Ketamine and sleep modulate neural complexity dynamics in cats

Abstract

There is increasing evidence that level of consciousness can be captured by neural informational complexity: for instance, complexity, as measured by the Lempel Ziv (LZ) compression algorithm, decreases during anesthesia and non-rapid eye movement (NREM) sleep in humans and rats, when compared to LZ in awake and REM sleep. In contrast, LZ is higher in humans under the effect of psychedelics, including subanesthetic doses of ketamine. However, it is both unclear how this result would be modulated by varying ketamine doses, and whether it would extend to other species. Here we studied LZ with and without auditory stimulation during wakefulness and different sleep stages in 5 cats implanted with intracranial electrodes, as well as under subanesthetic doses of ketamine (5, 10, and 15 mg/kg i.m.). In line with previous results, LZ was lowest in NREM sleep, but similar in REM and wakefulness. Furthermore, we found an inverted U-shaped curve following different levels of ketamine doses in a subset of electrodes, primarily in prefrontal cortex. However, it is worth noting that the variability in the ketamine dose-response curve across cats and cortices was larger than that in the sleep-stage data, highlighting the differential local dynamics created by two different ways of modulating conscious state. These results replicate previous findings, both in humans and other species, demonstrating that neural complexity is highly sensitive to capture state changes between wake and sleep stages while adding a local cortical description. Finally, this study describes the differential effects of ketamine doses, replicating a rise in complexity for low doses, and further fall as doses approach anesthetic levels in a differential manner depending on the cortex.

Spectral slope and Lempel-Ziv complexity as robust markers of brain states during sleep and wakefulness

“…Our findings corroborate previous research which demonstrated that the spectral slope and neural complexity are sensitive markers of sleep depth (Abásolo et al, 2015; Bódizs et al, 2021; Lendner et al, 2020; Pascovich et al, 2022; Schartner et al, 2017; Tagliazucchi et al, 2013). Building upon these findings, we leveraged repeated EEG recordings per subject and confirmed that the two parameters can robustly differentiate all sleep stages from wakefulness.…”

Fluctuations in Neural Complexity During Wakefulness Relate To Conscious Level and Cognition

“…Since this result, others have shown that the complexity of spontaneous neural activity, as measured by LZ, can distinguish between sleep states, 2 and increases above the level of normal resting state (RS) during an altered state of consciousness due to psychoactive drugs, such as LSD. [4][5][6] These results have provided a striking impetus for the continued development of consciousness science, since they are robust and highly reproducible. However, despite these successes, progress in the science of conscious level has been limited in recent years for a number of reasons.…”

“…Since this result, others have shown that the complexity of spontaneous neural activity, as measured by LZ, can distinguish between sleep states, 2 and increases above the level of normal resting state (RS) during an altered state of consciousness due to psychoactive drugs, such as LSD. 4–6…”

Ketamine and sleep modulate neural complexity dynamics in cats

“…We aim to add to the characterization of the interaction between psychedelic states and perturbational states in intracranial recordings and via dose-dependent manner because our own work suggests a modulation by task (Mediano et al, 2020(Mediano et al, , 2021 while others do not (Farnes et al, 2020). Accordingly (Pascovich et al, 2019), the following hypotheses were proposed: (1) LZ would reflect sleep level: LZ in wakefulness would be just above REM sleep. REM sleep would be above light sleep (LS), and NREM sleep would have the lowest complexity value; (2) LZ would be increased during the initial period of drug infusion compared with baseline wakefulness;…”