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What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.
Introduction
Understanding the brain basis of consciousness remains one of the outstanding challenges in modern science. While rigorous definitions are still mainly lacking, consciousness can be defined rather broadly as that which “vanishes every night when we fall into dreamless sleep” and returns the next morning when we wake up1. Equally, when we are conscious, our conscious experiences are populated by a variety of perceptions, thoughts, and feelings that collectively form an integrated conscious scene. These observations lead to an intuitive distinction between conscious level (how conscious one is) and conscious content (what one is conscious of, when one is conscious). The large majority of recent neuroscientific research into consciousness has treated these dimensions separately2,3,4,5. Investigations of conscious level typically contrast global changes in brain activity among different states including wakeful awareness, various sleep stages, and different forms of anaesthesia. Many of these studies attempt to isolate neural changes that accompany alterations of conscious level independently of changes in general physiological arousal. Studies of conscious content have focused primarily on uncovering differences in brain activity between closely matched conscious and unconscious perception, while conscious level is maintained constant6.
Recently, following early suggestions that increased conscious level may be related to an increased range of conscious contents3,7, there has been growing interest in characterising how conscious level and conscious content may relate2,5. One empirical approach to this question is to apply emerging measures of conscious level to experimental manipulations that primarily affect conscious content. Here, we capitalise on the profound effects on conscious phenomenology elicited by psychedelic compounds, specifically LSD, psilocybin, and subanesthetic doses of ketamine. These drugs normally have profound and widespread effects on conscious experiences of self and world. More specifically, they appear to “broaden” the scope of conscious contents, vivifying imagination8 and positively modulating the flexibility of cognition9,10. At the same time, the states they induce are not accompanied by a global loss of consciousness or the marked changes in physiological arousal as seen in sleep or anaesthesia. These observations raise the question of whether theoretically-grounded measures of conscious level would be changed in the psychedelic state.
Empirical measures of conscious level have reached a new benchmark with the development of the perturbational complexity index, PCI11. The PCI quantifies the diversity across channels and observations of the EEG response to a transcranial magnetic stimulation (TMS) pulse and has been shown to robustly index levels of consciousness6, ranging from anaesthesia induced by various substances11,12, sleep stages11 and graded disorders of consciousness such as (emergence from) the minimally conscious state11,13. Notably, all these comparisons resulted in lower PCI values compared to a baseline state of wakeful awareness.
One disadvantage of the PCI approach is that it requires brain stimulation, which limits its applicability and generalisability. A complementary approach is therefore to measure signal diversity of spontaneous neural activity recorded under various manipulations of conscious level. Following early studies of anaesthetics14,15,16 and natural sleep states17,18, we recently found reliable reductions in neural signal diversity with diminished conscious level across a range of measures and experimental manipulations, focusing on spontaneous electrophysiological recordings. These measures include: versions of Lempel-Ziv complexity (LZc, LZs), which quantify the number of distinct patterns present in the data; amplitude coalition entropy (ACE), which reflects the entropy over time of the constitution of the set of most active channels; and synchrony coalition entropy (SCE), which reflects the entropy over time of the constitution of the sets of synchronous channels. These measures of signal diversity robustly index levels of propofol sedation19 and sleep stages20,21 when applied to spontaneous electrophysiological recordings. As with the PCI studies, these measures were reliably higher for conscious than for unconscious conditions.
Measures of entropy and Lempel-Ziv complexity both capture the diversity of a signal. In the limit of an infinitely long binary string, Lempel-Ziv complexity22 becomes directly proportional to the entropy of the process generating the string, provided the process is ergodic. Further, it can provide a good approximation to the entropy of a binary string if its length is of order of magnitude 1000 or greater23, a length easily obtainable for MEG/EEG data segments spanning just a few seconds. Note however, that a reordering of the components of a string can change the Lempel-Ziv complexity. For example, if all the 1 s are grouped together then the Lempel-Ziv complexity goes to approximately zero. By contrast, reordering does not affect the entropy. The Lempel-Ziv complexity and entropy measures considered here (LZc, LZs, ACE, SCE) go beyond characterising a single binary string (except LZs), e.g. for the coalition entropy measures each component in the considered string is a subset of the set of observed channels. Thus, the relations between these measures is more complicated. Indeed, these measures have been shown to diverge in their behaviour in certain scenarios19, such as when there is high correlation between channels. Thus, it is valuable to consider the behaviour of these measures collectively, when characterising signal diversity.
Functional MRI-based measures of entropy have previously been found to be greater in the psychedelic state than in normal waking consciousness8,24,25,26 and this effect has been related, both theoretically8,24 and empirically8,26, to the phenomenal qualities of the psychedelic state. Given that Lempel-Ziv complexity can quantify the true entropy of certain stochastic processes more accurately than direct approximate entropy measures23, it is arguably more sensitive to signal diversity than entropy measures that have been applied previously to psychedelic data. Moreover, no such measures have previously been applied to data derived from EEG or MEG recordings of the psychedelic state. EEG/MEG data have far higher temporal resolution than fMRI and therefore are much better suited for signal diversity analyses. In addition, using Lempel-Ziv complexity allows analyses of the psychedelic state to be compared with similar analyses applied to more global changes in conscious level, as previously described19,20,21.
Here, we sought to test the hypothesis that three different psychedelic drugs (psilocybin, LSD and sub-anaesthetic ketamine), known to produce unusual altered states of consciousness, characterised by rich phenomenal content, would yield scores of signal diversity exceeding those for normal waking consciousness. For parsimony, ketamine is referred to as a ‘psychedelic’, while acknowledging that its pharmacology and subjective effects are somewhat different to those of the ‘classic’ serotonergic psychedelics, such as LSD and psilocybin. We did this by re-analysing multidimensional spontaneous MEG recordings using our measures of spontaneous signal diversity. We compared signal diversity for two conditions: post-placebo and post-psychedelic drug. We further examined whether changes in measured signal diversity could be related to subjective phenomenological descriptions obtained following drug administration, in order to test whether these changes reflected specific aspects of the altered phenomenology of the psychedelic state, and to shed additional light on the complex relations linking conscious level and content. |
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