Capacity for consciousness under ketamine anaesthesia is selectively associated with activity in posteromedial cortex in rats

Abstract

It remains unclear how specific cortical regions contribute to the brain’s overall capacity for consciousness. Clarifying this could help distinguish between theories of consciousness. Here, we investigate the association between markers of regionally specific (de)activation and the brain’s overall capacity for consciousness. We recorded electroencephalographic responses to cortical electrical stimulation in six rats and computed Perturbational Complexity Index state-transition (PCIST), which has been extensively validated as an index of the capacity for consciousness in humans. We also estimated the balance between activation and inhibition of specific cortical areas with the ratio between high and low frequency power from spontaneous electroencephalographic activity at each electrode. We repeated these measurements during wakefulness, and during two levels of ketamine anaesthesia: with the minimal dose needed to induce behavioural unresponsiveness and twice this dose. We found that PCIST was only slightly reduced from wakefulness to light ketamine anaesthesia, but dropped significantly with deeper anaesthesia. The high-dose effect was selectively associated with reduced high frequency/low frequency ratio in the posteromedial cortex, which strongly correlated with PCIST. Conversely, behavioural unresponsiveness induced by light ketamine anaesthesia was associated with similar spectral changes in frontal, but not posterior cortical regions. Thus, activity in the posteromedial cortex correlates with the capacity for consciousness, as assessed by PCIST, during different depths of ketamine anaesthesia, in rats, independently of behaviour. These results are discussed in relation to different theories of consciousness.

The activity of deep cortical layers characterizes the complexity of brain responses during wakefulness following electrical stimulation

“…The “ITPC drop time” was defined as the time point (in seconds) of the last significant ITPC value, averaged across a broadband frequency range of 6-80 Hz, in a time window of 800 ms following the stimulation. To quantify the phase coherence between different cortical areas and layers we calculated “inter site phase clustering” (ISPC) as previously described (Cohen 2014, Arena, Comolatti et al 2021, Arena, Juel et al 2022). ISPC represents the consistency of the phase difference between EEG/LFP signals of two channels across trials, at each time-frequency point.…”

“…The dB values above the 95% percentile were conserved, not significant values below set to 0. The phase coherence of ERPs across trials was calculated using inter-trial phase clustering (ITPC, (Cohen 2014, Arena, Comolatti et al 2021, Arena, Juel et al 2022)), for each, channel, wavelet frequency and time point and averaged across trials. ITPC ranges from 0 (no phase-locking) to 1 (maximum phase-locking).…”

“…in slow-wave sleep or anesthesia, the cortical responses become briefer, with simpler, and stereotyped yielding low PCI values (Massimini, Ferrarelli et al 2005, Casali, Gosseries et al 2013. Similarly, recent experiments in rats have shown that general anesthesia decreases PCI and global functional connectivity following electrical stimulation in vivo (Arena, Comolatti et al 2021, Arena, Juel et al 2022. In vitro studies in cortical slices, found that application of noradrenaline and a cholinergic agonist increased the PCI (D'Andola, Rebollo et al 2018), whereas GABA antagonists reduced PCI (Barbero-Castillo, Mateos-Aparicio et al 2021).…”

Subsets of cortico-cortical evoked potentials propagate as traveling waves

“…Cortico-cortical evoked potentials (CCEPs) provide rich insights into the structural and functional organization of the brain. 1 These responses to direct electrical stimulation have been used for many different applications-for example, mapping distinct types of connectivity [2][3][4] , quantifying signal complexity across levels of consciousness [5][6][7][8] , and tracking the effects of stimulation on neural plasticity. 9,10 Thus, CCEPs may be a valuable tool for extracting causal information about large-scale brain networks and their spatiotemporal dynamics.…”

Laminar evoked responses in mouse somatosensory cortex suggest a special role for deep layers in cortical complexity

“…In contrast, when consciousness is lost or strongly reduced, for example, in slow-wave sleep or anaesthesia, the cortical responses are short-lasting and stereotypic, resulting in low PCI values (Casali et al, 2013;Massimini et al, 2005). Similarly, recent experiments in rats and mice have shown that general anaesthesia and deep sleep reduce PCI and global functional connectivity following electrical stimulation in vivo (Arena et al, 2021(Arena et al, , 2022Cavelli et al, 2023;Claar et al, 2023). In vitro studies in cortical slices showed that the application of noradrenaline and a cholinergic agonist increased the PCI (D'Andola et al, 2018), whereas GABA antagonists reduced PCI (Barbero-Castillo et al, 2021).…”