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

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
openlabel 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 subanaesthetic 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.