Exploring consciousness: Investigating local wakefulness during anaesthesia

Consciousness has long been an intriguing and controversial field of research in physiology and neuroscience. Based in part on the role of gods directing human actions in the Iliad, and the lack of words for ‘thought’ or ‘mind’ in that text, Jaynes (1976) proposed that Bronze Age humans lacked modern consciousness and instead had a ‘bicameral mind’ in which the right hemisphere communicated major decisions to the left via auditory hallucinations perceived as divine commands. Although Jaynes’ definition of consciousness might be better described as introspection rather than awareness of subjective experience, or ‘qualia,’ his influential work helped popularize the concept of the non-unitary self (Cavanna et al., 2007). This and other concepts central to Jaynes’ theory emerged from the split-brain research of Sperry and Gazzaniga, who described ‘two independent streams of conscious awareness, one in each hemisphere, each of which is cut off from and out of contact with the mental experiences of the other’ (Sperry, 1968). What of split consciousness vs. unconsciousness? The traditional perspective of consciousness as a singular global brain state has advanced to recognize a more nuanced interplay between global and local states. Flying and swimming animals can exhibit split sleep, with one hemisphere maintaining locomotion and sensory awareness (Mukhametov et al., 1977). Humans can exhibit local EEG signatures of wakefulness during global sleep (Nobili et al., 2011) and the opposite, namely local sleep amid awake electroencephalogram and behaviour, has been observed in rats (Vyazovskiy et al., 2011). However, much less is known about unconsciousness induced by anaesthetics. Now, in this issue of The Journal of Physiology, Pardo-Valencia (2024) describe the use of chemogenetic methods to study loss of consciousness induced by anaesthetics in mice. First, they built on the work of Bharioke et al. (2022), who showed that global layer V synchronization is a common signature of unconsciousness across several anaesthetics. Pardo-Valencia (2024) demonstrated that, although the respiration rate and layer V multiunit activity rise and fall with lighter and deeper anaesthetic doses, respectively, and even spontaneously rise and fall together at a single dose, interhemispheric synchrony remained high even across different doses of isoflurane. That is, respiration rate and layer V multiunit activity appear to be sensitive measures of anaesthetic depth, but global synchrony is sustained except during actual wakefulness. Next, echoing studies that used intracortical microstimulation to evoke specific percepts (Romo et al., 1998) or shift spatial attention (Moore & Armstrong, 2003), they induced local wakefulness of one hemisphere using chemogenetic stimulation of layer V cortical neurons. Such local stimulation increased layer V multiunit activity locally and disrupted the observed interhemispheric synchrony in sensorimotor cortex. The overall unconsciousness state, however, was unaffected: respiration did not rise and animals never responded to toe pinches. Moreover, in behavioural experiments, the same chemogenic stimulation did not affect the speed of anaesthetic induction or speed of recovery of consciousness after cessation of anaesthesia. This suggests that both non-conscious and conscious-like states can coexist during periods of anaesthetic unconsciousness, leading us to consider the possibility of a similar segregation between conscious and non-conscious states during wakefulness. A recent study investigated several common anaesthetics at various dosages employing calcium wide-field optical imaging to study the mouse cortex (Curic et al., 2024). In line with the study by Pardo-Valencia (2024), Curic et al. (2024) observed calcium transients resembling quiet wakefulness under surgical-plane levels of isoflurane, resembling an awake-like recording, but not a sufficient condition for consciousness. This supports the notion of both conscious-like and unconscious-like states co-existing in the behaviourally unconscious brain. In addition to broadening our understanding of anaesthetic unconsciousness, the findings of Pardo-Valencia (2024) could potentially be used to improve electrophysiological or optogenetic studies by allowing for awake-like local dynamics in a globally anaesthetized animal, especially in regions such as the posterior parietal cortex that may be more affected by anaesthesia. In summary, recent research into consciousness, as explored by Pardo-Valencia (2024), suggests that islands of consciousness or at least conscious-like neural activity can exist in globally anaesthetized brains. This idea parallels Jaynes' concept of the ‘bicameral mind’, as well as Sperry's split brain, which posit a division between different modes of mental functioning and awareness. These findings underscore a shift from viewing consciousness as a singular global state to recognizing a complex interplay between global and local brain states. As we advance our understanding into consciousness, studies such as that by Pardo-Valencia (2024) afford a deeper comprehension of consciousness that bridges historical theories and contemporary scientific discoveries (Fig. 1). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. No competing interests declared. G.B. and D.C.: were responsible for the conception or design of the work; drafting the work or revising it critically for important intellectual content; and approving the final version of the manuscript submitted for publication. Both authors agree to be accountable for all aspects of the work. None.