Ann. N.Y. Acad. Sci. ISSN 0077-8923

A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S Issue: Rethinking Mortality: Exploring the Boundaries between Life and Death

Near-death experience: arising from the borderlands of consciousness in crisis Kevin R. Nelson Department of Neurology, University of Kentucky, Lexington, Kentucky Address for correspondence: Kevin R. Nelson, Department of Neurology, University of Kentucky Medical Center, KY Clinic (Wing D)-L445, Lexington, KY 40536-0284. [email protected]

Brain activity explains the essential features of near-death experience, including the perceptions of envelopment by light, out-of-body, and meeting deceased loved ones or spiritual beings. To achieve their fullest expression, such near-death experiences require a confluence of events and draw upon more than a single physiological or biochemical system, or one anatomical structure. During impaired cerebral blood flow from syncope or cardiac arrest that commonly precedes near-death, the boundary between consciousness and unconsciousness is often indistinct and a person may enter a borderland and be far more aware than is appreciated by others. Consciousness can also come and go if blood flow rises and falls across a crucial threshold. During crisis the brain’s prime biologic purpose to keep itself alive lies at the heart of many spiritual experiences and inextricably binds them to the primal brain. Brain ischemia can disrupt the physiological balance between conscious states by leading the brainstem to blend rapid eye movement (REM) and waking into another borderland of consciousness during near-death. Evidence converges from many points to support this notion, including the observation that the majority of people with a near-death experience possess brains predisposed to fusing REM and waking consciousness into an unfamiliar reality, and are as likely to have out-of-body experience while blending REM and waking consciousness as they are to have out-of-body experience during near-death. Keywords: near-death experience; consciousness; death

All mental processes, even the most complex psychological processes, derive from operations of the brain.1 Eric Kandel, neuroscientist and Nobel laureate It does not do harm to the mystery to know a little more about it. Richard Feynman, physicist and Nobel laureate As Kandel expresses, a fundamental tenet of neuroscience holds that all human experience arises from the brain.1 This inescapably leads to the brain participating in the sublime moments of spiritual experience. For reasons beyond neuroscience alone, in our time, near-death experiences dominate the discussion of spiritual experience. The drama of going through a tunnel, being enveloped by “the light,” floating above one’s body, or meeting de-

ceased loved ones or spiritual beings before returning constitutes a widely acknowledged narrative thoroughly portrayed by the media. Near-death fulfills William James’ conception of a spiritual experience whereby “feelings, acts and experiences” touch “whatever they may consider the divine”; yet James, writing at the beginning of the 20th century, makes little mention of near-death in his seminal work The Varieties of Religious Experience.2 Although cardiac arrest may not be the most common trigger for near-death experience, it certainly stands as one of the most dramatic, which adds to the profundity already surrounding near-death experience, and together the excitement and profundity blinds some people to the fact that brain function underlies the experience. Regrettably, some investigators3 use the term clinical death to signify a period of unconsciousness caused by insufficient blood supply to the brain

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because of inadequate blood circulation, breathing, or both. By this definition, even common syncope is clinical death. Several facts underscore why this ambiguity between clinical death and syncope misleads: harmless syncope produces features indistinguishable from near-death,4 syncope itself commonly triggers near-death,5 and only half of those experiencing near-death are medically in peril.6 Linking near-death to clinical death erroneously implies near-death experiences happen when the brain has died and the neurons have lysed,7 a hallmark of brain death. Near-death is not a return from death experience. The brain is very much alive during near-death experience. The inseparable relationship between syncope and near-death clashes with the misconception that near-death experience happens only when a person is facing truly imminent death. Upwards of one-third of people faint within their lifetime,8 often while feeling endangered, thereby making syncope fertile ground for spiritual experience. Muddling cardiac dysrhythmia and clinical death has led one author to suggest that these experiences are direct scientific evidence for consciousness beyond life.9 Neuroscience offers no support for this bold assertion. From the untold number of known near-death narratives, there comes no credible scientific evidence for the brain being dead or “completely shut down”10 during near-death experience. After accounting for selective, suggestible, reconstructed, and imperfect memory, as well as the difficulty of knowing at what point in the crisis an experience occurred, nothing about near-death— including out-of-body—offers objective evidence that consciousness can exist without a living brain. Claims of consciousness beyond the brain lie in the realm of faith, for neuroscience and faith reign in separate dominions. When exploring brain function during spiritually transforming experiences, it is not just the fervor over near-death that blinds some to the brain’s importance in near-death. The brain’s magnificence, exemplified by, for example, Shakespeare’s plays and Einstein’s theories, also overwhelms near-death, but in a completely different way, for its splendor leads to overlooking the brain’s prime biologic and evolutionary purpose lying at the heart of many spiritual experiences. First and foremost, the brain needs to keep itself alive, and at no time does this ring truer than during a life-threatening crisis when we see 2

human spirituality inextricably bound to our primal brain. Crucial to its prime purpose, the brain governs its blood flow each second of life. Brain activity relies upon aerobic metabolism that requires a constant supply of oxygen and glucose at rest, in exercise, and during physiological and emotional stress. Controlling cerebral blood flow depends partially upon mechanisms intrinsic to the cerebrovasculature, but the greatest determinant is the arterial baroreflex that, in turn, hinges on the yoked opposition of cholinergic and adrenergic neurons in the peripheral and central nervous systems.11 Fading cerebral blood flow with looming unconsciousness, often the proximate circumstance leading to near-death experience, signals a crisis to the brain that then orchestrates a cascade of survival responses, including the familiar fight-or-flight response,12 that have guided our ancestors’ survival for millions of years. In the initial seconds of failing cerebral blood flow and dimming consciousness, there is no reason to expect that the brain reacts differently between simple syncope and cardiac dysrhythmia. Often, the border between consciousness and unconsciousness is neither abrupt nor absolute. Between the hazy edges of consciousness and unconsciousness lies a borderland of consciousness entered when the brain is ischemic. If blood flow drops below the threshold of 23 mL/100 g of brain/min, the cerebral cortex fails,13 and loss of consciousness occurs after 10 s or so.14 Consciousness can come and go if cerebral blood flow rises and falls across this threshold, which often happens in clinical settings. Surprisingly, the eyes remain open at syncope’s onset,15 and, in conscious moments during the episode, the person may be far more aware of events than appreciated by others tending to immediate medical urgencies, and those stricken may later recall some of the episode even if their memory structures had been impaired. Simply because one does not respond while in shock or a faint does not mean that the individual is unconscious or dead (for example, see the cases of Ms. Martin16 and Jan17 ). Even with sustained cerebral blood flow, there exists a second threshold below which neurons begin to die. This threshold increases over hours to eventually reach a plateau of 17–18 mL/100 g of brain/minute. Neural death begins within minutes after cerebral blood flow completely ceases. A great deal has been made of the fact that sometimes the

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precise instant of brain death may be unmeasurable, thus leaving open the possibility that experiences can happen when the brain is dead. While a precise moment of brain death might be elusive or even nonexistent, for near-death experience it is unimportant. A single cell dying does not bring the brain to death, and massive numbers of dead neurons with scattered survivors may not sustain life or human consciousness. At the same time, huge numbers of neurons lost in the thalamus and cortex can lead to minimally conscious or vegetative states. There exists a continuum between one neuron and all neurons dying, and the borderland that a brain can enter and then viably return from is large and murky. Another borderland of consciousness in neardeath arises when the conscious states of waking and rapid eye movement (REM) sleep blend, forming a hybrid state. In crisis, an awake and attentive brain is expected to meet the threat head on. This expectation seems so intuitively obvious that it typically escapes scrutiny. But survival demands that the brain not take the proper conscious state for granted. Only in waking consciousness can attention suddenly orient to whatever survival requires. Therefore, consciousness finds itself in lockstep with fight-or-flight action orchestrated by the brainstem and the limbic system. To understand how conscious states interplay during a crisis like near-death, it is necessary to understand how the brainstem regulates conscious states. Epinephrine and the corresponding neurotransmitter norepinephrine in the brain serve vital functions in danger. Elemental to fight-or-flight behavior is the brain’s nearly exclusive source of norepinephrine, the pontine brainstem’s locus coeruleus (LC). From right and left, minuscule clusters of 16,000 LC neurons project diffusely throughout the brain to help regulate consciousness and expedite critical behaviors. The pontine arousal system, of which the LC is a part, acts as the fulcrum of a reciprocal swing between colossal neurochemical systems sweeping through the brain.18 The REM promoting cholinergic pedunculopontine (PPT) and laterodoral tegmental (LDT) nuclei counterbalance the waking actions of the serotonergic dorsal raphae and noradrenergic LC nuclei. Like a metronome of consciousness, the LC constantly discharges during wakefulness. In primates, not only are LC discharges tightly linked to specific

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behaviors, but also LC activity goes further by anticipating the expression of attention behavior.19 Low discharge rates correspond to low arousal, with the animal inattentive to the world around it. Moderate rates (with synchronized bursts) are seen with focused attention. High LC discharge rates correlate to the animal visually scanning the environment and rapidly shifting its attention.19 Swiftly directing attention to meet the demands of an often hostile world is an essential role for the LC.20 In waking consciousness, the LC assists vigilance in response to stress.21,22 Feelings of fear, hypoxia, hypotension and hypercapnia, often present during near-death, all vigorously stimulate the LC, increasing its tonic discharge rates.23–25 What becomes of the activated LC? Physiological mechanisms function neither unchecked nor in isolation. A classic example is the reciprocal action between the cholinergic and adrenergic portions of the peripheral autonomic nervous system. The principle of physiological balance means that damping the LC could be central to an arousal system predisposed to the blending of REM and waking into a borderland of consciousness during near-death. Systems promoting REM consciousness are the most powerful inhibitors of the LC, since only during REM consciousness does the LC become virtually silent.26 The fact that the LC discharge pattern anticipates attention behavior as well as the onset of REM consciousness27 attests to the importance of this structure to both. If scanning attention becomes maladaptive, or if circumstances call for focused attention or lying still, then counterbalances linked to the cholinergic REM system could come into play to diminish adrenergic LC activity. Still, it appears counterintuitive that LC suppression would tilt the brain into REM consciousness at a supposedly inopportune moment for survival—counterintuitive perhaps until the brainstem mechanisms of consciousness are examined further. REM consciousness is named for rapid saccadic eye movements that accompany the robust visual system activation characterizing this conscious state. During REM, pontogeniculooccipital (PGO) waves travel widely, originating in the pons before propagating to the lateral geniculate nucleus of the thalamus, and then to the visual cortex. Cerebral cortical activation similar to wakefulness and atonia of nonrespiratory muscles also distinguish the REM state. The most frequent and complex dreaming

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takes place during REM sleep in cortical regions far removed from the pontine brainstem, triggering REM. Importantly, these different elements of REM consciousness fragment at times, becoming individually expressed. When consciousness transitions between REM and waking, these REM fragments can merge with wakefulness to create another borderland of consciousness in upwards of 24% of the general population.5 The blending of REM and waking consciousness takes the form of complex visual and auditory hallucinations, as well as the atonia of sleep paralysis or cataplexy. This borderland is unstable, lasting seconds or minutes before reverting to a more stable conscious state. How can REM and waking consciousness influence each other? The REM consciousness switch located near the LC shifts the brain between REM and wakefulness;28 the switch has several components. Some elements tilt consciousness to REM and others tilt to wakefulness. Almost, but not always, the switch operates in an all or none, flipflop fashion, moving the brain completely between REM and waking. How does the REM switch react to crisis? A critical component of the pontine REM switch is the ventrolateral portion of the periaqueductal gray (vlPAG).28 The vlPAG actively tilts consciousness toward waking and away from REM and is fundamental to suppressing REM.29 The vlPAG reacts intriguingly to crisis. Pain, hypoxia, and moderate blood loss each stimulate the vlPAG,30 which may help sustain wakefulness under these conditions when the LC discharges rapidly. But the vlPAG significantly changes if systemic blood flow becomes profoundly low. Here, vlPAG neurons act to diminish the peripheral adrenergic cardiovascular tone, bringing the cholinergic system to dominance,31 thereby causing barely a sustained blood pressure to fall even further. Why does the vlPAG do that? As the vlPAG retracts the peripheral adrenergic nervous system, the once agitated animal with shifting attention becomes quiet and inattentive,32 disengaging from its surroundings; remaining quiet and still with a severe or inescapable injury may be an effective survival strategy.33 Whatever the survival advantage, this behavioral response must be important for it to become embedded within our evolutionarily ancient and conserved brainstem. As vlPAG activity subdues peripheral adrenergic cardiovascular activity, presumably the LC shifts from high tonic discharge rates of agitation to 4

the slow rates of low arousal. Normally, when the vlPAG’s influence on the REM switch subsides, REM consciousness follows. Whether the vlPAG neurons responsible for suppressing the peripheral adrenergic response in the face of hypotension are the same or functionally related to the vlPAG neurons within the REM consciousness switch is not known. Yet, it seems unlikely that the adrenergic withdrawal in two physiological domains coordinated by the same brainstem region bears no relationship. The established connections between the REM switch and LC emphasize the imperative that successful behaviors, such as lying still or fight or flight, couple with the proper conscious state. These brainstem mechanisms offer a means of bringing about REM consciousness during crisis, and evidence from many points converges to support this notion. Recently, electroencephalographic recordings during cardiac arrest in animals have shown unexpected brain activity. A gamma rhythm (centered around 40 Hz) characterizes both waking and REM consciousness,34 and a frontotemporal distribution may be important in the expression of lucid dreaming during which the dreamer is aware of his/her dreaming.35 After cardiac arrest, a burst of gamma activity appears 10–30 s later, well before severe brain injury.36 This suggests a passage of cortical arousal like that of waking or REM consciousness, or both, briefly emerging from the unconsciousness of cerebral ischemia. Blending REM and waking consciousness is not a fluke, although it commonly eludes recognition. The REM atonia of sleep paralysis happens in the lifetime of 6% of the general population,37,38 often combined with visual or auditory hallucinations.39–42 Cataplexy is less common at 3.2% or less,37,43 whereas REM visual activation during wakefulness transpires in 19–28% of people.37,38,41 The borderland between REM and waking consciousness underlies other clinical conditions, especially narcolepsy. Here, the cardinal abnormality is the inability to control the boundaries between REM and waking consciousness,44 typically with incessant and florid consequences. Narcoleptics have an orexin deficiency, causing their REM switches, including the vlPAG, to tilt rapidly, frequently, and incompletely between waking and REM consciousness.28,45 Of those who survive a cardiac arrest with sufficient recovery to tell about it, 6.3–12% report

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a near-death experience.3,46,47 What distinguishes the brains of those with a near-death experience is their REM switches’ enhanced predisposition to entering the borderland between REM and waking consciousness. Sixty percent had REM intrusion sometime in their life, compared to 24% of ageand gender-matched controls who never reported a near-death experience.5 Of note, those with neardeath experiences have the same incidence of sleep paralysis (46%)5 as narcoleptics (50%).38 The diversely rich experience of near-death draws upon more than a single physiological or biochemical system, or anatomical structure, and requires a confluence of events to achieve its fullest expression. Oftentimes, a key factor is the psychological reaction to danger. Those in danger can feel detached or psychologically dissociated from the world or their bodies.48 They may also sense heightened awareness with thoughts sped up or experienced as lucid. Some feel powerfully in control of themselves or the event, whereas others may cede control to fate or a higher power. These reactions to danger likely reflect neural pathways and a limbic system striving to reduce panic and improve survival. Such responses may also come into play during syncope.4 Near-death experiences can emerge from danger alone,49 keeping with the fact that only about half of those having near-death are in medical peril.6 The appearance of “enhanced light” serves as one of the few features transpiring more often with physiological threat.6 As sensitive as brain function is to low blood flow, it stands that the retina fails first with hypotension. The visual “blackout” of syncope develops as a tunnel-like peripheral to central visual loss, progressing over 5–8 s during retinal ischemia, while consciousness lingers.50 Distorted ambient light emerges at the end of the tunnel, for the eyes remain open in syncope15 and cardiac arrest. Smudges of outside light at the end of the tunnel may be all the brain’s visual system can see while crossing the border to unconsciousness. Light is the prime sensation of REM consciousness, and the often cited light of near-death could receive a contribution from visual activation brought on by REM mechanisms. In the absence of retinal input, pontine REM mechanisms dominate the visual relay to the cortex.51 Cortical impairment from ischemia alone would not prevent REM light and visions. The primary visual (striate) cortex may not even be where the light of REM enters consciousness. The cortically

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blind are capable of visual dream imagery,52 and during REM the striate visual cortex is deactivated,53 whereas the extrastriate visual cortex is activated.54 Simple and complex visual hallucinations are reported by a majority during the brain ischemia of syncope.55 Undoubtedly, the near-death conditions of danger, imperiled cerebral blood flow, and cardiorespiratory crisis heighten cardiorespiratory afferent peripheral nerve activity. Autonomic afferent fibers transmit information from stretch, pressure, mechanical, and chemical receptors located within the heart, and the vascular and pulmonary systems. These impulses are conveyed to the brainstem principally by the vagus, but also by the glossopharyngeal and trigeminal nerves. Visceral afferents make up approximately 80% of the cervical portion of the vagus.56 In animals, electrical stimulation of the vagus triggers the full physiological spectrum of REM, including visual and cortical activation as well as atonia.57–61 The transition to REM can be so brisk that it spawns the terms reflex REM narcolepsy60 and narcoleptic reflex.58 This rapid movement between conscious states fosters the merging of REM and waking consciousness in humans.42 Stimulating the left vagus in humans to treat epilepsy causes REM intrusion into non-REM consciousness.62 In addition, the cardiorespiratory instability arising from the autoimmune attack on peripheral cardiac, vascular, and respiratory autonomic fibers in patients with Guillain–Barr´e syndrome leads to florid intrusion of REM consciousness.63 How does the vagal cranial nerve with its visceral fibers shift human consciousness? Vagal afferents project upward to synapse within the medullary nucleus tractus solitarius (NTS). From here, neural fibers rise to the pontine parabrachial nuclear complex (PBN) serving as the principal relay for ascending cardiorespiratory afferents to the forebrain. The NTS and PBN also reciprocally connect with cholinergic REM structures.64,65 The PBN region forms an intersection where neurons functioning specifically during REM consciousness66,67 intermingle with neurons participating in cardiorespiratory function.68,69 Although these relationships establish a firm connection between the fight-or-flight response and consciousness during cardiorespiratory crisis, the full story of vagal afferents and REM consciousness remains incomplete. Nonetheless, cardiorespiratory nerves

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undeniably evoke REM, thereby transporting consciousness to unforeseen places. Out-of-body experience is a surprisingly frequent and normal experience. From a survey of over 13,000 individuals in the general population, 5.8% reported at least one out-of-body experience.70 Out-of-body is a sensational feature of near-death that occurs in 76% of individuals with near-death experiences,71 with danger alone,72 and does not discriminate those actually near medical death.6 These facts agree with the observation that syncope in the laboratory provokes out-of-body experience about 10% of the time.4 Out-of-body has a long-established relationship with REM consciousness. Narcoleptics are prone to out-of-body experience,17,73,74 the occurrence of which wanes as the narcolepsy is treated. Out-of-body appears in lucid dreams75 — a special expression of dreaming wherein the dreamer maintains insight that he is dreaming. In young healthy adults, out-of-body experience accompanies the sleep paralysis of REM intruding into waking consciousness.76 Directly stimulating the temporoparietal cortex produces out-of-body experience,77 probably by disturbing integration of visual, proprioceptive, and motion sense into the coherent self. Other temporoparietal disruptions cause out-of-body experience as well.78 The selective temporoparietal inactivation accompanying REM79 neatly explains the relationship between REM consciousness and out-of-body experience. Further evidence of the bond between REM consciousness and near-death comes from the observation that persons with a near-death experience are as likely to have out-of-body experience transitioning between REM and waking consciousness as they are to have it during near-death itself.71 Their out-of-body experience often accompanies sleep paralysis. Feelings of rapture, peace, or euphoria commonly present in near-death strongly suggest activation of the brain’s dopamine reward system. The REM consciousness promoting PPT and LDT nuclei are instrumental in facilitating reward behavior,80 in ways not fully clear. Pathways from these REM structures project to an integral part of the reward system, the midbrain ventral tegmental region,81 and during REM consciousness ventral tegmental neurons vigorously discharge.82 In animals, PPT injury reduces the reward-seeking behavior for many strong stimuli, including food83 and self-administered heroin.84 6

In humans, the limbic and paralimbic regions active in REM are also important in the reward system.85 The pleasant feelings also common to syncope likewise suggest engagement of reward pathways.4 REM consciousness during peril provides a mechanism for activating limbic and paralimbic structures that underlie the narrative, ineffable, transcendental, and paranormal qualities of neardeath. Such limbic phenomena have long been recognized in patients whose seizures arise from these limbic regions. During REM sleep, PET scans detect activity in the amygdala and anterior cingulate gyrus,53,85,86 and PGO waves propagate to the basolateral amygdala, cingulate gyrus, and hippocampus.87 REM consciousness could also account for the “dreaming” during syncope that pilots often report.50,88 That almost all mammals enter REM consciousness emphasizes the importance of this physiologic state. Yet the biologic purpose of dreams taking place in REM still evades neuroscience. The limbic system contributes emotions to dreams, and often that emotion is fear.89 Limbic structures active in REM appeared early in vertebrate evolutionary development, before the primate neocortex formed.90 Dreams have long been considered important to instinctual behavior, and perhaps dreams thus devise solutions to simulated threats?91,92 Many ancient and contemporary cultures regard dreams as predictors of the future and portals to the divine and deceased. REM dreaming and near-death experience share many narrative qualities, and fuller comparison is found elsewhere.17 One such example is sensing “someone’s presence.” This happens in 9% of people as REM intrudes into waking consciousness,70 and bears similarity to some presences sensed during near-death. These presences, like out-of-body, can arise by electrically stimulating the temporoparietal cortex.93 Obviously, dreams and near-death experiences differ. A shared dreaming mechanism expressed under the disparate contexts of routine sleep and neardeath should lead to different kinds of experiences. Near-death is often recalled with an intense realism that can seem “realer than real,” which contrasts with the sometimes outlandish (unreal) impressions that dreams leave upon awakening. The vivid recollection of near-death, like other dangers, contrasts with the faint memory of nightly dreams.

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In spite of these differences, near-death can be almost identical to lucid dreams,94 when the dreamer retains self-insight. This common manifestation of dreaming could conceivably arise should the dorsolateral prefrontal cortex activity, instrumental to logical executive cognition, persist during REM consciousness.95 Why some experiences seem real and others do not endures as a compelling question that applies to more experiences than just near-death. Dorsolateral prefrontal brain function, as REM blends with wakefulness in a moment when impaired cerebral metabolism sustains consciousness, may influence the expression of these experiences. In the end, the neuroscience of how the brain participates in near-death and its experience does not do harm to the mystery of why near-death comes to pass; the answer to why resides in the province of faith. And with respect to the power of neardeath experiences to steadfastly transform personal meaning and spirituality, perhaps we should heed the advice of James when he counseled on spiritual experience: “By their fruits ye shall know them, not by their roots.”2 Conflicts of interest The author declares no conflicts of interest. References 1. Kandel, E.R. 1998. A new intellectual framework for psychiatry. Am. J. Psychiatry 155: 457–469. 2. James, W. & M.E. Marty. 1982. The Varieties of Religious Experience: A Study in Human Nature. Harmondsworth, Middlesex, England; New York, NY: Penguin Books. 3. van Lommel, P. et al. 2001. Near-death experience in survivors of cardiac arrest: a prospective study in the Netherlands. Lancet 358: 2039–2045. 4. Lempert, T., M. Bauer & D. Schmidt. 1994. Syncope and near-death experience. Lancet 344: 829–830. 5. Nelson, K.R. et al. 2006. Does the arousal system contribute to near death experience? Neurology 66: 1003–1009. 6. Owens, J.E., E.W. Cook & I. Stevenson. 1990. Features of “near-death experience” in relation to whether or not patients were near death. Lancet 336: 1175–1177. 7. Hotchkiss, R.S. et al. 2009. Cell death. N. Engl. J. Med. 361: 1570–1583. 8. Schnipper, J.L. & W.N. Kapoor. 2001. Diagnostic evaluation and management of patients with syncope. Med. Clin. North Am. 85: 423–456, xi. 9. Lommel, P.V. 2010. Consciousness Beyond Life: The Science of the Near-Death Experience. New York: HarperOne. 10. Alexander, E. 2012. Proof of Heaven: A Neurosurgeon’s Journey into the Afterlife. Simon & Schuster.

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