Finding the self by losing the self: Neural correlates of ego‐dissolution under psilocybin

This single-blind placebo-controlled fMRI study (n=15) details the neural correlates of ego-dissolution. A correlation was found between decreased functional connectivity (FC), between the medial temporal lobe and high-level cortical regions, and ego dissolution.

Abstract

“Ego‐disturbances have been a topic in schizophrenia research since the earliest clinical descriptions of the disorder. Manifesting as a feeling that one’s “self,” “ego,” or “I” is disintegrating or that the border between one’s self and the external world is dissolving, “ego‐disintegration” or “dissolution” is also an important feature of the psychedelic experience, such as is produced by psilocybin (a compound found in “magic mushrooms”). Fifteen healthy subjects took part in this placebo‐controlled study. Twelve‐minute functional MRI scans were acquired on two occasions: subjects received an intravenous infusion of saline on one occasion (placebo) and 2 mg psilocybin on the other. Twenty‐two visual analogue scale ratings were completed soon after scanning and the first principal component of these, dominated by items referring to “ego‐dissolution”, was used as a primary measure of interest in subsequent analyses. Employing methods of connectivity analysis and graph theory, an association was found between psilocybin‐induced ego‐dissolution and decreased functional connectivity between the medial temporal lobe and high‐level cortical regions. Ego‐dissolution was also associated with a “disintegration” of the salience network and reduced interhemispheric communication. Addressing baseline brain dynamics as a predictor of drug‐response, individuals with lower diversity of executive network nodes were more likely to experience ego‐dissolution under psilocybin. These results implicate MTL‐cortical decoupling, decreased salience network integrity, and reduced interhemispheric communication in psilocybin‐induced ego disturbance and suggest that the maintenance of “self” or “ego,” as a perceptual phenomenon, may rest on the normal functioning of these systems.”

Authors: Alexander V. Lebedev, Martin Lövdén, Gidon Rosenthal, Amanda Feilding, David J. Nutt & Robin L. Carhart-Harris

Summary

Introduction

The concept of the self has been a topic of debate in philosophy and science since ancient times. In certain altered states of consciousness, the self can be observed to be vulnerable, such as in acute psychosis and temporal lobe epilepsy auras.

The self is a broad construct that encompasses many mental phenomena, including self-awareness, self-monitoring, self-recognition, self-identity, self-control, sense of agency and ownership, theory-of-mind, subject-object differentiation, reality-testing, and focused attention or goal-directed cognition.

Karl Jaspers distinguished several domains of ego-consciousness, which are useful for understanding the phenomenon that is the focus of the present article. These domains are incorporated into the ego pathology inventory, which has been successfully used in studies of psychedelic and psychotic states.

The ego can be studied from the standpoint of a sensory experience, but also as a system with functions, such as reality-testing, subserved by hierarchically higher brain circuits.

Psilocybin is a prodrug of psilocin, a classic psychedelic substance and an indolealkylamine. It has been found to alter a broad range of cognitive functions related to the self, including goal-directed behavior, reality-testing, and time perception.

The medial temporal lobe (MTL) has been linked to the “dreamlike” quality of the experience, as well as to the activation of the parahippocampal regions and the depersonalization of the self in psychotic states.

The parahippocampal cortex is a multimodal hub that mediates connectivity with major brain network hubs subserving higher cognition, and is also associated with dreamy state experiences. Decoupling of the PHC from the neocortex correlates positively with ego-dissolution.

Previous studies have found increased activation in the DMN during self-referential processing and other high-level cognitive functions related to the construct of “the self”, including theory-of-mind, mental time travel, and moral decision-making. Our previous fMRI and MEG studies have found decreased cerebral blood flow, functional connectivity, and oscillatory power within the DMN.

The salience network is rich in von Economo neurons, which are hypothesized to contribute to the brain mechanisms of self-awareness, higher cognition, and empathy in socially complex animals, as well as to psychosis and the aberrant salience model of positive psychotic symptoms.

It has previously been proposed that psychedelics are an ideal experimental means of perturbing the self or ego so that it can be studied scientifically, as well as to aid studies of some psychotic states.

In the present article, methods of large-scale network analysis were employed to test hypotheses about the neural correlates of drug-induced ego-dissolution.

Methods

Design and Participants

Fifteen volunteers with previous psychedelic experience were scanned on two occasions: (1) receiving saline injection (“placebo”), 12 min task-free fMRI scan, eyes closed; and (2) receiving 2 mg psilocybin infusion (“psilocybin”). All participants underwent health screens prior to enrolment.

Subjective Behavioral Measures

Twenty-two visual analogue scale (VAS) items were completed by the volunteers shortly after they exited the scanner. A principal component analysis was performed, and a first principal component (i.e. the item “I lost all sense of ego”) was used as a subsequent measure of interest.

Image acquisition

MR images were acquired using a 3T Siemens Trio Tim MRI scanner at Cardiff University’s Brain Research Imaging Centre. Two hundred and forty (240) T2*-weighted echo planar images were acquired during each session using a standardized sequence.

Image preprocessing

A standardized pipeline combining functions from SPM-8 and FSL-5.0 was implemented on the MATLAB environment, and the resulting high-resolution native and standardized MNI images were band-pass filtered to eliminate biologically nonrelevant signals and smoothed with 6 mm Gaussian kernel.

Parcellation schemes

We used Craddock’s atlas covering 200 regions-of-interest (ROIs) and replicated the results using the extended 600-ROI version of this atlas. We also calculated within-network mean clustering coefficients (one per each network).

Analysis of head motion

In order to rule-out possible contribution of motion-related artifacts to our results, we also performed analysis of head movements (6-parameter model), but found no significant impact on any of the network measures extracted from the motion-corrected data.

Assessment of temporal signal-to-noise ratio (tSNR)

To rule out the possibility that tSNR could account for the differences between conditions, mean BOLD signal from a ROI divided by its standard deviation was measured. Neither the mean signal nor its differences correlated with ego-dissolution phenomena.

Community structure and diversity coefficients

The community structure was estimated using placebo data employing fine-tune modularity algorithm. The relationship between the diversity coefficients for the selected ROIs and “ego-dissolution” was analyzed first, followed by an exploratory analyses using all 200 ROIs.

Hypothesis-free analysis of the between-ROI functional connectivity

The analysis of ego-dissolution phenomena was conducted by looking at bivariate correlations between 200 ROIs, using the Network Based Statistics toolbox.

Subjective Behavioral Measures

The first principal component explained 36.37% of the data variance and was strongly associated with ego-dissolution phenomena, as well as with “the experience had a spiritual/mystical quality” and “the experience had a supernatural quality”. The second principal component explained 13.97% of the variance.

Diversity Coefficients

The hypothesis-driven analysis revealed a strong negative correlation between the intensity of the ego-dissolution phenomena and the diversity of the aPHC connections. The ROI-based connectivity between the hippocampal formation and major brain networks also revealed an association between ego-loss and reduced MTL-cortical connectivity.

Diversity Coefficients: Hypothesis-Free Part

The hypothesis-free diversity coefficient analyses revealed that the left inferior frontal gyrus, left middle frontal gyrus and superior parietal lobule were associated with ego-dissolution under psilocybin.

Discussion

The study revealed that psilocybin-induced ego-dissolution was associated with a disrupted interplay between the MTL and the neocortex.

The DMN is the brain network most often associated with self-consciousness, and the PHC is particularly thought to mediate cross-talk between the DMN and the hippocampus. However, we did not find disintegration of the DMN to be associated with ego-dissolution in the present analysis.

The DMN is more related to the narrative self (ego-identity), whereas the salience network promotes other aspects of self-consciousness (minimal self, active inference, reality testing).

The salience network and its component regions have previously been linked with reasoning under uncertainty, mental effort, self-agency, time perception, and salience evaluation. They have also been put forward as potential neural correlates of self-consciousness and the “embodied self” in particular.

Dopaminergic stimulants are believed to play a role in modulating the switching between the default-mode and executive networks, and are also known to counteract effort-induced depletion of regulatory control. The salience network has been linked to perseverative behaviors including addiction. Pro-dopaminergic medication has been found to normalize abnormalities in the salience network and to reduce impulsivity, and there is historical and renascent support for the use of psychedelic drugs in the treatment of addiction.

A split-brain patient showed preserved self-awareness, but compromised “ownership” and agency. Interhemispheric connections involving the MTLs may be particularly important for the maintenance of a coherent sense of self.

The present analysis examined potential neurobiological predictors of response by looking at network metrics in the baseline data (placebo and pre-psilocybin states). It was found that individuals with a low diversity of connections in executive regions were the most likely to report ego-dissolution under the drug.

The present results can be interpreted from a Bayesian and free-energy minimization perspective, and suggest that psychedelics alter the core functions of the brain with the effect of diminishing confidence or “certainty” about perceived phenomena.

Implications for Psychosis Research

Similarities between early acute psychotic states and psychedelic states have been highlighted by many authors, and psychedelics offer a useful means of studying brain mechanisms underlying various psychotic phenomena including ego-disturbances.

The first principal component of psilocybin-induced psychedelic experience was strongly associated with ego-dissolution phenomena and favored “productive” features of the experience. This factor was relatively independent from the emotional valence of the experience.

A two-factor model of psychotic experience in schizophrenia has been reported previously, with a loss-of-boundary component being related to the majority of productive phenomena, and persecutory negatively charged delusions being relatively independent from other symptoms.

The presence of frightening aspects of the psychedelic experience was not explicitly associated with higher scores on the first component, but rather with negative loadings on the second component.

Although psychedelic states may be therapeutically useful, endogenous psychotic states may also manifest with positively charged and even mystical/spiritual content of the experiences. One of the principal distinguishing features between drug-induced ego-dissolution and endogenously occurring ego-disturbances may be that the former is anticipated and even welcomed.

We did not find effects of ego-loss on the diversity of the posteriomedial cortex, but rather the emotional valence of the experience was associated with higher functional diversity of the posterior DMN node, RSC. This supports the idea that ego-disturbances may be the sine qua non of psychotic states.

Limitations

Unlike most previous studies analyzing direct effects of psychedelics on brain dynamics, the present analyses focused on those aspects of the drug experience that were the most variable among subjects. The results showed that ego-dissolution was the most variable among subjects and closely related to many “productive” features of the experience.

The construct of ego-dissolution requires more work to develop its validity, and the extracted composite score may describe several phenomenologically and physiologically related processes. Multiple measures should be used to evaluate different aspects of ego-disturbances.

Conclusions

Psilocybin induces ego disturbances by decoupling the MTL and the cortex, decreasing salience network integrity, and reducing interhemispheric communication. This may explain how the ego can be compromised in different conditions.