Using magneto-encephalography to assess the processing depth of auditory stimuli in the sleeping human brain

Sleep can be defined as a behavioral state of rest in which consciousness of external stimuli vanishes and responsiveness to the environment is drastically reduced. When we sleep, however, we may still react and wake up to our name or to the alarm clock, suggesting that some processing of external stimuli remains. We address in the present work the question of how deeply external information is processed during sleep. We recorded brain activity in adult human subjects simultaneously in electro and magnetoencephalography (EEG and MEG) in response to auditory stimulation, before, during and after a short period of sleep. In order to test information integration through the brain hierarchy, we focused on hierarchical predictive coding capabilities, which enable the brain to anticipate the future from previous knowledge. Predictions occur at many if not all steps of the cortical hierarchy. Testing different levels of predictions enables us to assess the steps at which information integration is disrupted during sleep. We first tested the capacity of the sleeping brain to detect auditory novelty. We analyzed brain responses to violations of local and global temporal regularities, which are respectively reflected in EEG during wakefulness by two successive prediction error signals, the mismatch negativity (MMN) and the P300. Our analysis revealed that both the MMN and the P300 vanish during sleep, along with the loss of activations in prefrontal and parietal associative areas. The MMN gradually decreased in the descent to sleep, whereas the P300 vanished abruptly with the loss of awareness during N1 sleep. This all-or-none behavior strongly reinforces the hypothesis that the P300 is a marker of consciousness. Even so, we showed that sounds still activate sensory cortices, and that the brain remains able to detect new sounds and to habituate to them, but only in the limited context of sensory adaptation. Having demonstrated the disruption of predictive coding for arbitrary and newly acquired statistical regularities, in a second set of experiments we tested the capacity of the sleeping brain to develop predictions of future auditory stimuli for over-learned semantic knowledge stored in long-term memory. We presented sleeping subjects with simple arithmetic facts such as “two plus two is nine” and recorded brain responses to correct or incorrect results. We discovered that the sleeping brain was still able to detect arithmetic violations, with activations in part similar to wakefulness. We suggest that, although sleep disrupts explicit arithmetic computations, there is a preservation of prediction error signals for arithmetic facts stored in long-term memory. The present work clarifies the steps at which auditory information integration is disrupted during sleep, and which cognitive functions remain or vanish. The preservation of low-level sensory adaptation and of predictions from long term memory may account for the residual responsiveness that can be observed during sleep, while subjects are unconscious. Finally, these results also help to better understand why a given stimulus may or may not be processed during sleep. The depth of information integration is function of the ongoing spontaneous oscillations of the sleeping brain, but also of the nature of the stimulus, i.e. its salience, its knowledge, and its relevance.