Consciousness is a multifaceted concept that has two major components: awareness of environment of self (i.e., the content of consciousness) and wakefulness (i.e., the level of consciousness). Whereas the level of arousal reflects the overall state of activity in the brain, conscious awareness is a more dynamic and complex process involving various cerebral networks, including the cortico-thalamo-cortical loop.
Disorder of consciousness (DOC) is a broad category that encompasses a spectrum of cognitive dysfunction—from mild confusional states, delirium, and dementia to coma, locked-in syndrome (LIS), vegetative state (VS), minimally conscious state (MCS), and brain death. The distinction between VS (absence of responsiveness and awareness) and MCS (inconsistent but clearly discernible behavioral evidence of consciousness) can be subtle in many patients;3 thus diagnosis, prognosis, and ethical and legal elements should be carefully and thoughtfully considered in order to provide the most optimal treatment for these patients.[3,4] The currently available diagnostic tools used in the management of DOC may be useful in measuring levels of cognition and conscious awareness in patients, and may help clinicians make accurate diagnosis and prognosis; unfortunately, however, in many DOC patients, these tools may not adequately detect conscious awareness.
The bedside examination of consciousness in severely brain damaged patients often is very challenging because responses may be very low, inconsistent, and easily exhausted. Nonetheless, the use of clinical scales, such as the JFK Coma Recovery Scale-Revised (CRS-R), can be of help. CRS-R is a reliable and standardized tool that integrates neuropsychological and clinical assessment, and includes the current diagnostic criteria for coma, VS, and MCS,[3,5] which assist the clinician in assigning the patient to the most appropriate diagnostic category. However, an objective instrumental evaluation is still needed to provide a more realiable DOC diagnosis.
Electroencephalography (EEG) changes reflect the activity of the ascending reticular system, and thus allows investigation of the integrity and function of thalamocortical connections. Studies have shown a higher presence of delta activity in VS than in MSC. Also, the presence of normal sleep patterns (likely reflecting at least a partial functional brain integrity) could help in differentiating VS from MCS individuals. The evoked potentials (EPs) are used either in the diagnosis or in the prognostic evaluation of DOC. Auditory EPs may be attenuated, delayed, or absent, and the N20 cortical response is almost absent in VS.
In last 10 years, evidence has shown the importance of neuroimaging in the management of DOC patients.6 Indeed, a proper DOC diagnostic and prognostic assessment should use novel neuroimaging techniques (e.g., functional magnetic resonance imagine [fMRI], magnetic resonance (MR) spectroscopy, diffusion tensor imaging, fiber tracking, positron emission tomography) as complementary tools that may help in differentiating the effects of underarousal, sensory impairment, motor dysfunction, and cognitive disturbance as potential causes of behavioral unresponsiveness. Moreover, neuroimaging and noninvasive neurophysiological methods may help in diagnosing the patients suffering from a functional LIS, which can show an extreme behavioral motor dysfunction with a partial preservation of higher cognitive functions and cerebral connectivity.
Since the study of the sensory-motor system is unable to contribute to the generation of purposeful behaviors, the misdiagnosis rate in DOC is still high. To this end, novel neurophysiological approaches have been proposed in an attempt to overcome such problem. Indeed, it has been recently shown that transcranial current stimulation can unmask residual covert connectivity patterns in some DOC patients, including unresponsive wakefulness syndrome (UWS). Moreover, audiomotor and vistuomotor integration may be promising tools to potentiate the functional connectivity within large-scale sensory networks, thus allowing clinicians to differentiate MCS from UWS and LIS.[9,10] Furthermore, although it has been assumed that patients with DOC do not feel pain, the possibility of detecting residual pain perceptions by means of laser EPs may further help clinicians provide more optimum care of these patients.
Even though conscious experiences of a DOC patient may give rise to certain behaviors, we clinicians cannot fully deduce from these observed behaviors the levels of conscienceness or brain activity, nor can we deduce our patients’ first-person subjective experiences. The current state of cognitive neuroscience does not allow us to fully understand the thought processes of our DOC patients when based solely on inspection of their neural activity. Further studies should therefore be fostered in an attempt to shed new light on awareness detection in these very frail and vulnerable individuals.
Rocco Salvatore Calabrò and Antonino Naro
IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy
No funding was received for the preparation of this article. The authors have no conflicts of interest relevant to the content of this letter.
1. Calabrò RS, Cacciola A, Bramanti P, Milardi D. Neural correlates of consciousness: what we know and what we have to learn! Neurol Sci. 2015;36:505–513.
2. Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol. 2004;3:537–546.
3. Giacino JY, Ashwal S, Childs N, et al. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002;58:349–353.
4. De Salvo S, Bramanti P, Marino S. Clinical differentiation and outcome evaluation in vegetative and minimally conscious state patients: the neurophysiological approach. Funct Neurol. 2012;27:155–162.
5. Giacino JT1, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility Arch Phys Med Rehabil. 2004;85(12):2020–2029.
6. Di Perri C, Thibaut A, Heine L, et al. Measuring consciousness in coma and related states. World J Radiol. 2014;6:589–597.
7. Formisano R, D’Ippolito M, Catani S. Functional locked-in syndrome as recovery phase of vegetative state. Brain Inj. 2013;27:1332.
8. Naro A, Calabrò RS, Russo M, et al. Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients? Restor Neurol Neurosci. 2015;33:159–176.
9. Naro A, Leo A, Cannavò A, et al. Audiomotor Integration in Minimally Conscious State: Proof of Concept! Neural Plast. 2015;2015:391349.
10. Naro A, Leo A, Filoni S, et al. Visuo-motor integration in unresponsive wakefulness syndrome: A piece of the puzzle towards consciousness detection? Restor Neurol Neurosci. 2015;33:447–460.
11. de Tommaso M, Navarro J, Lanzillotti C, et al. Cortical responses to salient nociceptive and not nociceptive stimuli in vegetative and minimal conscious state. Front Hum Neurosci. 2015;9:17.