PT  - JOURNAL ARTICLE
AU  - Nadine Farnes
AU  - Bjørn E. Juel
AU  - André S. Nilsen
AU  - Luis G. Romundstad
AU  - Johan F. Storm
TI  - Increased signal diversity/complexity of spontaneous EEG in humans given sub-anaesthetic doses of ketamine
AID  - 10.1101/508697
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 508697
4099  - http://biorxiv.org/content/early/2019/01/02/508697.short
4100  - http://biorxiv.org/content/early/2019/01/02/508697.full
AB  - 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 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.