Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution

This theory-building article (2017) explores the phenomenological, neurophysiological and philosophical significance of drug-induced ego dissolution with classical psychedelics, dissociative anesthetics, and kappa-opioid receptor agonists and highlights their relevance for investigating the neurophysiological mechanisms underlying the representation and the sense of self.

Abstract

“There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other hand, it suggests that ordinary conscious experience might involve a minimal kind of self-awareness rooted in multisensory processing, which is what appears to fade away during DIED.”

Authors: Raphaël Millière

Summary

INTRODUCTION

Hallucinogenic drugs can produce profound changes in consciousness, including a dramatic breakdown of one’s sense of self. This phenomenon is commonly referred to as ego dissolution, and the study of drug-induced ego dissolution can help us understand the neurobiological basis of the sense of self.

This article presents an interdisciplinary perspective on DIED, which will be based on an analysis of subjective reports and quantitative data from questionnaires. It will also discuss the relevance of DIED for cognitive neuroscience, and the hypothesis that DIED consists in a disruption of the ”embodied” or ”minimal” self.

THE PHENOMENOLOGY OF DIED

Experimental studies with mescaline have shown that it can cause schizophrenic self-disturbances, including anomalous body experiences and the feeling of merging with one’s surroundings.

Others concluded that mescaline could replicate the symptoms of depersonalization disorder, and Aldous Huxley himself described a feeling of unity with everything. In the 1950s and 1960s, experimental studies with lysergic acid diethylamide (LSD) reached similar conclusions regarding the drug’s ability to produce depersonalization-like experiences. The expression ”ego dissolution” seems to have emerged in the 50s to describe these effects as observed with LSD and mescaline. Many studies published during this period compared the reported effects of hallucinogenic drugs to symptoms of depersonalization disorder or putatively nonpathological mystical states. Some authors also described these effects as ”self-disturbances”, a term introduced by Hans Gruhle to characterize passivity experiences in schizophrenia.

The Oceanic Boundlessness (OBN) and Dread of Ego Dissolution (DED) questionnaires measure positively felt depersonalization, derealization and feelings of unity, whilst the VR questionnaire measures negatively experienced ego dissolution. A meta-analysis of eight experimental studies found that psilocybin significantly increased scores on the OBN and DED scales in a dose-dependent manner, with higher doses being associated with high scores on the OBN scale. A recent study used a 23-item rating scale questionnaire to assess the effects of 2 mg psilocybin on self-consciousness. The authors found that participants scored highly on the item ”I experienced a disintegration of my self or ego” after drug administration.

Most recent studies directly investigating the phenomenon of ego dissolution rely on a single questionnaire item to measure it, but single-item measurements are less reliable and more ambiguous than scales with multiple items. In a recent double-blind, placebo-controlled study, 15 participants completed a custom questionnaire made of 22 Visual Analogue Scale (VAS) items after receiving an injection of 2 mg psilocybin. The first principal component of the questionnaire was associated with items describing ego dissolution and a loss of separation from my environment.

In this study, 691 participants completed an online VAS questionnaire assessing ego dissolution, ego inflation and unity experiences. The 8-item EDI demonstrated discriminant validity against ego inflation items and convergent validity with MEQ items.

The 8-item EDI was found to be valid, has a single-factor psychometric structure and measures a valid construct. It was strongly associated with experiences induced by classical psychedelics, as opposed to those induced by cocaine and alcohol. The EDI is a valid measure of DIED, but it does not seem to shed light on the nature of DIED beyond its standard account as a loss/disintegration/dissolution of the self/ego.

Anecdotal self-reports from drug users can be analyzed on the website Erowid.org2. A quantitative analysis of randomly selected trip reports regarding Salvia yielded significantly high score for the category ”ego dissolution”. A computer-assisted analysis of narrative reports from Erowid.org suggests that 7% of trip reports involve the description of an ego dissolution experience, which involves the loss of self-awareness, the feeling of dying, the loss of boundaries between self and world, and the failure to recognize oneself. While Erowid.org reports are somewhat noisy and potentially biased, the unprecedented sample size and sophisticated machine learning algorithm increase the significance of the results.

Early anecdotal reports, data from validated questionnaires and the above quantitative analysis of narrative reports indicate that a range of psychoactive substances significantly alter the sense of self in similar ways. However, the question lingers whether DIED is a unified phenomenon. The OBN and DED scales are designed to measure positive and negative aspects of the experience, but the main difference between the two scales lies in the emotional valence of the drug-induced state. Due to its dramatic intensity, DIED can be a very frightening experience. However, experienced users seem to have a much more positive experience with DIED, as they do not fear for their lives and are not trying to resist the effects of the drug.

Nour et al. (2016) observed that long-term well being and life satisfaction were positively correlated with EDI score, and that psychotic ego dissolution is sometimes reported as a pleasant experience.

A recent psychometric evaluation of the APZ questionnaire found that its three-dimensional organization was not ideal to measure altered states of consciousness accurately. Instead, 11 clusters were formed from 42 of the 66 original items. Lebedev et al. (2015) found that DIED was relatively independent from the emotional valence of the experience, and that the first principal component was also loosely associated with two items related to anxiety.

THE NEUROPHYSIOLOGY OF DIED

The term hallucinogen does not define a homogenous class of molecules, but can be broken down into three main neuropharmacological categories: psychedelics, dissociative anesthetics and KOR agonists.

Classical Psychedelics

Psychedelics are drugs that act on the central nervous system as agonists of the serotonin 2A (5-HT2A) receptor subtype. They produce strong visual effects, such as simple and complex hallucinations, which are less prominent in other classes of psychoactive substances. Phenylalkylamine hallucinogens are selective for 5-HT2 serotonin receptor subtypes, while indolealkylamine hallucinogens bind non-selectively to all 5-HT receptors. 5-HT2A receptor activation is specifically responsible for mediating the main subjective effects of all psychedelics.

Serotoninergic hallucinogens have complex neurophysiological effects, with 5-HT2A receptors being most densely expressed on excitatory layer V pyramidal neurons in high-level association cortical areas associated with cognitive and perceptual processing. These neurons are likely to be the cause of the desynchronization of cortical activity recorded by EEG and MEG after the administration of psilocybin.

The DMN is involved in higher-order, metacognitive operations such as introspection and memory retrieval, and is also reduced during deep meditative states.

The neurobiological effects of psychedelics are linked to the default mode network (DMN), and the anti-correlation between the DMN and the task-positive network (TPN) may be necessary to maintain a clear distinction between what is internal/self-related and what is external/other-related at the personal level. Psilocybin decreased coupling between the PCC and the mPFC, increased coupling between the mPFC and task-positive areas such as the dlPFC, and decreased coupling between the DMN and the hippocampus. This suggests that DMN-MTL decoupling might play a role in DIED.

Serotoninergic hallucinogens produce a disorganized brain state characterized by a higher neural entropy than normal waking consciousness. The DMN is responsible for the emergence of a coherent sense of self. The parahippocampal cortex (PHC) mediates the connectivity of the hippocampus with major network hubs, including the PCC and the dorsomedial prefrontal cortex (dMPFC). Decoupling of the PHC from the neocortex was hypothesized to correlate with DIED. The intensity of DIED was strongly anticorrelated with the diversity of connections in the anterior part of the PHC, while the diversity of connections in the posteriomedial cortex did not correlate with DIED. DIED was found to be associated with the decoupling of MTL regions from the neocortex, as predicted, but also with the decoupling of the salience network, which was unexpected. DIED was also found to correlate with reduced interhemispheric connectivity.

Several recent studies have investigated the correlates of LSD-induced ego dissolution, using single-item measurements rather than the heterogeneous PCA-driven measurement previously used by Lebedev et al. (2015). The increase in global functional connectivity in high-level association cortices and the thalamus was found to be associated with the experience of ego dissolution. The TPJ and insular cortex might be involved in the maintenance of a sense of self, and heautoscopic experiences may be caused by the disintegration of visuo-somatosensory signals with interoceptive signals. A separate analysis of the same fMRI data found that DIED was correlated with a disintegration of the DMN, a decrease in resting state functional connectivity within the network, and a decrease in delta and alpha power in the PCC.

Recent studies with psilocybin and LSD suggest that ego dissolution is linked to increased global cortical connectivity and increased entropy, but psilocybin-induced ego dissolution is also linked to decreased regular oscillatory rhythms in the PCC and decreased communication between the parahippocampus and the neocortex.

Dissociative Anesthetics

Dissociative anesthetics are psychoactive substances that induce ego dissolution experiences. These effects are similar to those of schizophrenia, and have led researchers to use NMDA receptor antagonists to model the neurobiological mechanisms of psychosis. Dissociative anesthetics like ketamine increase glutamate release, which in turn increases activity at non-NMDA receptors. Lamotrigine, a drug that inhibits glutamate release, is believed to reduce the psychosis-like effects of ketamine.

Ketamine was shown to increase glutamate release in the mPFC and to decrease activity in the ventral tegmental area, the substantia nigra, the PCC and the visual cortex in rats. Ketamine also increased activity in the striatum and entorhinal cortex in primates. Deakin et al. (2008) performed two experiments using resting-state fMRI to investigate the effects of ketamine on regional BOLD signal. They concluded that the increase of glutamate release provoked by NMDA receptor blockade results in aberrant perceptual processing and a focal suppression of the OFC-SC and temporal pole. It is worth noting that psilocybin and ketamine produce similar feelings of disembodiments, and both substances score highly on the ”ego consistency” subscale of the EPI questionnaire. This suggests that the neurophysiological basis of DIED is broadly similar across cases involving distinct pharmacological etiologies.

The third class of substances seemingly associated with DIED is constituted by KOR agonists such as salvinorin-A, which may interact indirectly with the brain’s endocannabinoid system. Salvia users report that the effects of salvinorin-A are less visual distortions, more intense, and less enjoyable than serotoninergic hallucinogens and dissociative anesthetics. However, there is evidence that salvinorin-A and other selective KOR agonists can induce ego dissolution experiences. Salvinorin-A, a KOR receptor agonist, was found to increase scores on the OBN subscale of the APZ questionnaire while decreasing scores on the DED subscale in healthy volunteers. However, this ability has yet to be demonstrated with a direct validated measure of DIED.

KOR agonists may activate KORs in the claustrum, which may lead to alterations in bodily self-consciousness. Further investigations using brain imaging are required to gain a better understanding into the mode of action of selective KOR agonists.

THE SIGNIFICANCE OF DIED FOR COGNITIVE NEUROSCIENCE

If DIED is a genuine phenomenon associated with specific neurophysiological mechanisms, then studying the neurophysiological changes associated with subjective reports of DIED might reveal which functional brain configuration is essential to the maintenance of a sense of self.

The Search for Neural Correlates of the Sense of Self

There has been considerable debate about the methodological issues surrounding the search for the neural correlates of consciousness, and the range of cases in which the neural correlation holds. The available neurophysiological data on DIED does not indicate a minimal neural system sufficient for having a sense of self. Instead, the brain states of DIED subjects seem to correlate with the absence of a sense of self.

Some neural properties of non-DIED subjects that are changed in DIED cases are necessary for the maintenance of a sense of self, at least in normal human brains. However, it is unwarranted to infer from such experimental results that these neural properties are sufficient for the maintenance of a sense of self. Brain imaging studies of DIED can have an indirect role in assessing hypotheses regarding the neural correlates of the sense of self, just as imaging of non-conscious processing can cast doubt on hypotheses regarding the neural underpinning of consciousness.

The Broad Dichotomy between Two Concepts of Self

The word ”self” is as ambiguous as the word ”correlates”, and there is no consensus on its meaning in cognitive neuroscience.

To understand DIED experiences, it is necessary to determine what definition of the ”self” is at play. There is little agreement on how to understand this notion, and the very notion of a sense of self is controversial. Within cognitive neuroscience, there has been a debate over the interpretation of experimental results regarding the activity of cortical midline structures, which are purported to give us insight into the neurobiological basis of the ”self”. Legrand and Ruby (2009) have introduced a distinction between self-related and self-specifying processes. A recent article argues that the self is not entirely reducible to reflective processes in which one represents oneself, because the self is also a subject of conscious experience with a first-person perspective on the world.

In contemporary philosophy, notions of phenomenal selfhood have been developed that are similar to those of Husserl and Sartre. These notions include the notion of pre-reflective self-awareness, which is a first-personal aspect of consciousness that is implemented at the subpersonal level.

Researchers have proposed to interpret the neuropharmacological mechanisms of DIED by dwelling on another distinction, between the narrative self and the minimal/embodied self. The minimal/embodied self is the basic experience of being a self rooted in bodily sensorimotor processes.

The self is constituted by high-level reflective processes involving introspection, self-evaluation and autobiographic memory retrieval, and the DIED experience seems to disrupt low-level perceptual and bodily processes.

Multisensory integration is the process by which information from several sensory modalities is integrated to improve perception and solve crossmodal conflicts. Full-body illusions can dissociate three self-referential components of ordinary conscious experience, namely self-identification with a body, self-location in space, and the experienced origin of the visuospatial perspective. The idea that self-identification to a physical or hallucinated body is necessary for minimal selfhood has been challenged by experiences in which subjects lack the experience of having a body.

Recently, it has been proposed that the loss of self/world boundaries in psychosis might be linked to a disruption of self-location and PPS representation. Moreover, psychedelic drug intake can lead to a breakdown of the integration of congruent visuotactile and vestibular signals underlying self-location. Recent fMRI studies suggest that the PCC plays a key role in encoding self-location, and that ego dissolution induced by psilocybin and LSD is associated with decreased oscillatory rhythms in the PCC. This is an additional evidence that DIED is caused by aberrant multisensory integration of self-related inputs, resulting in a loss of self-location and self/world boundaries.

DIED and Computational Models of Minimal Selfhood

The self is continuously updated on the basis of incoming information, and the self/non-self distinction is implemented by subpersonal feedback loops.

The authors argue that the DMN underlies narrative rather than embodied aspects of selfhood, and that attention-demanding tasks do not suppress the experience of being an embodied subject and agent underpinned by self-specifying processes.

The Bayesian brain theory describes the brain as a hypothesis testing machine that modulates its integration of sensory stimuli through top-down modulation. This top-down modulation is consistent with the free energy principle and predictive coding. Recent theories have suggested that psychedelic drugs produce a ”disorganized” brain state characterized by a higher neural entropy than the baseline state, which could explain some of the subjective effects of hallucinogenic drugs.

The minimal/embodied self converges in suggesting that a Bayesian perspective may contribute to explain how DIED experiences arise. This model involves the integration of congruent predictions regarding self-related and self-generated (endogenous) multisensory stimuli in high-level supramodal regions. The hypothesis is that in normal conditions, the sense of self is generated by a model of the single cause of congruent multisensory inputs that are ”most likely to be me” across exteroceptive, somatosensory, interoceptive and vestibular domains.

This hypothesis could shed light on disturbances of self-experience such as those found in psychosis, or indeed in drug-induced cases. It is based on the idea that the mechanisms underlying reafferent/exafferent signaling are not functioning properly, which can lead to difficulties in distinguishing between endogenous and exogenous stimuli.

Hallucinogenic drugs might disturb the continuity and consistency of the embodied self, resulting in alien experiences. They might also improve the accuracy of participants on a range of tasks in which standard top-down control normally causes a performance decline. Pharmacological models of psychosis emphasize the similar role of disrupted prediction errors signaling in psychotic and drug-induced cases. This is linked to the generation of mismatch negativity (MMN), which decreases in response to unexpected stimuli in schizophrenia patients and healthy participants pre-treated with ketamine.

It can be hypothesized that ego dissolution is linked to a disruption of top-down and bottom-up processes modulating the multisensory integration of self-related stimuli that normally implement self-location and a self/world boundary.

THE SIGNIFICANCE OF DIED FOR PHILOSOPHY OF MIND

Although the phenomenon of DIED has not gone unnoticed in neuropharmacological and psychiatric research, philosophers have rarely mentioned it, despite its potential relevance to philosophical debates about selfhood.

Self-Awareness

The phenomenology of DIED puts pressure on the claim that one is self-aware whenever one is conscious. However, several authors have argued that phenomenal consciousness has another aspect, namely its subjective character. The subjective character of a conscious state is the fact that it is like something for me to be in a given state. According to subjectivity theories of consciousness, the subjective character of consciousness is a necessary condition of phenomenal consciousness.

(SCP) Necessarily, a mental state is phenomenally conscious if and only if it has subjective character.

Although there is some ambiguity about the notion of subjective character, many publications in neuroscience, psychology and philosophy have endorsed the general idea that consciousness necessarily involves some kind of sense of self or self-awareness.

(SAP) Necessarily, whenever one is in a conscious state, one is minimally self-aware.

If it were shown that there are instances in which a subject is in a phenomenally conscious state without being self-aware in any way, then subjectivity theories would be prima facie invalidated on empirical grounds. However, a number of pathological cases have been brought up as potential threats to such a claim. Although subjective reports of ego dissolution experiences suggest that they lack this first-personal aspect altogether, self-reports clearly converge in indicating that DIED is a conscious experience, and one that is memorable.

The proper assessment of SAP depends on whether there is indeed a kind of minimal self-awareness or sense of self surfacing at the personal level in conscious experience. DIED experiences seem to threaten SAP because they indicate that the sense of self is otherwise part of one’s conscious experience. In normal situations, minimal phenomenal selfhood might not be a salient feature of one’s conscious states, but might only come to the fore when self-specifying processes start dysfunctioning. There are at least two different interpretations of DIED that do not threaten SAP. One is that DIED impairs reflective or conceptual self-consciousness without undermining the subjective character of consciousness. According to a second alternative interpretation, DIED does not subtract something from the experience, but rather adds something to the ordinary structure of consciousness, such as a feeling of alienation. However, this interpretation does not sit well with the hypothesis that DIED undermines bodily awareness. According to another interpretation, DIED alters self-awareness through a dissociation of automatic processing from the self.

GENERAL SUMMARY AND FUTURE DIRECTIONS

This article reviewed current knowledge about DIED, a phenomenon that occurs following the intake of certain psychoactive drugs at high doses. The neurophysiological etiology of DIED is not yet fully understood, but appears to be related to DMN disintegration, increased global functional connectivity and increased neural entropy.

The extent to which each psychoactive compound can produce ego dissolution can be reliably measured using validated questionnaires. However, there are well-documented differences between the subjective effects of classical psychedelics, dissociative anesthetics and KOR agonists.

DIED experiences are often described as the loss of one’s sense of self, and recent neurocomputational models suggest that they might be related to the abnormal processing of multisensory endogenous stimuli, leading to the loss of self/world boundary and self-location, and eventually feelings of non-existence. DIED experiences challenge the claim that minimal self-awareness is necessary for consciousness, but they also seem consistent with the idea that ordinary conscious experience involves a minimal kind of self-awareness.

Future research could benefit from fine-grained descriptions of DIED experiences, using proven methods to avoid theoretical and cognitive biases. First-person methods could also be incorporated within neurocognitive studies, in the spirit of ”neurophenomenology”.

DIED experiences are so remote from normal waking consciousness that researchers must rely on detailed and reliable subjective descriptions.