How and to what extent electrical brain activity reflects pharmacologically altered states and contents of consciousness, is not well understood. Therefore, we investigated whether 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 experience. High-density 62-channel EEG was used to record spontaneous brain activity and responses evoked by transcranial magnetic stimulation (TMS) in 10 healthy volunteers before and during 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 EEG responses to 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). Although no significant difference was found in TMS-evoked complexity (PCI) between the sub-anaesthetic ketamine condition and normal wakefulness, all measures of spontaneous EEG signal diversity (LZc, ACE, SCE) showed significantly increased values in the sub-anaesthetic ketamine condition. This increase in signal diversity 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. The results suggest that PCI and spontaneous signal diversity may reflect distinct, complementary aspects of changes in brain properties related to altered states of consciousness: the brain’s capacity for information integration, assessed by PCI, might be indicative of the brain’s ability to sustain consciousness, while spontaneous complexity, as measured by EEG signal diversity, may be indicative of the complexity of conscious content. Thus, sub-anaesthetic ketamine may increase the complexity of the conscious content and the brain activity underlying it, while the level or general capacity for consciousness remains largely unaffected.

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.

Background and aimsWhile psychedelic agents are known to have powerful, but largely unexplained, effects on contents of consciousness, there is an increasing interest in the potential clinical usefulness of such drugs for therapy, and legalization is discussed in some countries. Thus, it is relevant to study the effects of psychedelic compounds not only on experience, but also on behavioral performance.MethodsSeven healthy participants performed a motor response inhibition task before, during, and after sub-anesthetic doses of intravenously administered ketamine. The infusion rate was individually adjusted to produce noticeable subjective psychedelic effects.ResultsWe observed no statistically significant impact of sub-anesthetic ketamine on reaction times, omission errors, or post error slowing, relative to the preceding drug-free condition. However, we did observe significant correlations between performance impairment and self-reported, subjective altered states of consciousness, specifically experience of “anxiety” and “complex imagery.”ConclusionsConsidering the limited number of participants and large variation in strength of self-reported experiences, further studies with wider ranges of ketamine doses and behavioral tasks are needed to determine the presence and strength of potential behavioral effects.