Connectivity biomarkers can differentiate patients with different levels of consciousness Yvonne Höller a,b,⇑ , Aljoscha Thomschewski a,b , Jürgen Bergmann c , Martin Kronbichler c,d , Julia S. Crone a,c,d , Elisabeth V. Schmid a , Kevin Butz a , Peter Höller a,b , Raffaele Nardone a,b,e , Eugen Trinka a,b a Department of Neurology, Christian-Doppler-Klinik, Paracelsus Medical University, Salzburg, Austria b Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria c Neuroscience Institute & Center for Neurocognitive Research, Christian-Doppler-Klinik, Paracelsus Medical University, Salzburg, Austria d Department of Psychology & Center for Neurocognitive Research, University of Salzburg, Austria e Department of Neurology, Franz Tappeiner Hospital, Merano, Italy article info Article history: Accepted 11 December 2013 Available online xxxx Keywords: DOC MCS VS Coherence GPDC DTF Classification highlights  No voluntary brain activation is needed to examine the level of consciousness.  Connectivity in the EEG distinguishes different levels of consciousness.  Partialized coherence, directed transfer function, and generalized partial directed coherence distin- guish MCS from VS patients. abstract Objective: In the present study, we searched for resting-EEG biomarkers that distinguish different levels of consciousness on a single subject level with an accuracy that is significantly above chance. Methods: We assessed 44 biomarkers extracted from the resting EEG with respect to their discriminative value between groups of minimally conscious (MCS, N = 22) patients, vegetative state patients (VS, N = 27), and – for a proof of concept – healthy participants (N = 23). We applied classification with sup- port vector machines. Results: Partial coherence, directed transfer function, and generalized partial directed coherence yielded accuracies that were significantly above chance for the group distinction of MCS vs. VS (.88, .80, and .78, respectively), as well as healthy participants vs. MCS (.96, .87, and .93, respectively) and VS (.98, .84, and .96, respectively) patients. Conclusions: The concept of connectivity is crucial for determining the level of consciousness, supporting the view that assessing brain networks in the resting state is the golden way to examine brain functions such as consciousness. Significance: The present results directly show that it is possible to distinguish patients with different lev- els of consciousness on the basis of resting-state EEG. Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction Distinguishing between patients in a minimally conscious state (MCS), vegetative state (VS, also known as unresponsive wakeful- ness syndrome), and conscious patients is still a matter of research. It is a current debate if it is better to examine consciousness by using active paradigms, like motor imagery or voluntary counting (Owen et al., 2006; Boly et al., 2007; Bekinschtein et al., 2009; Schnakers et al., 2008b; Monti et al., 2009; Schnakers et al., 2009a; Monti et al., 2010; Cruse et al., 2011; Fellinger et al., 2011; Goldfine et al., 2011; John et al., 2011; Lechinger et al., 2012; Liang et al., 2012), or if it is more appropriate to distinguish patients without tasks that require active cooperation. The rationale for the first type of consciousness-test is obvious. If a patient is able to follow commands he does not fulfill the criteria of being unresponsive to the environment, and, as such, falls out 1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2013.12.095 ⇑ Corresponding author at: Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria. Tel.: +43 662 4483 3966. E-mail address: y.hoeller@salk.at (Y. Höller). Clinical Neurophysiology xxx (2014) xxx–xxx Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph Please cite this article in press as: Höller Y et al. Connectivity biomarkers can differentiate patients with different levels of consciousness. Clin Neurophy- siol (2014), http://dx.doi.org/10.1016/j.clinph.2013.12.095