We would like to thank Per M. Knutsen for help in preparation of the experimental set-up and Charlotte Boccara for advice regarding the writing. We are especially grateful to Marcello Massimini, Andrea Pigorini, Matteo Fecchio and Simone Russo for their valuable comments, suggestions, and support along the way. Renzo Comolatti's current affiliation: Department of Biomedical and Clinical Sciences "L.

The capacity of the human brain to sustain complex dynamics consistently drops when consciousness fades. Several recent studies in humans found a remarkable reduction of the complexity of cortical responses to local stimulation during dreamless sleep, general anaesthesia, and coma. So far, this perturbational complexity has never been estimated in non-human animals in vivo. Here, we quantify the complexity of electroencephalographic responses to intracranial electrical stimulation in rats, comparing wakefulness to propofol, sevoflurane, and ketamine anaesthesia. We confirm the changes previously observed in humans: from highly complex evoked activity during wakefulness, to simpler responses, suppression of high frequencies, and reduced phase-locking with propofol and sevoflurane.We then deepen our mechanistic understanding by analyzing functional connectivity, and by showing how these parameters dissociate with ketamine, and depend on intensity and site of stimulation. This approach opens the way for further direct investigations of the mechanisms underlying brain complexity and consciousness. hypothesis that neuronal hyperpolarization might prevent cortical neurons from engaging in durable, complex interactions 12,13,14,15 . RESULTS Single pulse electrical stimulation triggered complex ERPs during wakefulness, but not during propofol anaesthesiaWe recorded epidural EEG activity from 16 screw electrodes chronically implanted through the skull in head-and body-restrained male, adult rats. Recording electrodes were in contact with the dura and organized in a symmetric grid, covering most of the cortex in both hemispheres (M2, secondary motor cortex; M1, primary motor cortex; S1, primary somatosensory cortex; RS, retrosplenial cortex; PA, parietal associative cortex; V1, primary visual cortex; V2, secondary visual cortex; GND, ground electrode over cerebellum). We stimulated right M2 by single monophasic, electrical current pulses (typically: 1 ms duration, 50 µA amplitude, at 0.1 Hz) via a chronically implanted bipolar electrode, located 4.38 ± 0.26 mm rostral from bregma, 0.47 ± 0.09 mm below the cortical surface, mainly corresponding to layer II/III (based on histology after recording, 8 rats; Fig. 1a; all values are reported as mean ± SEM). Pulse trains delivered at similar coordinates triggered coordinated whisker deflections 16 , whereas EEG responses following single stimuli were not measurably contaminated by movements ( Supplementary Fig. 1, Video 1-2) and were reproducible throughout recording sessions and across days (Supplementary Fig. 2). No correlation between the stimulating electrode locations and ERP amplitude or duration was found (Supplementary Fig. 3).We performed electrophysiological recordings in 9 rats during wakefulness and propofol anaesthesia (∼1.1 mg/kg/min, i.v.) at a depth that produced spontaneous, slow, high-amplitude EEG oscillations and was sufficient to abolish any detectable motor response to pain stimuli. The redistribution of EEG power from high to low frequencies was confirmed ...

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.

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 (EEG) responses to cortical electrical stimulation in 6 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 (HF/LF) from spontaneous EEG activity at each electrode. We repeated these measurements during wakefulness, and under the influence of ketamine anaesthesia at two doses: 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 down with deeper anaesthesia. The high-dose effect was selectively associated with reduced HF/LF 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.These findings seem to support the claim that the posteromedial cortex may play a primary role for the capacity for consciousness. Such region-specific associations between cortical activation and the overall capacity for consciousness must be accounted for by theories of consciousness.

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