The vegetative and minimally conscious states are examples of what are referred to as disorders of consciousness. Patients in these conditions are more or less oblivious to goings-on in their surroundings – they exhibit few, if any, signs of conscious awareness, and are usually unable to communicate in any way. It is, therefore, extremely difficult to establish what these patients are experiencing, and the consciousness disorders are among the least understood, and most commonly diagnosed, conditions in medicine.
Although technologies such as functional neuorimaging have enabled clinicians to gain some insight into these conditions, proper assessment and diagnosis of patients are still major challenges, and there are big ethical questions regarding how they should be treated. However, researchers from the University of Cambridge have made what could be a significant advance.
In a paper published online in Nature Neuroscience, they report that some minimally conscious and vegetative patients appear to be capable of learning simple associations between two stimuli, and that this ability is strongly correlated with subsequent recovery. The findings point to a reliable method for evaluating and diagnosing patients suffering from consciousness disorders, and also may enable clinicians and relatives to make informed decisions about treatment.
Disorders of consciousness are typically defined by behavioural assessment – patients in the so-called minimally conscious state exhibit intermittent evidence of awareness, while those in the vegetative state exhibit no awareness whatsoever. Most patients are usually unresponsive to external stimuli, but this gives no indication of the state of brain function, or of cognitive processes. It is clear that the behavioural criteria for diagnosis of these disorders are inadequate, and it is estimated that approximately 40% of patients have been misdiagnosed.
It is also now clear that at least some patients are aware of what is going on around them, despite showing no outward signs of awareness. Several neuroimaging studies have shown that auditory regions in the brains of vegetative patients become activated in response to speech. And another study provided evidence of specific brain activation patterns in a vegetative patient when she was asked to imagine playing tennis or moving around her house.
In some cases, the prognosis, or outcome, of such patients, is inaccurate too. It was also long assumed that patients who have existed in such conditions for long periods cannot recover. However, it is now clear that is not always the case. In 2007 researchers used an experimental surgical procedure called deep brain stimulation to improve brain function in a patient who had been in a minimally conscious state for more than six years. Almost immediately, the patient opened his eyes, and responded to voices. In the following months, he became capable of speaking, swallowing and reaising a cup to his mouth. Then there is the remarkable case of Terry Wallis, who went into a vegetative state following an accident in 1984, only to emerge from it 19 years, despite doctors’ insistence that he would never recover.
In the new study, Tristan Bekinschtein of the MRC Cognition and Brain Sciences Unit at the University of Cambridge and his colleagues used classical conditioning to test whether any traces of conscious processing are preserved in minimally conscious and vegetative patients. This procedure is also referred to as Pavlovian conditioning, after the Russian physiologist Ivan Pavlov, who first showed, over 100 years, ago that dogs quickly learn to associate the sound of a ringing bell with the presentation of food, so that after a number of pairings of the two stimuli, they begin to salivate in anticipation of being fed when presented with the bell alone.
The researchers used the same procedure with 22 patients, all of whom had been in a minimally conscious or vegetative state, for at least 6 months. In 70 learning trials, the patients were presented with a tone, followed half a second later by a puff of air into the eye, which produces a reflexive blinking response. In 70 subsequent trials, the tone was presented alone. This was also carried out on 16 healthy, conscious controls, and on 12 patients undergoing a standard medical procedure, during which they were rendered unconscious by the anaesthetic propofol.
If an association between the two stimuli has been learned, the tone should elicit a blinking response when presented by itself during the second block of 70 trials. Learning was assessed using event-related potentials (ERPs), by which electrical activity in the brain associated with specific events is measured with electrodes placed on the scalp. An electromyograph was also used to monitor the electrical activity of the eye muscles. Learning in this case would be associated with an increase in activity in specified electrodes during the anticipatory period – the 500 milliseconds after the tone was presented – and peaking at the time at which the puff of air was expected, as well as electrical activity in the eye muscles, which is correlated with the blink response.
These effects were recorded in the healthy conscious control group and in some of the experimental group of vegetative and minimally conscious patients, but not in the unconscious controls who had been under anaesthesia during the task. Significantly, learning effects were observed in both vegetative and minimally conscious patients. From their results, the researchers could predict, with an accuracy of more than 70%, which of the patients had been diagnosed as being in minimally conscious state and which were in a vegetative state. They could also predict, with even greater accuracy, which had suffered a traumatic brain injury, and which had incurred their consciousness disorder as a result of prolonged oxygen deprivation. Furthermore, it was found that learning was accurate predictor of future recovery – the condition of patients who showed signs of learning subsequently improved much more than those patients in whom the effects were not observed, as measured by the Revised Coma Recovery Scale.
These results can be interpreted in two ways. One interpretation is that patients with consciousness disorders still retain conscious processing to some extent. The other is that the classical conditioning demonstrated in the experimental group can occur in the absence of consciousness. The fact that the anaesthetized patients in the second control group did not exhibit associative learning suggests that the first interpretation is the more likely one. Either way, the findings suggest that those in the experimental group who did show signs of learning had properly functioning medial temporal lobe structures, such as the hippocampus and surrounding structures, which are crucial for memory formation and in learning the time interval between two stimuli during classical conditioning.
The findings of this study have important implications for the treatment of patients with disorders of consciousness. First, testing for signs of associative learning could help clinicians to distinguish between the different states, and to assess patients’ levels of arousal more reliably. The knowledge that learning effects predict future recovery could also provide a means of accurate prognosis, and help relatives of patients who have been in an a minimally conscious or vegetative state for long periods of time to make informed decisions based on realistic possible outcomes.
Bekinschtein, T., et al. (2009). Classical conditioning in the vegetative and minimally conscious state. Nat. Neurosci. DOI: 10.1038/nn.2391