Machado C. Consciousness as a definition of death: its appeal and complexity. Clin
Electroencephalogr. 1999 Oct;30(4):156-64.
Institute of Neurology and Neurosurgery
CONSCIOUSNESS AS A DEFINITION OF DEATH:
ITS APPEAL AND COMPLEXITY
Author: Calixto Machado, MD, Ph.D.
Word count :7534
Correspondence:
I
Calixto Machado, MD, Ph.D.
Instituto de Neurología y Neurocirugía
29 y D, Vedado
Ciudad de La Habana 10400
CUBA
Tel/Fax:53-7-322233
E.mail: braind@infomed.sld.cu
Havana, Cuba
1998
1
Machado C. Consciousness as a definition of death: its appeal and complexity. Clin
Electroencephalogr. 1999 Oct;30(4):156-64.
ABSTRACT
Many controversies in the actual discussions on human death concern the lack of
rigorous separation and ordered formulation of three distinct elements: the definition of
death, the medical criterion (anatomical substratum) for determining that death has
occurred, and the tests to prove that the criterion has been satisfied. In this paper I
review the three brain-oriented standards of death (whole brain, brainstem and higher
brain) according to these three distinct elements, and will propose a new formulation of
death, based on the basic physiopathological mechanisms of consciousness generation
in human beings. Two physiological components control conscious behavior: arousal
and awareness (content of consciousness). We cannot simply differentiate and locate
arousal as a function of the ascending reticular activating system, and awareness as a
function of the cerebral cortex. Substantial interconnections among the brainstem,
subcortical structures and the neocortex, are essential for subserving and integrating
both components of human consciousness. Therefore, consciousness generation is
based on
anatomy and physiology throughout the brain. The three brain-oriented
standards are inconsistent because they present discrepancies among the elements:
definition-criterion-tests. I propose a standard of human death that includes
consciousness as the most important function of the body, because it provides the
capacity for integrating the main human attributes with an integrative functioning of the
body. I have also emphasized that consciousness does not bear a simple one-to-one
relationship with higher or lower brain structures, because the physical substratum for
consciousness is based on anatomy and physiology throughout the brain. This notion of
consciousness as the ultimate integrative function is more consistent with the
biologically-based systems than the more philosophically-based notions of personhood
2
INTRODUCTION
Many controversies in the actual discussions on human death are mainly due to "the
lack of rigorous separation and ordered formulation of three distinct elements: the
definition of death, the medical criterion (anatomical substratum) for determining that
death has occurred, and the tests to prove that the criterion has been satisfied".
1-7
To
define death is mainly a philosophical task, meanwhile the criterion and tests are
medical chores. Specific criteria and tests must harmonize with a given definition. The
definition must recognize the "quality that is so essentially significant to a living entity
that its loss is termed death". 1-3,7
During the last decades, three main brain-oriented formulations of death have been
discussed: whole brain, brainstem death and higher brain standards.
8,9
The whole
brain criterion refers to the irreversible cessation of all intracranial structure functions. 15,10-19
It has been accepted by society mainly for practical reasons. 8 Physicians have
constructed batteries of bedside tests (and of confirmatory laboratory procedures) to
show that this criterion of death has been satisfied.
10,12,13,19-21
Until recently, whole
brain strategists had not provided a conceptual framework to support specific criteria
and tests. 10-12 Moreover, this view has not answered the key point question about the
critical number and location of neurons, subserving the essential brain activities to
execute the functioning of the "organism as a whole" 22-27
Christopher Pallis has powerfully articulated the brainstem death view.
were also practical reasons that promoted this view,
33-35
28-32
There
because according to Pallis 28
"a dead (i. e, irreversibly non-functioning) brainstem can be diagnosed at bedside,
without resort of complicated investigations, and it predicts inevitable asystole within a
3
short while". Therefore, so-called brainstem death was adopted in several
Commonwealth countries. 28-36 Pallis emphasized that the "capacity for consciousness"
and “respiration” are the two hallmarks of life of the human being, and that brainstem
death predicts an inescapable asystole.
28-32
The physiopathological review of
consciousness generation and respiration will provide a framework for not accepting
Pallis' definition of death. 8,9,37 Moreover, recent clinical cases have shown that brain
death will not always predict an "inevitable asystole within a short while".
37
Higher brain theorists have defined human death as the "the loss of
consciousness", (definition) related to the irreversible destruction of the neocortex
(criterion), or “higher brain”. 38-44 In this paper, I will explain that consciousness does
not bear a simple one-to-one relationship with higher or lower brain structures, and
therefore, the higher brain formulation is wrong, because the definition (consciousness)
does not correspond directly to the criterion (neocortex). 9 I will also review the three
brain-oriented standards using to the three distinct elements proposed by Bernat and
others,1-7 and will propose a new formulation of death, based on the basic
physiopathological mechanisms of consciousness generation in human beings.
8,9
PHYSIO-PATHOLOGICAL MECHANISMS OF CONSCIOUSNESS
GENERATION IN HUMAN BEINGS
Before proceeding, it is necessary to review the physiopathological mechanisms of
consciousness generation.
4
Plum and Posner
18
defined consciousness as “the state of awareness of self and
the environment”. Two physiological components control conscious behavior: arousal
and awareness. 9,18 Arousal represents a group of behavioral changes that occurs
when a person awakens from sleep or transits to a state of alertness.
45
"Normal
consciousness requires arousal, autonomic-vegetative brain function subserved by
ascending stimuli from the pontine tegmentum, posterior hypothalamus and thalamus
that activate wakefulness". 46 The most discernible change that occurs when waking is
the eyes opening. 9,18,45,46 Arousal is also known as capacity for consciousness. 9,28-32
Awareness, also known as content of consciousness, represents the sum of
cognitive and affective mental functions, and denotes the knowledge of one's existence,
and the recognition of the internal and external worlds. 9,18 It has been argued that
consciousness has two dimensions: wakefulness and awareness. 46 Awareness is the
same as the content of consciousness.
9
Wakefulness is provided by the arousal.
9,18,45,46
Plum 47 has recently defined not two but three components, subdividing the content
of consciousness in two levels or components. According to this author, the second
component or level, "which importantly regulates the sustained behavioral state function
of affect, mood, attention, cognitive integration, and psychic energy (cathexis) depends
on the integrity of the limbic structures including the hypothalamus, the basal forebrain,
the amygdala, the hippocampal complex, the cingulun, and the septal area". The limbic
system is important for the homeostasis of the internal milieu, and hence the second
component of consciousness is crucial for integrating affective, cognitive and vegetative
functions. Plum considers the third component as the "cerebral level, along with the
5
thalamus and basal ganglia". This component is related to the processes of higher
levels of perception, self-awareness, language, motor skill, and planning. Memory can
be impaired by injury of either cerebral or limbic levels.
In summary, a human being's state of consciousness reflects both his or her level of
arousal that depends on subcortical arousal-energizing systems and, the sum of the
cognitive, affective, and other higher brain functions (content of consciousness or
awareness), related to "complex physical and psychologic mechanisms by which limbic
systems and the cerebrum enrich and individualize human consciousness". 48
Therefore, I will use the term arousal when referring to those subcortical arousalenergizing systems, and awareness, to denote the sum of those complex brain
functions, related to limbic and cerebrum levels.
9,18,48
Unfortunately, most authors 38,41,43 mention human consciousness, without
considering its two components originally described by Plum and Posner . 18 For
example, higher brain theorists 38-44 habitually describe the persistent vegetative state
(PVS) as patients with "irreversible loss of consciousness" or "permanent
unconscious", but in these patients arousal is preserved, while awareness is apparently
lost. On the other hand, some authors refer to the higher brain criterion as "the
irreversible loss of the capacity for consciousness", 41 but they are really referring to
awareness. As the use of the term "capacity for consciousness",
28-32
could be
confusing, I will identify this function with the original term used by Plum and Posner,
i. e., arousal. I will use awareness as a synonym for content of consciousness.
18
8,9
Arousal depends on the integrity of physiological mechanisms that take their origin in
the ascending reticular activating system (ARAS): "it originates in the upper brainstem
6
reticular core and projects through synaptic relays in the thalamus to the cerebral
cortex, where it increases excitability". 48 Moruzzi and Magoun, 49 in their pioneer
studies, discovered “the presence in the brainstem of a system of ascending reticular
relays, whose direct stimulation activates or desynchronizes the EEG, replacing highvoltage low waves with low voltage fast activity”. Nonetheless, Steriade et al . 48,50-59
have recently emphasized that this desynchronization related to wakefulness “is now
more apparent than real”, because although large slow waves disappear during waking,
the EEG shows high frequency oscillations (30-40 Hz), known as gamma oscillations,
that reflect synchronized and enhanced intracortical and corticothalamic activity.
Bogen 60 has emphasized that the intralaminar nuclei complex of the thalamus is a
cardinal component of the ARAS. The thalamic intralaminar neurons receive inputs
from many sensory modalities and widely project to the cerebral cortex. Moreover,
these nuclei are a major target for the brainstem reticular formation involved in waking.
Recent reports strengthen the idea that intralaminar nuclei are thus essential in
coordinating activity among cortical areas, and contribute to the formation of global
perception to complex stimuli. 60,61
The connections from the brainstem to the cerebral cortex, relayed through
intralaminar and other thalamic nuclei, and their main neurotransmitters (acetylcoline
and glutamate) have been identified.
48
Additional important pathways participating in
arousal have been recently recognized. 45 There are neurotransmitter systems that take
origin in the brainstem, hypothalamus and basal forebrain, projecting monosynaptically
to the cerebral cortex without relaying through the thalamus. These systems include
different neurotransmitter projections: cholinergic from the basal forebrain and
7
mesopontine reticular formation, serotoninergic from the brainstem raphe nuclei,
histaminergic from the posterior hypothalamus and noradrenergic from the brainstem
locus coeruleus. Experimental studies have also shown that an almost complete
destruction of the thalamus does not block cortical activation. Furthermore, the EEG
arousal pattern characterized by desynchronization disappears with the administration
of drugs to block serotoninergic and cholinergic transmission. 18,62 Therefore, it is
reasonable that arousal is due to several ascending systems stimulating the cerebral
cortex and thalamus in parallel. 9,45 Thus, "thalamo-cortical transmission may not be
sufficient or even necessary to produce cortical activation". 18
The discovery that the cerebral cortex is organized in vertical columns that represent
functional units was crucial for further understanding of the functional organization of
the brain. "The basic functional unit of the neocortex is a vertically oriented group of
cells extending across the cellular layers and heavily interconnected in the vertical
direction, sparsely so horizontally". 63 At present there are arguments that the functional
organization of the entire cerebral cortex is a complex of these vertical columns.
Contiguous columns are interconnected by local circuits into "information-processing
modules", characterized by specific afferent and efferent connections with other
modular units from other cortical and subcortical areas. 45,63
It seems that the brain operates in "parallel processing", because cortical regions are
linked in parallel networks with each other and with subcortical structures. Thus, a
specific component of a certain cognitive function is scattered among interconnected
regions, each one implicated in a distinct aspect of the cognitive ability.
45,64
According
8
to Feinberg,
65
one of the most remarkable peculiarities of the brain is "the seemingly
enormous redundancy, parallelism, and distributiveness" of its connections.
The cerebral cortex and thalamus make up "a unified oscillatory machine" that
exhibit spontaneous rhythms and that are conditional to behavioral state and vigilance.
51
The brain uses spatiotemporally distributed systems to "capture high-order
perceptual features". 65 Singer and Gray 66 have argued that fast rhythms of
corticothalamic neurons, known as gamma oscillations, are probably implicated in
synchronizing mechanisms that respond to different features of the same perceptual
object, leading to several hypothesis of high cognitive mechanisms.
Normal conscious behavior requires both arousal and awareness. 18 Patients in
coma are unconscious because both arousal and awareness are disturbed . 9,18
The Multi-Society Task Force in PVS has classified the causes of PVS in 3 main
groups: Acute injuries, where the most common causes are traumatic and hypoxicischemic encephalopathy; degenerative and metabolic disorders, including dementia;
developmental malformations, where the most important is anencephaly. Nonetheless,
the most prevalent causes of acute PVS in all ages are head trauma and hypoxicischemic encephalopathy. These causes have been taken as models to describe the
three main patterns of the neuropathological damage in PVS cases.
In persistent vegetative state (PVS) cases arousal is preserved (the PVS has periods
of wakefulness), but awareness is seemingly is lost. 9 Thus, in PVS there is an apparent
dissociation of awareness from arousal. 9,45 It has been argued that "separate anatomic
pathways mediate arousal and awareness, and that brain diseases can differentially
affect each component of consciousness".
45
9
This raises the question: Why is awareness lacking in PVS, while arousal is
preserved? The neuropathology in the PVS provides a suitable background to discuss
the pathophysiology of consciousness generation. Kinney 45 has recently presented a
detailed review of this subject. According to this author, PVS denotes a "locked-outsyndrome" because "the cerebral cortex is disconnected from the external world, and all
awareness of the external world is lost". She suggested that the loss of awareness in
the PVS is caused by three main patterns: widespread and bilateral lesions of the
cerebral cortex, diffuse damage of intra- and subcortical connections in the cerebral
hemispheres white matter, and necrosis of the thalamus.
In widespread and bilateral lesions of the cerebral cortex, hypoxic-ischemic
encephalopathy is the main etiology. It is the consequence of acute hypoxic-ischemic
insults after cardio-respiratory arrest, strangulation, suffocation, near-drawing,
prolonged hypotension, and perinatal asphyxia in neonates.
45,67
The description of this
pattern was the reason that PVS was first known as "apallic syndrome", characterized
by the destruction of the "pallium, the cortical gray matter that covers the
thelencephalon". 68 In the cerebral cortex a laminar necrosis is found that is multifocal
or diffuse and extensive. Other ischemic lesions may be superimposed mainly in the
border zones of the main intracranial cerebral arteries, as the parasagittal parietooccipital region, for example. 45,69
Other damages, such as neuronal loss and small infarcts, are also typically found in
the cerebellum, basal ganglia, thalamus and hippocampus; the later being particularly
sensitive. Other anatomical structures of the brain are relatively undamaged: brainstem,
10
hypothalamus, basal forebrain and amygdala. This distribution of brain damage reflects
the differential vulnerability of brain regions to hypoxia-ischemia. 45,68,70
In PVS cases with diffuse damage of the cerebral cortex the lack of awareness is
understandable. The widespread involvement of the association cortices combined with
primary and secondary cortices damage, is the faultfinding anatomical ground. 45 It has
been suggested that in diffuse cerebral cortical lesions, the brainstem and the thalamus
can maintain arousal.
9,45
Nonetheless, other parallel pathways projecting
monosynaptically to the cerebral cortex without relaying through the thalamus could
partake to maintain the arousal in these cases. Thus, arousal could be preserved
without a functional cerebral cortex. This has been also supported by experimental
data. In animals with a total removal of the cerebral cortex or transection at the rostral
midbrain level, arousal is preserved, showing waking/ sleep cycles.
71
been argued that the brainstem alone could be sufficient for arousal.
Therefore, it has
45,71
The mechanism of this pattern could be explained in head trauma and hypoxicischemic injury. After head trauma, a widespread damage of axons in the cerebral
hemispheres white matter occurs, known as diffuse axonal injury (DAI). The DAI is
probably caused by the acceleration suffered by the head immediate after the injury.
45,72
The cerebral hemisphere white matter could be also damaged after hypoxic-ischemic
accidents in a pattern known as "leukoencephalopathy".
73
It is characterized by
"extensive symmetrical necrotic lesions in the central white matter of the cerebral
hemispheres, with minimal or no damage to gray matter structures".
45
These patients
11
yield antecedents of prolonged periods of hypotension, hypoxemia and increased
venous pressure. 45,72,73
This pattern also provides a disconnection of the cerebral cortex from the
environment that can explain the lack of awareness in the PVS. The functionally
unaltered brainstem and thalamus preserve arousal. The participation of other parallel
pathway not relaying through the thalamus has to be also considered.
9
Reports in PVS patients and experimental data of diffuse axonal injury to cerebral
hemispheres with cerebral cortex remaining largely normal suggest that, "acute diffuse
disconnection of the cerebral cortex from its subcortical activating mechanisms can
block arousal as well as cognitive activity in the primate brain".
47
Other pattern is characterized by a selective necrosis of the thalamus and, although
the cortex is not totally spared, the lesions are focal and restricted.
45,74
It has been
explained by several possible factors, such as: partial or immediately reversed
transtentorial herniation, cerebral edema causing hypoxia-ischemia, and intrinsic
metabolic vulnerability of the thalamus.
45
The lesions of the thalamus provide a disconnection of the cerebral cortex from the
external world, and therefore, all awareness from the environment is lost. The lack of
awareness in this pattern is not only a consequence of lesions destroying the sensory
relay nuclei that block sensory information from the external world, but the damage of
the thalamic intralaminar nuclei is probably the critical anatomical substratum . 45,61,69
These thalamic nuclei receive inputs from many sensory modalities and project over
wide areas of the cerebral cortex with a “non discernible topography”. 45 These nuclei
integrate important pathways to subserve fundamental cognitive and affective functions
12
such as the attention to the external world.
45,69
It has been argued that lesions in a
thalamic nucleus that is preferentially connected with an association cortex provoke
functional impairments similar to damage in the association cortex itself.
69,75
For
instance, contrary to the generalized expectancy, the neuropathological examination of
Karen Ann Quinlan's brain showed a disproportional severe damage of the thalamus,
as compared with the cerebral cortex. 69 Bilateral thalamic infarcts are commonly
accompanied by mental impairment, such as dementia and amnesia . 60,76
In this pattern arousal could be preserved by a functionally intact brainstem and the
other parallel pathways which project to the cerebral cortex, without relaying through the
thalamus. 9 It has been argued that "the thalamus is critical for cognition and
awareness and may be less essential for arousal".
69
The Multi-Society Task Force in PVS 46 has defined the precise use of the terms
"persistent" and "permanent". "Persistent refers only to a condition of past and
continuing disability with an uncertain future, whereas permanent implies irreversibility".
The Multi-society Task Force likewise addressed that "A patient in a persistent
vegetative state becomes permanently vegetative when the diagnosis of irreversibility
can be established with a high degree of clinical certainty". According to the etiology, a
period of observation has been proposed to define that a "persistent vegetative state",
has become a "permanent vegetative state.
PVS patients reflect the only situation in which an apparent dissociation of both
components of consciousness is found. 9,45 Conversely, recent evidence has shown
that cortical-subcortical interactions are necessary to subserve and make both
components active. 9,47 Regarding the above-mentioned subjects, two main questions
13
may arise: Are subcortical structures capable of mediating some form of awareness? Is
the lack of awareness in the PVS really permanent or irreversible? There is striking
evidence that subcortical structures are capable of mediating some form of awareness.
9 Plum
has emphasized that the "non-specific mechanisms ascending from the rostral
brainstem and diencephalon importantly and possibly inseparably activate and integrate
both the arousal and the cognitive aspects of human consciousness". The participation
of the thalamus to provide the awareness has been already mentioned.
Additionally, Shewmon
77
9,45,69
has discussed some examples of clear participation of
subcortical structures in awareness. Experimental animals with complete decortication
have shown to be capable of complex interactions with the environment, which is
evidence of some awareness. 78 In lesions of the somatosensory cortex an evident loss
of tactile, vibration and joint position sense is observed; nonetheless, conscious
experience of pain and temperature is preserved, mediated by subcortical structures,
probably the thalamus. 77,79 This author also commented that two hydranencephalic
patients ("prenatal destruction of the cerebral hemispheres with intact skull and scalp")
unquestionably manifested conscious behavior. These two cases are examples of the
brainstem "plasticity" in newborns. 77,81 Clinical and experimental evidence convincingly
suggests that the brainstem of newborns is potentially capable of much more complex
integrative functioning. This includes some functions commonly considered to be
cortical, even in animals. 81 Based on these subjects, the potential presence of some
primitive form of awareness in anencephalics, and the possibility of subjective feeling of
pain, has been suggested. 77,81 Thus, according to Shewmon 77 "the human brainstem
14
and diencephalon, in the absence of cerebral cortex, can mediate consciousness and
purposeful interaction with the environment".
The use of deep brain stimulation (DBS) has shown possible that the cerebral
hemispheres could mediate arousal producing some wakefulness behavior, even after
complete loss of the brainstem's reticular activating system. 9 Hassler 82 used DBS in
"apallic" or "coma vigil" cases (PVS patients), stimulating the reticular formation in the
thalamus and in the pallidum. It caused these patients to awaken with an undoubted
recovery of awareness (recognition of their families and emotional expressions).
Katayama et al., 83 also employing DBS of the ARAS (mesencephalic reticular
formation and/or non-specific thalamic nuclei) in PVS cases, have reported a persistent
increment in pain-related P250, which indicates non-specific cortical activation. Sturm et
al. 84 reported the use of DBS at the thalamic level, in a case with probable dysfunction
of the mesencephalic reticular formation due to the rupture of a sacular aneurysm at
the tip of the basilar artery. DBS resulted in autonomic and behavioral reactions and
the patient was able to respond to simple commands. Kohadon and Richer,
85
from a
series of 25 PVS cases treated by DBS, reported a definitive improvement in arousal
with some degree of awareness and interpersonal relationship, in 13 of them.
PVS provides a model in which arousal is preserved and awareness is apparently
9
lacking. Therefore, it has been suggested that both component of consciousness "are
mediated by distinct anatomic, neurochemical and/or physiological systems".
45
Nonetheless, the potential plasticity of the brain has demonstrated that subcortical
structures could mediate awareness, even with the complete absence of the cerebral
cortex. 77 Austin and Grant 86 reported 3 cases who undergone total hemispherectomy
15
(comprising cortex, white matter and basal ganglia), that continued speaking and were
aware of their environment during the operation, done under local anesthesia.
Thus, awareness is not only related to the function of the neocortex (although it is
primary important), but to complex physical and psychological mechanisms, due to the
interrelation of the ARAS, limbic system, and the cerebrum.
9,47
Plum 47 has emphasized that the ARAS substantially and inseparably activates and
integrates both the arousal and the cognitive aspects of human consciousness. He
recognized a brainstem-diencephalic participation not only in arousal, but also in
cognitive function. In lesions affecting thalamic-mesencephalic structures that comprise
the ARAS, the presence of important cognitive and affective deficits can be found.
Alterations in the cerebral cortex after severe damage restricted to mesencephalicdiencephalic activating systems have been reported. They reflect transneural
degeneration, and suggest that these pathways not only activate the cerebral cortex but
they also trophically influence cortical neurons.
9,47
Therefore, it can be concluded that we cannot simply differentiate and locate arousal
as a function of the ARAS, and awareness as a function of the cerebral cortex.
Substantial interconnections among the brainstem, subcortical structures and the
neocortex, are essential for subserving and integrating both components of human
consciousness.
9,18,47,77
The above considerations lead one to conclude that there is no single anatomical
place of the brain "necessary and sufficient for consciousness".
77
Shewmon has
discussed the existence of a "physiological kernel of consciousness"
28-32
or a "reticular
formation/cortical unit". 77 In a broad sense this "physiological kernel of consciousness"
16
or "reticular formation/cortical unit" (RF/CU) is conformed by the widespread
interconnections among the ARAS, diencephalon, other subcortical structures, and the
cerebral cortex. 9,77
BRAIN ORIENTED STANDARDS OF DEATH
The whole brain criterion
James Bernat and his collaborators have presented the most complete defense of
this standard. 1-5, 87-92 He has been one the main advocates to recognize that any
standard should include three distinct elements: definition-criterion-tests. Bernat
proposed the following standard:
DEFINITION
CRITERION
TESTS
The permanent cessation of The permanent cessation of
 The permanent
the functioning of the
the functioning of the entire
absence of breathing
organism as a whole
brain
and heartbeat.
 Brain cessation tests
Definition
Early whole brain advocates failed to propose a conceptual framework to support
this criterion. 9 Nonetheless, Bernat and his colleagues
1-5, 87-91
fully elaborated this
17
standard of death clearly presenting the three main elements: definition-criterion-tests.
These authors defined death as "the permanent cessation of the functioning of the
organism as a whole". They also emphasized that by "organism as a whole" they are
not referring to the "whole organism", as a sum of its parts, "but rather to that
characteristics that makes the living organism greater than the sum of its parts".
Moreover, they explained their view of integration in physiological terms: "functions of
the organism as a whole include respiration, temperature control, fluid and electrolyte
homeostasis, consciousness, food-seeking behavior, sexual behavior, neuroendocrine
regulation, and autonomic control”. 5 Bernat sustained that the organism as a whole
could be kept functioning despite destruction of some subsystems.
2,4,5
Criterion
"The permanent cessation of the functioning of the entire brain".
Tests
Bernat 1-5,92 proposed two sets of tests for determining this criterion. The
cardiorespiratory standard is used to document the permanent loss of all brain
functions, because a prolonged absence of circulation or respiration will inevitably
cause ischemia, anoxia and necrosis of the brain. The neurological standard included
preconditions and a battery of tests and clinical procedures performed at bedside. It is
applied "in all cases except when death needs to be declared in a patient with
heartbeat on a ventilator".
5
18
Critique
Several authors have described patients "whole-braindead" and yet expressed
surprise when they find that the EEG was still retained. The persistence of EEG activity
is however incompatible with the diagnosis of "whole brain death".
22-24,93,94
Other
authors have reported the preservation of visual evoked potentials in primary brainstem
lesions. 95 The persistence of hypothalamic neuroendocrine functions in "whole braindead" patients has been also advocated against this formulation.
25-27,96-99
Bernat 92 slightly modified his definition to "the permanent cessation of the critical
functions of the organism as a whole". This author referred that the critical functions
consist of "three distinct and complementary categories": 1) "vital functions of
spontaneous breathing and autonomic control of circulation". 2) "Integrating functions
that assure homeostasis of the organism, including the appropriate physiologic
responses to baroceptors, chemoreceptors, neuroendocrine feedback loops". 3)
"Consciousness, which is required for the organism to respond to requirements for
hydration, nutrition, and protection, among other needs". Nonetheless, "this modified
position still doesn't answer the above mentioned electrophysiological findings in
"whole-braindead patients", and it is difficult to know when the persistence of
hypothalamic neuroendocrine functions in these cases is related or not to a
"neuroendocrine feedback loop". Moreover, Bernat now includes consciousness as the
third category of the critical integrative functions, but as I will demonstrate,
consciousness is the ultimate integrative function of the body.
These arguments pointed out again a controversy in the fulfillment of the three main
elements of any standard of death (definition-criterion-tests), because the whole brain
19
criterion does not, and which is the critical number and location of neurons, subserving
the essential activities of the hemispheres, diencephalon and brainstem to execute the
functions of the "organism as a whole", that permanently cease functioning?
8
Brainstem (brain as a whole) criterion
Pallis, 28-32,93,100-102 has proposed the following standard, that I will separate
according the three main elements: definition, criterion and tests.
DEFINITION
CRITERION
TESTS
There is only one kind of
The permanent cessation of
 No brainstem reflexes
human death: the
the functioning of brainstem
 Apnea
irreversible loss of the
capacity for
consciousness, combined
with the irreversible loss of
the capacity to breathe
(and hence to sustain a
spontaneous heart beat)
20
Definition and criterion.
In his definition, Pallis 28 emphasizes that the "capacity for consciousness" and
respiration are the two hallmarks of life of the human being, and that brainstem death
predicts an inescapable asystole.
According to Pallis, 28,101 the ascending reticular formation discovered by Moruzzi
and Magoun 49 produces a generalized activation of the cortex, producing the
necessary arousal to endow the functioning of the "brain as a whole". This author also
emphasized that the physiological and anatomical background is the irreversible
damage of the paramedial tegmental areas of the mesencephalon and rostral pons.
Since ancient times, respiration was considered the vital function which defined the
frontiers between life and death. 28,100,101 Pallis has also emphasized that in many older
cultures death was considered: "the departure of the soul from the body", and that the
words that stand for "soul" are in many idioms the same as those standing for "breath".
28
He also emphasized that the "loss of breath" locates its anatomical and
physiological basis in irreversible damage of the lower brainstem. Moreover, he
considered that the anatomical and physiological basis to produce an irreversible apnea
is an irreversible damage to the lower brainstem, where "crucial mechanisms
concerned with breathing are located".
28,100
Pallis 28 presented a detailed review to answer the question: "How long may cardiac
action persist after a diagnosis of brain death?" He suggested that in most cases
asystole occurred within days. This author emphasized that time variations in somatic
survival after brain death presumably reflect three main factors:
21

“The time on the ventilator before the diagnosis of brain death was made”

“The quality of ‘care’ administered”

“The age composition of the sample”
Tests
Pallis 28,101 addressed that as the "brainstem death is a clinical concept", "a dead
brainstem" can be diagnosed at bedside. It is necessary to diagnose an unconscious
patient, with irreversible apnea and irreversible loss of brainstem reflexes, provided that
"all reversible causes of brainstem dysfunction have been excluded”.
Critique
Pallis 28-32,93,100-102 includes in his definition “the capacity for consciousness”, or
arousal, as has been previously discussed. Nonetheless, in any definition that
incorporates consciousness as a main hallmark, both components should be included,
because a normal conscious behavior demands integration or widespread
interconnections among the ARAS, subcortical structures, and the neocortex, i. e., an
interaction of both components.
9
Moreover, some authors using deep brain stimulation have found non-specific
cortical activation in PVS and comatose patients. 82-85 Then, in cases fulfilling the
brainstem criteria of brain death with primary brainstem lesions and spared cerebral
hemispheres, stimulation of the non-specific thalamic nuclei might produce some
degree of arousal. 9 In primary brainstem lesions a quasi-normal EEG could be
recorded. 22-24,93-95
22
The other hallmark of Pallis’ definition is respiration.
28
I had previously discussed
that if by respiration is meant gases exchange in the lungs or oxidative processes
taking place at the cellular level, mechanically ventilated patients are capable of
"breathing". 8 In patients with a non-brain functioning the heart beat, pulmonary and
circulatory functions are preserved, and the physiological changes associated with
normal respiration are in fact taking place, at the cellular level.
8,104
Brainstem function
is not necessary for this to happen, provided one is situated in an intensive care unit.
105
In fact, what is irreversibly absent in the in brain-dead is ventilation. 8
Patients affected with polio, may be incapable of spontaneous ventilation, i. e., they
fulfill one of the hallmarks of Pallis' definition of death: "the irreversible loss of the
capacity to breathe", 28 but the patients are not dead. 8 Before the era of modern types
of ventilatory assistance, such patients would have not survived.
8,105
Nowadays, the
recognition that pulmonary gas exchange may be maintained successfully for prolonged
periods by mechanical ventilation in the intensive care environment 106,107 leads to
conclude that respiration (and more particularly, ventilation) is not so essential to life,
that its loss constitutes death. 8
Recent reports shows that some brain-dead patients do not develop an inevitable
asystole within hours or days. 108-110 Shewmon 104 has recently presented a detailed
review of prolonged survivals in about 156 braindead patients. This author made a
compilation of cases with survival of more than "a few days, i. e. one week or more",
taking this information from sources including, personal experience, the medical
literature and the news media. He described a striking case, may be the record of
23
prolonged somatic survival, who was diagnosed (well documented) as "braindead", 14
years ago.
The age factor at onset of brain death plays a significant role in somatic survival:
"the younger the age, the greater the capacity for survival".
77,104
Shewmon 104 also
addressed two other factors involved in survival: 1) "associated systemic injuries directly
due to whatever caused the brain insult", and 2) "systemic pathology secondarily
induced by the process of brain herniation". Withdrawal of life support is a "confounding
factor", because it leads to underestimate the survival potential in brain-dead cases.
Other factors related to somatic survival could be: the quality of nursing care, an
adequate homeostatic control, prevention and early treatment of infections, etc.
28
Therefore, an “inevitable asystole” can’t be a justification for accepting a brainoriented standard of death.
Higher brain criterion
The "higher brain" view is closely related to the management of PVS patients, and
has been mainly defended by philosophers.
7,38-44,111-114
DEFINITION
CRITERION
TESTS
The loss of that which is
The permanent cessation of
No cognitive and affective
significant to the nature of
the functioning of the
man
neocortex
functions
24
Definition
"Higher brain" formulations proposed defining death as "the loss of that which is
significant to the nature of man". 38 "Higher brain" constructionists sustained that the
irreversible loss of perception, sentience and cognition was necessary and sufficient for
diagnosing death.7-38-44,111-14 Bartlett and Youngner 7 stated "we believe that only the
higher brain functions, consciousness and cognition, define the life and death of a
human being".
Robert M. Veatch 38-40,114 was a pioneer of this standard of death, and one of its
main defenders. This author 114 argued to include in the definition either of “capacity for
consciousness or social interaction”, and presented a detailed discussion about “the
functions considered to be ultimately significant to human life”: rationality,
consciousness, personal identity, and social interaction. He concluded that death
should be appropriately defined “as the irreversible loss of embodied capacity for social
interaction”. Some authors have also advocated this definition as the "loss of
personhood" 42,44
Criterion and Tests
Higher brain advocates emphasized that the neocortex assumes a critical role by
providing the consciousness and cognition, that characterize a human being 7,38-44,111114
They proposed to functionally classify the brain into the lower brain (brainstem), that
25
governs primarily vegetative functions, and the higher brain (the cerebral hemispheres,
particularly the neocortex), that controls consciousness and cognition.
Veatch 114 emphasized that "we could be quite conservative and hold that the entire
brain must be destroyed in order to be sure that the capacity for consciousness and
social interaction is lost". This author referred to the "higher brain locus", or used other
terms, such as "cerebral", "cortical", or "neocortical". Veatch clearly argued that
elaborating a set of tests to measure the irreversible loss of the capacity for
consciousness or social interaction is rather difficult.
38-40,114
Critique
I have shown that we cannot simply differentiate and locate arousal as a function of
the ARAS, and the content of consciousness as a function of the cerebral cortex,
because substantial interconnections among the brainstem, subcortical structures and
the neocortex, are essential for subserving and integrating both components of human
consciousness. 9,18,44,47 Consciousness does not bear a simple one-to-one relationship
with higher or lower brain structures, and therefore, the identification of the definition
(consciousness, capacity for consciousness or social interaction, personal identity, etc.)
does not correspond directly to the criterion (higher brain, cerebral hemispheres,
neocortex) that most, if not all, higher brain defenders have used. In fact, the physical
substratum for consciousness is based on anatomy and physiology throughout the
brain. 9 Some reports about “neocortical death” have presented a neuropathological
substratum of a “dead neocortex” with the brainstem relatively spared, suggesting that
"higher brain-dead *patients" could preserve brainstem reflexes and spontaneous
26
breathing.
22,24,93,95
I have discussed that three neuropathological patterns are found in
these patients, rather than simply one related to the destruction of the neocortex.
9
Moreover, it is necessary to discuss the potential reversibility of the awareness in
the PVS. As it has previously discussed, the use of deep brain stimulation (DBS) has
shown the possibility that the cerebral hemispheres could mediate arousal producing
wakefulness behavior, even after complete loss of the brainstem's reticular activating
system, and an undoubted recovery of awareness (recognition of their families and
emotional expressions) has been reported in PVS cases.
81-84
Some reports of misdiagnosis or recovery in PVS have also appeared in recent
literature. Unexpected and well-documented recoveries of cognitive functions have
been described in patients, where it was believed that neurologists experienced and
skilled in the diagnosis of this condition correctly applied the criteria.
115-118
Childs 119
reported that 37 % of 49 cases admitted in a special unit for rehabilitation were
incorrectly diagnosed. Andrews et al. 120 reported that 43% of patients also admitted in
a rehabilitation unit were incorrectly diagnosed.
Therefore, the main inconsistencies of higher brain theorists are: 1) the definition of
death (consciousness, capacity for consciousness or social interaction, personal
identity, etc.) does not correspond directly to the criterion (higher brain, cerebral
hemispheres, neocortex), because they don’t confuse the physiopathological
substratum of consciousness with the neocortex; 2) the classify PVS case as dead.
27
NEW STANDARD OF HUMAN DEATH
DEFINITION
CRITERION
TESTS
Irreversible loss of the
Irreversible destruction of
Unresponsiveness, no
capacity for integrating the
the anatomo-functional
arousal to any stimuli, no
main human attributes with
substratum for subserving
cognitive and affective
an integrative functioning of
both components of
functions
the body
consciousness: arousal and
awareness
Definition
Several authors 114,121,122 have quoted words used by Beecher, Chairman of the
Harvard Committee, in his address to the American Association for the Advancement of
Science, when he explained the importance of the brain for human life: “the individual’s
personality, his conscious life, his uniqueness, his capacity for remembering, judging,
reasoning, acting, enjoying, worrying, and so on”. Cranford 42 stated: "our major premise
is that consciousness is the most critical moral, legal, and constitutional standard, not
for human life itself, but for human personhood". Therefore, higher brain defenders
stressed that consciousness provides the most significant attributes of human
existence. 38,42,43
28
Botkin and Post
123
presented an interesting dichotomy considering major and minor
clusters of attributes related with life. For example, braindead patients retain several
attributes associated with life, as skin color, warm skin, heartbeat, kidney function, etc.
Even, subjects diagnosed as dead by the cardiorespiratory standard will preserve
during day's vestiges of life attributes: hair and nails still grow.
6,9
Therefore, I completely agree with higher brain defenders that consciousness
provides the most significant attributes that characterize human life. Hence, It is
reasonable to state that any vestige of consciousness is inconsistent with death.
29
Integration
Korein, applying thermodynamics and information theory powerfully defended the
notion of integration. 16,124 He argued that all living organisms could be classified as
open systems that exchange energy and matter with environment. He emphasized that
within any organism there is a critical system which "supersedes all other subsidiary
systems" or subsystems. This author proposed that the "critical system" of the human
being is the brain, "which is irreplaceable by an artifice, be it biological, chemical, or
electromechanical". Therefore, according to this view if the brain is irreversibly
destroyed, the critical system is abolished. Even if, other subsystems are functioning
spontaneously or overtaken by machines, the organism as an individual assemblage no
longer exists. Varela125 also assumed that living organisms are complex dynamical
systems with energy states characterized as a discontinuous "eigenbehavior", and
discontinuities in state transition.
The Swedish Committee 126 also applied the notion of integration to define death:
"total and irreversible loss of all capacity for integrating and co-ordinating the functions
of the body -physical and mental- into a functional unit.
Shewmon 77,78 had also emphasized the central role of the brain "in the coordination
or performance of virtually all functions necessary for the unity of the post-embryonic
human body, including internal homeostasis, adaptative interaction with the
environment, and the intimate connection between mental and physiological states".
Nonetheless, this author made recently a complete turn in his position, emphasizing
that the brain is not the "central integrating organ of the body".
104
He remarked that
30
"clinical evidences of brain death is more attributable to multisystem damage and spinal
shock than to destruction of the brain per se", and proposed to return to a "circulatoryrespiratory" standard of death. However, this author accepted that the brain plays a role
in integrating functions of the intact organism. He used as an example the field of
psychoneuroimmunology, emphasizing that "the brain role is one of modulating, finetuning, and enhancing an already established and well functioning immune system". If
we accept Shewmon's view, then a specific emotional state could influence the immune
system, either diminishing or enhancing the immune response. We can ask ourselves:
Can we consider this brain's effect over other systems, of "modulating" or "finetuning", "the highest level of integration within the organism"?
According to Bernat, 5 the brain produces signals "for breathing through brainstem
ventilatory centers, and aids in the control of circulation through medullary blood
pressure control centers". For example, if a young man meets in front of him, his girl
friend (love), or sees a lion (fear), we can explain a complex mechanism of brain control
over the whole body. After the visualization of the visual target (girl friend or lion), and
recognition comparing with backup memory, complex signals are generated, through
interconnected pathways spread throughout extensive brain areas (neocortex,
diencephalon and other limbic structures, brainstem, reticular formation, etc.) that
produces faster heartbeats and deeper ventilatory movements. 127 Trained Yoga
practitioners are capable of slowing heartbeats until they are almost imperceptible to
auscultation. 128 Psychological influences in menstrual cycle, and in reproduction in
general, both in humans and in other animal species, have been vastly discussed in the
31
literature.
129
Conscious behavior has allowed human beings to transform and govern
their environment. 8,38
These examples show how consciousness controls and regulate the functioning of
the organism. It can be considered as "modulating" or "fine tuning",
104
but it is in fact,
the highest level of control in the hierarchy of integrating functions within the organism.
At the same time consciousness integrates, in a single individual, the human attributes
with the integrative functioning of the body. Each subject reacts differently to stimuli and
daily life situations, according to his personality and knowledge. I am not denying the
existence of multiple complex processes such as controlled by subsystems not directed
commanded by consciousness, as most of the so-called vegetative functions.
Nonetheless, consciousness can overcome any subsystem in the control of any specific
vegetative function, and it is the ultimate integrating function. Plum extensively
discusses this issue,
47
when he describes the importance of the second component in
the regulation and integration of affect, mood, attention, cognitive integration, and
psychic energy (cathexis) by limbic structures.
Therefore, my notion of consciousness as the ultimate integrative function is more
consistent with the biologically-based systems concepts of Korein 16,124 and Bernat et
al. 1-5,87-92 than the more philosophically-based notions of personhood favored by
Veatch, 38-40,114 Barlett and Youngner, 7 Wikler, 44,111,112 and others. 42,43
Criterion
32
As it has been shown, substantial interconnections among the brainstem, subcortical
structures and the neocortex, are essential for subserving and integrating both
components of human consciousness.
9,18,47,77
Therefore, consciousness generation
is based on anatomy and physiology throughout the brain (criterion). Feinberg 65
quoted an interesting Sherrington's address: "Where it is a question of mind the
nervous system does not integrate itself by centralization upon one pontifical cell".
Tests
Establishing a reliable system to measure the irreversible loss of consciousness is
very difficult. The already difficult physiologic proof of loss of consciousness is
compounded by the philosophic complexity of assessing the subjective dimension of
consciousness. 60,65
Most sets of brain cessation tests require evidence of unresponsiveness. This is
mainly measured by applying painful stimuli.
10,12,131
Reactivity to pain explores the
arousal component of consciousness that endows cognitive and affective functions. 9
The substratum for consciousness is based on anatomy and physiology throughout
the brain. 9,18,47,77 Therefore, sets of criteria should include tests to evaluate both
brainstem and cerebral hemispheres.
Comparing this standard of death, with whole brain, brainstem, and higher brain
views, differences and similarities can be found.
WHOLE BRAIN VIEW
33
SIMILARITIES
DIFFERENCE
 Both views are based on anatomy and
 In my view, only one function is
physiology throughout the brain (criterion)
 PVS cases are classified as alive
considered (consciousness) as the
hallmark of the definition rather than
all functions of the brain
BRAINSTEM VIEW
SIMILARITIES
DIFFERENCE
 In both views one of the components of

In the brainstem view, the
consciousness is included as a hallmark
brainstem is only considered as the
(capacity for consciousness or arousal)
anatomical substratum (criterion).
 PVS cases are classified as alive
HIGHER BRAIN
SIMILARITIES
DIFFERENCE
34
 In
both
views
consciousness
is
considered as hallmark for defining death
 In this view, the neocortex is only
considered
as
the
anatomical
substratum (criterion).
 PVS cases are classified as dead
 My
definition
consciousness
identifies
as
the
ultimate
integrating function
 My notion of consciousness as the
ultimate integrative function is more
consistent
based
with
systems
the
than
philosophically-based
biologicallythe
more
notions of
personhood
Persistent vegetative state patients are alive!
The main finding in PVS is the preservation of arousal with an apparently loss of
awareness. 9,78 As has been previously discussed, according to Kinney,
45
PVS denotes
a "locked-out-syndrome", because the “cerebral cortex is disconnected from the
external world”, explained by three main neuropathological patterns. Can we deny the
existence of internal awareness in PVS, because they apparently seem to be
35
disconnected from the external world? The subjective dimension of awareness is
philosophically impossible to test.
65
The Karen Ann Quinlan's brain showed a severe damage of the thalamus, with the
cerebral hemispheres relatively spared.
69
We can ask ourselves if in a case like this,
other activating pathways projecting to the cerebral cortex without relaying through the
thalamus, could stimulate the cerebral cortex to provide internal awareness, although
an apparently disconnection to the outer world is found by physicians.
9
The use of
deep brain stimulation showed that the cerebral hemispheres could mediate arousal
producing some wakefulness behavior, even after complete loss of the brainstem's
reticular activating system.
82-85
it has been discussed that there is striking evidence that
subcortical structures are capable of mediating some forms of awareness.
9,45
Therefore, in PVS cases it is impossible to deny a possible preservation of internal
awareness, because according to the neuropathological pattern, either subcortical
structures could provide internal awareness, or some remaining activating pathways
projecting to the cerebral cortex without relaying through the thalamus, could stimulate
the cerebral cortex.
9
As consciousness is based on anatomy and physiology
throughout the brain, it is impossible to classify a PVS case as dead, where the brain is
damaged, but not fully and irreversible destroyed.
Some reports of misdiagnosis or recuperation in PVS have also appeared in recent
literature. Unexpected and well-documented recoveries of cognitive functions have
been described in patients, where it was believed that the criteria were correctly applied
by neurologists experienced and skilled in the diagnosis of this condition. 132,
133
Moreover, it is necessary to consider the potential reversibility of the awareness in the
36
PVS, as has been reported by some authors using deep brain stimulation.
82-85
it is
crucial to develop controlled multi-centered studies to test and elaborate new protocols
for sensory and pharmacologic stimulation.
117,132
In fact, the possibility of brain function
restoration in such patients, by actual or still not developed techniques, are a challenge
for the near future. 9
FINAL REMARKS
In conclusion, I propose a standard of human death that includes consciousness as
the most important function of the body, because it provides the capacity for integrating
the main human attributes with an integrative functioning of the body. I have
emphasized that consciousness does not bear a simple one-to-one relationship with
higher or lower brain structures, because the physical substratum for consciousness is
based on anatomy and physiology throughout the brain.
37
ACKNOWLEDGMENTS
I would like to thanks Dr. Stuart Younger because of his careful reviews and precise
suggestions, during the elaboration of this paper.
38
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