A simple test for determining whether a patient is conscious or not

January 21 2009

Is it possible to determine whether a patient is conscious by observing the activity of his/her brain? The thorny scientific question is crucial for clinicians managing non-communicative patients in intensive care or patients emerging from unconscious states such as coma or a vegetative state. A French team from Inserm and the Groupe Hospitalier Pitié-Salpêtrière (Paris Public Hospital Authority, AP-HP) directed by Dr. Lionel Naccache, and associating Dr. Tristan Bekinschtein, an Argentinean post-doctoral neuroscientist, and Prof. Stanislas Dehaene, Director of the Inserm/CEA unit 'Cognitive neuroimaging' with Neurospin, has just developed a test combining the principles of the psychology of auditory perception with recording brain activity. The test enables detection of the existence of conscious mental life without being based on the frequently limited signs obtained by clinical examination.

The work, to be published in the next early online edition of the Proceedings of the National Academy of Sciences (PNAS), is in line with a recent movement in applied neuroscience research on comatose, vegetative and non-communicative states which is tending to modify our view of those diseases and investigate for new innovative methods of communication.

Is it possible to determine whether a subject is conscious by observing his/her brain activity? Answering that question constitutes an issue for the management of numerous diseases characterized by inability to communicate. In those diseases, it is, in fact, extremely difficult or even impossible to determine a state of consciousness on the basis of traditional neurological examination. In the absence of that information, the diagnosis and, necessarily, prognosis are sometimes problematic.

Initially, Lionel Naccache's team developed a test based on the brain response to a particular auditory stimulus recorded using a helmet fitted with electrodes. In the first test, specific cerebral electrical activity was observed in response to emission of a different sound after a series of identical sounds: e.g. AAAAB after a series of AAAAA. The researchers called the sign a 'violation of local temporal regularity'. Since the nineteen-seventies, we have known that the brain in that situation generates specific electrical signals, certain non-conscious (mismatch negativity or MMN) and others reflecting awareness of a novelty (late evoked potential or late components of response P300). It is, however, very difficult to precisely determine what is linked to awareness.

In France, a few rare clinical neurophysiology departments have been using various versions of the technique daily on resuscitation and intensive care patients since the end of the nineteen-nineties. The technique enables identification of patients who are still sensitive to the environment when the clinician is unsure with regard to the degree of cerebral function and prognosis. Thus, Dr. Catherine Fischer's team at the Hospices Civils neurological hospital in Lyon and Lionel Naccache's team at the Groupe Hospitalier Pitié-Salpêtrière in Paris have been using the technique. A comatose patient who presents with an MMN response has a prognosis of returning to consciousness in the following days or weeks of the order of 80%. However, the type of test does not enable precise distinction between conscious and unconscious processing. How then can an unconscious patient be distinguished from a conscious patient who is unable to move or speak?

The researchers then developed a second test which was more complex and exploited the principle of local irregularity while adding an overall irregularity. In order for the subject to understand the rule associated with a series of sounds, the subject has to integrate auditory information over several tens of successive tests and must thus be conscious. (AAAAB, AAAAB, AAAAB, AAAAA, etc.). In this series, 'AAAAB' is normality and 'AAAAA' violates the rule. In order for the subject to detect that 'AAAAA' violates the rule, the subject must be conscious. The authors were then able to isolate the electrical signal of the brain's response to the overall irregularity.

Above: the cerebral electrophysiological signature of the local effect evidences a set of early cortical responses (time indicated below in milliseconds). Below: the cerebral electrophysiological signature of the overall effect evidences a set of late cortical responses that are only observed in subjects conscious of the auditory rule used.

Above: the cerebral electrophysiological signature of the local effect evidences a set of early cortical responses (time indicated below in milliseconds). Below: the cerebral electrophysiological signature of the overall effect evidences a set of late cortical responses that are only observed in subjects conscious of the auditory rule used.

After having verified in healthy subjects that the presence of that brain response was a very specific marker of the conscious state, the researchers used functional MRI to analyze the brain networks activated. The results confirmed that the cerebral response emitted in the second test specifically activated the frontal and parietal lobes of the brain, zones known to be associated with conscious work.

Lastly, the researchers validated the test on 8 patients. Four of the patients were in a vegetative state, i.e. presenting with wake-sleep cycles but no voluntary or intentional activity during the waking phases. The other four subjects were in a state of 'minimal consciousness', a fluctuating state of consciousness that is frequently difficult to characterize. None of the vegetative patients showed an overall effect in line with the clinical evaluation. In contrast, 3 out of the 4 patients in a minimal conscious state presented an overall effect, again confirming the clinical diagnosis. Considered overall, these results show that the test could be of value in numerous patients whose state of consciousness is difficult to establish on the basis of the clinical examination alone.

This innovative work has enabled proposal of a fairly simple and relatively inexpensive method of detecting the existence of a conscious state in non-communicative subjects and in numerous situations in which it is difficult to decide on the basis of the clinical data alone. The authors nonetheless stress that the test only has positive predictive value: the presence of an overall effect indicates a conscious state with certainty, while the absence of an overall effect does not enable negative conclusions to be drawn (the patient may be asleep during the test or present with memory disorders). Nonetheless, this tool should enable enhancement of the difficult management of the diseases in question and, in particular, earlier identification of a return to consciousness in order to initiate communication with the patients.

This work received financial support from the Institut du Cerveau et de la Moelle épinière (ICM), which will shortly be opening its doors to numerous French and international neuroscience teams with a view to enhancing the understanding and management of neurological diseases.


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Source
"Neural signature of the conscious processing of auditory regularities"

Tristan Bekinschtein1, Stanislas Dehaene1,2, Benjamin Rohaut1, François Tadel1, Laurent Cohen1,3,4, Lionel Naccache1,3,4

1 Inserm, Unité de neuroimagerie cognitive, Institut Fédératif de Recherche (IFR) 49, Gif sur Yvette, France.
2 CEA, I2BM, Centre Neurospin, Gif sur Yvette, France
3 Assistance Publique - Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Pôle des Maladies du Système Nerveux, Paris, France.
4 Université Pierre et Marie Curie Paris 6, Paris, France.

Proceedings of the National Academy of Sciences (PNAS)
Early edition

Research contact
Lionel Naccache
Unité Inserm 562 « Neuroimagerie cognitive »
Département de Neurophysiologie Clinique
Groupe Hospitalier Pitié-Salpêtrière
47-83 Bd de l'Hôpital / 75013 PARIS
Tel. 33 1 42 16 19 86


Press contact
Anne Mignot
Tel. 33 1 44 23 60 73

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