A Theoretically Based Index of Consciousness Independent of Sensory Processing and Behavior

A theory-derived index of consciousness, which quantifies the complexity of the brain’s response to a stimulus, measures the level of consciousness in awake, sleeping, anesthetized, and brain-damaged subjects. Quantifying the Unquantifiable Manipulation of consciousness is an everyday medical trick—think anesthesia—but physicians have only the crudest of tools to detect when a person is not aware. The usual question or physical stimulus does not always provide reliable reactions, and a more precise index is needed to avoid, for example, the conclusion that people who have locked-in syndrome (in which they are aware but cannot respond) are unconscious. Here, Casali et al. have extended their previous work on electrical correlates of consciousness to define an electroencephalographic-derived index of human consciousness [the perturbational complexity index (PCI)] that reflects the information content of the brain’s response to a magnetic stimulus. The PCI could allow tracking of consciousness in individual patients. The authors used data already collected from previous experiments, in which they had stimulated people’s brains with transcranial magnetic stimulation. By calculating the likely brain regional sources of the signals and then comparing the unique information in each, the authors derived PCI values. The values ranged from 0.44 to 0.67 in 32 awake healthy people, but fell to 0.18 to 0.28 during nonrapid eye movement (NREM) sleep. Then, to see whether a completely different way of inducing unconsciousness had the same effect on PCI, the authors assessed data from patients given various amounts of the anesthetics midazolam, xenon, and propofol. These agents too caused low “unconscious” values for the PCI: midazolam deep sedation, 0.23 to 0.31; propofol, 0.13 to 0.30; and xenon, 0.12 to 0.31. However, what about patients who suffer brain damage and who exhibit various levels of consciousness by conventional assessment methods? In these people, consciousness varies widely, as does the underlying damage from stroke or trauma. Here, too, the authors found promising results in those who had emerged from coma but were in a vegetative state or minimally conscious state, or exhibited locked-in syndrome. The PCI values from these patients clearly reflected the state of their consciousness, with the six patients in a vegetative state clearly unconscious (0.19 to 0.31), the two with locked-in syndrome clearly aware (0.51 to 0.62), and those in a minimally conscious state showing intermediate values (0.32 to 0.49). The validity of PCI for clinical application will need to be assessed in prospective trials, but it has the advantage of being derived from a simple noninvasive measurement. The new index reported by Casali et al. appears to be a robust measure that distinguishes conscious from unconscious states well enough to be used on an individual basis, a prerequisite for deployment in the clinic. One challenging aspect of the clinical assessment of brain-injured, unresponsive patients is the lack of an objective measure of consciousness that is independent of the subject’s ability to interact with the external environment. Theoretical considerations suggest that consciousness depends on the brain’s ability to support complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). We introduce and test a theory-driven index of the level of consciousness called the perturbational complexity index (PCI). PCI is calculated by (i) perturbing the cortex with transcranial magnetic stimulation (TMS) to engage distributed interactions in the brain (integration) and (ii) compressing the spatiotemporal pattern of these electrocortical responses to measure their algorithmic complexity (information). We test PCI on a large data set of TMS-evoked potentials recorded in healthy subjects during wakefulness, dreaming, nonrapid eye movement sleep, and different levels of sedation induced by anesthetic agents (midazolam, xenon, and propofol), as well as in patients who had emerged from coma (vegetative state, minimally conscious state, and locked-in syndrome). PCI reliably discriminated the level of consciousness in single individuals during wakefulness, sleep, and anesthesia, as well as in patients who had emerged from coma and recovered a minimal level of consciousness. PCI can potentially be used for objective determination of the level of consciousness at the bedside.