Original Article
Willful Modulation of Brain Activity in Disorders of Consciousness
N Engl J Med 2010; 362:579-589February 18, 2010
- Abstract
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.
Media in This Article
Figure 1
Mental-Imagery Tasks.Figure 2
Localizer Scans.Article Activity
- Article
In recent years, improvements in intensive care have led to an increase in the number of patients who survive severe brain injury. Although some of these patients go on to have a good recovery, others awaken from the acute comatose state but do not show any signs of awareness. If repeated examinations yield no evidence of a sustained, reproducible, purposeful, or voluntary behavioral response to visual, auditory, tactile, or noxious stimuli, a diagnosis of a vegetative state — or “wakefulness without awareness” — is made.1-5 Some patients remain in a vegetative state permanently. Others eventually show inconsistent but reproducible signs of awareness, including the ability to follow commands, but they remain unable to communicate interactively. In 2002, the Aspen Neurobehavioral Conference Work Group coined the term “minimally conscious state” to describe the condition of such patients, thereby adding a new clinical entity to the spectrum of disorders of consciousness.6
There are two main goals in the clinical assessment of patients in a vegetative or minimally conscious state. The first goal is to determine whether the patient retains the capacity for a purposeful response to stimulation, however inconsistent. Such a capacity, which suggests at least partial awareness, distinguishes minimally conscious patients from those in a vegetative state and therefore has implications for subsequent care and rehabilitation, as well as for legal and ethical decision making. Unfortunately, the behavior elicited from these patients is often ambiguous, inconsistent, and constrained by varying degrees of paresis, making it very challenging to distinguish purely reflexive from voluntary behaviors. Nevertheless, in the absence of an absolute measure, awareness has to be inferred from a patient's motor responsiveness; this fact undoubtedly contributes to the high rate of diagnostic errors (approximately 40%) in this group of patients.7-9
The second goal of clinical assessment is to harness and nurture any available response, through intervention, into a form of reproducible communication, however rudimentary. The acquisition of any interactive and functional verbal or nonverbal method of communication is an important milestone. Clinically, consistent and repeatable communication demarcates the upper boundary of a minimally conscious state.6
In this article, we present the results of a study conducted between November 2005 and January 2009 in which functional magnetic resonance imaging (MRI) was routinely used in the evaluation of a group of 54 patients with a clinical diagnosis of being in a vegetative state or a minimally conscious state. In light of a previous single-case study that showed intact awareness in a patient who met the clinical criteria for being in a vegetative state,10 our investigation had two main aims. The first aim was to determine what proportion of this group of patients could also reliably and repeatedly modulate their functional MRI responses, reflecting preserved awareness. The second aim was to develop and validate a method that would allow such patients to functionally communicate yes-or-no responses by modulating their own brain activity, without training and without the need for any motor response.
Methods
Patients
A convenience sample of 54 patients with severe brain injury, including 23 in a vegetative state and 31 in a minimally conscious state, underwent functional MRI as a means of evaluating their performance on motor and spatial imagery tasks. Characteristics of the patients are shown in Table 1Table 1
Characteristics of the Patients., and the inclusion criteria are described in the Supplementary Appendix, available with the full text of this article at NEJM.org. Written informed consent was obtained from the legal guardians of all patients. The motor and spatial imagery tasks have been well validated in healthy control subjects10-12 and are known to be associated with distinct functional MRI activity in the supplementary motor area and the parahippocampal gyrus.The method to detect functional communication was first tested for feasibility and robustness in 16 healthy control subjects (9 men and 7 women) with no history of a neurologic disorder. Once validated, the tasks were given to one patient (Patient 23 in Table 1 and Figure 1Figure 1
Mental-Imagery Tasks.), who had received a diagnosis of being in a permanent vegetative state 17 months after a traffic accident; this diagnosis was confirmed by a month-long specialized assessment 3.5 years after the injury. At the time of admission for functional MRI scanning (5 years after the ictus), the patient was assumed to remain in a vegetative state, although extensive behavioral testing after the functional MRI revealed reproducible, but inconsistent, responses indicative of a minimally conscious state. (The Supplementary Appendix includes detailed results and a description of the clinical assessment of this patient.)Imagery Tasks
While in the functional MRI scanner, all patients were asked to perform two imagery tasks. In the motor imagery task, they were instructed to imagine standing still on a tennis court and to swing an arm to “hit the ball” back and forth to an imagined instructor. In the spatial imagery task, participants were instructed to imagine navigating the streets of a familiar city or to imagine walking from room to room in their home and to visualize all that they would “see” if they were there. First, two so-called localizer scanning sessions were conducted in which the patients were instructed to alternate 30-second periods of mental imagery with 30-second periods of rest. Each scan included five rest–imagery cycles. The beginning of each imagery period was cued with the spoken word “tennis” or “navigation,” and rest periods were cued with the word “relax.”
Communication Task
After the localizer scans had been obtained, all 16 control subjects and 1 patient underwent functional MRI during which they attempted to answer questions by modulating their brain activity, and a set of so-called communication scans were obtained. Before each of these imaging sessions, participants were asked a yes-or-no question (e.g., “Do you have any brothers?”) and instructed to respond during the imaging session by using one type of mental imagery (either motor imagery or spatial imagery) for “yes” and the other for “no.” The nature of the questions ensured that the investigators would not know the correct answers before judging the functional MRI data. Participants were asked to respond by thinking of whichever imagery corresponded to the answer that they wanted to convey. Communication scanning was identical to localizer scanning with the exception that the same neutral word “answer” was used to cue each response to a question (with “relax” used as the cue for rest periods). Cues were delivered once, at the beginning of each period. Three communication scans (with one question per scan) were obtained for each of the 16 healthy control subjects. To maximize statistical power, six communication scans (with one question per scan) were obtained for the patient.
Statistical Analysis
Analyses were performed with the use of FSL software, version 4.1.13 Data analysis included standard functional MRI preprocessing steps (functional MRI acquisition and preprocessing are described in the Supplementary Appendix). For each scan, a general linear model contrasting periods of active imagery with periods of rest was computed. All contrasts were limited to the brain locations within the supplementary motor area and the parahippocampal gyrus, as defined in the Harvard–Oxford Cortical Structural Atlas (available in FSL software), and a threshold was established, with gaussian random-fields theory, at a cluster-level z value of more than 2.3 (corrected P<0.05). The defined regions of interest were transformed from standard space (according to the criteria of the Montreal Neurological Institute) to fit each subject's structural image, with the use of a method involving 12 degrees of freedom.
To determine whether the imagery tasks produced the expected activations in predefined neuroanatomical locations, two scans were compared for each participant: motor imagery and spatial imagery. The multiple localizer scanning sessions of the patient who also underwent communication scanning were averaged with the use of a fixed-effects model.
Answers provided during the communication scanning were assessed with the use of a two-step procedure. First, activity in the two regions of interest (the supplementary motor area and the parahippocampal gyrus) identified during the localizer scanning was quantitatively characterized (with the use of the average generalized linear model estimate for each region of interest). Next, a similarity metric (described in the Supplementary Appendix) was computed to quantify how closely the activity in the regions of interest on each communication scan matched each localizer scan.
Results
Responses to the Imagery Tasks
Among the 54 patients, we identified 5 who could willfully modulate their brain activity (Figure 1). In all five of these patients, the functional MRI scans associated with motor imagery, as compared with spatial imagery, showed considerable activation in the supplementary motor area. In four of the five patients, the scans associated with spatial imagery, as compared with motor imagery, showed activation in the parahippocampal gyrus. Furthermore, the time course of activity within the two regions of interest was sustained for 30 seconds and was associated with the delivery of the verbal cues (Figure 2Figure 2
Localizer Scans.). These results closely match the pattern observed in the healthy control subjects (Figure 1, and the Supplementary Appendix). Four of the five patients were considered to be in a vegetative state (including Patient 4, who has been described previously10), and all five patients had a traumatic brain injury (Table 1).Responses to the Communication Task
Each of the 16 healthy control subjects underwent functional MRI to obtain three communication scans. For all 48 questions in the communication task, the correct answer was determined with 100% accuracy by comparing the activations shown on the communication scans with the activations shown on two localizer scans. In all subjects, the pattern produced in response to each question was quantitatively more similar to the pattern observed in the localizer scan for the imagery task that was associated with the factually correct answer; this answer was verified after the analysis. Figure 2B and 2D and Figure 3B and 3DFigure 3
Communication Scans. show this similarity in a healthy control. In this subject, the activation associated with the imagery period as compared with the rest period for question 1 resulted in extensive activation in the supplementary motor area and minimal activity in the parahippocampal gyrus (Figure 4Figure 4
Region-of-Interest Data.). This pattern was almost identical to that observed in the activation associated with the motor imagery period as compared with the rest period in the motor localizer scan. Conversely, the imagery period as compared with the rest period for questions 2 and 3 was associated with extensive activation of the parahippocampal gyrus and, to a lesser extent, the supplementary motor area; these findings closely matched the activation seen in the spatial localizer scan. Similar patterns were observed in 9 of 16 control subjects. In the remaining seven control subjects, the distinction between tasks was even clearer; thus, a double dissociation was observed between activity in the supplementary motor area for motor imagery and activity in the parahippocampal gyrus for spatial navigation (see the Supplementary Appendix).To assess whether such an approach could be used in a patient with impaired consciousness, one of the patients who had reliable responses during the two imagery tasks (Patient 23) was also asked six yes-or-no autobiographical questions and instructed to respond by thinking of one type of imagery (either motor imagery or spatial imagery) for an affirmative answer and the other type of imagery for a negative answer.
In this patient, the activity observed on the communication scan in response to five of the six questions closely matched that observed on one of the localizer scans (Figure 2A and 2C and Figure 3A and 3C). For example, in response to the question “Is your father's name Alexander?” the patient responded “yes” (correctly) with activity that matched that observed on the motor-imagery localizer scan (Figure 3A). In response to the question “Is your father's name Thomas?” the patient responded “no” (also correctly) with activity that matched that observed in the spatial-imagery localizer scan (Figure 3C).
The relative-similarity analysis confirmed, quantitatively, that the activity observed on the communication scans accurately reproduced that observed on the localizer scans within the bounds of normal variability for five of the six questions (Figure 4, and Tables A1 and A2 in the Supplementary Appendix). In addition, for those same five questions, the pattern produced always matched the factually correct answer. Only one question, the last one, could not be decoded. However, this was not because the “incorrect” pattern of activation was observed, but rather because virtually no activity was observed within the regions of interest.
Discussion
In this study, functional MRI was used to determine the incidence of undetected awareness in a group of patients with severe brain injuries. Of the 54 patients, 5 with traumatic brain injuries were able to modulate their brain activity by generating voluntary, reliable, and repeatable blood-oxygenation-level–dependent responses in predefined neuroanatomical regions when prompted to perform imagery tasks. No such responses were observed in any of the patients with nontraumatic brain injuries. Four of the five patients who were able to generate these responses were admitted to the hospital with a diagnosis of being in a vegetative state. When these four patients were thoroughly retested at the bedside, some behavioral indicators of awareness could be detected in two of them. However, the other two patients remained behaviorally unresponsive at the bedside, even after the functional MRI results were known and despite repeated testing by a multidisciplinary team. Thus, in a minority of cases, patients who meet the behavioral criteria for a vegetative state have residual cognitive function and even conscious awareness.14,15
We conducted additional tests in one of the five patients with evidence of awareness on functional MRI, and we found that he had the ability to apply the imagery technique in order to answer simple yes-or-no questions accurately. Before the scanning was performed, the patient had undergone repeated evaluations indicating that he was in a vegetative state, including a month-long specialized assessment by a highly trained clinical team. At the time of scanning, however, thorough retesting at the bedside showed reproducible but highly fluctuating and inconsistent signs of awareness (see the Supplementary Appendix), findings that are consistent with the diagnosis of a minimally conscious state. Nonetheless, despite the best efforts of the clinical team, it was impossible to establish any functional communication at the bedside, and the results of the behavioral examination remained ambiguous and inconsistent. In contrast, the functional MRI approach allowed the patient to establish functional and interactive communication. Indeed, for five of the six questions, the patient had a reliable neural response and was able to provide the correct answer with 100% accuracy. For the remaining question — the last question of the imaging session — the lack of activity within the regions of interest precluded any analysis of the results. Whether the patient fell asleep during this question, did not hear it, simply elected not to answer it, or lost consciousness cannot be determined.
Although the functional MRI data provided clear evidence that the patient was aware and able to communicate, it is not known whether either ability was available during earlier evaluations. It is possible that he was in a vegetative state when the diagnosis was received at 17 months and again 3.5 years after injury and subsequently regained some aspects of cognitive functioning. Alternatively, the patient may have been aware during previous assessments but unable to produce the necessary motor response required to signal his state of consciousness. If this was the case, then the clinical diagnosis of a vegetative state was entirely accurate in the sense that no behavioral markers of awareness were evident. That said, the diagnosis did not accurately reflect the patient's internal state of awareness and level of cognitive functioning at the time. Given that all previous assessments were based on behavioral observations alone, these two possibilities are indistinguishable.
Among 49 of the 54 patients included in this study, no significant functional MRI changes were observed during the imagery tasks. In these patients, it is not possible to determine whether the negative findings were the result of the low “sensitivity” of the method (e.g., failure to detect small effects), or whether they genuinely reflect the patients' limited cognitive abilities. Some patients, for example, may have been unconscious (permanently or transiently) during scanning. Similarly, in some awake and aware patients who were in a minimally conscious state, the tasks may simply have exceeded their residual cognitive capabilities. Deficits in language comprehension, working memory, decision making, or executive function would have prevented successful completion of the imagery tasks. However, positive results, whether observed with or without corroborative behavioral data, do confirm that all such processes were intact and that the patient must have been aware.
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.14-16 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 function17-20 and awareness.10
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.
Supported by grants from the Medical Research Council (U.1055.01.002.00007.01 and U.1055.01.002.00001.01), the European Commission (Disorders and Coherence of the Embodied Self, Mindbridge, Deployment of Brain–Computer Interfaces for the Detection of Consciousness in Nonresponsive Patients, and Consciousness: A Transdisciplinary, Integrated Approach), Fonds de la Recherche Scientifique, the James S. McDonnell Foundation, the Mind Science Foundation, the Reine Elisabeth Medical Foundation, the Belgian French-Speaking Community Concerted Research Action, University Hospital of Liege, the University of Liege, and the National Institute for Health Research Biomedical Research Centre (Neurosciences Theme).
No potential conflict of interest relevant to this article was reported.
Dr. Monti and Ms. Vanhaudenhuyse contributed equally to this article.
This article (10.1056/NEJMoa0905370) was published on February 3, 2010, at NEJM.org.
We thank Daniel Gary Wakeman for his helpful discussions.
Source Information
From the Medical Research Council Cognition and Brain Sciences Unit (M.M.M., A.M.O.), the Impaired Consciousness Study Group, Wolfson Brain Imaging Centre, University of Cambridge (M.R.C.), and the Division of Academic Neurosurgery, Addenbrooke's Hospital (J.D.P.) — all in Cambridge, United Kingdom; and the Coma Science Group, Cyclotron Research Center, University of Liege (A.V., M.B., S.L.), and the Departments of Neurology (S.L., M.B.) and Neuroradiology (L.T.), University Hospital of Liege, Liege; and Fonds de la Recherche Scientifique, Brussels (A.V., S.L., M.B.) — all in Belgium.
Address reprint requests to Dr. Owen at the Medical Research Council Cognition and Brain Sciences Unit, 15 Chaucer Rd., Cambridge CB2 7EF, United Kingdom, or at adrian.owen@mrc-cbu.cam.ac.uk.
- References
References
1
Jennett B ,Plum F . Persistent vegetative state after brain damage: a syndrome in search of a name. Lancet 1972;1:734-737
CrossRef | Web of Science | Medline2
Jennett B. The vegetative state: medical aspects, ethical and legal dilemmas. Cambridge, England: Cambridge University Press, 2002.
3
Laureys S . The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci 2005;9:556-559
CrossRef | Web of Science | Medline4
The Multi-Society Task Force on PVS
Full Text | Web of Science | Medline5
The vegetative state: guidance on diagnosis and management. London: Royal College of Physicians of London, 2003.
6
Giacino JT ,Ashwal S ,Childs N , et al. The minimally conscious state: definition and diagnostic criteria. Neurology 2002;58:349-353
Web of Science | Medline7
Andrews K ,Murphy L ,Munday R ,Littlewood C . Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit. BMJ 1996;313:13-16
CrossRef | Web of Science | Medline8
Childs NL ,Mercer WN ,Childs HW . Accuracy of diagnosis of persistent vegetative state. Neurology 1993;43:1465-1467
Web of Science | Medline9
Schnakers C ,Vanhaudenhuyse A ,Giacino J , et al. Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment. BMC Neurol 2009;9:35-35
CrossRef | Web of Science | Medline10
Owen AM ,Coleman MR ,Boly M ,Davis MH ,Laureys S ,Pickard JD . Detecting awareness in the vegetative state. Science 2006;313:1402-1402
CrossRef | Web of Science | Medline11
Boly M ,Coleman MR ,Hampshire A , et al. When thoughts become action: an fMRI paradigm to study volatile brain activity in non-communicative brain injured patients. Neuroimage 2007;36:979-992
CrossRef | Web of Science | Medline12
Weiskopf N ,Mathiak K ,Bock SW , et al. Principles of a brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI). IEEE Trans Biomed Eng 2004;51:966-970
CrossRef | Web of Science | Medline13
Smith SM ,Jenkinson M ,Woolrich MW , et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004;23:Suppl 1:S208-S219
CrossRef | Web of Science | Medline14
Owen AM ,Coleman MR . Functional neuroimaging of the vegetative state. Nat Rev Neurosci 2008;9:235-243
CrossRef | Web of Science | Medline15
Monti MM ,Coleman MR ,Owen AM . Neuroimaging and the vegetative state: resolving the behavioral assessment dilemma? Ann N Y Acad Sci 2009;1157:81-89
CrossRef | Web of Science | Medline16
Laureys S ,Owen AM ,Schiff ND . Brain function in coma, vegetative state, and related disorders. Lancet Neurol 2004;3:537-546
CrossRef | Web of Science | Medline17
Coleman MR ,Rodd JM ,Davis MH , et al. Do vegetative patients retain aspects of language comprehension? Evidence from fMRI. Brain 2007;130:2494-2507
CrossRef | Web of Science | Medline18
Monti MM ,Coleman MR ,Owen AM . Executive functions in the absence of behavior: functional imaging of the minimally conscious state. Prog Brain Res 2009;177:249-260
CrossRef | Web of Science | Medline19
Schnakers C ,Perrin F ,Schabus M , et al. Voluntary brain processing in disorders of consciousness. Neurology 2008;71:1614-1620
CrossRef | Web of Science | Medline20
Laureys S ,Faymonville ME ,Peigneux P , et al. Cortical processing of noxious somatosensory stimuli in the persistent vegetative state. Neuroimage 2002;17:732-741
CrossRef | Web of Science | Medline
- Citing Articles (84)
Citing Articles
1
Steven Laureys, Nicholas D. Schiff. (2012) Coma and consciousness: Paradigms (re)framed by neuroimaging. NeuroImage 61:2, 478-491
CrossRef2
M. Ní Lochlainn, S. Gubbins, S. Connolly, R. B. Reilly. (2012) The vegetative and minimally conscious states: a review of the literature and preliminary survey of prevalence in Ireland. Irish Journal of Medical Science
CrossRef3
C. Schnakers, C. Chatelle, A. Demertzi, S. Majerus, S. Laureys. (2012) What about Pain in Disorders of Consciousness?. The AAPS Journal
CrossRef4
Mélanie Boly, Marcello Massimini, Marta Isabel Garrido, Olivia Gosseries, Quentin Noirhomme, Steven Laureys, Andrea Soddu. (2012) Brain Connectivity in Disorders of Consciousness. Brain Connectivity120418121148007
CrossRef5
(2012) Proceedings of the 2012 Spring meeting of the Society of British Neurological Surgeons. British Journal of Neurosurgery 26:2, 132-174
CrossRef6
Jussi Jylkkä. (2012) Natural Concepts, Phenomenal Concepts, and the Conceivability Argument. Erkenntnis
CrossRef7
Stephen J. Morse. 2012. Neuroimaging Evidence in Law: A Plea for Modesty and Relevance. , 341-357.
CrossRef8
Kirsten Brukamp. (2012) Right (to a) Diagnosis? Establishing Correct Diagnoses in Chronic Disorders of Consciousness. Neuroethics
CrossRef9
Timothy Lane. (2012) Toward an explanatory framework for mental ownership. Phenomenology and the Cognitive Sciences
CrossRef10
(2012) Bildgebungsverfahren decken hohe Fehlerquote auf. ProCare 17:1-2, 18-18
CrossRef11
Judy Illes, Christine Stables. (2012) Ask the Neuroethicist: Should Patients in Disordered States of Consciousness Be Enrolled in Research? How to Decide. Neurology Today 12:4, 30
CrossRef12
Alison K. Godbolt, Staffan Stenson, Maria Winberg, Christer Tengvar. (2012) Disorders of consciousness: Preliminary data supports added value of extended behavioural assessment. Brain Injury 26:2, 188-193
CrossRef13
Sébastien Marti, Mariano Sigman, Stanislas Dehaene. (2012) A shared cortical bottleneck underlying Attentional Blink and Psychological Refractory Period. NeuroImage 59:3, 2883-2898
CrossRef14
Frank Tong, Michael S. Pratte. (2012) Decoding Patterns of Human Brain Activity. Annual Review of Psychology 63:1, 483-509
CrossRef15
M. Rosanova, O. Gosseries, S. Casarotto, M. Boly, A. G. Casali, M.-A. Bruno, M. Mariotti, P. Boveroux, G. Tononi, S. Laureys, M. Massimini. (2012) Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients. Brain
CrossRef16
Atira S. Bick, Arnaldo Mayer, Netta Levin. (2012) From research to clinical practice: Implementation of functional magnetic imaging and white matter tractography in the clinical environment. Journal of the Neurological Sciences 312:1-2, 158-165
CrossRef17
Nicolas Weiss, Jean-Marc Tadie, Frederic Faugeras, Jean-Luc Diehl, Jean-Yves Fagon, Emmanuel Guerot. (2012) Can fast-component of nystagmus on caloric vestibulo-ocular responses predict emergence from vegetative state in ICU?. Journal of Neurology 259:1, 70-76
CrossRef18
Frédéric Faugeras, Benjamin Rohaut, Nicolas Weiss, Tristan Bekinschtein, Damien Galanaud, Louis Puybasset, Francis Bolgert, Claire Sergent, Laurent Cohen, Stanislas Dehaene, Lionel Naccache. (2012) Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness. Neuropsychologia
CrossRef19
Martin M. Monti, John D. Pickard, Adrian M. Owen. (2012) Visual cognition in disorders of consciousness: From V1 to top-down attention. Human Brain Mappingn/a-n/a
CrossRef20
Luigi Francesco Agnati, Diego Guidolin, Pietro Cortelli, Susanna Genedani, Camilo Cela-Conde, Kjell Fuxe. (2012) Neuronal correlates to consciousness. The "Hall of Mirrors" metaphor describing consciousness as an epiphenomenon of multiple dynamic mosaics of cortical functional modules. Brain Research
CrossRef21
Michael A. Cohen, Daniel C. Dennett. (2012) Response to Fahrenfort and Lamme: defining reportability, accessibility and sufficiency in conscious awareness. Trends in Cognitive Sciences
CrossRef22
James L. Bernat. 2012. Coma, Vegetative State, and Brain Death. , 2294-2299.
CrossRef23
Orsolya Friedrich. (2011) Knowledge of Partial Awareness in Disorders of Consciousness: Implications for Ethical Evaluations?. Neuroethics
CrossRef24
Andrew M. Goldfine, Nicholas D. Schiff. (2011) What is the role of brain mechanisms underlying arousal in recovery of motor function after structural brain injuries?. Current Opinion in Neurology 24:6, 564-569
CrossRef25
Damian Cruse, Srivas Chennu, Camille Chatelle, Tristan A Bekinschtein, Davinia Fernández-Espejo, John D Pickard, Steven Laureys, Adrian M Owen. (2011) Bedside detection of awareness in the vegetative state: a cohort study. The Lancet 378:9809, 2088-2094
CrossRef26
Valdas Noreika, Leila Jylhänkangas, Levente Móró, Katja Valli, Kimmo Kaskinoro, Riku Aantaa, Harry Scheinin, Antti Revonsuo. (2011) Consciousness lost and found: Subjective experiences in an unresponsive state. Brain and Cognition 77:3, 327-334
CrossRef27
George A. Mashour. (2011) Consciousness versus responsiveness: Insights from general anesthetics. Brain and Cognition 77:3, 325-326
CrossRef28
Morten Overgaard, Rikke Overgaard. (2011) Measurements of consciousness in the vegetative state. The Lancet 378:9809, 2052-2054
CrossRef29
Daniela Tarquini, Maria Congedo, Fabio Formaglio, Maddalena Gasparini, Norina Marcello, Corinna Porteri, Eugenio Pucci, Silvia Zullo, Carlo A. Defanti. (2011) Persistent vegetative state: an ethical reappraisal. Neurological Sciences
CrossRef30
Marie-Aurélie Bruno, Steve Majerus, Mélanie Boly, Audrey Vanhaudenhuyse, Caroline Schnakers, Olivia Gosseries, Pierre Boveroux, Murielle Kirsch, Athena Demertzi, Claire Bernard, Roland Hustinx, Gustave Moonen, Steven Laureys. (2011) Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients. Journal of Neurology
CrossRef31
D. Borsook. (2011) Neurological diseases and pain. Brain
CrossRef32
Emily B. Rubin, James L. Bernat. (2011) Ethical Aspects of Disordered States of Consciousness. Neurologic Clinics 29:4, 1055-1071
CrossRef33
Henry T. Greely. (2011) Reading minds with neuroscience – Possibilities for the law. Cortex 47:10, 1254-1255
CrossRef34
Andrew M. Goldfine, Jonathan D. Victor, Mary M. Conte, Jonathan C. Bardin, Nicholas D. Schiff. (2011) Determination of awareness in patients with severe brain injury using EEG power spectral analysis. Clinical Neurophysiology 122:11, 2157-2168
CrossRef35
Daniela Seixas, Deolinda Lima. (2011) Accuracy, reliability, validity and limitations of functional and structural magnetic resonance imaging data. Cortex 47:10, 1266-1269
CrossRef36
G. Bryan Young. (2011) Preface. Neurologic Clinics 29:4, xiii-xiv
CrossRef37
Christian Schwarzbauer, Burkhard Schafer. (2011) fMRI in disorders of consciousness: Future diagnostic opportunities, methodological and legal challenges. Cortex 47:10, 1243-1245
CrossRef38
Ron Hirschberg, Joseph T. Giacino. (2011) The Vegetative and Minimally Conscious States: Diagnosis, Prognosis and Treatment. Neurologic Clinics 29:4, 773-786
CrossRef39
Walter P. Sinnott-Armstrong. (2011) Neurolaw and consciousness detection. Cortex 47:10, 1246-1247
CrossRef40
Andrew M. Goldfine, Nicholas D. Schiff. (2011) Consciousness: Its Neurobiology and the Major Classes of Impairment. Neurologic Clinics 29:4, 723-737
CrossRef41
Antonio Candelieri, Maria Daniela Cortese, Giuliano Dolce, Francesco Riganello, Walter G. Sannita. (2011) Visual Pursuit: Within-Day Variability in the Severe Disorder of Consciousness. Journal of Neurotrauma 28:10, 2013-2017
CrossRef42
Nikolaus Weiskopf. (2011) Real-time fMRI and its application to neurofeedback. NeuroImage
CrossRef43
Cristina Rosazza, Ludovico Minati. (2011) Resting-state brain networks: literature review and clinical applications. Neurological Sciences 32:5, 773-785
CrossRef44
Ralf J. Jox, Katja Kuehlmeyer. (2011) Introduction: Reconsidering Disorders of Consciousness in Light of Neuroscientific Evidence. Neuroethics
CrossRef45
Per M. Aslaksen, Torgil R. Vangberg, Christoph Schäfer. (2011) Probing for consciousness after severe brain injury by functional magnetic resonance imaging (fMRI). Journal of Neurology
CrossRef46
Tom Buller. (2011) Neurotechnology, Invasiveness and the Extended Mind. Neuroethics
CrossRef47
Pietro Pietrini. (2011) From molecules to mind and back…. Current Opinion in Neurology 24:4, 354-356
CrossRef48
Mélanie Boly. (2011) Measuring the fading consciousness in the human brain. Current Opinion in Neurology 24:4, 394-400
CrossRef49
J. Andrew Billings, Senior Associate Editor. (2011) Terminal Extubation of the Alert Patient. Journal of Palliative Medicine 14:7, 800-801
CrossRef50
Marie-Aurélie Bruno, Audrey Vanhaudenhuyse, Aurore Thibaut, Gustave Moonen, Steven Laureys. (2011) From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. Journal of Neurology 258:7, 1373-1384
CrossRef51
A. Demertzi, D. Ledoux, M.-A. Bruno, A. Vanhaudenhuyse, O. Gosseries, A. Soddu, C. Schnakers, G. Moonen, S. Laureys. (2011) Attitudes towards end-of-life issues in disorders of consciousness: a European survey. Journal of Neurology 258:6, 1058-1065
CrossRef52
Francesca Pistoia, Marco Sarà. (2011) Is There a Cartesian Renaissance of the Mind or Is It Time for a New Taxonomy for Low Responsive States?. Journal of Neurotrauma110525140842040
CrossRef53
Dongha Lee, Bumhee Park, Changwon Jang, Hae-Jeong Park. (2011) Decoding brain states using functional magnetic resonance imaging. Biomedical Engineering Letters 1:2, 82-88
CrossRef54
Barbara A Wilson. (2011) ‘Cutting Edge’ Developments in Neuropsychological Rehabilitation and Possible Future Directions. Brain Impairment 12:1, 33-42
CrossRef55
Jukka Varelius. (2011) Pascal’s Wager and Deciding About the Life-Sustaining Treatment of Patients in Persistent Vegetative State. Neuroethics
CrossRef56
Marie-Aurélie Bruno, Olivia Gosseries, Didier Ledoux, Roland Hustinx, Steven Laureys. (2011) Assessment of consciousness with electrophysiological and neurological imaging techniques. Current Opinion in Critical Care 17:2, 146-151
CrossRef57
E. Roy John, James P. Halper, R. Sandlin Lowe, Henry Merkin, Philip Defina, Leslie S. Prichep. (2011) Source imaging of QEEG as a method to detect awareness in a person in vegetative state. Brain Injury 25:4, 426-432
CrossRef58
Stanislas Dehaene, Jean-Pierre Changeux. (2011) Experimental and Theoretical Approaches to Conscious Processing. Neuron 70:2, 200-227
CrossRef59
Jeremy F. Magland, Christopher W. Tjoa, Anna Rose Childress. (2011) Spatio-temporal activity in real time (STAR): Optimization of regional fMRI feedback. NeuroImage 55:3, 1044-1053
CrossRef60
Peter Sörös. (2011) The neural correlates of consciousness: Electrophysiological and neuroimaging evidence for conscious processing in vegetative state. Clinical Neurophysiology 122:4, 641-642
CrossRef61
J. C. Bardin, J. J. Fins, D. I. Katz, J. Hersh, L. A. Heier, K. Tabelow, J. P. Dyke, D. J. Ballon, N. D. Schiff, H. U. Voss. (2011) Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury. Brain 134:3, 769-782
CrossRef62
Damian Cruse, Martin M Monti, Adrian M Owen. (2011) Neuroimaging in disorders of consciousness: contributions to diagnosis and prognosis. Future Neurology 6:2, 291-299
CrossRef63
Marie Thonnard, Mélanie Boly, Marie-Aurélie Bruno, Camille Chatelle, Olivia Gosseries, Steven Laureys, Audrey Vanhaudenhuyse. (2011) La neuro-imagerie : un outil diagnostique des états de conscience altérée. médecine/sciences 27:1, 77-81
CrossRef64
Davinia Fernández-Espejo, Tristan Bekinschtein, Martin M. Monti, John D. Pickard, Carme Junque, Martin R. Coleman, Adrian M. Owen. (2011) Diffusion weighted imaging distinguishes the vegetative state from the minimally conscious state. NeuroImage 54:1, 103-112
CrossRef65
Jörgen Borg, Cecilie Röe, Annette Nordenbo, Nada Andelic, Catharina de Boussard, Jean-Luc af Geijerstam. (2011) Trends and Challenges in the Early Rehabilitation of Patients with Traumatic Brain Injury. American Journal of Physical Medicine & Rehabilitation 90:1, 65-73
CrossRef66
Sonja C. Kleih, Tobias Kaufmann, Claudia Zickler, Sebastian Halder, Francesco Leotta, Febo Cincotti, Fabio Aloise, Angela Riccio, Cornelia Herbert, Donatella Mattia, Andrea Kübler. 2011. Out of the frying pan into the fire—the P300-based BCI faces real-world challenges. , 27-46.
CrossRef67
J.A. Stockman. (2011) Willful Modulation of Brain Activity in Disorders of Consciousness. Yearbook of Pediatrics 2011, 398-399
CrossRef68
Haiwen Chen, Jane Epstein, Emily Stern. (2010) Neural Plasticity After Acquired Brain Injury: Evidence from Functional Neuroimaging. PM&R 2:12, S306-S312
CrossRef69
Damian Cruse, Adrian M Owen. (2010) Consciousness revealed: new insights into the vegetative and minimally conscious states. Current Opinion in Neurology 23:6, 656-660
CrossRef70
Oliver R. Goodenough, Micaela Tucker. (2010) Law and Cognitive Neuroscience. Annual Review of Law and Social Science 6:1, 61-92
CrossRef71
Rimona S Weil, Geraint Rees. (2010) Decoding the neural correlates of consciousness. Current Opinion in Neurology 23:6, 649-655
CrossRef72
Joel Gutiérrez, Calixto Machado, Mario Estévez, Ana Olivares, Héctor Hernández, Jesus Perez, Carlos Beltrán, Gerry Leisman. (2010) Heart rate variability changes induced by auditory stimulation in persistent vegetative state. International Journal on Disability and Human Development 9:4, 357-362
CrossRef73
G. Bauer, S. Golaszewski, Franz Gerstenbrand. (2010) Das Locked-In-Syndrom. Psychopraxis 13:5-6, 18-22
CrossRef74
Caroline Schnakers, Camille Chatelle, Steve Majerus, Olivia Gosseries, Marie De Val, Steven Laureys. (2010) Assessment and detection of pain in noncommunicative severely brain-injured patients. Expert Review of Neurotherapeutics 10:11, 1725-1731
CrossRef75
Sally Wang, Jeremy O. Bressman, Jay S. Reidler. (2010) Recent Case Developments in Health Law. The Journal of Law, Medicine & Ethics 38:3, 708-716
CrossRef76
A. Plotkin, L. Sela, A. Weissbrod, R. Kahana, L. Haviv, Y. Yeshurun, N. Soroker, N. Sobel. (2010) From the Cover: Sniffing enables communication and environmental control for the severely disabled. Proceedings of the National Academy of Sciences 107:32, 14413-14418
CrossRef77
Anish N. Sen, Peter G. Campbell, Sanjay Yadla, Jack Jallo, Ashwini D. Sharan. (2010) Deep brain stimulation in the management of disorders of consciousness: a review of physiology, previous reports, and ethical considerations. Neurosurgical FOCUS 29:2, E14
CrossRef78
Rainer Goebel, Anna Zilverstand, Bettina Sorger. (2010) Real-time fMRI-based brain–computer interfacing for neurofeedback therapy and compensation of lost motor functions. Imaging in Medicine 2:4, 407-415
CrossRef79
Carl E. Fisher, Paul S. Appelbaum. (2010) Diagnosing Consciousness: Neuroimaging, Law, and the Vegetative State. The Journal of Law, Medicine & Ethics 38:2, 374-385
CrossRef80
(2010) Willful Modulation of Brain Activity in Disorders of Consciousness. New England Journal of Medicine 362:20, 1936-1938
Full Text81
CIARAN J. POWERS, ROBERT J. DEMPSEY. (2010) Thoughts on Consciousness. Neurosurgery 66:4, N22-N23
CrossRef82
(2010) News in brief. Nature Medicine 16:3, 252-253
CrossRef83
Ropper, Allan H., . (2010) Cogito Ergo Sum by MRI. New England Journal of Medicine 362:7, 648-649
Full Text84
John G. Milton. (2010) Quantitative Neuroscience: From Chalk Board to Bedside. Mathematical Modelling of Natural Phenomena 5:2, 1-4
CrossRef
- Letters
