1. Introduction

The brain is our most glorious organ. To survey the majesty of human achievement is to survey the brain's majesty. Plato's philosophy, Shakespeare's plays, Beethoven's symphonies, and Einstein's theories are but a few of the brain's triumphs that come readily to mind. And in our most sublime moments, spirituality must be touching the brain if we seriously consider the words of Shakespeare and Kandel. The brain's grandeur and power is dazzling, yet at the same time this splendor blinds us to the brain's prime purpose-to keep us alive.

Key to this primal role, the brain tightly regulates it's own blood supply each second of life. The brain depends on aerobic metabolism, and so must control its blood flow at rest, in exercise, as well as during physiological and emotional stress. Cerebral blood flow is maintained through the arterial baroreflex (Benarroch, 2008) that in turn relies on the yoked opposition of cholinergic and adrenergic neurons in the peripheral and central nervous systems, as well as mechanisms intrinsic to the cerebrovasculature (Deegan et al., 2010).

Fading cerebral blood flow with looming unconsciousness signals a crisis to the brain. When the brain finds itself in crisis, we will see how it calls upon crucial impulses that have guided our forbearers' survival for tens upon tens of millions of years.

2. Consciousness in Crisis

One such crisis is near-death experience, whose frequent cause includes transient cardiac dysrhythmia. For reasons beyond biology alone, near-death has become a social stereotype of going through a tunnel, being enveloped by "the light", and floating above one's body, often combined with transcendental or mystical elements. Each near-death experience is colored by the person's life experiences and psychology. Philosopher Sir Alfred Ayer recounts, while near-death, that he had crossed the River Styx, writing afterwards "I have not wholly put my classical education behind me" (Ayer, 1988). Carl Jung visualized burning lamps surrounding a door leading to the inside of a stone temple during his near-death, and the psychiatrist later remarked that "I had once actually seen this when I visited the Temple of the Holy Tooth at Kandy in Ceylon" (Jung and Jaffé, 1989).

Whereas some Americans have sighted Elvis in their near-death experiences (Moody, 1987), Elvis is not featured in experiences of children nor in adults of other cultures (Morse et al., 1986, Pasricha and Stevenson, 1986).

Although there is little mention of near-death experience by William James, near-death does meet his conception of a spiritual experience whereby "feelings, acts and experiences" touch "whatever they may consider the divine" (James and Marty, 1982).

All the clamor over near-death has blinded us, until recently, to the fact that first and foremost near-death experience is consciousness in crisis (Nelson et al., 2006).

3. The Brain's Three Conscious States

There are three mental states possible for the brain: waking, REM sleep and non-REM sleep. We expect in crisis to be awake and attentive so we can meet the danger head on. This is so intuitively obvious that it's rarely given thought. But the brain must not take for granted that it will be in the right conscious state during crisis. Waking consciousness must immediately orient attention to whatever is required for survival, and so consciousness must be in lock step with "flight-or-fight" action. It is the brain (specifically the limbic system) that orchestrates the "fight-or-flight" to survive (figure 1).

4. The First Borderland of Consciousness ’ The border between consciousness and unconsciousness is not always abrupt and absolute. Between the hazy edges of consciousness and unconsciousness lies the first borderland of consciousness entered by someone whose brain is ischemic, starving for blood. The brain is in crisis if blood flow drops below the threshold of 23cc/100 grams of brain/minute, whereupon the cerebral cortex fails (Jones et al., 1981), and consciousness is lost after ten seconds or so (Brenner, 1997).

Consciousness can come and go if cerebral blood flow waxes and wanes across this threshold, which often happens in clinical settings.

Neuronal death begins within minutes after cerebral blood flow completely ceases. But even with sustained flow there is a second threshold below which neurons die. This threshold increases over hours to eventually reach a plateau of 17 to 18 ml/100 grams of brain/minute (Jones et al., 1981).

In the initial seconds of failing blood flow and fading consciousness, there is no reason to expect that the brain reacts differently between simple syncope and cardiac dysrhythmia. This explains why in a series of near-death subjects, otherwise harmless syncope was the most common event leading to near-death (Nelson et al., 2006). Even in the controlled safety of the laboratory, the syncope experience can be nearly indistinguishable from near-death (Lempert et al., 1994a), which reinforces the finding that only half of those experiencing near-death are actually medically threatened (Owens et al., 1990). Together these observations clash with the popular misconception that the near-death experience happens only in the face of truly eminent death. Upwards of one third of people faint within their lifetime, often while feeling endangered, and this makes syncope potentially fertile ground for spiritual experience.

5. A Metronome of Waking Consciousness

Epinephrine (adrenaline) in the body, and the corresponding neurotransmitter nor-epinephrine (nor-adrenaline) in the brain serve vital functions when peril confronts us. Elemental to "fight-or-flight" behavior is the brain's source of norepinephrine, the locus coeruleus (LC). From the brainstem pons, LC neurons project widely throughout the brain to help regulate consciousness and actively promote behaviors critical to survival (figure 2).

The pontine arousal system is the fulcrum of a reciprocal swing between colossal neurochemical systems that sweep through the brain (Hobson et al., 1975). The REM promoting cholinergic pedunculopontine (PPT) and laterodorsal tegmental (LDT) nuclei (figure 3), are in counterbalance to the waking actions of the serotonergic dorsal raphe (DR) and noradrenergic LC nuclei.

The locus coeruleus constantly discharges during waking consciousness. In primates, LC discharges are tightly linked to specific behaviors. There is some evidence to suggest that the firing patterns of this tiny nucleus anticipate certain primate behaviors. Low discharge rates correspond to low arousal when the animal is 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 attentiveness (Aston-Jones et al., 2000). Swiftly directing attention to meet the demands of the outside world is a fundamental role for the LC (Benarroch, 2009) (figure 4).

During waking consciousness the activity of the LC is extremely important to maintaining vigilance in response to stress (Rajkowski et al., 1994, Abercrombie and Jacobs, 1987). Feelings of fear, hypoxia, hypotension and hypercarbia, often present during near-death, all vigorously stimulate the LC, increasing its tonic discharge rates (Kaehler et al., 1999, Valentino et al., 1991, Bodineau and Larnicol, 2001).

6. What Becomes of the Activated Locus Coeruleus?

Physiologic mechanisms do not function unchecked in isolation. A classic example is the reciprocal action between the cholinergic and adrenergic portions of the peripheral autonomic nervous system. The LC could be central to an arousal system predisposed to blending REM and waking consciousness. Although factors activating the LC have been extensively investigated, much less is known about how LC activity is tempered. Conditions promoting REM consciousness powerfully inhibit the LC. Only during REM consciousness is the LC relatively silent (Reiner, 1986). Since LC suppression anticipates both behavior and REM consciousness (Foote et al., 1980), conceivably if scanning attention becomes maladaptive, or focused attention necessary in crisis, then counterbalances like the cholinergic REM system could act on the adrenergic LC.

7. An Inopportune Consciousness

The functioning of the LC provides a clue to how the brain might, counter-intuitively, shift from waking to REM consciousness at a most inopportune moment for survival. Further exploring how the brain could tilt to REM consciousness, when all consciousness is about to cease, requires us to know more about REM consciousness itself.

8. The Consciousness of Light

The visual system comes to the fore during REM consciousness. Light and visual impressions are among the many sensations experienced during REM (McCarley and Hoffman, 1981), and give rise to what can be called REM consciousness. Rapid eye movements (REM) during the dreaming stage of sleep is accompanied by visual system activation. Ponto-geniculo-occipital (PGO) waves, as the name indicates, travel widely from the pons in the brainstem to the (lateral) geniculate nucleus in the thalamus, and then to the visual cortex, thus triggering powerful visual sensations when dreaming. REM consciousness is also characterized by cerebral cortical activation and atonia of nonrespiratory muscles so that individuals do not act on their dreams (Lu et al., 2006, Anaclet et al., 2010). Dreaming, another hallmark of REM consciousness, takes place in cortical areas physically far removed from the brainstem (Bischof and Bassetti, 2004).

It is believed all mammals enter REM consciousness, which testifies to this conscious state's importance. Yet the biologic purpose of dreams remains elusive. The limbic system contributes emotions to our dreams, and sometimes that emotion is fear (Merritt et al., 1994). Limbic structures appeared early in vertebrate evolutionary development, before the primate neocortex formed (Crosby and Schnitzlein, 1982). Dreams have long been considered important to instinctual behavior, and it is argued that one role of our dreams is to simulate and then rehearse solutions to threats (Jouvet, 1973, Valli and Revonsuo, 2009).

9. Into a Second Borderland of Consciousness

Different REM elements can be independently expressed. When consciousness transitions between REM and waking, REM can fragment and leave its traces in waking consciousness. REM intrusions into waking consciousness can take the form of complex visual and auditory hallucinations, as well as the atonia of sleep paralysis or cataplexy. Although a person can get stuck in the borderland between REM and waking, this borderland is unstable--within seconds or minutes consciousness reverts to a more stable REM or waking state. How does someone get caught in this second borderland, the one between REM and waking consciousness? The REM consciousness switch, located near the LC, shifts us between these two states (Lu et al., 2006). The switch is made up of several components. Some of these components tilt consciousness to REM, and others tilt us awake. The switch operates in an all or none flip-flop fashion, and most but not all of the time, it crisply moves the brain between REM and waking.

10. The REM Consciousness Switch in Moments of Crisis

A critical component of the REM switch is the ventrolateral portion of the periaqueductal grey (vlPAG) (Lu et al., 2006). When it activates, consciousness tilts towards waking and away from REM. The vlPAG is fundamental to suppressing REM consciousness (Sapin et al., 2009).

It is fascinating what the vlPAG region does or doesn't do in response to hypotension (with low cerebral blood flow). The vlPAG activates during pain, hypoxia, or moderate blood loss (Keay et al., 2002). This is also when the LC is very active. But something profoundly changes when blood pressure becomes profoundly low. Here vlPAG neurons cause the peripheral adrenergic response to recede, bringing the cholinergic system to dominance (Vagg et al., 2008). The heart, instead of beating rapidly to maintain blood pressure, slows and blood pressure falls even further.

Why would the vlPAG do that?

As the vlPAG retracts the adrenergic nervous system, the once agitated animal with shifting attention becomes quiet and inattentive (Persson and Svensson, 1981), disengaging from its surroundings. Remaining quiet and still when an injury is severe or inescapable may be an effective survival strategy (Bandler et al., 2000). Whatever its advantage, this response to crisis is effective enough to have become imbedded within our evolutionarily ancient and conserved brainstem. Presumably the LC shifts from high discharge rates to the slow pulse of low arousal.

What brings the LC to this sluggish beat?

Normally when the vlPAG subsides, REM consciousness immediately follows. Is the REM system, the powerful brake on the LC, engaged in crisis?

It is uncertain if the vlPAG neurons responsible for diminishing peripheral adrenergic nervous system activity in the face of hypotension are the same, or even if they are functionally related to the neurons within the REM consciousness switch. That question lies before us. Yet it strains probability to dismiss as simply coincidence the adrenergic withdrawal in two physiological domains coordinated by the same brainstem region.

The known connections between the REM switch and LC emphasizes that successful behaviors like "fight-or-flight", or lying quietly must be coupled to the right conscious state. Although these connections indicate how our visceral responses might bring us into REM consciousness during crisis, what evidence supports this notion?

11. Blending REM and Waking Consciousness is not a Fluke

Blending REM into waking consciousness frequently occurs but is infrequently recognized. The REM atonia of sleep paralysis happens in the lifetime of roughly six percent of people (Ohayon et al., 2002, Aldrich, 1996), often combined with visual or auditory hallucinations (Ohayon et al., 1999, Fukuda et al., 1987, Cheyne et al., 1999, Takeuchi et al., 1992). Cataplexy is less common, occurring in 1.2% to 3.2% (Ohayon et al., 2002, Hublin et al., 1994). REM visual activation during waking consciousness is found in 19 to 28 % of people (Aldrich, 1996, Ohayon et al., 2002, Cheyne et al., 1999).

The borderland between REM and waking consciousness underlies other clinical conditions, and nowhere is this truer than for narcolepsy. Here the cardinal abnormality is an inability to control the boundaries between REM and waking consciousness (Broughton et al., 1986). Patients with narcolepsy have a hypocretin deficiency causing their REM switch, including the vlPAG, to tilt rapidly and frequently between waking and REM consciousness (Lu et al., 2006, Kaur et al., 2009).

It is reasonable to expect that the brains are different in the 6.3% to 12% who survive cardiac dysrhythmia with a near-death experience (Parnia et al., 2001, Greyson, 2003, van Lommel et al., 2001). In fact, persons with a near-death experience have an arousal system predisposed to entering the borderland of REM and waking consciousness (Nelson et al., 2006). Sixty percent had in their life some form of REM blending into waking consciousness. This is greater than the twenty-four percent of age and gender matched controls. Remarkably, the forty-six percent of those near-death who also had sleep paralysis compares similarly to the fifty percent of narcoleptics with sleep paralysis (Aldrich, 1996).

12. An Origin of Near-Death Experience

The experience of near-death requires a confluence of events. Oftentimes one key factor is the psychological reaction to danger. Survivors of danger can feel detached or psychologically dissociated from the world or their body (Noyes et al., 1977). They may also experience heightened arousal with thoughts speeded up, sharp or lucid. A sense of greater control is common, and all of this likely reflects neural pathways that improve survival by diminishing panic. These pathways may also be utilized during syncope in the absence of danger (Lempert et al., 1994b).

Near-death experiences can rise from danger alone and be nearly indistinguishable from those emerging during physiological crisis like cardiac dysrhythmia (Owens et al., 1990). One of the few discerning features is the appearance of "enhanced light" during genuine physiological threat.

13. The Tunnel and Light

At the beginning of syncope, a tunnel-like peripheral to central visual loss develops over 5 to 8 seconds from retinal ischemia, while brain cortical functions remain (Lambert and Wood, 1946). Ambient light is at the end of the tunnel. The eyes are kept open during syncope (Lempert and von Brevern, 1996), allowing light to strike an ischemic and failing retina. Smudges of outside light at the end of the tunnel may be all the brain is capable of seeing while on the threshold of unconsciousness. Light is the prime sensation in REM consciousness, and the often cited light of near-death could also arise from visual system activation brought on by REM mechanisms. In the absence of retinal input, pontine REM mechanisms are the dominant influence over the visual relay to the cerebral cortex (McCarley et al., 1983).

Cortical ischemia alone would not prevent REM light and visions. The cortically blind are capable of visual dream imagery (Solms, 1997), although during REM the primary visual (striate) cortex is deactivated (Braun et al., 1997), the extrastriate visual cortex is activated (Braun et al., 1998). Moreover, simple and complex visual hallucinations are reported by a majority during the brain ischemia of syncope (Lempert et al., 1994b).

14. Nerves of the Heart Draw Us into the Borderland of Consciousness

Undoubtedly the near-death conditions of danger, imperiled cerebral blood flow and cardio-respiratory crisis heighten cardio-respiratory afferent nerve activity. Autonomic nervous system afferent fibers transmit information from stretch, pressure, mechanical, and chemical receptors located within the heart, vascular and pulmonary systems. These impulses are conveyed to the brainstem principally by the vagus, but also by the glossopharygeal and trigeminal nerves. The cervical portion of the vagus is made up of approximately 80% visceral afferents (Agostoni et al., 1957). Vagal afferents alone robustly bring the brain into REM consciousness.

Electrical stimulation of the vagus in animals triggers the visual, cortical and atonic physiological facets of REM consciousness (Puizillout and Foutz, 1976, Valdes- Cruz et al., 2002, Fernandez-Guardiola et al., 1999, Puizillout and Foutz, 1977, Foutz et al., 1974). The transition from waking to REM can be so brisk that it spawned the terms "reflex REM narcolepsy" (Puizillout and Foutz, 1977) and "narcoleptic reflex" (Valdes-Cruz et al., 2002). This rapid transition between conscious states is the very condition that in humans causes REM and waking consciousness to merge (Takeuchi et al., 1992).

When the vagus nerve is stimulated in humans to treat epilepsy, REM intrudes into non-REM consciousness (Malow et al., 2001). Furthermore, the cardio-respiratory instability arising from an autoimmune attack on cardiac, vascular and respiratory autonomic nerve fibers in patients with Guillain-Barré syndrome leads to florid intrusion of REM consciousness (Cochen et al., 2005).

How can the vagus nerve shift consciousness?

Vagal afferents project upwards to synapse within the medullary nucleus tractus solitarius. From here, neural fibers rise to the pontine parabrachial nuclear complex (PBN) that is the principal relay for ascending cardio-respiratory afferents to the forebrain. In addition, the nucleus tractus solitarius and the PBN reciprocally connect with cholinergic REM structures (Semba and Fibiger, 1992, Quattrochi et al., 1998). The PBN region forms an intersection where neurons promoting and functioning specifically during REM consciousness (Datta et al., 1992, Datta and Hobson, 1994) intermingle with neurons participating in cardio-respiratory function (Chamberlin and Saper, 1992, Chamberlin and Saper, 1994).

Although these relationships lead to a connection between fight-or-flight, consciousness, and cardio-respiratory crisis, the full story of vagal afferents and REM consciousness remains to be seen. What is clear is that through its nerves the heart can cause REM consciousness, thereby transporting consciousness to unexpected places.

15. Out-of Body Experience and REM Consciousness

Out-of body experience (autoscopy) is an astonishingly common and normal experience. In a survey of over 13,000 people, 5.8% reported at least one autoscopic experience (Ohayon, 2000). Autoscopy is a common feature of near-death, that occurs with danger alone (Noyes and Kletti, 1976), and surprisingly does not distinguish between those who are or are not medically near death (Owens et al., 1990). This is consistent with the observation that syncope in the safe laboratory provokes autoscopy about 10% of the time (Lempert et al., 1994b).

Autoscopy has a long and established relationship with REM consciousness. Narcoleptics are prone to autoscopy (Mahowald and Schenck, 1992, Overeem et al., 2001), and its frequency wanes as the narcolepsy is treated. Autoscopy may appear in lucid dreams, a special expression of dreaming when the dreamer possesses the insight they are dreaming (LaBerge et al., 1988). In young healthy adults autoscopy accompanies the sleep paralysis of REM consciousness (Cheyne and Girard, 2009).

Autoscopy is directly produced by stimulating the temporoparietal region (Blanke et al., 2002), probably by disturbing sensory integration into the coherent self. Other temporoparietal disruptions cause autoscopy as well (Blanke et al., 2004). The temporoparietal region is also selectively inactive during REM consciousness, directly suggesting how REM consciousness and autoscopy are related (Maquet et al., 2005) (figure 5).

Autoscopy is particularly forceful during REM consciousness. Persons with a near-death experience are as likely to have autoscopy transitioning between REM and waking consciousness as they are to have autoscopy during near-death itself (Nelson et al., 2007). Often their autoscopy occurs during sleep paralysis.

16. Heaven-like Rewards

The brain's reward system could underlie the feelings of rapture, peace or euphoria often present during near-death. The REM consciousness promoting PPT and LDT nuclei are also instrumental to promoting reward behavior (Yeomans et al., 1993). Pathways from these REM structures project to an integral part of the reward system, the brainstem ventral tegmental region (Oakman et al., 1995). During REM consciousness ventral tegmental neurons vigorously discharge (Dahan et al., 2007). In animals, PPT injury reduces the reward seeking behavior for many strong stimuli including food (Alderson et al., 2002) and self administered heroin (Olmstead et al., 1998). In humans, the limbic and paralimbic regions active in REM sleep are also important in the reward system (Nofzinger et al., 1997). Pleasant or positive feelings are common during syncope (Lempert et al., 1994b), suggesting these reward pathways have been activated.

17. Divine-like Dreams

REM consciousness during peril provides a mechanism for activating limbic and paralimbic structures believed to underpin the narrative, ineffable, transcendental and paranormal qualities of near-death. In REM sleep, amygdala and anterior cingulate gyrus activity is detected on PET scan (Nofzinger et al., 1997, Braun et al., 1997, Maquet et al., 1996), and PGO waves propagate to the basolateral amygdala, cingulate gyrus, and hippocampus (Calvo and Fernandez-Guardiola, 1984). REM consciousness could also underlie the "dreaming" during syncope that pilots report (Lambert and Wood, 1946, Forster and Whinnery, 1988).

Many ancient and modern cultures regard dreams an augur of the future, and connection to the divine and deceased. There are many shared narrative qualities of dreaming and near-death, and a fuller comparison is found elsewhere (Nelson, 2011). One such example is sensing "someone's" presence. This happens in 9% of people as REM intrudes into waking consciousness (Ohayon, 2000), and bears similarity to the presences sensed during near-death. These presences, like autoscopy, can arise directly by stimulating the temporoparietal cortex (Arzy et al., 2006).

Obviously dreams and near-death differ. Near-death is recalled with an intense sense of realness that sharply contrasts to dreams. Near-death narratives lack the bizarreness of dreams. Yet near-death can be almost identical to lucid dreams (LaBerge and Rheingold, 1990), when the dorso-lateral prefrontal region, instrumental to logical executive cognition, may remain active during REM consciousness(Hobson, 2009).

Why some experiences seem real and others do not is a compelling ambiguity. But one thing is certain; our sense of reality profoundly shifts in unexpected ways in REM consciousness. Our dreams seem so real at the time regardless of how strange we find them on awaking. Inactivating the dorso-lateral prefrontal brain during REM consciousness might contribute to suspending waking reality. How does this brain region function as REM blends with waking consciousness in crisis?

REM consciousness blurs the borders of reality. We must expect an unfamiliar and baffling reality when REM and waking consciousness merge to form a borderland of consciousness.

18. Epilogue

The notion that REM consciousness physiologically contributes to the experience of near-death falls within the realm of reasonable neurological probability. To understand the brain during near-death experience we needn't resort to extraordinary supernatural explanations when ordinary natural explanations suffice. Nonetheless, even if we know how the brain works during spiritual experience, the mystery of why lives on.