EEG paradigms as a supplemental tool to behavioral assessments of DOC

Introduction Diagnosis and prediction of recovery in the acute phase of disorders of consciousness (DOC) are critical for subsequent medical decisions. However, reliable assessment remains elusive due to the inability of current validated clinical scales to take into account motor and drive deficits. Recently, the Motor Behaviour Tool (MBT), a novel clinical scale, has been developed to address this caveat (1). In this context, neuroimaging and brain-computer interface (BCI) have also been proposed to improve the diagnosis and prognosis of these patients.(2). Objectives This pilot study aims to investigate the diagnostic and prognostic value of two electroencephalography (EEG)-based paradigms in patients with DOC, i.e., coma, Unresponsive Awareness Syndrome (UWS) or Minimally Conscious State (MCS). As a second step, we will employ them as evidence to further establish the added value of the MBT (i.e., assessment of minimal responses suggesting remaining conscious processing) combined with the Coma Recovery Scale-Revised (CRS-R), a standardized validated scale commonly used to assess consciousness in this population (3). Patients & Methods Acute DOC patients undergo CRS-R and MBT assessment prior to two EEG paradigms. Firstly, a motor attempt EEG-BCI coupled with Functional Electrical Stimulation (FES) is used (4). We hypothesize that replacing the need for overt movements with motor attempt can alleviate the tendency of CRS-R to underestimate the level of awareness in case of cognitive-motor dissociation (CMD) (5). In addition, a second EEG protocol presents patients with FES-tactile (T), auditory (A), and audio-tactile (AT) stimuli both in actionable and non-actionable space. EEG evoked potentials observed in the actionable space are expected to show a non-linear addition of sensory stimuli (i.e., A+T ≠ AT) indicating multisensory integration and the capacity of conscious processing (6). Results Pending elaborate analysis, preliminary findings show (Fig. 1) that BCI accuracy is significantly above chance only for a patient who was diagnosed as UWS by the CRS-R evaluation, but exhibited a motor behavior classified as CMD confirmed by the MBT tool, and not for one in real UWS (same diagnosis based on CRS-R and MBT), implying the presence of the hypothesized relation between motor EEG correlates and awareness (7). Average EEG evoked potentials of 8 patients during the second EEG paradigm highlight a difference between within (solid line) vs. outside (dashed line) the actionable space (Fig. 2), suggesting awareness-dependent modulation. Future analyses will explore correlations of such EEG descriptors with the clinical outcomes. Conclusion EEG correlates extracted from these EEG paradigms are promising tools for diagnosis of DOC and may supplement current clinical scales to help the validation of new tools like the MBT. References J. M. Pignat, E. Mauron, J. Jöhr, C. Gilart De Keranflec'h, D. Van De Ville, M. G. Preti, D. E. Meskaldji, V. Hörnberg, S. Laureys, B. Draganski, R. Frackowiak, K. Diserens, Outcome prediction of consciousness disorders in the acute stage based on a complementary motor behavioural tool, PLOS ONE 11(6), e0156882 (2016). A. M. Owen, M. R. Coleman, M. Boly, M. H. Davis, S. Laureys, J. D. Pickard, Detecting awareness in the vegetative state, Science, 313, 1402 (2006). J. T. Giacino, K. Kalmar, J. Whyte, The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility, Arch. Phys. Med. Rehabil. 85(12), 2020-9 (2004). T. Corbet, R. Leeb, A. Biasiucci, S. Perdikis, J. del R. Millán et al. BCI-NMES therapy enhances effective connectivity in the damaged hemisphere in stroke patients. 6th International Brain-Computer Interface Meeting, Asilomar, California, USA (2016). N. D. Schiff, Cognitive motor dissociation following severe brain injuries, JAMA Neurol. 72(12), 1413–1415 (2015). J. P. Noel, C. Pfeiffer, O. Blanke, A. Serino, Full body peripersonal space as the space of the bodily self, Cognition 144, 49-57 (2015). A. M . Goldfine, J. D. Victor, M. M. Conte, J. C. Bardin, N. D. Schiff, Determination of awareness in patients with severe brain injury using EEG power spectral analysis, Clin. Neurophysiol. 122(11), 2157-68 (2011).

Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool

Bogdan Draganski, Richard Frackowiak, Djalel Eddine Meskaldji, Maria Giulia Preti, Dimitri Nestor Alice Van De Ville

Introduction Attaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction. Methods From the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann-Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model. Results Fifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation between classes; longitudinal regression modelling of the CRS-R data identified distinct outcome evolution, but not earlier than 19 days. Second, the MBT yielded a significant outcome predictability in the acute phase (p0.81). Third, a statistical comparison of the CRS-R subscales weighted by MBT became significantly predictive for DOC outcome (p

Public Library of Science2016

Neuroscience robotics to investigate multisensory integration and bodily awareness

Olaf Blanke, Dominique Chapuis, Julio Duenas, Roger Gassert, Silvio Ionta, Roberto Martuzzi, Christian Pfeiffer

Humans experience the self as localized within their body. This aspect of bodily self-consciousness can be experimentally manipulated by exposing individuals to conflicting multisensory input, or can be abnormal following focal brain injury. Recent technological developments helped to unravel some of the mechanisms underlying multisensory integration and self-location, but the neural underpinnings are still under investigation, and the manual application of stimuli resulted in large variability difficult to control. This paper presents the development and evaluation of an MR-compatible stroking device capable of presenting moving tactile stimuli to both legs and the back of participants lying on a scanner bed while acquiring functional neuroimaging data. The platform consists of four independent stroking devices with a travel of 16-20 cm and a maximum stroking velocity of 15 cm/s, actuated over non-magnetic ultrasonic motors. Complemented with virtual reality, this setup provides a unique research platform allowing to investigate multisensory integration and its effects on self-location under well-controlled experimental conditions. The MR-compatibility of the system was evaluated in both a 3 and a 7 Tesla scanner and showed negligible interference with brain imaging. In a preliminary study using a prototype device with only one tactile stimulator, fMRI data acquired on 12 healthy participants showed visuo-tactile synchrony-related and body-specific modulations of the brain activity in bilateral temporoparietal cortex.

2012

Peri-personal space encoding in patients with disorders of consciousness and cognitive-motor dissociation

Maria Manuela da Silva Marques, Jean-Paul Noel, Serafeim Perdikis, Andrea Serino

Behavioral assessments of consciousness based on overt command following cannot differentiate patients with disorders of consciousness (DOC) from those who demonstrate a dissociation between intent/awareness and motor capacity: cognitive motor dissociation (CMD). We argue that delineation of peri-personal space (PPS) - the multisensory-motor space immediately surrounding the body - may differentiate these patients due to its central role in mediating human-environment interactions, and putatively in scaffolding a minimal form of selfhood. In Experiment 1, we determined a normative physiological index of PPS by recording electro-physiological (EEG) responses to tactile, auditory, or audio-tactile stimulation at different distances (5 vs. 75 cm) in healthy volunteers (N = 19). Contrasts between paired (AT) and summed (A + T) responses demonstrated multisensory supra-additivity when AT stimuli were presented near, i.e., within the PPS, and highlighted somatosensory-motor sensors as electrodes of interest. In Experiment 2, we recorded EEG in patients behaviorally diagnosed as DOC or putative CMD (N = 17, 30 sessions). The PPS-measure developed in Experiment 1 was analyzed in relation with both standard clinical diagnosis (i.e., Coma Recovery Scale; CRS-R) and a measure of neural complexity associated with consciousness. Results demonstrated a significant correlation between the PPS measure and neural complexity, but not with the CRS-R, highlighting the added value of the physiological recordings. Further, multisensory processing in PPS was preserved in putative CMD but not in DOC patients. Together, the findings suggest that indexing PPS allows differentiating between groups of patients whom both show overt motor impairments (DOC and CMD) but putatively distinct levels of awareness or motor intent.