Sep 23 2009

Learning in the Comatose

Neurologists are often confronted with patients who have a disorder of consciousness and are asked to predict their probability of recovery. The more severe the neurological damage the easier prediction is, but there are many patients in the gray zone – they have enough damage that they may never have a significant recovery, but there is also enough preserved function that they may improve – even to the point of crossing an important functional milestone, for example being able to communicate.

Traditionally we have relied upon the clinical exam to determine the the level of impairment – for example, whether a patient is in a persistent vegetative state (PVS) or a minimally conscious state (MCS). However, there are limits to the exam (patients, for example, may be unable to move because they are paralyzed rather than due entirely to lack of consciousness) and a recent study has shown that errors in the distinction between PVS and MCS are not uncommon.

Making this distinction is also becoming increasingly important as neuroscientists develop possible techniques to treat patients with disorders of consciousness to help them recover. For example, patients have been treated with transcranial magnetic stimulation or with implanted chips to stimulate brain activity. It is not inconceivable that within 10-20 years we will be able to augment brain function in those in a MCS and help them regain significant consciousness.

Efforts are therefore underway to develop better tools for assessing residual conscious function in patients in a PVS or MCS and to correlate these findings with recovery (for better prediction). For example, functional MRI scanning has been used to look for conscious processing in those in an apparent PVS.

Now, researchers have employed a clever technique to look for conscious processing in comatose patients – exploiting the learned response, or Pavlovian conditioning. They played one of two tones to patients, one tone was followed by a puff of air against the cornea which could produce a blink response. They established a baseline response in conscious patients and compared this to a group of patients in a PVS or MCS and also to an unconscious control group – intact patients under anaesthesia with propofol. They looked for a conditioned response to the tone, anticipating the coming puff of air.

They found a significant conditioned response in the patients with disorders of consciousness, more than the propofol group but less than the conscious control group. This is especially interesting because up to now it has been thought that a conditioned response requires conscious processing.

The authors acknowledge two basic ways to interpret these results. The first is that learning a conditioned response is not dependent upon conscious processing. It may be mediated partly by unconscious processing. I think this may be very likely, especially in light of other evidence for unconscious learning.

The other possibility is that some of the patients in this study had more preserved consciousness than was evident on clinical exam. This too is plausible, and in fact both explanations may have some truth and may vary from patient to patient. Preserved conscious processing, in my opinion, should not be equated with conscious awareness. Patients in PVS and MCS may have some conscious processing, but not enough to generate any kind of awareness that they will remember.

While these results are interesting, the biggest question is whether or not these findings can be used to make predictions about individual patients. The researcher therefore looked at this. First, they compared their findings to various clinical assessments, but only found one that correlated with the demonstration of a conditioned response – brain atrophy. This suggests that their results are meaningful – they are actually telling us something about brain function. However, I don’t think this helps us distinguish between conscious vs unconscious processing contributing to the conditioned response – as overall brain atrophy will correlate with damage to both types of processing in the brain.

Further, and most significantly in my opinion, the researchers compared the degree of conditioned response in individual patients to their outcome over the next 6 months to 2 years, and they found again that there was a good correlation. Conditioned response was 86% predictive of later improvement in clinical function – some improvement in the specific grade of coma.

As always I must caution that we are talking about a modest improvement in neurological function – patients went from a PVS to a MCS, or to a higher degree of MCS, or in some cases to being severely disabled but able to communicate. I don’t want to minimize the significance of such improvement to the patient and their family, but I also don’t want to give the impression that some of these patients “woke up” and had anything close to normal neurological function.

This study needs to be replicated to see if this effect is reliable, and if so it may add to our options for assessing patients with disorders of consciousness. There is unlikely to be one definitive test of consciousness any time soon, but if we can combine the clinical exam, anatomical studies, electrical activity (EEG), response on functional MRI scanning, and this new effect – the ability to generate a conditioned response – we will get more and more accurate in our assessments.

Increased accuracy will in turn enable us to give families better information with which to make decisions about ongoing care, and eventually may help us predict which patients will be good candidates for experimental treatments, like implantable chips.

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