Detecting Awareness After Severe Brain Injury

PERSPECTIVES Recently, the results of some functional SCIENCE AND SOCIETY MRI (fMRI) and EEG studies have called into question the extent to which we can Detecting awareness after severe reliably consider a patient unaware simply because they exhibit no overt behavioural brain injury response to external stimulation8–11. Indeed, these studies have revealed a subset of patients who are aware but entirely physi- Davinia Fernández-Espejo and Adrian M. Owen cally unresponsive; thus, although they Abstract | Recent developments in functional neuroimaging have provided a fulfil all internationally agreed criteria for number of new tools for assessing patients who clinically appear to be in a the vegetative state, which are based on vegetative state. These techniques have been able to reveal awareness and even behavioural signs, clear signs of command- following can be demonstrated using fMRI allow rudimentary communication in some patients who remain entirely or EEG. In some cases, these developments behaviourally non-responsive. The implications of these results extend well beyond in functional neuroimaging technology have the immediate clinical and scientific findings to influencing legal proceedings, even allowed such patients to communicate raising new ethical questions about the withdrawal of nutrition and hydration and with the outside world for the first time since 10 providing new options for patients and families in that decision-making process. their brain injury . In this Perspective article, we begin by The findings have also motivated significant public discourse about the role of reviewing the ‘state‑of‑the-art’ of the two neuroscience research in society. methods — fMRI and EEG — that have been successfully used to detect covert aware- The definition and assessment of conscious- The vegetative state is a clinical condi- ness in the vegetative state, with a focus on ness is still one of the most challenging areas tion that is often described as ‘wakefulness the major developments that have emerged of contemporary neuroscience. Empirically, without awareness’ (REF. 6) (BOX 1). These within the past 5 years. We then describe the consciousness is often separated into two patients open their eyes, frequently move paradigmatic case of a recent patient who, components: wakefulness (also known as spontaneously and will often exhibit despite fulfilling all of the accepted diagnos- ‘arousal’, referring to the level of conscious- sleeping and waking cycles. Hence, the tic criteria for the vegetative state 12 years ness) and awareness (the contents of con- waking component of consciousness is after a serious brain injury, was shown — sciousness)1. Wakefulness is a state in which demonstrably preserved. However, careful using both fMRI and EEG — to be fully the eyes are open and in which, typically, and repeated examination of the patient’s aware and able to communicate cognitively there is a degree of motor arousal, whereas spontaneous and elicited behaviour will and therapeutically relevant information awareness is accompanied by the ability to yield no evidence of a sustained, repro- about his condition. Last, we use this case have (and the act of having) an experience of ducible, purposeful or voluntary behav- and the broader issues that it raises to guide some kind2. Wakefulness is relatively easy to ioural response to visual, auditory, tactile a discussion about how these new methods measure by confirming that the eyes are open or noxious stimulation. In short, such are affecting diagnosis, prognosis and legal and/or that the resting state electroencepha- patients exhibit no spontaneous pur- decision making, with reference to their lography (EEG) recording exhibits a pattern poseful behaviour and are entirely non- specific challenges and limitations. that is typical for the normal waking state. responsive to any form of prompting or Measuring awareness is much more difficult. stimulation (beyond simple reflexes), and State‑of‑the-art Indeed, objective functional biomarkers of it is on this basis that it is assumed that the fMRI responses as evidence of awareness. In awareness are lacking (Supplementary infor- awareness component of consciousness is 2006, we introduced a method for eliciting mation S1 (box)) and, clinically, the ability absent. It is now well accepted3–5 that when covert command-following (and there- to follow commands — either verbally or specialized clinical teams examine these fore detecting the awareness component behaviourally — has to be used as a proxy patients, up to 43% will show inconsist- of consciousness) with fMRI9. Using this measure for awareness. However, consistent ent, but reproducible, behavioural signs technique, a patient who fulfilled all of the command-following is not always possible in of awareness and will be reclassified as internationally agreed clinical criteria for severely brain-injured patients and residual being in a minimally conscious state7. the vegetative state was shown to be cov- awareness has to be inferred on the basis of Nevertheless, it remains likely that some ertly aware and able to wilfully respond to any behaviour that is observed. The subjec- covertly aware patients will escape detec- commands by simply modulating her fMRI tive nature of this inference undoubtedly tion, even by experienced teams, and will activity. Specifically, while in the scanner, contributes to the well-documented rate of remain erroneously diagnosed as being in a the patient was asked to imagine hitting a misdiagnosis in this population3–5. vegetative state8. tennis ball back and forth to an imaginary NATURE REVIEWS | NEUROSCIENCE VOLUME 14 | NOVEMBER 2013 | 1 © 2013 Macmillan Publishers Limited. All rights reserved PERSPECTIVES Box 1 | Vegetative state: a syndrome in search of a name intention of the participant to generate and sustain a response to the given instruction. Before 1972, there was no universally accepted term to refer to patients who did not exhibit Such (neural) behaviour provides a proxy normal levels of consciousness after a brain injury. Until then, the only reports available in the for a motor action and is therefore an appro- literature were single-case studies in which various terms were used to refer to these patients. priate vehicle for reportable awareness22. Some of the most common were ‘apallic syndrome’, ‘akinetic mutism’, ‘post-traumatic dementia’ or the still widely used ‘coma vigil’. In 1972, Jennett and Plum6 coined the term ‘vegetative state’ in an Indeed, given the complexity of the tasks article entitled ‘Persistent vegetative state after brain damage. A syndrome in search of a name’. used and the specificity of the responses They chose this term to stress the (relative) preservation of the ‘vegetative’ (that is, non-conscious) measured, one can draw far more elaborate functions of the brain in these patients, such as sleep–wake cycles, respiration, digestion and conclusions about the mental state of these thermoregulation. At that time, ‘persistent’ was used to indicate that the condition had lasted for patients than the fact that they are merely at least a month post-injury. Forty years on, ‘vegetative state’ is still the most widely used term for ‘conscious’. For example, at the very least, this condition in the medical and scientific communities. However, given the pejorative sustained attention (required to maintain connotations, a European Task Force on Disorders of Consciousness has recently proposed the focus through each task), language compre- neutral descriptive term ‘unresponsive wakefulness syndrome’ (REF. 64). The authors hension (required to understand the task acknowledged the problems inherent in making strong claims about awareness in patients with instructions), response selection (required severe brain damage, as highlighted by recent functional neuroimaging studies, and shifted the terminological focus from the lack of awareness to the lack of response. Since it was introduced in to switch between alternative tasks or con- 2010, the new term has received modest support from the medical and scientific communities. ditions) and working memory (required to remember which task to perform when instructed) must all be substantially pre- coach when she heard the word ‘tennis’ and hand in order to establish whether motor served. These are all aspects of ‘top-down’ to imagine walking from room to room in preparation could be used as proxy for cognitive control that are typically associated her house when she heard the word ‘house’. extant command-following. Although no with normal levels of conscious awareness. When a group of control volunteers were overt muscular activity was detected in any asked to perform the same two mental of the patients, two out of five patients exhib- EEG responses as evidence of awareness. In imagery tasks12, imagining playing tennis ited fMRI activity in the dorsal premotor spite of its demonstrable success in detect- was associated with robust activity in the cortex contralateral to the side of the hand ing covert awareness, performing fMRI supplementary motor area (SMA) in each that they were instructed to move, suggest- in patients who are in a vegetative state is and every one of the participants. By con- ing that they were at least attempting to exceptionally challenging. Considerations of trast, imagining moving around their houses follow the command. In another example20, cost, scanner availability and physical stress activated the parahippocampal cortices a patient was asked to either just listen to

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