Woman in persistent vegetative state shows brain activity associated with consciousness

I talked earlier this year about a patient who recovered from a coma after 20 years. In that post, I discussed how -- with respect to the diagnostic criteria -- the difference between a persistent vegetative state and a minimally conscious state is the difference between someone who has only autonomic nervous activity and episodic conscious activity. In this way, someone who is in a minimally conscious state -- as that patient was -- still has the possibility for recovery even if recovery is very rare.

Here is another case of a woman in a persistent vegetative state discussed in the journal Science. In the study, Owen et al. placed her in a fMRI to measure what residual brain activity she might still have with surprising results:

In July 2005, a 23-year-old woman sustained a severe traumatic brain injury as a result of a road traffic accident. Five months later, she remained unresponsive with preserved sleep-wake cycles. Clinical assessment by a multidisciplinary team concluded that she fulfilled all of the criteria for a diagnosis of vegetative state according to international guidelines...

We used functional magnetic resonance imaging (fMRI) to measure her neural responses during the presentation of spoken sentences (e.g., "There was milk and sugar in his coffee"), which were compared with responses to acoustically matched noise sequences. Speech-specific activity was observed bilaterally in the middle and superior temporal gyri, equivalent to that observed in healthy volunteers listening to the same stimuli...Furthermore, sentences that contained ambiguous words (italicized) (e.g., "The creak came from a beam in the ceiling") produced an additional significant response in a left inferior frontal region, similar to that observed for normal volunteers. This increased activity for ambiguous sentences reflects the operation of semantic processes that are critical for speech comprehension.

An appropriate neural response to the meaning of spoken sentences, although suggestive, is not unequivocal evidence that a person is consciously aware. For example, many studies of implicit learning and priming, as well as studies of learning during anesthesia and sleep, have demonstrated that aspects of human cognition, including speech perception and semantic processing, can go on in the absence of conscious awareness.

To address this question of conscious awareness, we conducted a second fMRI study during which the patient was given spoken instructions to perform two mental imagery tasks at specific points during the scan. One task involved imagining playing a game of tennis and the other involved imagining visiting all of the rooms of her house, starting from the front door. During the periods that she was asked to imagine playing tennis, significant activity was observed in the supplementary motor area. In contrast, when she was asked to imagine walking through her home, significant activity was observed in the parahippocampal gyrus, the posterior parietal cortex, and the lateral premotor cortex. Her neural responses were indistinguishable from those observed in healthy volunteers performing the same imagery tasks in the scanner.

These results confirm that, despite fulfilling the clinical criteria for a diagnosis of vegetative state, this patient retained the ability to understand spoken commands and to respond to them through her brain activity, rather than through speech or movement. Moreover, her decision to cooperate with the authors by imagining particular tasks when asked to do so represents a clear act of intention, which confirmed beyond any doubt that she was consciously aware of herself and her surroundings. (Citations removed. Emphasis mine.)

Here is the figure from the paper illustrating the activation in the mental imaging tasks described -- from the pateint and from controls for comparison (Click to enlarge):

There are two troublesome issues that this case poses: a diagnostic issue and a philosophical issue.

With respect to the diagnostic issue, the present diagnostic paradigm for the persistent vegetative state is predicated on the idea that the absence of mental activity can be measured by the failure to respond to external stimuli. This study suggests that assumption is suspect.

Here are the criterion for the persistent vegetative state from my earlier post:

1) No evidence of awareness of self or environment and an inability to interact with others;

2) No evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli;

3) No evidence of language comprehension or expression;

4) Intermittent wakefulness manifested by the presence of sleep-wake cycles;

5) Sufficiently preserved hypothalamic and brainstem autonomic functions to permit survival with medical and nursing care;

6) Bowel and bladder incontinence; and

7) Variably preserved cranial nerve (pupillary, oculocephalic, corneal, vestibulo-ocular, gag) and spinal reflexes.

From a cursory glance you can see that if we believe the fMRI, this patient does not fulfill several of these criterion. The ability to evoke mental imagery from verbal instructions certainly constitutes some awareness of environment. Also, comphrehension of language appears to have been likewise spared even with some preservation of semantic perception. Yet, we would have never known any of this is this woman had not been placed in an MRI because under the present diagnostic paradigm the ability to react is the standard for consciousness. Thus, this paper stands a very solid argument for using fMRI as a diagnostic tool for determining the level of consciousness.

On the other hand, a solid counterargument could be made that what you are measuring in the fMRI is not consciousness -- even if knew entirely what you are measuring, and I am certain that several readers will hasten to point out that you don't. Skirting for the moment the issue of the usefulness of fMRIs in measuring activity -- that is a road I don't have time to go down now -- does activation in a particular brain area of the patient necessarily suggest that information is being processed there in a similar manner to a totally normal patient? Experimentally we make that assumption every time we try and interpret fMRI data, but this is not necessarily true.

This begs the question related to the second issue: how are we defining consciousness? Are we willing to reify language comprehension into the activation of the language cortex? Are we willing to reify mental imagery of tennis into activation of the supplementary motor area? Wherein does the soul lie? I use the word soul in this case not for the religious meaning of the word, but rather meaning that special transcendent and indivisible quality that constitutes and defines personhood. I use it because I don't really think there is a better word for it.

I don't really have a good answer for these questions, and I suspect that any answers we arrive at are going to be personal.

For my piece, I refuse to imbue a particular brain area or set of brain areas with personhood. I believe there is some emergent quality derived from the activity in the brain rather than it substratum that defines us as people. The extension of this view is very pragmatic and almost mercenary with respect to determining whether someone is conscious: consciousness is defined by the capacity for meaningful interaction. In each person that we meet, we recognize personhood by their capacity to interact and their consistency in that interaction -- not in the sense of behaving the same way but in the coherence of the multiple interactions as believably originating from a single being.

Unfortunately, this view requires dismissing fMRI images like these as flickers of life but not the substance of soul. Am I being fair? I don't really know.

What I take away from this paper in a practical sense is a couple of things:

1) Our diagnostic criterion may need to be amended. As technology increases so to does our capacity to detect activity. If we are missing some response in this patient allowing her to slide through, then we need to find other ways to diagnose.

2) People who would rush to judgment with this respect to this case and say, "You see. All vegetative patients have activity and could recover," should know a couple of things. First, this is a diagnostic issue not a prognostic issue. Whether or not, this poor woman has recognizable conscious activity does not bear on her likelihood of improvement. It was noted in the paper that she has been in this state for nearly a year. After 6 months of so, the possibility of recover drops to near nil. She has shown some improvements in condition, prompting her doctors to try and reclassify her as minimally conscious, but even then the prognosis is not good.

Second, the authors suggest that it is unlikely that most patients diagnosed as in a vegetative state possess similar activity. Partly this is because of the nature of her injury. In a NYTimes article on the paper they talk about the big picture:

Dr. Nicholas Schiff, a neuroscientist at Weill Cornell Medical College in New York, said that the study provided "knock-down, drag-out" evidence for mental awareness, but that it was not clear "whether we'll see this in one out of 100 vegetative patients, or one out of 1,000, or ever again."

In a more recent exam, more than 11 months after her injury, the patient exhibited a sign of responsiveness: she tracked with her eyes a small mirror, as it was moved slowly to her right, and could fixate on objects for more than five seconds, said Dr. Steven Laureys, a neurologist at the University of Liège and an author of the study. This means by definition that the young woman has transitioned from an unresponsive, vegetative state to a sometimes responsive condition known as a minimally conscious state, Dr. Laureys said in an interview. An estimated 100,000 Americans exist in this state of partial consciousness, and some of them eventually regain full awareness.

The chances that an unresponsive, brain-damaged patient will eventually emerge depend on the type of injury suffered, and on the length of time he or she has been unresponsive. Traumatic injuries to the head, often from car accidents, tend to sever brain cell connections and leave many neurons intact. About 50 percent of people with such injuries recover some awareness in the first year after the injury, studies find; very few do so afterward. By contrast, brains starved of oxygen -- like that of Ms. Schiavo, whose heart stopped temporarily -- often suffer a massive loss of neurons, leaving virtually nothing unharmed. Only 15 percent of people who suffer brain damage from oxygen deprivation recover some awareness within the first three months. Very few do after that, and a 1994 review of more than 700 vegetative patients found that none had done so after two years.

Also, I just thought I would throw this passage in at the end from Lionel Naccache in an Science editorial on the paper:

Despite the patient's very poor behavioral status, the fMRI findings indicate the existence of a rich mental life, including auditory language processing and the ability to perform mental imagery tasks. On one hand, this single case makes a strong argument for the development of fMRI and other neurophysiological tools (such as monitoring electroencephalogram brain responses to external stimuli) to evaluate cognition in such patients. On the other hand, we should not generalize from this single patient, who suffered relatively few cerebral lesions, to most other vegetative state patients, who typically have massive structural brain lesions.

Is this woman conscious? Most current behavioral and neuroimaging evidence suggests that conscious processing is abolished during a vegetative state. Such patients do not report mental states, nor do they spontaneously engage in intentional actions or interactions with their environment, two key properties of conscious processing in humans. Moreover, several studies have reported residual local and specific brain activation patterns in vegetative state patients, whereas long-range neural integration observed during conscious processing was lacking (4, 5). Nevertheless, on the basis of their findings, Owen et al. argue that the patient in their study was probably conscious of herself and her surroundings during fMRI testing. This hypothesis opens another issue: If this patient is actually conscious, why wouldn't she be able to engage in intentional motor acts, given that she had not suffered functional or structural lesion of the motor pathways?

The debate over whether vegetative state patients can engage in conscious processing is reminiscent of the Turing test in artificial intelligence: Can we distinguish a conscious human from a computer solely on the basis of a question-answer method (6)? Adapting the Turing test to the present debate, we might ask: Can we determine whether a person is conscious solely on the basis of a question-brain activation method? Whereas these questions have stimulated intense philosophical debate about artificial intelligence, most cognitive neuroscientists have adopted a more naturalistic approach. Consciousness is univocally probed in humans through the subject's report of his or her own mental states. A subject who reports, "I read the word consciousness on this page," can be considered as conscious (7). The ability to report one's own mental state is the fundamental property of consciousness.

Owen et al. did not directly collect such a subjective report. When conscious reporting is not possible, an alternative solution is to examine the three other psychological attributes of conscious processing: (i) active maintenance of mental representations; (ii) strategical processing; and (iii) spontaneous intentional behavior (8). Clearly, one of the most impressive aspects of the work by Owen et al. is the demonstration that activation of task-related neural networks is actively maintained. During each experimental task, instructions were delivered only once, and the corresponding neural network remained activated throughout the entire 30-s period. In contrast, unconscious mental representations observed in many clinical and experimental contexts are fleeting, lasting a few seconds or less (9-11).