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1. WILLFUL MODULATION of BRAIN ACTIVITY (NEJM, 2010)
2. “PROBING CONSCIOUSNESS”, Additional Research on awareness in patients with a diagnosis of P.V.S.
3. PROF. ADRIAN OWEN - Investigator of [and crusader for] the Unconscious
IN 2010 an article appeared in The New England Journal of Medicine that changed almost-universally held convictions concerning the persistent vegetative state - much to the frustration and consternation of those who advocate routinely discontinuing nutrition and hydration in these patients. The authors demonstrated that the rate of misdiagnosis of the persistent vegetative state is 40%, and that 10% of the patients they studied who fulfilled the clinical criteria for the persistent vegetative state were “able to willfully modulate their brain activity”. More recent studies have confirmed these findings using both functional MRI scanning and other innovative techniques (e.g., Faugeras and Rohout, “Probing consciousness with event-related potentials in the vegetative state” Neurology 77 July 19, 2011: §2, below)
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F[unctional]MRI SCANNER |
FMRI 3-d scan |
One of the researchers and contributors to this article, Prof. Adrian Owen has continued his efforts to demonstrate these capacities in other patients and to establish communication with those who are capable of responding to questions. A dramatic British television documentary on this work aired on Nov. 14, 2012.
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_1.
WILLFUL
MODULATION
of
BRAIN
ACTIVITY
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Published at www.nejm.org February 3, 2010 (10.1056/NEJMoa0905370)
Martin M. Monti, Ph.D., Audrey Vanhaudenhuyse, M.Sc., Martin R. Coleman, Ph.D., Melanie Boly, M.D., John D. Pickard, F.R.C.S., F.Med.Sci., Luaba Tshibanda, M.D., Adrian M. Owen, Ph.D., and Steven Laureys, M.D., Ph.D.
Background The differential diagnosis of disorders of consciousness is challenging. The rate of misdiagnosis is approximately 40%, and new methods are required to complement bedside testing, particularly if the patient’s capacity to show behavioral signs of awareness is diminished.
Methods At two major referral centers in Cambridge, United Kingdom, and Liege, Belgium, we performed a study involving 54 patients with disorders of consciousness. We used functional magnetic resonance imaging (MRI) to assess each patient’s ability to generate willful, neuroanatomically specific, blood-oxygenation-level–dependent responses during two established mental-imagery tasks. A technique was then developed to determine whether such tasks could be used to communicate yes-or-no answers to simple questions.
Results Of the 54 patients enrolled in the study, 5 were able to willfully modulate their brain activity. In three of these patients, additional bedside testing revealed some sign of awareness, but in the other two patients, no voluntary behavior could be detected by means of clinical assessment. One patient was able to use our technique to answer yes or no to questions during functional MRI; however, it remained impossible to establish any form of communication at the bedside.
Conclusions These results show that a small proportion of patients in a vegetative or minimally conscious state have brain activation reflecting some awareness and cognition. Careful clinical examination will result in reclassification of the state of consciousness in some of these patients. This technique may be useful in establishing basic communication with patients who appear to be unresponsive.
In summary, the results of this study show the potential for functional MRI to bridge the dissociation that can occur between behavior that is readily observable during a standardized clinical assessment and the actual level of residual cognitive function after serious brain injury.Thus, among 23 patients who received a diagnosis of being in a vegetative state on admission, 4 were shown to be able to willfully modulate their brain activity through mental imagery; this fact is inconsistent with the behavioral diagnosis. In two of these patients, however, subsequent assessment at the bedside revealed some behavioral evidence of awareness, a finding that underscores the importance of thorough clinical examination for reducing the rate of misdiagnosis in such patients. Nonetheless, in the two remaining patients, no evidence of awareness could be detected at the bedside by an experienced clinical team, even after the results of the functional MRI examination were known. This finding indicates that, in some patients, motor function can be so impaired that bedside assessments based on the presence or absence of a behavioral response may not reveal awareness, regardless of how thoroughly and carefully they are administered. In patients without a behavioral response, it is clear that functional MRI complements existing diagnostic tools by providing a method for detecting covert signs of residual cognitive function and awareness
In addition, this study showed that in one patient with severe impairment of consciousness, functional MRI established the patient’s ability to communicate solely by modulating brain activity, whereas this ability could not be established at the bedside. In the future, this approach could be used to address important clinical questions. For example, patients could be asked if they are feeling any pain, and this information could be useful in determining whether analgesic agents should be administered. With further development, this technique could be used by some patients to express their thoughts, control their environment, and increase their quality of life.
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_2.
PROBING
CONSCIOUSNESS
WITH
EVENT-RELATED
POTENTIALS
in the
VEGETATIVE
STATE
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THESE researchers employed both the functional MRI approach described in the 2010 New England Journal article and a test of their own devising, in order to determine whether simpler, more widely-available tests can be administered at the bedside to determine whether patients with a diagnosis of persistent vegetative state may be ocasionally aware or able to voluntarily modulate brain activity.
ABSTRACT
Objective: Probing consciousness in noncommunicating patients is a major medical and neuroscientific challenge. While standardized and expert behavioral assessment of patients constitutes a mandatory step, this clinical evaluation stage is often difficult and doubtful, and calls for complementary measures which may overcome its inherent limitations. Several functional brain imaging methods are currently being developed within this perspective, including fMRI and cognitive event-related potentials (ERPs). We recently designed an original rule extraction ERP test that is positive only in subjects who are conscious of the long-term regularity of auditory stimuli.
Methods: In the present work, we report the results of this test in a population of 22 patients who met clinical criteria for vegetative state.
Results: We identified 2 patients showing this neural signature of consciousness. Interestingly, these 2 patients showed unequivocal clinical signs of consciousness within the 3 to 4 days following ERP recording.
Conclusions: Taken together, these results strengthen the relevance of bedside neurophysiological tools to improve diagnosis of consciousness in noncommunicating patients.
Neurology 2011; 77:264–268
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3.
PROF.
ADRIAN
OWEN: Scott Routley |
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MOST
recently, various popular articles and a television program in Britain
highlighted Prof. Owen's work with a patient who had been diagnosed as being in
a persistent vegetative state for more than a decade. The patient was able
to communicate that he was not in any pain. Details of this work will be
published in a peer-reviewed journal in 2013.
[Abstracts and titles of
Dr. Owen's publications follow].
Scott Routley hasn't spoken or even followed family members with his eyes since his car accident 12 years ago. But he managed to indicate to doctors this spring that he was not in pain.
And he did it by imagining his playing tennis as researchers watched for certain areas of his brain scan to light up during an fMRI, something he and neuroscientist Adrian Owen worked out as a signal for "no" over a series of sessions. The breakthrough technique proved Routley isn't in a vegetative state, as doctors thought. He's aware of the world around him.
"Some people can look like they're vegetative but still have awareness inside their head. I think it's a very important finding," said Bryan Young, the neurologist at University Hospital in London, Ontario, who has treated Routley for the past decade.
ABC News, Nov. 14, 2012
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f[unctional]NRIS SCANNER |
Disorders of consciousness. - Owen AM - Ann N Y Acad Sci - 01-MAR-2008; 1124: 225-38
Abstract:
The vegetative state and other so-called disorders of consciousness present
some of the most significant practical and ethical challenges in modern
medicine. It is extremely difficult to assess residual cognitive function in
these patients because their movements may be minimal or inconsistent, or
because no cognitive output may be possible. In recent years, behavioral and
neuroimaging techniques developed within the cognitive neurosciences have
provided a number of new approaches for investigating these disorders,
leading to significant advances in current understanding. In several cases,
residual cognitive function and even conscious awareness have been
demonstrated in patients who are assumed to be vegetative yet retain
cognitive abilities that have evaded detection using standard clinical
methods. In this article, I review these data, focusing primarily on the
vegetative and minimally conscious states.
Functional neuroimaging of the vegetative state. - Owen AM - Nat Rev Neurosci - 01-MAR-2008; 9(3): 235-43
Abstract:
A number of recent studies have demonstrated a role for state-of-the-art
neuroimaging methods in the assessment of patients in the vegetative state
and other so-called 'disorders of consciousness'. In several cases,
functional MRI has been used to show that aspects of speech perception,
emotional processing, language comprehension and even conscious awareness
might be retained in some patients who behaviourally meet all of the
criteria that define the vegetative state. This work has profound
implications for clinical care, diagnosis, prognosis and medical-legal
decision making (relating to the prolongation, or otherwise, of life after
severe brain injury), as well as for more basic scientific questions about
the nature of consciousness and the neural representation of our own
thoughts and intentions.
Detecting awareness in the vegetative state. - Owen AM - Ann N Y Acad Sci - 01-JAN-2008; 1129: 130-8
Abstract:
The assessment of residual brain function in the vegetative state, is
extremely difficult and depends frequently on subjective interpretations of
observed spontaneous and volitional behaviors. For those patients who retain
peripheral motor function, rigorous behavioral assessment supported by
structural imaging and electrophysiology is usually sufficient to establish
a patient's level of wakefulness and awareness. However, it is becoming
increasingly apparent that, in some patients, damage to the peripheral motor
system may prevent overt responses to command, even though the cognitive
ability to perceive and understand such commands may remain intact. Advances
in functional neuroimaging suggest a novel solution to this problem; in
several recent cases, so-called "activation" studies have been used to
identify residual cognitive function and even conscious awareness in
patients who are assumed to be vegetative, yet retain cognitive abilities
that have evaded detection using standard clinical methods.
Hampshire A, Thompson R, Duncan J, Owen AM.
Lateral Prefrontal Cortex Subregions Make Dissociable Contributions during
Fluid Reasoning. Cerebral Cortex, 21(1):1-10. 2011.
Fernandez-Espejo, D., Bekinschtein, T., Monti, M.M., Pickard, J.D., Junque,
C., Coleman, M.R., Owen, A.M.
Diffusion weighted imaging distinguishes the vegetative state from the
minimally conscious state, Neuroimage; 54(1) :103-12, 2011.
Cruse, D., Monti. M.M. Owen, A.M. Neuroimaging in disorders of consciousness: contributions to diagnosis and prognosis. Future Neurology, 6(2), 2011.
Bekinschtein T, Manes F, Villarreal M, Owen AM, Della Maggiore V. Functional imaging reveals movement preparatory activity in the vegetative state. Frontiers in Human Neuroscience 2011; 5: 1-11.
Huntley, J; Bor, D; Hampshire, A; Owen, A.M.; Howard, R. Working memory task performance and chunking in early Alzheimer’s disease. The British Journal of Psychiatry 2011 198: 398-403.
Bekinschtein, T.A.; Davis, M.H.; Rodd, J.M; Owen, A.M. Why clowns taste funny: the relationship between humour and semantic ambiguity. Journal of Neuroscience, 31(26):9665-9671, 2011.
Bruno, M.A., Fernandez-Espejo, D., Lehembre, R., Tshibanda, L., Vanhaudenhuyse, A., Gosseries, O., Lommers, E., Napolitani, M. Noirhomme, Q., Boly, M., Papa, M., Owen, A.M., Maquet, P., Laureys, S., Soddu, A. Multimodal neuroimaging in patients with disorders of consciousness showing “functional hemispherectomy. Progress in Brain Research 2011; 193:323-33
Cruse, D., Chennu, S., Chatelle, C., Bekinschtein, T.A., Fernandez-Espejo, D., Pickard, D.J., Laureys, S., Owen, A.M. Bedside detection of awareness in the vegetative state. The Lancet. 2011 DOI:10.1016/S0140-6736(11)61224-5.
Monti, M.M, Pickard, J.D, Owen, A.M. Visual Cognition in Disorders of Consciousness: from V1 to top-down attention. Human Brain Mapping, in press.
Hampshire, A., Chaudry, A., Owen, AM., Roberts, A. Dissociable roles for Lateral Orbitofrontal Cortex and Lateral Prefrontal Cortex during preference driven reversal learning. Neuroimage, in press.
Cruse, D., Chennu, S., Chatelle, C., Fernández-Espejo, D., Bekinschtein, T. A., Pickard, J. D., Laureys, S., & Owen, A.M. The relationship between aetiology and covert cognition in the minimally conscious state. Neurology, in press.
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