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Assessing the level of consciousness of noncommunicative brain-damaged patients is difficult, as one has to make inferences based on the patients' behavior. However, behavioral responses of brain-damaged patients are usually limited not only by their cognitive dysfunctions, but also by their frequent motor impairment. For these reasons, it is essential to resort to para-clinical markers of the level of consciousness. In recent years, a number of studies compared brain activity in comatose and vegetative state patients to that in healthy volunteers, and in other conditions of reduced consciousness such as sleep, anesthesia, or epileptic seizures. Despite the increasing amount of experimental results, no consensus on the brain mechanisms generating consciousness has yet been reached. Here, we discuss the need to combine a theoretical approach with current experimental procedures to obtain a coherent, parsimonious explanation for the loss of consciousness in several different conditions, such as coma, vegetative state, sleep, anesthesia, and epileptic seizures. In our view, without a theoretical account of how conscious experience is generated by the brain, it will remain difficult to understand the mechanisms underlying the generation of consciousness, and to predict reliably its presence or absence in noncommunicative brain-damaged patients. In this context, we review current theoretical approaches to consciousness, and how well they fit with current evidence on the neural correlates of experience. Specifically, we emphasize the principled approach provided by the Integrated Information Theory of Consciousness (IITC). We describe the different conditions where the theory predicts markedly reduced states of consciousness, and discuss several technical and conceptual issues limiting its applicability to measuring the level of consciousness of individual patients. Nevertheless, we argue that some of the predictions of the theory are potentially testable using available imaging techniques.

How do we evaluate a brain's capacity to sustain conscious experience if the subject does not manifest purposeful behaviour and does not respond to questions and commands? What should we measure in this case? An emerging idea in theoretical neuroscience is that what really matters for consciousness in the brain is not activity levels, access to sensory inputs or neural synchronization per se, but rather the ability of different areas of the thalamocortical system to interact causally with each other to form an integrated whole. In particular, the information integration theory of consciousness (IITC) argues that consciousness is integrated information and that the brain should be able to generate consciousness to the extent that it has a large repertoire of available states (information), yet it cannot be decomposed into a collection of causally independent subsystems (integration). To evaluate the ability to integrate information among distributed cortical regions, it may not be sufficient to observe the brain in action. Instead, it is useful to employ a perturbational approach and examine to what extent different regions of the thalamocortical system can interact causally (integration) and produce specific responses (information). Thanks to a recently developed technique, transcranial magnetic stimulation and high-density electroencephalography (TMS/hd-EEG), one can record the immediate reaction of the entire thalamocortical system to controlled perturbations of different cortical areas. In this chapter, using sleep as a model of unconsciousness, we show that TMS/hd-EEG can detect clear-cut changes in the ability of the thalamocortical system to integrate information when the level of consciousness fluctuates across the sleep-wake cycle. Based on these results, we discuss the potential applications of this novel technique to evaluate objectively the brain's capacity for consciousness at the bedside of brain-injured patients.

Disorders of consciousness (DOC) raise profound scientific, clinical, ethical, and philosophical issues. Growing knowledge on fundamental principles of brain organization in healthy individuals offers new opportunities for a better understanding of residual brain function in DOCs. We here discuss new perspectives derived from a recently proposed scheme of brain organization underlying consciousness in healthy individuals. In this scheme, thalamo-cortical networks can be divided into two, often antagonistic, global systems: (i) a system of externally oriented, sensory-motor networks (the "extrinsic" system); and (ii) a system of inward-oriented networks (the "intrinsic" or default system). According to this framework, four distinct mental states would be possible that could be relevant for understanding DOCs. In normal healthy volunteers and locked-in syndrome patients, a state of high functionality of both the extrinsic and intrinsic or default systems is expected--associated with full awareness of environment and self. In this case, mental imagery tasks combined with fMRI can be used to detect covert awareness in patients that are unable to communicate. According to the framework, two complementary states of system imbalance are also possible, in which one system is in a hyperfunctional state, while the other is hypoactive. Extrinsic system hyperfunction is expected to lead to a state of total sensory-motor "absorption" or "lost self." In contrast, intrinsic or default system hyperfunction is expected to lead to a state of complete detachment from the external world. A state where both extrinsic and intrinsic systems are hypofunctional is predicted to lead to markedly impaired consciousness as seen in DOCs. Finally, we review the potential use of ultra-slow fluctuations in BOLD signal as a tool for assessing the functional integrity of extrinsic and intrinsic systems during "resting state" fMRI acquisitions. In particular, we discuss the potential provided by assessment of these slow spontaneous BOLD fluctuations as a novel tool in assessing the cognitive state and chances of recovery from brain pathologies underlying DOCs.