Increased signal diversity/complexity of spontaneous EEG, but not evoked EEG responses, in ketamine-induced psychedelic state in humans

Abstract

Objective : It is not well understood how and to what extent electrical brain activity is affected in pharmacologically altered states of consciousness, where the phenomenological content rather than the level is consciousness is mainly altered. An example is the moderately «psychedelic» state caused by low doses of ketamine. Therefore, we investigated whether and how measures of evoked and spontaneous electroencephalographic (EEG) signal diversity are altered by sub-anaesthetic levels of ketamine compared to normal wakefulness, and how these measures relate to subjective assessments of consciousness. Methods: High-density electroencephalography (EEG, 62 channels) was used to record spontaneous brain activity and responses evoked by transcranial magnetic stimulation (TMS) in 10 healthy volunteers before and after administration of sub-anaesthetic doses of ketamine in an open-label within-subject design. Evoked signal diversity was assessed using the perturbational complexity index (PCI), calculated from the global EEG responses to local TMS perturbations. Signal diversity of spontaneous EEG, with eyes open and eyes closed, was assessed by Lempel Ziv complexity (LZc), amplitude coalition entropy (ACE), and synchrony coalition entropy (SCE). Results: Although no significant difference was found in the index of TMS-evoked complexity (PCI) between the sub-anaesthetic ketamine condition and normal wakefulness, all the three measures of spontaneous EEG signal diversity showed significantly increased values in the sub-anesthetic ketamine condition. This increase in apparent signal diversity also correlated with subjective assessment of altered states of consciousness. Moreover, spontaneous signal diversity was significantly higher when participants had eyes open compared to eyes closed, both during normal wakefulness and during influence of sub-anaesthetic ketamine doses.Conclusion: Three different measures of spontaneous EEG signal diversity all showed significantly increased values in the sub-anesthetic ketamine condition, whereas the index of TMS-evoked complexity (PCI) did not change significantly. These results seem to suggest that PCI and spontaneous signal diversity may measure different aspects of consciousness.Thus, our results seem compatible with PCI being indicative of the brain's ability to sustain a certain level of consciousness, as indicated by previous research, while spontaneous EEG Page 2 of 32 signal diversity may be indicative of the complexity of conscious content. The observed sensitivity of the latter measures to visual input seems to support such an interpretation. Thus, sub-anaesthetic ketamine may increase the complexity of both the conscious content (experience) and the brain activity underlying it, as assessed by spontaneous signal diversity measures, while the "level" or "degree" of consciousness, assessed by PCI, remains largely unaffected.

Increased signal diversity/complexity of spontaneous EEG, but not evoked EEG responses, in ketamine-induced psychedelic state in humans

“…Co-author Bjørn E. Juel is presently also affiliated with The Department of Psychiatry, Center for Sleep and Consciousness, University of Wisconsin, Madison, WI, USA. Results from this work were previously presented at two conferences in 2017 [58,59] and as a preprint manuscript in January 2019 [60].…”

Proposed EEG measures of consciousness: a systematic, comparative review.

“…Finally, both ERP and signal diversity based measures have been shown to be influenced by processes that are unlikely to relate to the presence of consciousness per se. For example, some ERP based measures like the auditory evoked P300b response has been shown to disappear if the subject is paying attention to something else than the auditory stimulus (Bekinschtein et al, 2009) , and the signal diversity based measure LZc has been shown to be reduced when subjects close their eyes (Farnes et al, 2020) or increase during psychedelic experiences (Schartner, Carhart-Harris, et al, 2017) . In other words, certain non-rest cognitive or physiological conditions in which subjects are conscious could serve as a test against false negatives.…”

“…However, newer results have shown that signal diversity might be regionally differentiated and that global measures may not be sufficiently specific (Schartner, Pigorini, et al, 2017) . For example, when measuring EEG with eyes closed, synchronous alpha-activity in occipital regions may lead to a drop in the global measures of signal diversity even without an overall change in state of consciousness (Farnes et al, 2020) .…”

Consciousness as a multidimensional phenomenon: implications for the assessment of disorders of consciousness

“…Several complexity measures have also been found to increase for ketamine-induced states compared to normal waking consciousness ( Schartner et al. 2017b ; Farnes et al. 2019 ).…”