The clinical evaluation of disorders of consciousness (DOCs) in severely brain-injured patients relies on their ability of processing incoming inputs from the surrounding environment and of demonstrating their subjective experience through motor output. To overcome this clinical problem, it has been recently developed a theory-driven, objective measure of the level of consciousness (Perturbational Complexity Index - PCI) calculated as the algorithmic complexity of the spatiotemporal pattern of the cortical responses obtained by perturbing the cortex with transcranial magnetic stimulation (TMS) (Casali et al. Sci Tr Med 2014). In awake healthy subjects, the scalp EEG response to TMS (TEP) shows multiple components possibly reflecting recurrent and causal interactions among different cortical areas (Sarasso et al. Clin EEG Neurosci 2014) and results in high values of PCI. On the contrary, in vegetative state patients as well as in anesthesia and during the deepest stages of sleep (non-REM sleep), TEPs result in a positive-negative deflection highly resembling sleep slow-waves associated to low values of PCI. It is well known that spontaneous sleep slow-waves emerge from the bistable dynamics given by the alternation of neuronal intense firing (up-states) and silence (down-states) (Steriade et al. J Neurosci 1993). It has been suggested, by means of intracranial electrical stimulation and recordings, that neuronal bistability could be responsible for loss of complexity in non-REM sleep (Pigorini et al. NeuroImage 2015). However, a direct link among bistability, loss of complexity and loss of consciousness is still missing. To this aim, the present work combines intracortical single pulse electrical stimulation (SPES) in humans undergoing pre-surgical evaluation, simultaneous intracortical recordings and scalp high-density electroencephalography (hd-EEG, 256 channels). Results show that during wakefulness the complex spatiotemporal dynamics observable at the scalp level are sustained by recurrent, causal interactions among different cortical areas. During non-REM sleep, when consciousness fades, the occurrence of cortical down-states after a transient activation (i.e. bistability) prevents the emergence of deterministic interactions leading to low PCI at the scalp level. These results draw a first link between local bistable dynamics characterizing cortical neurons during sleep and loss of complexity, a theoretical requirement for consciousness. Importantly, similar sleep-like mechanism seem to play a key role in the collapse of thalamo-cortical complexity detected by perturbations in pathological conditions in which consciousness is lost, such as DOCs patients (Rosanova, Fecchio et al. Nature Comm 2018), but also in conscious patients with severe brain lesions (Sarasso et al. in preparation). Future computational studies should take advantage of these non-invasive and invasive recordings to model brain lesions, shading a light on their underpinning neural mechanisms and their role in loss of consciousness.

Dr. Andrea Pigorini received his PhD degree in Physiology from the University of Milan, Italy. He is currently a postdoctoral Research Fellow in Marcello Massimini’s Lab, at the Department of Clinical Sciences “L. Sacco”, University of Milan. His research focuses on the analysis of electroencephalographic activity recorded simultaneously at the scalp level and within the brain in treatment-resistant epileptic patients implanted with intracerebral electrodes for presurgical evaluation. During his doctorate he investigated the role of bistable dynamics in the reduction the level of consciousness occurring during NREM sleep with respect to wakefulness. Before that he studied biomedical engineering at the Politecnico di Milano (Italy) with an emphasis in advanced signal processing. His master degree thesis was focused on the development of a new method for time-frequency spectral analysis of EEG potentials evoked by transcranial magnetic stimulation.