EEG signal diversity during propofol sedation: an increase in sedated but responsive, a decrease in sedated and unresponsive subjects

Abstract

Transitions between wakefulness and anesthesia are accompanied by profound changes in brain functioning. A key challenge is thus to disentangle neuronal mechanisms specific to loss and recovery of consciousness, from more general effects that are not directly related to the capacity for conscious experience. Measures of neuronal diversity have been recently proposed to constitute a robust correlate of the global states of consciousness. In the present study we investigated whether EEG signal diversity is indeed related to behavioral responsiveness during propofol sedation, or rather to the general drug-related effects. To this end, we reanalyzed data collected from 20 subjects sedated with propofol. Based on the responsiveness to auditory stimuli all subjects were subdivided into two subgroups -responsive (n = 13), who remains awake throughout the experiment, and drowsy (n = 7), who becomes unresponsive during moderate sedation. Resting state EEG recorded during wakefulness and sedation was characterized by the Mean Information Gain (MIG) and Fluctuation complexity (FC) -information-theory measures estimating signal diversity or complexity, respectively. The main finding is that the drowsy group exhibited a decrease in diversity during sedation but, unexpectedly, the responsive group exhibited a robust increase in diversity (ANOVA group x state interaction: F(3) = 7.81, p < 0.001; BF 10 > 197). However, signal complexity neither differentiated the subgroups, nor decreased reliably during sedation (t-test wake vs. moderate sedation: t(19) = 2.57, p = 0.092; BF 10 = 3.08). Further, we show that a change in signal diversity is negatively correlated with a delta power change (r = -0.62, p = 0.002), and positively correlated with a beta power change (r = 0.84, p < 0.001). Finally, we show that MIG behaves in a qualitatively similar manner to Lempel-Ziv -another diversity measures used in several recent studies.Overall, we revealed that propofol sedation is initially related to an increase in EEG signal diversity, and that only upon loss of responsiveness EEG diversity decreases. The qualitatively different pattern of changes in the responsive and drowsy groups makes EEG diversity a robust indirect index of responsiveness and, presumably, consciousness.

Responsiveness variability during anaesthesia relates to inherent differences in brain structure and function of the fronto-parietal networks

“…To address this gap, we asked whether the connectivity within and between three networks that are primary sites of propofol-induced sedation and key to conscious cognition — the DAN, ECN and DMN — underlie individual responsiveness differences under anaesthesia. Consistent with previous studies (Chennu et al, 2016; Bola et al, 2019), we observed substantial individual differences in reaction times and hit rates under moderate anaesthesia. These were not related to differences in perceptual or high-level attention processes.…”

“…A first step to understanding consciousness is to define what it is 57 not. To this end, anaesthesia combined with functional neuroimaging provides a powerful 58 approach for studying the brain mechanisms that change as consciousness fades (Vatansever 59 during mild and moderate propofol anaesthesia reported that the participants' varying levels 78 of responsiveness were differentiated by alpha band connectivity during wakefulness 79 (Chennu et al, 2016), and changing patterns of EEG signal diversity from wakefulness to 80 moderate sedation (Bola et al, 2019). However, the brain regional-or network-bases for this these is related to individual differences in performance variability (Kelly 2008), and directly 116 supports sustained attention (Kucyi et al, 2020).…”

“…Propofol is the most common anaesthetic agent in clinical interventions that require the reversible suppression of consciousness. Two recent electroencephalography (EEG) studies that measured variable behavioural responsiveness during mild and moderate propofol anaesthesia reported that the participants' varying levels 4 of responsiveness were differentiated by alpha band connectivity during wakefulness (Chennu et al, 2016), and changing patterns of EEG signal diversity from wakefulness to moderate sedation (Bola et al, 2019). However, the brain regional-or network-bases for this substantial individual variability (Searle and Hopkins 2009;Palanca et al, 2009), and its potential link to cognitive function, remain unknown.…”

“…Anaesthesia has been used for over 150 years to reversibly abolish consciousness in clinical medicine, but its effect can vary substantially between individuals. At moderate dosages, the intended suppression of behavioural responsiveness is highly variable (Chennu et al, 2016; Bola et al, 2019), and at deep anaesthesia dosages, in rare cases (0.1-0.2%; Mashour and Avidan 2015; Sandin et al, 2000), individuals retain conscious awareness, also known as ‘unintended intraoperative awareness’ (Pandit et al, 2017; Sanders et al, 2017; Sandin et a., 2000; Mashour and Avidan 2015). A much higher percentage of patients presumed to be unconscious during general anaesthesia (22%; Leslie et al, 2007) may have subjective experiences, such as dreaming.…”

Brain activity complexity has a nonlinear relation to the level of propofol sedation

“…The general correlations between LempeleZiv complexity and the spectral power of particular frequencies are to be expected based on simulations 20 and experimental reports. 29,30 However, we show that the increase in EEG complexity for high performance subjects is not the mere reflection of an increase (or decrease) of power within any particular frequency range. Instead, we propose it is based on modulation of the broad temporal dynamics of different brain processes.…”