Pain anticipation is a new behavioural sign of minimally conscious state

Abstract

Probing cognition and consciousness in the absence of functional communication remains an extremely challenging task. In this perspective, we imagined a basic clinical procedure to explore pain anticipation at bedside. In a series of 61 patients with a disorder of consciousness, we tested the existence of a nociceptive anticipation response by pairing a somaesthetic stimulation with a noxious stimulation. We then explored how nociceptive anticipation response correlated with (i) clinical status inferred from Coma Recovery Scale-Revised scoring, (ii) with an EEG signature of stimulus anticipation-the contingent negative variation-and (iii) how nociceptive anticipation response could predict consciousness outcome at 6 months. Proportion of nociceptive anticipation response differed significantly according to the state of consciousness: nociceptive anticipation response was present in 5 of 5 emerging from minimally conscious state patients (100%), in 10 of 11 minimally conscious state plus patients (91%), but only in 8 of 17 minimally conscious state minus patients (47%), and only in 1 of 24 vegetative state/unresponsive wakefulness syndrome patients (4%) (χ ² P < 0.0001). Nociceptive anticipation response correlated with the presence of a contingent negative variation, suggesting that patients with nociceptive anticipation response were more prone to actively expect and anticipate auditory stimuli (Fisher's exact test P = 0.05). However, nociceptive anticipation response presence did not predict consciousness recovery. Nociceptive anticipation response appears as a new additional behavioural sign that can be used to differentiate minimally conscious state from vegetative state/unresponsive wakefulness syndrome patients. As most behavioural signs of minimally conscious state, the nociceptive anticipation response seems to reveal the existence of a cortically mediated state that does not necessarily reflect residual conscious processing.

Keywords: EEG; disorder of consciousness; intensive care; pain anticipation; trace conditioning.

Graphical Abstract

Figure 1

Flowchart (A) and stimulus design (B): in the trace-conditioning paradigm, we gently touched the middle finger of the patient for about 2 s (neutral CS), and then, after a SOA of about 3 s, we applied a noxious pressure on the nail bed of the middle finger of the same hand (aversive or noxious US). In the ‘delay-like’ conditioning paradigm, we delivered the same stimuli but without delay between the end of the tactile stimulation and the noxious stimulation.

Figure 2

(A) NAR+ and (B) NTAR+. EMCS, emerging from minimally conscious state; MCS+, minimally conscious state plus; VS/UWS, vegetative state/unresponsive wakefulness syndrome. *P< 0.05, **P < 0.01, ***P < 0.001, Fischer’s exact test.

Figure 3

Proportion of CNV according to clinical state (A) and NAR (B). EMCS, emerging from minimally conscious state; MCS+, minimally conscious state plus; VS/UWS, vegetative state/unresponsive wakefulness syndrome. *P < 0.05 (χ² in A and Fischer’s exact test in B).