Scientific Commentaries

This scientific commentary refers to ‘Neural detection of complex sound sequences in the absence of consciousness’, by Tzovara et al. (doi:10.1093/ brain/awv041). Event related potentials (ERPs), classically measured by EEG, are the electrophysiological brain responses to a stimulus. Somatosensory and auditory ERPs have been used as a noninvasive tool for assessing brain functions and predicting outcomes in disorders of consciousness and coma (for review see Bruno et al., 2011). While early ERPs (such as the absence of cortical responses on somatosensory-evoked potentials) predict poor outcomes, cognitive ERPs may be indicative of recovery of consciousness after coma (Vanhaudenhuyse et al., 2008). Auditory cognitive ERPs permit assessment of residual higherorder processing, such as echoic memory (e.g. using mismatch negativity potentials), acoustic and semantic discrimination (e.g. P3 or P300 evoked potentials), and incongruent language detection (e.g. N400 potentials). Classically, these ERP paradigms are based on the detection of a stimulus in violation of an auditory regularity, composed of two neural events, each characterized at the EEG level by a stereotypical morphology and latency: a mismatch negativity followed by a later complex named P300 further divided into an early (P300a) and a late component (P300b). The mismatch negativity is thought to reflect unconscious processing (Daltrozzo et al., 2009), whereas the P300b has been linked to consciousness (Bekinschtein et al., 2009). Neither of these ERP components are specific to auditory stimuli and both can be elicited by other sensory modalities. However, auditory cognitive ERPs have been used most extensively in the field of coma because they are easy to deliver and—in contrast to visual ERPs—can be easily acquired in eyes closed conditions. Given the difficulties inherent in the differentiation between P300a and P300b, Bekinschtein and Naccache et al. (2009) developed an elegant ERP paradigm (local-global paradigm) composed of two embedded levels of auditory regularity, one local (at the single trial level) and one global (across trials). Applying such a paradigm, they demonstrated that, while violations of local regularities elicited measurable ERPs both in conscious and unconscious conditions, responses to violations of global regularities are reliably detectable only in the presence of conscious perception—in line with the ‘global neuronal workspace’ hypothesis of consciousness (Noirhomme et al., 2010). In this issue of Brain, Tzovara and colleagues use the local-global auditory ERP technique to challenge the notion that detection of global violations is linked to conscious processing, showing for the first time that responses to such violations can be elicited even in comatose patients (Tzovara et al., 2015). The local-global paradigm relies on the delivery of five brief sounds in a row, the first four identical, while the fifth can be either identical to the previous or deviant—the nature of the fifth sound establishing the local regularity (or its violation). The global regularity within a block of trials is established by selecting one of the two series as the global standard and the other as the global deviant; this is achieved by delivering the two kinds of trials in a pseudorandom manner within each block (i.e. 80% of trials being global standards and 20% deviants). At variance with the original method developed by Bekinschtein et al. (2009), who manipulated the pitch of the stimuli to create deviants, in Tzovara et al. (2015), regularity violations are obtained by varying stimulus duration. Using this paradigm, the authors investigated differential EEG responses to global standard versus global deviant sounds in 21 healthy controls and 24 comatose patients with anoxic-ischaemic coma. For each patient two EEG recordings were performed, the first under therapeutic hypothermia and the second in normothermic conditions within 48 h of coma onset. The age-matched control group was divided into an ‘active group’ (asked to count the number of global deviant series) and a ‘passive group’ (instructed to let their minds wander while listening to the sounds). A multivariate decoding analysis (Tzovara et al., 2012, 2013) modelled voltage topographies of single-trial EEG activity for each recording. The model estimation was performed on a portion of the trials (the training data set) and then used to classify the category of sounds (standard/deviant) in a BRAIN 2015: 138; 1129–1137 | 1129