Loss of differentiation and complexity in the sleeping human brain: a multi-scale analysis

Abstract Complexity, defined as the coexistence of functional differentiation and functional integration is a general property of thalamo-cortical circuits that can be characterized at a multiscale level. Previous studies suggest that local dynamics occurring at the micro/meso-scale, such as sleep-like neuronal bistability, can be responsible for the collapse/emergence of global patterns of complex interactions among brain areas at the macro-scale. Here, we link the two scales by combining, for the first time, intracerebral single pulse electrical stimulation (SPES) with simultaneous invasive recordings (stereo-EEG, SEEG) and scalp high-density EEG (hdEEG) during both wakefulness and sleep. This work includes data collected during presurgical evaluation from 30 epileptic subjects. SEEG was recorded trough ∼150 intracerebral contacts connected to a 192-channel amplifier together with simultaneous scalp recordings using a 256 channels hdEEG. Recordings of simultaneous SEEG and hd-EEG activity were combined with SPES (5 mA, 1/0.5ms, 0.5Hz).100 stimulation sessions were performed by delivering SPES during wakefulness at rest in different areas. 66 stimulation sessions were repeated during NREM sleep (stages N2 or N3). We show that (1) the overall complexity, as assessed by the Perturbational Complexity Index, was significantly higher in wakefulness with respect to NREM (p<0.05) and that (2) the differentiation of the response to SPES, evaluated by performing the Principal Component Analysis across all sessions and comparing the ensuing number of components across states, was significantly higher in wakefulness with respect to NREM over the parietal areas (p<0.05). These results allow linking bistable dynamics (neuronal downstates in the Local Field Potential) and their effects on local cortico-cortical interactions with the overall connectivity and complexity assessed at the scalp level. Importantly, combining multiple stimulation sites across different states strongly suggests that during NREM sleep the reduction of complexity is mainly due to loss of differentiation. Research Category and Technology and Methods Basic Research: 15. Electroencephalography (EEG) Keywords: SEEG, Bistability, Sleep, hd-EEG