Letters to the Editor

ENDORPHINS AT THE APPROACH OF DEATH

The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings of peace, bliss and timelessness, life review, the sensation of traveling through a tunnel and an irreversible threshold. Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism. Anecdotal accounts of the similarity between NDEs and certain drug-induced altered states of consciousness prompted us to perform a large-scale comparative analysis of these experiences. After assessing the semantic similarity between $\approx$15,000 reports linked to the use of 165 psychoactive substances and 625 NDE narratives, we determined that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine consistently resulted in reports most similar to those associated with NDEs. Ketamine was followed by Salvia divinorum (a plant containing a potent and selective $\kappa$ receptor agonist) and a series of serotonergic psychedelics, including the endogenous serotonin 2A receptor agonist N,N-Dimethyltryptamine (DMT). This similarity was driven by semantic concepts related to consciousness of the self and the environment, but also by those associated with the therapeutic, ceremonial and religious aspects of drug use. Our analysis sheds light on the long-standing link between certain drugs and the experience of “dying“, suggests that ketamine could be used as a safe and reversible experimental model for NDE phenomenology, and supports the speculation that endogenous NMDA antagonists with neuroprotective properties may be released in the proximity of death.

Memories of Near-Death Experiences (NDEs) most often are recounted as emotionally positive events. At present, no satisfactory explanatory model exists to fully account for the rich phenomenology of NDEs following a severe acute brain injury. The particular population of patients with locked-in syndrome (LIS) provides a unique opportunity to study NDEs following infratentorial brain lesions. We here retrospectively characterized the content of NDEs in 8 patients with LIS caused by an acute brainstem lesion (i.e., “LIS NDEs”) and 23 NDE experiencers after coma with supratentorial lesions (i.e., “classical NDEs”). Compared to “classical NDEs”, “LIS NDEs” less frequently experienced a feeling of peacefulness or well-being. It could be hypothesized that NDEs containing less positive emotions might have a specific neuroanatomical substrate related to impaired pontine/paralimbic connectivity or alternatively might be related to the emotional distress caused by the presence of conscious awareness in a paralyzed body.

To measure brain activity in near-death experiencers during a meditative state.

In two separate experiments, brain activity was measured with functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) during a Meditation condition and a Control condition. In the Meditation condition, participants were asked to mentally visualize and emotionally connect with the “being of light” allegedly encountered during their “near-death experience”. In the Control condition, participants were instructed to mentally visualize the light emitted by a lamp.

In the fMRI experiment, significant loci of activation were found during the Meditation condition (compared to the Control condition) in the right brainstem, right lateral orbitofrontal cortex, right medial prefrontal cortex, right superior parietal lobule, left superior occipital gyrus, left anterior temporal pole, left inferior temporal gyrus, left anterior insula, left parahippocampal gyrus and left substantia nigra. In the EEG experiment, electrode sites showed greater theta power in the Meditation condition relative to the Control condition at FP1, F7, F3, T5, P3, O1, FP2, F4, F8, P4, Fz, Cz and Pz. In addition, higher alpha power was detected at FP1, F7, T3 and FP2, whereas higher gamma power was found at FP2, F7, T4 and T5.

The results indicate that the meditative state was associated with marked hemodynamic and neuroelectric changes in brain regions known to be involved either in positive emotions, visual mental imagery, attention or spiritual experiences.

Cardiac arrest is associated with a number of cognitive processes as well as long term psychological outcomes. Recent studies have indicated that approximately 10–20% of cardiac arrest survivors report cognitive processes, including the ability to recall specific details of their resuscitation from the period of cardiac arrest. In addition it has been demonstrated that these cognitive processes are consistent with the previously described near death experience and that those who have these experiences are left with long term positive life enhancing effects. There have also been numerous studies that have indicated that although the quality of life for cardiac arrest survivors is generally good, some are left with long term cognitive impairments as well as psychological sequelae such as post-traumatic stress disorder.

This paper will review near death experiences, cognitive function and psychological outcomes in survivors of cardiac arrest.

The three events, viz. schizophrenia, dissociative anaesthesia and Near-Death Experience, despite their seemingly unrelated manifestation to each other, have nevertheless similar functional basis. All three events are linked to the glutamate sensitive N-methyl-d-aspartate (NMDA) receptor complex, which serves as their common functional denominator. Arguments and speculations are presented in favor of the view that, the three events might be considered as functional models of each other. Antagonism to the recognition NMDA-site of the receptor induces dissociative anaesthesia and precipitates Near-Death Experience. Agonist reinforcement at the modulatory glycine-site of the receptor counteracts negative symptoms of schizophrenia. Both types of challenges towards the receptor are compatible with a glutamate deficiency concept which underlies the meeting of the three events at the NMDA receptor.