MMN and novelty P3 in coma and other altered states of consciousness: a review

Abstract

In recent decades, there has been a growing interest in the assessment of patients in altered states of consciousness. There is a need for accurate and early prediction of awakening and recovery from coma. Neurophysiological assessment of coma was once restricted to brainstem auditory and primary cortex somatosensory evoked potentials elicited in the 30 ms range, which have both shown good predictive value for poor coma outcome only. In this paper, we review how passive auditory oddball paradigms including deviant and novel sounds have proved their efficiency in assessing brain function at a higher level, without requiring the patient's active involvement, thus providing an enhanced tool for the prediction of coma outcome. The presence of an MMN in response to deviant stimuli highlights preserved automatic sensory memory processes. Recorded during coma, MMN has shown high specificity as a predictor of recovery of consciousness. The presence of a novelty P3 in response to the subject's own first name presented as a novel (rare) stimulus has shown a good correlation with coma awakening. There is now a growing interest in the search for markers of consciousness, if there are any, in unresponsive patients (chronic vegetative or minimally conscious states). We discuss the different ERP patterns observed in these patients. The presence of novelty P3, including parietal components and possibly followed by a late parietal positivity, raises the possibility that some awareness processes are at work in these unresponsive patients.

Figures

Figure 1

Example of the usefulness of high-pass filtering to properly detect N1 and MMN in coma recordings. The data were recorded in a patient during the first week of a coma of vascular origin using a classical oddball paradigm (standard tone-bursts 75 ms; deviant tone-bursts 30 ms, probability 0.15; stimulus onset asynchrony 610 ms). Averaged response to Standards (thick line, 1145 events averaged), to Deviants (thin line, 242 events averaged) and deviance-specific response (Deviants minus Standards, dotted line) at the frontal electrode Fz. Left panel: 30 Hz low-pass filter (Butterworth, order 6). Right panel: with additional 2 Hz high-pass filter (Butterworth, order 4).

Figure 2

Grand averages obtained from 52 healthy subjects, 33 coma patients with N1 and MMN, and 51 coma patients showing an N1 but no MMN. Responses to Standards (thick line), to Deviants (thin line) and deviance-specific response (Deviants minus Standards, dotted line). The data were recorded from a single derivation, with Fz as active electrode and the right mastoid as reference. Digital filter 3–30 Hz (Butterworth). Adapted from Fischer et al. 1999.

Figure 3

Time elapsed between recording and awakening in the 95 patients who awakened from a series of 128 patients recorded during coma, as a function of the presence of N1 and MMN at the time of recording. The delay was found to be significantly longer in patients with no N1 than in the other two populations with N1, whether MMN was present or not (Kruskal-Wallis p

Figure 4

Responses to the subject’s own first name uttered by a familiar and a non-familiar voice presented as novel stimuli in a novelty oddball paradigm (probability p = 0.02 for each Novel). Grand averages obtained from 15 healthy subjects. Left panel: averaged waveforms recorded at 3 midline electrodes (Fz, Cz, Pz) with nose reference (non-familiar voice, thin line; familiar voice, thick line). Right panels: Mean scalp potential distributions for the 2 types of stimuli; above in the 2 stages of the novelty P3 averaged over the 220–300 ms and 300–380 ms, respectively; below over the 450–625 ms and 625–800 time intervals including late slow waves. Adapted from Holeckova et al. 2006.

Figure 5

Typical responses to the subject’s own name presented as a novel in 2 individual coma patients. Upper panel: responses at the three midline electrodes Fz, Cz, Pz (with a nose reference). At each electrode, the window with significantly positive potentials (unilateral bootstrap p