Abstract
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.
Highlights
Understanding the nature and mechanisms of consciousness is widely regarded as one of the deepest unsolved problems of neuroscience and science in general [1,2,3,4,5,6]
Our main aim was to investigate whether information integration and differentiation as measured by perturbational complexity index (PCI), and spontaneous signal diversity as measured by Lempel-Ziv complexity (LZc), amplitude coalition entropy (ACE), and synchrony coalition entropy (SCE), is affected by sub-anaesthetic doses of ketamine compared to normal wakefulness
In accordance with these observations, we found no significant difference between PCI values for normal wakefulness and sub-anaesthetic ketamine (mean = 0.55, SE = 0.03, t (9) = -0.87, p = 0.41, r = 0.27, Fig 2)
Summary
Understanding the nature and mechanisms of consciousness is widely regarded as one of the deepest unsolved problems of neuroscience and science in general [1,2,3,4,5,6]. To advance the field it is crucial to develop ways to measure alterations in states and content of consciousness To this end, general anaesthetic drugs are among the most powerful interventional tools as they allow quite specific and graded manipulation of the state of consciousness [7], without suppressing many lower-level brain functions [5, 8, 9], and have been crucial for a series of recent discoveries of brain function. General anaesthetic drugs are among the most powerful interventional tools as they allow quite specific and graded manipulation of the state of consciousness [7], without suppressing many lower-level brain functions [5, 8, 9], and have been crucial for a series of recent discoveries of brain function These include changes in network activity and connectivity in the anaesthetized state compared to the normal wakeful state using non-invasive neural measures such as fMRI, TMS and EEG [7, 10]. This is thought to reflect the structural and functional complexity of the underlying system, including both its interconnectedness (integration), and the diversity of its available states of activity (differentiation)
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