain maps function as
operative images (Krämer 2009; 2022)—they enable scientists to
reach and explore the disorder’s otherwise inaccessible underlying
neuropathophysiology, thus producing new medical insights into
and generating visual evidence of its physiological reality. This case
study draws on Krämer’s (2022, 266 – 67) claim that the operative
images’ referentiality, i.e., their ability to provide access to the object
they visualize, is neither immediate nor reducible to mimetic similarity.
Therefore, of interest here is how the referentiality of f brain
maps, understood as a precondition of their knowledge-generating
potential, is established through the articulation (Latour 1999) of
’s neuropathophysiological underpinnings.
As defined by Latour (1999, 142), articulation comprises all
experimental interventions that jointly enable the emergence of new
insights into a phenomenon of interest through the process of
scientific mediation. Importantly, Latour emphasizes the distinctly
processual character of articulation. Instead of being a one-off event
accomplished in a single step, it involves a chain of successive,
interrelated interventions that progressively transform a “mute,
unknown, undefined” phenomenon into a well-articulated and hence
potentially knowable entity (Latour 1999, 143). Along this chain, the
phenomenon of interest is brought into relation to other entities,
instruments, models, measurements, inscriptions, and interpretations
to draw out its differences. Latour (1999, 69 –79) thus designates
articulation as the movement along the chain of transformations. He
also insists that when scientific images facilitate the articulation of
phenomena of interest, the images’ referentiality is established
through the chains of traceable transformations that underpin the
images’ production and link each image to a cascade of other
images, measurements, protocols, tags, and heterogeneous
inscriptions that precede it. Latour thus interchangeably uses the
terms chain of transformations and referential chain.
However, whereas Latour focuses on tracing the sequencing of
intermediary steps that form a chain, this analysis highlights the
decisions that researchers make at each step to enable the
movement along the chain of transformations, thus enacting the
articulation of the phenomenon of interest. To emphasize this
recalibrated focus, the term chain of operations is used here instead
of a referential chain. Moreover, as used here, articulation designates
the process of linking to its underlying neural basis through the
mediation of f with the aim of generating empirical evidence for
the physiological reality of patient’s experiences of . This case
study addresses how such articulation is performed in scientific
practice. Accordingly, the analysis does not concentrate on the visual
features of brain maps as the empirical output of an f study
because, as argued here, such images should not be approached as
straightforward representations of ’s neuropathology. Instead, the
focus of analysis is on the chains of operations that underpin the
production of brain maps as epistemic tools within concrete
experimental setups and on how these operations change across
experiments depending on the research questions posed.
Methodologically, the analysis is based on a close reading of two
pioneering f studies, one that approached from the clinical
perspective of its fluctuating symptom manifestations, whereas the
other asked a more technically framed question about potential -
related disturbances in neural signal conduction via a specific brain
region. Specifically, a team of researchers based in the published
the first f study that explored aberrant patterns of brain activity
underlying , a cardinal feature of (Cook et al. 2017).
Conversely, a group of Australian researchers authored the first f
study that combined resting-state and task-based functional
connectivity analyses to examine patients’ impaired brainstem
connectivity (Barnden et al. 2019).
To trace how the articulation of different aspects of ’s
neuropathology was enacted in these studies depending on the
specific research questions their authors aimed to answer, the
operations the researchers performed in the four successive stages
of each f experiment will be analyzed. While the operations are
sequentially described in the methods section of each f study, this
analysis will unpack the assumptions underlying each operation. The
four successive stages are: first, selecting study participants; second,
defining the experimental procedure; third, collecting data; and fourth,
processing and analyzing data. The case study’s conclusion will
discuss the differences in how the articulations of ’s
neuropathology were performed in the two f studies.
Overall, the goal here is not to make overarching claims about the
f maps’ ability to offer reliable access to ’s neuropathology
nor to identify general conditions under which such reliable access
could be achieved. Rather, the aim is to disclose the immense work
involved in scientific image-making in f-based research on .
While this work remains invisible beyond specialists’ circles, it
underpins the images’ ability to deliver visual evidence for the physical
reality of patients’ subjective experiences of chronic fatigue, thus
effectively countering their dismissal as simulation.
Articulating the Neurophysiology of
As a defining clinical feature of , post-exertional malaise ()
denotes patients’ “pathological low-threshold fatigability” (Carruthers
et al. 2011, 331). It manifests as a delayed exacerbation of patients’
diverse symptoms—including pain, cognitive difficulties, and fatigue—
following even mild physical or cognitive exertion. has been
investigated by multiple physiological studies (Carruthers et al. 2011,
331–32). However, Cook et al. (2017) were the first to deploy f in
an attempt to articulate how , induced under controlled laboratory
conditions, affects patients’ brain function.
In an f study’s initial stage, which precedes data acquisition,
researchers select suitable participants by defining inclusion and
exclusion criteria. As will be shown, participant selection already
partakes in articulating ’s neuropathology by transforming patients
into study participants who exhibit characteristics aligned with the
selection criteria. In Cook et al.’s study, which comprised a group of
patients and a control group, the focus was on selecting a
relatively homogeneous patient sample. This proved challenging as
the current research on struggles with diagnosis misclassification
due to the parallel use of disparate diagnostic criteria that define
cases differently (Nacul et al. 2019). To mitigate potential
misclassification, Cook et al. decided not to rely solely on the Fukuda
et al. (1994) criteria, as these, although dominant in research, have
been increasingly criticized for being “overly inclusive” (Committee on
the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue
Syndrome 2015, 48) while ignoring as a central feature.
Instead, Cook et al. (2017, 88) recruited patients who simultaneously
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met the Fukuda et al. (1994) and the more stringent Carruthers et al.
(2003) criteria. Moreover, to avoid confounding factors that could
introduce unwanted neurophysiological variability into f data, Cook
et al. excluded from their sample patients diagnosed with
psychiatric comorbidities or substance abuse and those receiving
immunomodulatory medication.
The joint aim of these operations was to increase the diagnostic
specificity of the patient sample by disregarding more ambiguous
cases, which abound in clinical practice. It can be assumed that this
focus on selecting patients with stringently delineated core
symptoms was seen as a precondition for isolating and quantifying
the -related exacerbation of these symptoms. However, because
of such strict selection criteria, Cook et al. recruited only fifteen
patients. Thus, the price for this diagnostic specificity was decreased
statistical power of their imaging findings due to the small sample
size, which, in turn, potentially limited the statistical validity and
reliability of their findings.
The researchers also recruited fifteen healthy control subjects who
matched the patients’ age and gender. The control subjects were
further selected to closely match the patients’ weight, height, and
varying levels of physical activity (Cook et al. 2017, 88). Such
unusually comprehensive matching of bodily features between the
groups was epistemically significant. It aimed to minimize the
differential non-disease-specific effects that the physical exercise
during the experimental procedure could have on patients and control
subjects. It also had an added benefit for the subsequent statistical
analysis of f data as it reduced the impact that weight and fitness
level differences “may have on neurological morphology and function”
(Maksoud et al. 2020, 11).
Notably, the study’s sample consisted of exclusively female
patients. is more frequently diagnosed in women (60– 65
percent) than in men (Valdez et al. 2019). Female patients are,
therefore, overrepresented in neuroimaging studies, some of which
have purely female samples (Maksoud et al. 2020, 11). Although
the implicit inscription of gender into f findings through patient
sampling is not visible in the brain maps, it has semantic effects. As
Cook et al. (2017, 97) emphasized, it remains unclear if the obtained
neuroimaging results can be generalized to male patients since the
potential role of gender differences in the neuropathology of is
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unexplored. More problematically, such findings tacitly reinforce the
current biased perception of as a predominantly female disorder,
which is implicitly stigmatizing (Lian and Bondevik 2015, 932).
In the next stage, Cook et al. defined the conditions of their
experimental procedure. Since they aimed to articulate how
induced under controlled laboratory conditions affected patients’
brain function, they implemented a pre-test–post-test design,
spreading their experimental procedure across three days. Day one
entailed the initial acquisition of neuroimaging and non-imaging data.
A week later, on day two, participants returned to the laboratory for
additional measurements and to perform the -inducing exercise.
Finally, 24 hours later, on day three, the researchers collected the
second round of f and non-imaging data.
Besides temporally structuring their experimental procedure, Cook
et al. specified the -provoking exercise and defined the
experimental tasks. They chose a submaximal protocol, a well-
established approach for controlled induction in physiological
research. It involved a 25-minute steady-state aerobic exercise on
a stationary bicycle at an intensity equivalent to 70 percent of each
participant’s age-predicted maximum heart rate (Cook et al. 2017,
89). Importantly, this standard protocol allowed the researchers to
model moderate acute physical exertion—meant to induce in
patients—while avoiding physiologically overstressing the
participants, which would have introduced confounding physiological
effects.
A particularly epistemologically significant aspect of the study was
how the researchers designed the experimental tasks that their
participants performed during f scanning. In task-based f
studies, experimental tasks enable researchers to isolate the
differential neurophysiological and cognitive effects of various task
components during subsequent data analysis. Hence, the choice of
tasks is typically grounded in researchers’ assumptions about which
cognitive processes are implicated in the phenomenon they study and
influenced by the continually evolving theories of the neural basis of
cognition (Muhr 2022, 283 – 285). This was also the case in Cook et
al.’s study.
To explore how acute exercise affects patients’ diverse
physical and cognitive symptoms at the level of neural activity, Cook
et al. deployed three separate tasks, which participants executed in
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sequence. The first was a non-fatiguing motor task called finger
tapping. During this task, participants were asked to “open and close
their right hand, bringing their four fingers in contact with their thumb”
at a predetermined rate (Cook et al. 2017, 89). The second was a
non-fatiguing cognitive task that entailed simple auditory monitoring
and number recognition. During this task, participants listened to a
series of numbers from one to ten and had to press a button when
they heard the number seven. Unlike the previous two tasks, the third
was designed to induce mental fatigue during f scanning and was
a modified version of the standardized Paced Auditory Serial Addition
Task (). In the standard , participants listen to a series of
numbers from one to nine, silently adding each new number to the
previous one, and are instructed to press the button when the sum of
two consecutive numbers equals 10. Initially developed to measure
the effects of concussion on the speed of information processing, the
is currently deployed in research for multifactorial assessment
of “sustained attention, working memory” and cognitive performance
under time constraints (Tombaugh 2006, 65). In the modified
used by Cook et al. (2017, 89), the participants were additionally
exposed to distracting visual stimuli in the form of rapidly and
randomly changing numbers on the screen that they had to watch
while adding the numbers they were hearing.
Based on the above description, it can be argued that Cook et al.
designed a complex combination of multiple tasks, each targeting and
isolating a particular aspect of the participants’ neurocognitive
performance in a graded manner. This tailored multiplication of the
tasks served to articulate the unknown associations between
and the changes in the neural activity underpinning experimental tasks
of varying difficulty. Therefore, the tasks were strategically stratified
from a non-fatiguing motor over a non-fatiguing cognitive to a mentally
fatiguing cognitive task. The tacit assumption guiding this stratification
was that , an exertion-induced exacerbation of heterogeneous
symptoms, is a cognitively multifactorial and highly variable
phenomenon whose explorative f-based decomposition requires a
sufficiently complex combination of mutually independent tasks.
Moreover, the researchers’ decision to modify the standard version of
the and make it more difficult by including distracting elements
indicates that they were particularly invested in articulating the
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