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NeuroRehabilitation. Author manuscript; available in PMC 2024 February 27.
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Published in final edited form as:

NeuroRehabilitation. 2024 ; 54(1): 23–42. doi:10.3233/NRE-230123.

Covert consciousness
Michael J. Younga,*, Brian L. Edlowa,b, Yelena G. Bodiena,c
aDepartment of Neurology, Center for Neurotechnology and Neurorecovery, Massachusetts
General Hospital, Harvard Medical School, Boston, MA, USA
bAthinoulaA. Martinos Center for Biomedical Imaging, Massachusetts General Hospital,
Charlestown, MA, USA
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cDepartment of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard

Medical School, Boston, MA, USA

Abstract
Covert consciousness is a state of residual awareness following severe brain injury or neurological
disorder that evades routine bedside behavioral detection. Patients with covert consciousness have
preserved awareness but are incapable of self-expression through ordinary means of behavior or
communication. Growing recognition of the limitations of bedside neurobehavioral examination in
reliably detecting consciousness, along with advances in neurotechnologies capable of detecting
brain states or subtle signs indicative of consciousness not discernible by routine examination,
carry promise to transform approaches to classifying, diagnosing, prognosticating and treating
disorders of consciousness. Here we describe and critically evaluate the evolving clinical
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category of covert consciousness, including approaches to its diagnosis through neuroimaging,

electrophysiology, and novel behavioral tools, its prognostic relevance, and open questions
pertaining to optimal clinical management of patients with covert consciousness recovering from
severe brain injury.

Keywords
Coma; cognitive motor dissociation; vegetative state; unresponsive wakefulness syndrome; covert
consciousness; fMRI; EEG; minimally conscious state

1. Introduction
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Covert consciousness is a state of residual awareness following severe brain injury or

neurological disorder that evades routine bedside behavioral detection. Patients with covert
consciousness have preserved awareness but are incapable of self-expression through
ordinary means of communication or behavior (Schiff, 2015; Bodien et al., 2022). Growing
recognition of the shortcomings of standardized, bedside neurobehavioral examination

*
Address for correspondence: Michael J. Young, MD, MPhil, Department of Neurology, Massachusetts General Hospital, Boston, MA
02114, USA. [email protected].
Conflict of interest
The authors have no conflicts of interest to report.
 Young et al. Page 2

techniques in reliably detecting consciousness, along with advances in neurotechnologies

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capable of discerning brain states or subtle signs indicative of consciousness, carry

promise to transform approaches to classifying, diagnosing, prognosticating and treating
disorders of consciousness (DoC), including covert consciousness (Edlow, 2018; Young
& Edlow, 2021b). Here we explain and critically evaluate the evolving clinical category
of covert consciousness, including approaches to its diagnosis through neuroimaging,
electrophysiology, and novel behavioral tools, its prognostic relevance, and open questions
pertaining to its optimal clinical management.

We begin with an approach to conceptualizing and operationalizing covert consciousness

in research and practice, and explore how it problematizes prevailing taxonomies and
diagnostic approaches in DoC that revolve predominantly around assessment of a patient’s
overt behavioral repertoire. After describing and critically evaluating emerging methods
of detecting covert consciousness, including neuroimaging, electrophysiology, and novel
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behavioral approaches, we describe issues pertaining to the clinical management of covert

consciousness. We conclude with a discussion of underexplored questions in the diagnosis,
prognosis and management of covert consciousness. Growing needs for consensus building,
research and quality improvement efforts to modernize and sensitize faltering DoC nosology,
diagnostic approaches, and prognostic paradigms to the possibility of covert consciousness
are emphasized throughout.

2. What is covert consciousness?

Recognizing that there are currently no consensus-based definitions of covert consciousness
or guidelines standardizing its diagnosis or management, and building upon the evolving use
of the term in the scientific literature and clinical practice, we operationally define covert
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consciousness as a state of residual awareness following severe brain injury or neurological

disorder that evades routine bedside behavioral detection.

This definitional attempt by no means intends to be definitive; it is instead a starting

point for our analysis that reflects the term’s general usage in the scientific and medical
literature. By ‘awareness’ here, we refer to the capacity to subjectively experience any
aspect of the self or environment (Massimini & Tononi, 2018). It should be noted that the
residual cognitive capacities of a patient with covert consciousness may or may not extend
beyond awareness simpliciter to include higher-order cognitive capacities (Graham, 2021);
this operational approach thus aims only to describe minimum conditions constitutive of
covert consciousness (Hucklenbroich, 2014). The nature and scope of awareness in a patient
with covert consciousness could conceivably range from elemental to elaborate (Bayne et
al., 2020; Diserens et al., 2023).
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Philosophers and scientists have described various forms that awareness can take, including
perceptual awareness (i.e., experience of sense perceptions) (Aquila, 1974), emotional
awareness (Mitchell, 2019; Stout, 2019), reflexive inner-awareness (Chaturvedi, 2022), self-
awareness (Zahavi, 1999), bodily/interoceptive awareness (Nikolova et al., 2022), awareness
of awareness (Armstrong, 1963; Montague, 2017), interpersonal awareness (Decety &
Sommerville, 2003; Morin, 2006), among other forms beyond our present scope. Each of

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these states instantiate properties in virtue of which there is something it is like to be in that
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state (Kriegel, 2003; Lee, 2022).

The inherently subjective character of awareness and consciousness poses an inevitable

epistemic challenge to attempts at assessing its presence or absence (Bernal Velásquez,
2011; Giacino et al., 2009; Nagel, 1974). Unlike cardiac or respiratory function, for instance,
which can be directly visualized, measured, or auscultated, consciousness, except in the
first-person instance, may only be reasonably inferred by closely examining its supervening
manifestations, and to the extent possible, characterizing the integrity of what is known
about its putative substrate and neural correlates (Chen & Yoshimi, 2023; Edlow et al., 2023;
Plum & Posner, 1982; Young, 2018; Young et al., 2023).

As the phenomenology of covert consciousness remains underexplored (Graham, 2019;

Taylor et al., 2020), little is known about the first-person experience of covert consciousness
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and implications for quality of life and wellbeing (Graham, 2021; Graham & Naci, 2021)
but it is likely that the contours of this experience vary considerably from person to person
depending on the nature and extent of the culprit disorder, and the person’s pre-injury
characteristics (Young, Bodien, et al., 2021). Critical ethical and clinical decisions, including
those surrounding approaches to neurorehabilitation and the appropriateness of continuing
or limiting life-sustaining treatment, may hinge on implicit or explicit assumptions about
the nature and value (Bradford, 2022; Kriegel, 2019; O’Leary, 2021) of a patient’s level
of consciousness, implications for wellbeing, and capacity for recovery (Glannon, 2016;
Gosseries & Laureys, 2022; Graham, 2017; Lazaridis et al., 2021; Lee, 2019; Mertens et
al., 2022; Tung et al., 2020; Young et al., 2022). The magnitude and at times life-or-death
consequences of such decisions underscore the medical and moral imperatives to address
these questions in clinical practice and research, which at minimum require clarifying
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whether a behaviorally unresponsive patient is covertly conscious in the first place (Ezer et
al., 2020; Fins, 2015; Fins, 2016; Fins et al., 2020; Naci & Owen, 2022; Rohaut et al., 2019).
As we later examine, covert consciousness may be identified through a variety of potential
methods, including functional neuroimaging and electrophysiologic paradigms designed to
detect volitional modulation of brain activity, brain-computer interfaces (Lulé et al., 2013;
Pan et al., 2022; Xu et al., 2022; Young, Lin, et al., 2021), as well as through advanced
neurobehavioral examination techniques (Mat et al., 2022) designed to capture conscious
responses to which standard bedside assessment is insensitive.

‘Severe brain injury or neurological disorder’ is included in the operational definition

above in order to exclude patients with conditions like psychogenic coma (Ludwig et al.,
2016; Ryznar & Wilcox, 2019) or akinetic catatonia (Schnetzer et al., 2023). Although
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such patients might be considered covertly conscious if they are mistakenly regarded as
unconscious at the bedside, these conditions are outside of the scope of this paper and
inconsistent with evolving norms in the scientific literature which tend to limit application of
this term to patients with severe neurological disorders or trauma. The potential neurological
disturbances that may give rise to the syndromic phenotype of covert consciousness are
varied (Fig. 1). While covert consciousness is typically invoked in the settings of severe
brain injury, under this approach, a patient with stroke, toxic, metabolic, infectious or
autoimmune leukoencephalopathy, advanced amyotrophic lateral sclerosis (ALS) or severe

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polyneuropathy such as Guillain-Barré syndrome (GBS/acute demyelinating polyneuropathy

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(AIDP)) with complete paralysis and anarthria may be considered covertly conscious if
awareness is preserved but not evident at the bedside. In these conditions, weakness may
progress to the point that a patient is no longer able to reliably communicate or respond
to commands; patients with this profound degree of paralysis are more typically said
to be in the “complete locked-in state” (CLIS); while harboring intact awareness and
cognition, the capacity for self-expression is lost due to complete motor impairment with
quadriplegia, anarthria and oculomotor paresis (Hochberg & Cudkowicz, 2014). This is
distinguished from patients in an incomplete locked-in state, who retain the ability to
reliably communicate at least a binary “yes/no” signal, for example through vertical eye
movements (and in doing so can, with the assistance of a caregiver, spell out words
using a manual letterboard) (Murguialday et al., 2011). While some favor the term CLIS
when the condition is attributable to peripheral motor nerve or brainstem pathology and
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limit application of the term covert consciousness to circumstances where obstruction of

self-expression is attributable to supratentorial pathology, or otherwise limit application of
covert consciousness to circumstances where awareness is diminished but not altogether
extinguished, others employ overlapping terminology, and there is no universally accepted
etiological or localization-based approach to distinguishing these entities (de Jong, 2013;
Medici et al., 2011; Norton, Graham, et al., 2023; Schnetzer et al., 2023). Complicating
matters further, some have pointed out that it is a misnomer to classify some such states
as ‘disorders of consciousness’ if it is the case that consciousness is preserved (and thus
not inherently disordered, but rather limited in behavioral expression, as it might be in
select instances of covert consciousness and behavioral MCS) (de Jong, 2013; Diserens
et al., 2023; Hermann, Sangaré, et al., 2021). Whereas in conditions such as ALS and
GBS the expectation is that consciousness and cognition will generally remain intact
(Kotchoubey et al., 2003), in DoC following brain injury the expectation is that cognitive
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capacities will be impaired, which is why many of the assistive devices that have become
available to manage motor impairments of other etiologies have been challenging to
successfully apply in the DoC population. However, this dichotomy between conditions
that impair versus spare consciousness and cognition is not always straightforward to
apply in practice, considering the possibility for secondary complications of “pure”
sensorimotor conditions that could result in alterations in consciousness (e.g., respiratory
failure in GBS resulting in superimposed hypoxic brain injury), and in light of known
variants such as ALS with frontotemporal dementia (ALS-FTD) or Bickerstaff brainstem
encephalitis, a GBS variant, which may impact consciousness. Additionally, some contend
that consciousness is affected by the transition to the CLIS as evidenced by changes in
alpha band frequency and other electroencephalography (EEG) features (Colombo et al.,
2023; Khalili-Ardali et al., 2021; Maruyama et al., 2021; Rosburg, 2019), theorizing that
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“an extinction in goal-directed thinking in completely paralyzed patients” could ensue

if patients “lose the perception of the contingency between the required physiological
behaviour … and its consequences” (Kübler & Birbaumer, 2008). While these findings
may challenge the dichotomy between DoC and CLIS, some have argued that cognition may
be maintained in CLIS through “imagined response-effect contingencies” and potentially
restored through novel rehabilitative interventions, underscoring the clinical and ethical

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urgency to understand, identify, and manage these conditions (Soekadar & Birbaumer,
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2015).

“ … evades routine bedside detection” is used in the operational definition above to

sensitize this approach to the possibility of covert consciousness being detected through
non-routine behavioral techniques (such as video eye-tracking to immersive stimuli or other
subtle motor/behavioral signs like olfactory responses). Thus, unlike several other proposed
definitions, including those of cognitive motor dissociation (CMD), this approach does not
necessitate the use of advanced neuroimaging or electrophysiologic techniques in diagnosing
covert consciousness. For instance, Schiff describes CMD as a clinical syndrome of patients
who “demonstrate a vegetative state or a low-level, minimally conscious state (restricted to
nonreflexive behaviors, such as tracking, but lacking command following) behavioral profile
… and fMRI [functional magnetic resonance imaging] or electrophysiologic evidence of
command following” (Schiff, 2015) and Boerwinkle et al. define covert consciousness as
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a “state of MCS+ or eMCS identified when volitional brain activities is [sic] detected by
task-based fMRI or EEG in individuals who display behavioral features of coma, VS/UWS,
or MCS-, and thereby do not show command following at the bedside … [s]ynonymous
terms are covert cognition and cognitive motor dissociation (CMD)” (Boerwinkle et al.,
2023). While covert consciousness may indeed be indicated by task-based fMRI or EEG
evidence of command-following, covert consciousness may also be suggested by results of
other modalities, as explored in subsequent sections. While it is generally accepted that a
patient who is behaviorally considered to be comatose, in the vegetative state / unresponsive
wakefulness syndrome (VS/UWS), or minimally conscious state minus (MCS -) may be
covertly consciousness (Alkhachroum et al., 2023; Boerwinkle et al., 2023; Helbok et al.,
2022; Morlet et al., 2023; Thibaut et al., 2020), an open question is whether a patient who is
behaviorally in the minimally conscious state plus (MCS+) may be appropriately considered
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covertly conscious, if, for instance, their level of awareness is completely intact but due to
motor or other cognitive impairments are unable to demonstrate functional communication
or object use on standardized neurobehavioral testing such as the Coma Recovery Scale
– Revised (CRS-R) (Giacino et al., 2004). While some may contend that such a patient
cannot be appropriately considered covertly conscious since they already display overt
signs of consciousness, others may argue that such a patient can be justifiably considered
covertly conscious as, ex hypothesi, they are not ‘minimally conscious’ but rather are fully
conscious with impaired behavioral repertoire (i.e., minimally responsive but not minimally
conscious) (Bernat, 2002; de Jong, 2013; Hermann, Sangaré, et al., 2021). The solution
to this problem may hinge on a deeper debate in philosophy of mind concerning whether
consciousness is a binary or graded property (Godfrey-Smith, 2020; Lee, 2022; Naccache,
2018; Young, 2017). While a thorough analysis of this problem is beyond our present scope,
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a commitment to the position that consciousness is a graded is plainly reflected in clinical

language in common use (e.g., ‘levels of consciousness’, ‘depth of sedation’, ‘minimally
conscious’). According to this approach, a diagnosis of covert consciousness may be
made when the level of consciousness that can be reasonably inferred from the results
of advanced testing (including neurophysiology, neuroimaging and/or advanced behavioral
tests) exceeds that which is suggested by routine bedside behavioral exam. What might be
considered a reasonable inference will likely evolve over time with advances in clinical

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neuroscience. The development of consensus-based diagnostic qualifiers such as ‘possible’,

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‘probable’, and ‘confirmed’ covert consciousness may be considered to reflect varying levels
of diagnostic confidence depending on the nature and strength of available test results,
mirroring the typology of several other neurological conditions (Charidimou et al., 2022;
Menéndez-González, 2023; Tresker, 2020).

Many different terms for covert consciousness have been used, sometimes interchangeably
and at times with slight or substantial variations in meaning, CMD (Schiff, 2015), covert
command-following (Bodien et al., 2017; Forgacs et al., 2014), preserved cortical circuitry
(de Jong et al., 1997), hidden/preserved vitality (Shalit et al., 1970), loss of behavior
with remaining conscious perception (Ingvar & Ciria, 1975), covert cognition (Cruse et
al., 2012; Nachev & Hacker, 2010), complete locked-in syndrome (de Jong, 2013), covert
activity (Sontheimer et al., 2017), covert attention (Morlet et al., 2023; Pan et al., 2020),
covert awareness (Cruse et al., 2014; Fernandez-Espejo et al., 2014; Gibson et al., 2016;
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Graham et al., 2018; Graham et al., 2015; Owen et al., 2007; Peterson et al., 2013), covert
narrative capacity (Naci et al., 2017), preservation of mental life (Naci & Owen, 2022),
functional disconnection syndrome (Formisano et al., 2011; Laureys et al., 2006; Schiff,
2012), functional LIS (Formisano et al., 2013), functional minimally conscious, minimally
conscious state star (MCS*) (Thibaut et al., 2021), among others (Schnakers et al., 2022).
Meanwhile, prevailing clinical nomenclature (e.g., coma, VS / UWS, MCS), yoked to
behavioral diagnostic criteria remains unsensitized to the potential findings of methods for
detecting covert consciousness, and lumps together fundamentally different endotypes into
the same rough behavioral categories, glossing over important diagnostic differences and
risking mischaracterization of patients’ levels of awareness (Young & Edlow, 2021a; Young
& Peterson, 2022). This irregular patchwork of terminology and heterogeneity in real-world
uses underscores a pressing clinical and ethical need to develop a more organized approach
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to the taxonomy of covert consciousness (along with other DoCs), that is adapted to the
range of potential findings of advanced testing modalities, and is explicit about etiology (for
example, through a multi-axis or composite diagnostic approach). Such an approach stands
to benefit clinicians, researchers and surrogate decision-makers alike. Efforts to describe
endotypes of covert consciousness through objective, internal criteria are underway, and
promise to aid in mitigating the forgoing challenges afflicting DoC classification schemes
based solely on external behavioral or relational criteria (Hammond et al., 2021; Kondziella
et al., 2021; Kondziella & Stevens, 2022; Zachar, 2002).

3. Neuroimaging of covert consciousness

For nearly two decades, investigators have applied advanced neuroimaging techniques such
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as fMRI to identify awareness in patients with no signs of consciousness on the bedside

examination (Schiff, 2015).

Prior to 2018, advanced neuroimaging techniques for detecting covert consciousness

were used exclusively in the context of research. However, in recent years, clinical
guidelines published by the American Academy of Neurology (AAN), American Congress
of Rehabilitation Medicine (ACRM), National Institute on Disability, Independent Living,
and Rehabilitation Research (NIDILRR) (Giacino et al., 2018a, 2018b) and the European

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Academy of Neurology (EAN) (Kondziella et al., 2020) have recognized the benefits of
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integrating functional neuroimaging into clinical practice. In these guidelines, national and
international organizations recommend, for the first time, that functional neuroimaging tests
be considered in the diagnostic and prognostic evaluation of some patients with DoC. The
translation of these tools into clinical practice poses a challenge, as they require specific
hardware and software, expertise in analysis, and nuanced interpretation (Bodien et al.,
2023; Young et al., 2024). Nevertheless, over time we expect they will be integrated into a
multimodal battery of tests that will increase the certainty with which level of consciousness
is established. The development of a hub-and-spoke model system for DoC evaluation and
management may aid in the process of democratizing access to advanced tools (Peterson
et al., 2022; Young, 2022; Young & Edlow, 2021a). Below, we discuss the most common
functional neuroimaging modalities used to assess patients with DoC and review how these
modalities may be used to understand diagnosis and prognosis of severe brain injury.
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Functional neuroimaging modalities can be used to directly assess covert consciousness

by measuring the brain’s response to a specific task. Alternatively, data collected while
the brain is in a resting state (i.e., no external stimuli or instructions are presented to
evoke behavioral and/or neuronal responses), while the brain is passively stimulated (e.g.,
by auditory or visual stimuli), while the subject is asked to perform a task (e.g., target
detection), or following administration of a chemical compound may inform the more
nebulous “capacity” of consciousness, or grounds for possibility of conscious experience.
Understanding the advantages and limitations of each approach and the range of possible
interpretations of the data is critical to translating the results into a clinical tool.

3.1. Functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) measures the brain’s hemodynamic
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response to a stimulus or cognitive process, or simply at rest. During periods of increased

neuronal activity, the brain requires an influx of glucose and oxygen, which are delivered
through cerebral blood flow. This bolus of blood contains more oxygenated versus
deoxygenated blood, and, due to the ferrous MR signal-reducing properties of deoxygenated
blood, contributes to an overall enhanced MR signal (Kwong et al., 1992; Ogawa et
al., 1993; Ogawa et al., 1992). The Blood-Oxygen-Level Dependent (BOLD) response
measured by fMRI is therefore an indirect measurement of underlying neuronal activity
(Logothetis et al., 2001). However, during the resting state, in the absence of a stimulus or
task, the BOLD signal fluctuates spontaneously at a low frequency. The correlation of the
BOLD signal fluctuations in different brain regions is interpreted as functional connectivity
(Fox & Raichle, 2007). One of the most widely studied resting-state networks is the
default mode network (DMN), which is thought to mediate introspection and self-referential
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thought (Buckner et al., 2008; Levorsen et al., 2023; Menon, 2023; Wen et al., 2020).

3.2. Positron emission tomography

Positron Emission Tomography (PET) uses an intravenous radiotracer targeted towards brain
metabolism or specific neurotransmitter systems to quantify brain metabolism. A decaying
radiotracer emits a positron that interacts with an electron, resulting in the annihilation of
both particles into photons. When these photons are detected, their original position can be

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calculated to localize the source of the annihilation, which results in an image of radiotracer
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uptake. The most common radiotracer is 18F-fluorodeoxyglucose (FDG), which measures

brain metabolism. (Sweet, 1951; Wrenn et al., 1951). Although PET is used most often with
resting-state studies, it is possible to use FDG-PET (Jamadar et al., 2019) and 15O-water
PET to probe covert cognitive function (Mamach et al., 2018).

3.3. Functional near-infrared spectroscopy

Similar to fMRI, functional near-infrared spectroscopy (fNIRS) leverages the coupling
between neuronal firing and the hemodynamic response to measure brain function (Jobsis,
1977). fNIRS relies on a light that, when emitted onto the surface of the head in the
near-infrared spectrum of 700–900 nm, passes through the scalp and skull, and is absorbed
by oxygenated and deoxygenated hemoglobin. Changes in hemoglobin concentration are
detected by an optode sensor on the scalp. In contrast to fMRI, fNIRS can be performed
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at the bedside, is less prone to motion artifact, and has fewer safety risks. fNIRS is highly
portable and can be conducted at the bedside. However, the spatial resolution of fNIRS is
limited to activity occurring within a cortical depth of 2–4 mm.

3.4. Moving towards clinical implementation of functional neuroimaging techniques

Although the utility of clinical fMRI has been demonstrated in pre-surgical mapping
for tumor resection and epilepsy surgery, and FDG-PET is used clinically for diagnosis
of dementia, most functional neuroimaging tools have traditionally been considered
investigational. However, there are now notable exceptions supporting the use of the
techniques described here in clinical practice (Giacino et al., 2018a, 2018b; Kondziella et
al., 2020). Currently, only a small number of specialty centers have the hardware, software,
and expertise to implement these techniques and most have not undergone rigorous clinical
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validation (Young and Edlow, 2021). In almost all arenas, studies with large, well-controlled,
patient samples recruited from multiple sites and with meticulous blinding procedures
are needed to bridge this gap. Nevertheless, there is growing enthusiasm for clinical
implementation of functional neuroimaging technologies because of the unprecedented
opportunity to improve diagnostic and prognostic precision for patients with severe brain
injuries (Comanducci et al., 2020; Monti & Schnakers, 2022).

3.5. Diagnosing covert consciousness with functional neuroimaging

Over the last 15 years, neuroimaging (and electrophysiology) studies have consistently
shown that 10–20% of patients who appear unconscious on behavioral examination retain
conscious awareness when tested with fMRI (or EEG) using task-based motor imagery
paradigms (Kondziella et al., 2016; Schnakers et al., 2020; Stender et al., 2014). Among
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the first reports of CMD was a 2006 case report of a patient with a behavioral diagnosis
of VS/UWS (Owen et al., 2006). During an fMRI scan, when the patient was asked to
imagine playing tennis, a BOLD response was observed in the supplementary motor area
and when asked to imagine walking around her house, a BOLD response was observed
in the parahippocampal area. This finding paralleled the result obtained in healthy control
subjects. In 2010, a study of 54 patients confirmed the presence of CMD and fMRI was
also used to establish a channel of yes/no communication in a single subject who appeared
to fulfill criteria for the VS for 5 years prior to the assessment (Monti et al., 2010). Covert

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consciousness has also been reported in patients with acute severe TBI in the intensive
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care unit (Edlow et al., 2017). Covert consciousness has also been identified in the context
of pediatric brain injury, but has been relatively underexplored in comparison to the adult
population (Boerwinkle et al., 2023; Kim et al., 2022).

A substantial limitation of using fMRI to detect covert consciousness is the frequency with
which individuals with a behavioral MCS diagnosis, and even healthy control subjects, fail
to demonstrate the anticipated response to motor imagery paradigms. Motor imagery is
a complex task requiring multiple cognitive processes including language comprehension,
working memory and attention, to be intact. Some patients may be able to understand the
command but fail to perform the task with the consistency required to generate a BOLD
response. Fluctuations in arousal, sedating medications, and language impairment may also
contribute to false negative findings. For this reason, a positive response on an fMRI motor
imagery task in patients with a behavioral diagnosis of coma, VS, or MCS- is interpreted
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as CMD, but a negative response is ambiguous and does not suggest an absence of CMD.
On a prognostic plane, covert brain responses detected by fMRI in acutely unresponsive
patients following severe brain injury appear to portend greater likelihood of functional
recovery, as measured by Glasgow Outcome Scale at 6 months (Norton, Kazazian, et al.,
2023). Clinicians and researchers have emphasized the importance of facilitating responsible
integration of fMRI in clinical practice (Monti & Schnakers, 2022; Young et al., 2023;
Bodien et al., 2023).

PET has also been used to assess patients with CMD (Stender et al., 2014). However,
because PET is acquired most frequently in the resting state (i.e., in the absence of a
task that requires volitional cognition), consciousness cannot be directly inferred from this
approach. Notably, FDG-PET was validated as a measure of capacity for consciousness
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against the perturbation complexity index (PCI; derived from combined transcranial
magnetic stimulation (TMS) and EEG) (Bodart et al., 2017; Casali et al., 2013; Casarotto et
al., 2016; Massimini et al., 2009). When combined with EEG, FDG-PET identified patients
with a behavioral diagnosis of MCS with 94% sensitivity and 67% specificity suggesting
that this method may identify patients with CMD (Hermann, Stender, et al., 2021).

Neither PET nor fMRI can be used at the bedside, and therefore may not be feasible
tools for routine assessment of consciousness, especially in acute settings where respiratory
requirements, adventitious patient movements, and medical instability may preclude
prolonged recumbency in the scanner. fNIRS is a portable tool with fewer technical
limitations, but to date, only a limited number of studies have used task-based fNIRS
to detect CMD (Abdalmalak et al., 2021). In combination with fMRI and EEG, fNIRS
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may complement a multimodal battery of assessments aimed at detecting consciousness

in severe acute brain injury (Kazazian et al., 2021). Leveraging fNIRS measurements
in neurocritically ill patients, Bicciato et al. demonstrated covert responses to music
in the left prefrontal area in some behaviorally unresponsive patients (Bicciato et al.,
2022). More recently, resting-state fNIRS (rsFNIRS) has been used to identify putative
“consciousness-supporting networks” which may indicate the capacity for consciousness in
patients following severe brain injury (Chen et al., 2023; Liu et al., 2023).

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Functional neuroimaging is a powerful tool for understanding the pathophysiology of brain

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injury and may impact clinical diagnosis, prognosis and treatment efficacy. Its utility in
research is in part due to the wide range of approaches available for both data acquisition
and analysis. Functional neuroimaging techniques are typically more sensitive to brain
network abnormalities than are structural imaging techniques, particularly in patients with
mild brain injuries, and provide potential predictive and pharmacodynamic biomarkers
for treatment studies. Although the clinical utility and generalizability of functional
neuroimaging techniques continues to be limited by the lack of standardized methods and
the absence of large validation studies, for some patients with DoC, functional neuroimaging
is now indicated for diagnostic and prognostic purposes. Functional neuroimaging provides
a wide range of possibilities for addressing scientific questions, but this same flexibility
leads to high inter- and intra-individual variability that limits clinical interpretability.
Moreover, it is often challenging to determine whether functional imaging findings are
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causal or epiphenomena in patients with cognitive dysfunction due to brain injuries. Results
from large-scale international and collaborative studies such as Transforming Research and
Clinical Knowledge in TBI (TRACK-TBI, ClinicalTrials.gov NCT02119182), Collaborative
European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI (Burton, 2017)),
Late Effects of TBI (LETBI (Edlow et al., 2018)), Collaborative Neuropathology Network
Characterizing Outcomes of TBI (CONNECT-TBI (Smith et al., 2021)), Traumatic Brain
Injury Endpoints Development Initiative (TED (Manley et al., 2017)), the Enhancing
NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA (Thompson et
al., 2014)), Multimodal Resonance Imaging for Outcome Prediction on Coma Patients
(MRI-COMA (Velly et al., 2018)), Data-driven neuroEthics for COnsciousness DEtection
(DECODE, ClinicalTrials.gov NCT05010265), and the Neurocritical Care Society Curing
Coma Campaign (Provencio et al., 2020), are poised to further expand translation of
functional neuroimaging approaches into clinical practice.
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4. Electrophysiology of Covert Consciousness

Elctrophysiologic techniques including active task-based electroencephalography (EEG),
passive stimulus-based EEG, quantitative resting-state EEG, event-related potentials (ERPs),
and perturbational approaches such as TMS-EEG have been investigated to aid in
the assessment of consciousness and prediction of outcomes following brain injury
(Comanducci et al., 2020; Curley et al., 2018; Edlow, Claassen, et al., 2021; Hermann,
Stender, et al., 2021; Kondziella et al., 2016; Claassen et al., 2019; Egbebike et al., 2022;
Young, 2023). EEG-based techniques carry several advantages over neuroimaging, including
improved portability, lower cost, ease of administration at the bedside, and temporal
resolution, but have a much larger repertoire of analytic approaches making methodologic
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standardization challenging (Schnakers et al., 2020). Of these techniques, only task-based

EEG aimed at capturing volitional modulation of brain activity (i.e., command-following)
currently provides evidence of covert consciousness. However, other electrophysiological
techniques may provide informative data pertaining to the capacity for consciousness and
potential for recovery. ‘Capacity for consciousness’ here may be disambiguated between
two kinds of capacity: state-capacity (i.e., the capacity for consciousness in the current
specific condition) and person-capacity (i.e., a person’s general capacity for consciousness

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over a range of possible conditions, and not necessarily in the present state). Claims about
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capacity are notably distinct from claims about potentiality, which are future-oriented and
imply privation (Fisk, 1970; McMullin, 1970). To illustrate this distinction, consider the
proposition “Z, a healthy person, has the capacity to speak.” While this proposition would
hold true in the person-capacity sense if made while Z was in NREM sleep, it would be
false in the state-capacity sense under those same conditions. Like active task-based fMRI,
task-based EEG paradigms are designed to assess whether a patient who is behaviorally
unresponsive can follow commands, which is detected via measurement of volitional
modulation of brain activity, often aided by machine learning classifiers or power-spectra
analyses (Claassen et al., 2019; Cruse et al., 2011; Curley et al., 2022; Gibson et al., 2014;
Goldfine et al., 2011). The finding of covert consciousness discovered through EEG has
been associated with functional recovery as measured by CRS-R at 3 months (Pan et al.,
2020), and Glasgow Outcome Scale-Extended (GOS-E) at 3, 6 and 12 months post-injury
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(Claassen et al., 2019; Egbebike et al., 2022), indicating prognostic relevance in addition to
diagnostic relevance.

Task-based EEG techniques are affected by similar limitations as task-based fMRI, insofar
as they depend on a patient harboring residual motivation, cognitive and language capacities
to reliably respond to a command, even if covertly, and carry similarly high false-negative
rates (Formisano, Toppi, et al., 2019). These limitations have motivated the development
of passive paradigms which do not require high levels of cognitive effort, such as passive,
hierarchical language paradigms (Gui et al., 2020; Sokoliuk et al., 2021), music paradigms
(Edlow et al., 2017; Coleman et al., 2009; Lord & Opacka-Juffry, 2016; Okumura et al.,
2014; Wu et al., 2011), visual, tactile and olfactory (Pistoia et al., 2015; Schriever et
al., 2017), and stimulation paradigms (Jain & Ramakrishnan, 2020). However, potential
findings from passive paradigms are not dispositive of covert consciousness like finding
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of command-following, and are prone to similar confounds from sensory or processing

disturbances. In light of the epistemic gap in discerning whether a patient who demonstrates
intact passive responses to sensory stimuli is indeed subjectively aware and experiencing
the stimuli presented or is merely exhibiting a reflexive, non-conscious brain response, the
diagnostic label ‘covert cortical processing’ (Young et al., 2024) has been proposed in lieu
of ‘covert consciousness’ among patients with intact cortical responses to passive stimuli
but no discernible responses to active tasks (Claassen et al., 2021; Edlow, Claassen, et al.,
2021). The TMS-EEG PCI has been proposed as potentially superior passive approach for
the detection of capacity for consciousness that does not rely on intact sensory input and
sensory processing, but has not yet been shown to be dispositive of covert consciousness
(Edlow et al., 2023; Sarasso et al., 2014). These complexities recapitulate the need for a
refined DoC nomenclature to more precisely classify endotypes of consciousness sensitized
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to notions of complexity, capacity and cortical processing.

An International Federation for Clinical Neurophysiology (IFCN) Expert Group

comprehensively reviewed decades of literature on neurophysiology in evaluation of
patients with DoC (Comanducci et al., 2020), and proposed a “[m]ultimodal graded
neurophysiological assessment in patients with prolonged DoC. The operational stepwise
workflow include[s] multiple steps of instrumental evaluation with increasing complexity
starting from conventional neurophysiologic measures (standard EEG and SEPs) to ERPs

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 Young et al. Page 12

and finally advanced approaches (qEEG analysis, TMS/EEG and active EEG paradigms).
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This general scheme might help direct behaviorally unresponsive patients towards different
lines of evaluation based on objective markers of thalamo-cortical integrity” (Comanducci
et al., 2020). Each of these paradigms require a high level of expertise to perform and
interpret, and the current paucity of standardized performance and analysis pipelines limits
widespread diffusion in clinical practice.

The IFCN Expert Group also emphasized caution in the development of training datasets
for machine-learning [ML] classifiers, especially if “the classifier is initially trained to
differentiate VS/UWS from MCS patients based on behavioral labels [as the] clinical
diagnosis may fail to recognize brain-injured patients who are conscious but disconnected
and unresponsive [, and hence in these circumstance,] the true state-of-affairs (i.e. conscious
versus unconscious subjects) necessary for a correct training remains unknown, engendering
a circularity problem with potential impact on the accuracy and interpretability of the
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results.” The IFCN Expert Group suggests that to remedy this issue “the problem of
circularity can be addressed by refining the diagnostic labels by means of additional
paraclinical markers” while pointing out that “[a]nother potential disadvantage of ML-based
approaches to multivariate data is that, given their black-box nature, they do not necessarily
provide direct mechanistic insights into the underlying neuronal processes” (Comanducci et
al., 2020).

The 2020 EAN DoC guidelines issued several recommendations surrounding the use of
electrophysiological techniques in assessing some patients with DoC. Delineating the
relative utility and evidence-base for different electrophysiological techniques, the EAN
guideline provides modality-specific recommendations around clinical standard EEG, sleep
EEG, quantitative high-density EEG, active paradigms with high and low density EEG,
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and cognitive evoked potentials including P300, and TMS-EEG as part of multimodal
assessment of consciousness (Kondziella et al., 2020).

The EAN guideline concludes that “standardized clinical rating scales such as the CRS-
R and the FOUR [(Full Outline of UnResponsiveness)], including careful inspection of
voluntary eye movements, EEG-based techniques and functional neuroimaging (fMRI, PET)
should be integrated into a composite reference standard. This means that a given patient
should be diagnosed with the highest level of consciousness as revealed by any of the
three approaches (clinical [(i.e., behavioral)], EEG, neuroimaging)” (Kondziella et al., 2020;
Wijdicks et al., 2005).

In a similar vein, the AAN/ACRM/NIDILRR DoC guidelines describe that “ … injury

sequelae (such as severe hypertonus) may confound behavioral assessment and compromise
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diagnostic accuracy. Additionally, diagnostic findings may remain ambiguous despite serial
assessment due to the inconsistency or subtlety of the behavioral evidence. The largest
functional neuroimaging study conducted to date in patients with DoC reported that
ambiguous or erroneous findings clouded clinical diagnosis in 33 of 126 (27 percent)
of cases [(Stender et al., 2014)]” and recognizing these challenges, recommend (2e)
that “[i]n situations where there is continued ambiguity regarding evidence of conscious
awareness despite serial neurobehavioral assessments, or where confounders to a valid

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 Young et al. Page 13

clinical diagnostic assessment are identified, clinicians may use multimodal evaluations
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incorporating specialized functional imaging or electrophysiologic studies to assess for

evidence of awareness not identified on neurobehavioral assessment that might prompt
consideration of an alternate diagnosis” (Giacino et al., 2018a, 2018b). Unlike the
European guideline, however, the AAN/ACRM/NIDILRR guideline does not distinguish
between various types of electrophysiologic studies in its recommendation, as different
methodologies were used to establish the recommendations.

5. Novel behavioral markers of covert consciousness

While assessment of covert consciousness is most commonly tied to the use of
advanced neuroimaging and electrophysiologic techniques such as those discussed above,
it is important to note that approaches to detecting covert consciousness span beyond
neuroimaging and electrophysiologic tools to include novel behavioral examination
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techniques designed to elicit and capture signs of awareness that might ordinarily evade
routine bedside detection. These include covert eye tracking detected through wearable
eye trackers (Alkhachroum et al., 2023), olfactory sniffing (Arzi et al., 2020; Wang et al.,
2022), heart-rate variability (Liuzzi et al., 2023; Machado-Ferrer et al., 2013; Riganello
et al., 2010; Riganello et al., 2018), auditory localization (Carrière et al., 2020), startle
habituation (Hermann et al., 2020), nociceptive responses (Cortese et al., 2021), resistance to
eyelid opening (van Ommen et al., 2018), quantitative analysis of subtle facial expressions
(Chatelle, Hauger, et al., 2018; Obayashi et al., 2021), volitional swallowing tasks (Mélotte
et al., 2023), and alternative structured behavioral exam techniques such as the Motor
Behavior Tool Revised (MBT-R) (Jöhr et al., 2020; Pincherle et al., 2019), Sensory Modality
Assessment and Rehabilitation Technique (SMART) integrating visual, sound, tactile,
olfactory, and gustatory modalities (Gill-Thwaites & Munday, 2004), and the Music Therapy
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Assessment Tool for Awareness in Disorders of Consciousness (MATADOC) (Magee, 2018;

Magee et al., 2023; Magee et al., 2014); (Carrière et al., 2022; Diserens et al., 2023; Liuzzi
et al., 2023).

Some have advocated for greater inclusion of caregivers in the diagnostic process for
patients with DoC, capitalizing on their potentially greater attunement to subtle or
idiosyncratic cues of awareness that might be overlooked by standard techniques (Hermann
et al., 2019; Moretta et al., 2017; White, 2006) with one study suggesting that involving
primary caregivers with emotional stimulation may positively modulate patient performance
on the CRS-R (Formisano, Contrada, et al., 2019). The Social and Family Evaluation
(SAFE) scale has been proposed as a structured method for integrating family and caregiver
input into the diagnostic assessment of consciousness, but requires validation (Formisano,
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Contrada, et al., 2019). Substantially lower costs, ease of dissemination and fewer barriers
to clinical implementation make novel behavioral tests for covert consciousness promising
prospects for widespread translation and adoption.

6. Clinical management of covert consciousness

After receiving a diagnosis of covert consciousness, clinicians and surrogates may naturally
ask “what now?”. Many open questions pertaining to optimal clinical management of

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 Young et al. Page 14

patients with covert consciousness recovering from severe brain injury remain. The 2018
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AAN/ACRM/NIDILRR guideline on DoC recommends that “[i] situations where there is no

behavioral evidence of consciousness on clinical examination but functional neuroimaging
or electrophysiologic testing suggests the possibility of preserved conscious awareness,
frequent neurobehavioral reevaluations may be conducted to identify emerging signs of
conscious awareness and decisions to reduce the intensity of rehabilitation treatment may be
delayed for those individuals receiving active rehabilitation management, with the length of
time over which these are done determined by an agreement between the treating clinician
and the health care proxy given the lack of evidence to provide guidance” (Giacino et al.,
2018a, 2018b). In addition to conducting more frequent reevaluations and delaying decisions
to reduce intensity of rehabilitative treatment, the finding of covert consciousness should
prompt closer examination of potentially treatable barriers to behavioral self-expression,
including sensory, motor or cognitive impairments, or sedating medications (see Fig. 1,
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bottom row). Opportunities to leverage and engage patients’ covert capacities through
personalized neurorehabilitative approaches where possible should be recognized and
strengthened (Thengone et al., 2016). Pharmacologic therapies including neurostimulant
medications to promote potential recovery and expression of consciousness should be
carefully considered on a case-by-case basis (Barra et al., 2022). Techniques such as the
Individualized Quantitative Behavioral Assessment (IQBA) may be considered to closely
track and contextualize changes in volitional responses over time (Giacino & Smart, 2007).

Therapeutic decisions should ideally be made in multidisciplinary collaboration with a

patient’s physician(s) and clinical team, including physical therapy, occupational therapy,
speech and language therapy, and neuropsychology, with planning to meticulously monitor
changes in patient status before and after each therapeutic intervention or modification.
If concordant with a patient’s preferences, values and goals, consideration may also be
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given to clinical trial enrollment where appropriate, with careful attention to the ethical
nuances of research involving patients with DoC (Edlow, Sanz, et al., 2021; Lewis et al.,
2023; Thibaut et al., 2019; Young et al., 2022). Efforts to develop brain-computer interfaces
(BCIs) to restore communicative capacity to patients who are unable to speak but may be
able to leverage preserved abilities to volitionally modulate brain activity are underway, but
remain nascent (Chatelle, Spencer, et al., 2018; Lugo et al., 2020; Rohaut et al., 2019; Xu
et al., 2022; Young, Lin, et al., 2021). Emerging evidence highlights a potential role for
multisensory stimulation in enhancing recovery in CMD (Attwell et al., 2019), however
more study is necessary.

Since the recovery trajectories of patients with covert consciousness following severe
brain injury may be more favorable than behaviorally unresponsive patients without covert
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consciousness (Egbebike et al., 2022), some have suggested that this finding could inform
counseling of surrogates and determinations of who might optimally benefit from structured
rehabilitation settings. While positive findings might reasonably inform such decisions,
negative findings (i.e., the absence of evidence of covert consciousness) are not as clearly
actionable given limitations associated with false negative rates and low sensitivity of
available techniques. In other words, the absence of evidence of covert consciousness does
not constitute evidence of absence of covert consciousness. This important dimension of
diagnostic uncertainty should be carefully explained to caregivers and clinicians when

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 Young et al. Page 15

disclosing results of tests for covert consciousness and deciding on best next steps in
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management (Young et al., 2024).

7. Covert consciousness: Remapping the clinical and philosophical

landscape
In Philosophical Investigations, philosopher Ludwig Wittgenstein presciently described
the “feeling of an unbridgeable gulf between consciousness and brain processes … [in
discussing concepts such as ‘consciousness’, a] picture is conjured up which seems to fix
the sense unambiguously. The actual use, compared with that traced out by the picture,
seems like something muddied … In the actual use of these expressions, we, as it were,
make detours, go by side roads. We see the straight highway before us, but of course cannot
use it, because it is permanently closed” (Wittgenstein 1954; translated by Hacker, P.M.
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S., & Schulte, J. 2010). Decades have passed since these philosophical reflections were
published, and the gulf between consciousness and brain processes remains ever present,
but through innovations in clinical assessment tools and neurotechnologies, this gulf is
no longer unbridgeable. For patients with DoC, the discovery of these technologies and
techniques have triggered ongoing paradigm shifts in approaches to diagnosis, prognosis
and treatment. Patients with covert consciousness — a state of residual awareness following
severe brain injury or neurological disorder that evades routine bedside behavioral detection
— harbor preserved awareness but are incapable of self-expression through ordinary means
of behavior or communication. Further study is needed to determine the comparative
reliability of different neuroimaging, electrophysiologic and behavioral techniques in
detecting markers of covert consciousness.

In the absence of a ‘gold standard’ test for covert consciousness (owing to the inherently
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subjective character of conscious experience), combining multimodal techniques will

likely be required to advance precision assessment of consciousness. There are critical
and growing research opportunities to determine optimal clinical management of covert
consciousness and to improve the rigor and reliability of clinical assessment by aggregating
diagnostic evidence across different modalities. Similar opportunities and challenges have
been recognized in the process of aggregating validators for psychiatric diagnoses (Solomon,
2022). The establishment of a global registry for patients with covert consciousness may
be a natural opportunity to foster these goals. It is clinically and ethically imperative
that current systems of classifying and diagnosing disorders of consciousness be updated
through consensus-based methods to sensitize clinical practice to the possibility of covert
consciousness among patients who are behaviorally unresponsive. These efforts could be
buttressed by multilateral initiatives to facilitate responsible implementation of professional
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society guidelines to improve care for this vulnerable population around the world.

Acknowledgments
The authors acknowledge and dedicate this work to patients affected by disorders of consciousness and their
devoted caregivers, including members of the Patient and Family Advisory Board (PFAB) of the Lab for
Neuroimaging of Coma and Consciousness (NICC).

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 Young et al. Page 16

Funding
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This work was supported by the NIH BRAIN Initiative (F32MH123001), NIH Director’s Office (DP2HD101400),
National Institute on Disability, Independent Living and Rehabilitation Research (NIDILRR), Administration for
Community Living (90DPTB0011, 90DPTB0027, 90DP0039), Chen Institute MGH Research Scholar Award, and
the American Academy of Neurology (AAN) Palatucci Advocacy Award.

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Fig. 1.
Modeling the potential pathogenesis of covert consciousness. Covert consciousness is a
state of residual awareness following severe brain injury or neurological disorder that
evades routine bedside behavioral detection. Because the sensitivity of neurobehavioral
examination in detecting consciousness depends on intact afferent (sensory) and efferent
(motor) processing, the basic elements of which are displayed on the top panel, a patient
with deficit(s) affecting these pathways may be unable to appropriately respond at the
bedside even if consciousness is preserved. The middle panel models an example of a
common behavioral test used by clinicians to assess awareness at the bedside, “move your
hand”, and simplifies the localization of the necessary steps for a patient to appropriately
respond. The bottom panel row displays potential obstacle(s) to producing or detecting an
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appropriate behavioral response at each level of localization, which may cause or contribute
to the pathogenesis of covert consciousness when awareness is otherwise preserved.
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NeuroRehabilitation. Author manuscript; available in PMC 2024 February 27.