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Neuroimage. 2015 May 15;112:105-113. doi: 10.1016/j.neuroimage.2015.02.056. Epub 2015 Mar 4.

Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep.

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Department of Biomedical and Clinical Sciences "L. Sacco", Università degli Studi di Milano, Via G.B. Grassi 74, 20157 Milan, Italy.
Centre of Epilepsy Surgery "C. Munari", Department of Neuroscience, Niguarda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
Max Planck Institute for Human Development, Lentzeallee 94, 14195 Berlin, Germany.
Neuroscience Center, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland.
Department of Biomedical and Clinical Sciences "L. Sacco", Università degli Studi di Milano, Via G.B. Grassi 74, 20157 Milan, Italy; Don C Gnocchi Foundation IRCCS, Via Alfonso Capecelatro 66, 20148 Milan, Italy. Electronic address:


During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patients undergoing intra-cerebral stimulations/recordings for clinical evaluation. We observed that, while during wakefulness electrical stimulation triggers a chain of deterministic phase-locked activations in its cortical targets, during NREM the same input induces a slow wave associated with an OFF-period (suppression of power>20Hz), possibly reflecting a neuronal down-state. Crucially, after the OFF-period, cortical activity resumes to wakefulness-like levels, but the deterministic effects of the initial input are lost, as indicated by a sharp drop of phase-locked activity. These findings suggest that the intrinsic tendency of cortical neurons to fall into a down-state after a transient activation (i.e. bistability) prevents the emergence of stable patterns of causal interactions among cortical areas during NREM. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions in which thalamo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity.


Causality; Consciousness; Down-state; Intracranial; Phase-locking

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