Event Abstract

Back to Event

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

Andrea Pigorini1*, Simone Sarasso1*, Paola Proserpio2*, Caroline Szymansky3*, Gabriele Arnulfo4*, Silvia Casarotto1*, Matteo Fecchio1*, Mario Rosanova1*, Maurizio Mariotti1*, Giorgio Lo Russo2*, Matias Palva4*, Lino Nobili2* and Marcello Massimini1, 5
  • 1 University of Milan, Department of Biomedical and Clinical Sciences “L. Sacco”, Italy
  • 2 Niguarda Hospital, Department of Neuroscience, Italy
  • 3 Max Planck Institute for Human Development, Germany
  • 4 University of Helsinki, Neuroscience Center, Finland
  • 5 Don C Gnocchi Foundation IRCCS, Italy

INTRODUCTION During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive(Tononi and Massimini, 2008). Why is this? We hypothesized that the same neuronal mechanism that underlies sleep slow waves, that is bistability, between depolarized upstates and hyperpolarized downstate in cortical neurons (Steriade et al., 1993), may substantially impair information transmission within cortical networks. Specifically, we postulated that the inescapable occurrence of a silent, down-state after an initial activation couldbreak-off cortico-cortical causal interactions, thus impairing the ability of thalamocortical circuits to sustain long-range, deterministic patterns of activation, a theoretical requisite for consciousness(Tononi, 2008).Intracranial single-pulse electrical stimulation (SPES) and simultaneous stereotactic EEG (SEEG) recordings offer a unique opportunity to test this hypothesis. First, intracranial recordings allow a reliable detection of cortical down-states as a significant suppression of high frequency power above 20 Hz(Cash et al., 2009). Second, intracranial perturbations with SPES allow assessing cortico-cortical interactions from a causal perspective by calculating the phase locking factor (PLF)(Palva et al., 2005). METHODS We employedSPES and simultaneous stereotactic electroencephalography to compare cortico-cortical evoked potentials (CCEPs) recorded during wakefulness and NREM sleepin 8 epileptic patients undergoing intra-cerebral stimulations and recordings for clinical evaluation. The number of implanted electrodes (Figure 1) varied based on surgical requirements (max: 15 electrodes, 168 contacts). Stimulation trains (30 pulses, 0.2-1 Hz, 5mA) were delivered through one couple of adjacent contacts, while recordings of LFP were obtained from all other contacts (Figure 1). Preprocessing consisted in a median filtering to remove the artifact due to stimulation, abandpass filtering (0.5-300 Hz, Butterworth, 3rd order) and splitting of trials based on a digital trigger. Contacts showing spontaneous or evoked epileptic activity were removed from further analysis. Data analysis, consisting in time-frequency analysis (Wavelet, 3 cycles) and PLF, were performed using customized MATLAB scripts. RESULTS We observed that, while during wakefulness SPES triggers a widespread pattern of sustained causal effects (phase-locked activity), during NREM sleep the same initial activation induces a cortical downstate in its cortical targets – as reflected by a clear-cut suppression of high frequency (>20Hz) oscillations – that is followed by a break-off of PLF (~200 ms), in spite of restored levels of neuronal activity (Figure 2).These results were reproducible across contacts, significant across contacts at the single subject level (Wilcoxon ranksum test, p<0.05) and consistent at the population level (Wilcoxon ranksum test, p<0.05). Finally, significant correlations in each single subject showed (i) that, during NREM sleep, larger evoked slow waves corresponded to more pronounced suppressions of high frequencies and (ii) that earlier suppressions corresponded to an earlier dampening of PLF. CONCLUSIONS These results point to bistability as the underlying critical mechanism that prevents the emergence of complex interactions in human thalamocortical networks during NREM sleep. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions(Casali et al., 2013; Rosanova et al., 2012) where cortico-cortical communication and consciousness are impaired in spite of preserved neuronal activity.

References

Casali, A.G., Gosseries, O., Rosanova, M., Boly, M., Sarasso, S., Casali, K.R., Casarotto, S., Bruno, M.-A., Laureys, S., Tononi, G., Massimini, M., 2013. A theoretically based index of consciousness independent of sensory processing and behavior. Sci. Transl. Med. 5, 198ra105. doi:10.1126/scitranslmed.3006294

Cash, S.S., Halgren, E., Dehghani, N., Rossetti, A.O., Thesen, T., Wang, C., Devinsky, O., Kuzniecky, R., Doyle, W., Madsen, J.R., Bromfield, E., Eross, L., Halász, P., Karmos, G., Csercsa, R., Wittner, L., Ulbert, I., 2009. The human K-complex represents an isolated cortical down-state. Science 324, 1084–1087. doi:10.1126/science.1169626

Palva, J.M., Palva, S., Kaila, K., 2005. Phase synchrony among neuronal oscillations in the human cortex. J. Neurosci. Off. J. Soc. Neurosci. 25, 3962–3972. doi:10.1523/JNEUROSCI.4250-04.2005

Rosanova, M., Gosseries, O., Casarotto, S., Boly, M., Casali, A.G., Bruno, M.-A., Mariotti, M., Boveroux, P., Tononi, G., Laureys, S., Massimini, M., 2012. Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients. Brain 135, 1308–1320. doi:10.1093/brain/awr340

Steriade, M., Nuñez, A., Amzica, F., 1993. A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J. Neurosci. Off. J. Soc. Neurosci. 13, 3252–3265.

Tononi, G., 2008. Consciousness as integrated information: a provisional manifesto. Biol. Bull. 215, 216–242.

Tononi, G., Massimini, M., 2008. Why does consciousness fade in early sleep? Ann. N. Y. Acad. Sci. 1129, 330–334. doi:10.1196/annals.1417.024

Keywords: causality, Consciousness, Down-state, intracranial, phase-locking

Conference: B·DEBATE | A Dialogue with the Cerebral Cortex: Cortical Function and Interfacing (Workshop), Barcelona, Spain, 29 Apr - 30 Apr, 2015.

Presentation Type: Poster Presentation

Topic: SESSION 2: Stimulation to Explore and Control Brain Activity

Citation: Pigorini A, Sarasso S, Proserpio P, Szymansky C, Arnulfo G, Casarotto S, Fecchio M, Rosanova M, Mariotti M, Lo Russo G, Palva M, Nobili L and Massimini M (2015). Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep. Front. Syst. Neurosci. Conference Abstract: B·DEBATE | A Dialogue with the Cerebral Cortex: Cortical Function and Interfacing (Workshop). doi: 10.3389/conf.fnsys.2015.06.00007

Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.

The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.

Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.

For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.

Received: 21 Apr 2015; Published Online: 06 May 2015.

* Correspondence:
Dr. Andrea Pigorini, University of Milan, Department of Biomedical and Clinical Sciences “L. Sacco”, Milan, Italy, andrea.pigorini@unimi.it
Dr. Simone Sarasso, University of Milan, Department of Biomedical and Clinical Sciences “L. Sacco”, Milan, Italy, simone.sarasso@unimi.it
Dr. Paola Proserpio, Niguarda Hospital, Department of Neuroscience, Milan, Italy, paola.proserpio@tiscali.it
Dr. Caroline Szymansky, Max Planck Institute for Human Development, Berlin, Germany, szymanski@mpib-berlin.mpg.de
Dr. Gabriele Arnulfo, University of Helsinki, Neuroscience Center, Helsinki, Finland, gabriele.arnulfo@gmail.com
Dr. Silvia Casarotto, University of Milan, Department of Biomedical and Clinical Sciences “L. Sacco”, Milan, Italy, silvia.casarotto@unimi.it
Dr. Matteo Fecchio, University of Milan, Department of Biomedical and Clinical Sciences “L. Sacco”, Milan, Italy, matteo.fecchio@unimi.it
Dr. Mario Rosanova, University of Milan, Department of Biomedical and Clinical Sciences “L. Sacco”, Milan, Italy, mario.rosanova@unimi.it
Dr. Maurizio Mariotti, University of Milan, Department of Biomedical and Clinical Sciences “L. Sacco”, Milan, Italy, maurizio.mariotti@unimi.it
Dr. Giorgio Lo Russo, Niguarda Hospital, Department of Neuroscience, Milan, Italy, Giorgio.Lorusso@ospedaleniguarda.it
Prof. Matias Palva, University of Helsinki, Neuroscience Center, Helsinki, Finland, matias.palva@helsinki.fi
Prof. Lino Nobili, Niguarda Hospital, Department of Neuroscience, Milan, Italy, lino.nobili@gmail.com