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Background Making an accurate diagnosis in patients with disorders of consciousness remains challenging. 18F-fluorodeoxyglucose (FDG)–PET has been validated as a diagnostic tool in this population, and allows identifying unresponsive patients with a capacity for consciousness. In parallel, the perturbational complexity index (PCI), a new measure based on the analysis of the electroencephalographic response to transcranial magnetic stimulation, has also been suggested as a tool to distinguish between unconscious and conscious states. The aim of the study was to cross-validate FDG–PET and PCI, and to identify signs of consciousness in otherwise unresponsive patients. Methods We jointly applied the Coma Recovery Scale-Revised, FDG–PET and PCI to assess 24 patients with non-acute disorders of consciousness or locked-in syndrome (13 male; 19–54 years old; 12 traumatic; 9 unresponsive wakefulness syndrome, 11 minimally conscious state; 2 emergence from the minimally conscious state, and 2 locked-in syndrome). Results FDG–PET and PCI provided congruent results in 22 patients, regardless of their behavioural diagnosis. Notably, FDG–PET and PCI revealed preserved metabolic rates and high complexity levels in four patients who were behaviourally unresponsive. Conclusion We propose that jointly measuring the metabolic activity and the electrophysiological complexity of cortical circuits is a useful complement to the diagnosis and stratification of patients with disorders of consciousness.

Objective methods for distinguishing conscious from unconscious states in humans are of key importance for clinical evaluation of general anesthesia and patients with disorders or consciousness. Here, we test the generalizability of a DTF-based algorithm - a measure of effective connectivity - as an objective measure of conscious experience during anesthesia and correlate it with a well-tested index of consciousness: the Perturbational Complexity Index (PCI). We reanalyzed EEG data from an experimental study in which 18 healthy volunteers were randomly assigned to one of three types of general anesthesia: propofol, xenon, and ketamine. EEG was recorded before and during anesthesia, and DTF was calculated from every 1-second segment of the EEG data to quantify the effective connectivity between channel pairs. This was used to classify the state of each participant as either conscious or unconscious, and the classifications were compared with the participant’s delayed report of experience, and the PCI. The algorithm was more likely to classify participants as conscious in the awake state than during propofol and xenon anesthesia (p0.05). Furthermore, the DTF-based confidence of being classified as conscious was highly correlated with PCI (r2=0.48, p

OBJECTIVE: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). METHODS: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. INTERPRETATION: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior.

There have been a number of advances in the search for the neural correlates of consciousness — the minimum neural mechanisms sufficient for any one specific conscious percept. In this Review, we describe recent findings showing that the anatomical neural correlates of consciousness are primarily localized to a posterior cortical hot zone that includes sensory areas, rather than to a fronto-parietal network involved in task monitoring and reporting. We also discuss some candidate neurophysiological markers of consciousness that have proved illusory, and measures of differentiation and integration of neural activity that offer more promising quantitative indices of consciousness.

Pain is a subjective experience. Its assessment is based on the subject's direct verbal report. This method of assessment is, however, impossible in patients who cannot communicate their feelings. In this context, indirect measurements such as behavioral observations or physiological measurements are needed. To facilitate the assessment of pain in non-communicative patients, numerous standardized behavioral scales have been developed. The aim of this review is to discuss the main validated pain scales employed in end-stage dementia, newborn and preverbal children, and severely brain damaged patients with a disorder of consciousness such as coma, the vegetative state or the minimally conscious state.

Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain-behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting-state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel-based analyses identified a systematic impairment of associative frontoparieto-cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level-dependent (BOLD) systemwide patterns can also be found, in particular in the default-mode network, in several states of unconsciousness, such as coma, anesthesia, and slow-wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark.

Human brain function is regionally organised during paradoxical sleep (PS) in a very different way than during wakefulness or slow wave sleep. The important activity in the pons and in the limbic/paralimbic areas constitutes the key feature of the functional neuroanatomy of PS, together with a relative quiescence of prefrontal and parietal associative cortices. Two questions are still outstanding. What neurocognitive and neurophysiological mechanisms may explain this original organization of brain function during PS? How the pattern of regional brain function may relate to dream content? Although some clues are already available, the experimental answer to both questions is still pending.

This review aims at defining the link between physiological sleep and general anesthesia. Despite common behavioral and electrophysiological characteristics between both states, current literature suggests that the transition process between waking and sleep or anesthesia-induced alteration of consciousness is not driven by the same sequence of events. On the one hand, sleep originates in sub-cortical structures with subsequent repercussions on thalamo-cortical interactions and cortical activity. On the other hand, anesthesia seems to primarily affect the cortex with subsequent repercussions on the activity of sub-cortical networks. This discrepancy has yet to be confirmed by further functional brain imaging and electrophysiological experiments. The relationship between the observed functional modifications of brain activity during anesthesia and the known biochemical targets of hypnotic anesthetic agents also remains to be determined.

Functional cerebral imaging techniques allow the in vivo study of human cognitive and sensorimotor functions in physiological or pathological conditions. In this paper, we review the advantages and limitations of functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and magnetoencephalography (MEG). fMRI and PET measure haemodynamic changes induced by regional changes in neuronal activity. These techniques have a high spatial resolution (a few millimeters), but a poor temporal resolution (a few seconds to several minutes). Electroencephalogram (EEG) and MEG measure the neuronal electrical or magnetic activity with a high temporal resolution (i.e., milliseconds) albeit with a poorer spatial resolution (i.e., a few millimeters to one centimeter). The combination of these different neuroimaging techniques allows studying different components of the brain's activity (e.g., neurovascular coupling, electromagnetic activity) with both a high temporal and spatial resolution.

Improvement in functional neuroimaging allows researchers to disentangle the brain mechanisms involved in the pain modulation encountered during hypnosis. It has been shown that the anterior cingulate and prefrontal cortices are important in the modulation of incoming sensory and noxious input. Moreover, clinical studies in certain types of surgery (eg thyroidectomy, mastectomy and plastic surgery) have demonstrated that hypnosis may avoid general anesthesia.

The Locked-In Syndrome (LIS) is classically caused by an anterior pontine vascular lesion and characterized by quadriplegia and anarthria with preserved consciousness and intellectual functioning. We here review the definition, etiologies, diagnosis and prognosis of LIS patients and briefly discuss the few studies on their quality of life and the challenging end-of-life decisions that can be encountered. Some clinicians may consider that LIS is worse than being in a vegetative or in a minimally conscious state. However, preliminary data from chronic LIS survivors show a surprisingly preserved self-scored quality of life and requests of treatment withdrawal or euthanasia, though not absent, are infrequent.