TMS/EEG measures of cortical effective connectivity during wakefulness, NREM sleep, dreaming, anesthesia and coma.

Subjects are considered conscious if they can interact purposefully with the external environment and unconscious otherwise. However, one can be disconnected from the environment and yet be conscious, as is the case, for instance, when one dreams. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can interact rapidly and effectively (effective connectivity). In a series of recent studies, we have employed transcranial magnetic stimulation (TMS) together with high-density electroencephalography (EEG) to measure effective connectivity in conditions where consciousness was altered physiologically (NREM and REM sleep), pharmacologically (general anesthesia) and pathologically (brain injury). TMS/hd-EEG measurements showed that, while during wakefulness and REM sleep the brain is able to sustain long-range, complex patterns of activation, during NREM sleep and general anesthesia, when consciousness fades, this ability is lost: the thalamocortical system, despite being active and reactive, invariably responded to a direct TMS perturbation with a stereotypical response that remained local. Also, in vegetative state patients, who were open-eyed, behaviorally awake but unresponsive, TMS triggered a stereotypic, local response indicating a breakdown of effective connectivity, similar to the one observed in sleep or anesthesia. By contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behavior, TMS triggered rapidly changing, widespread responses similar to the ones recorded in locked-in and healthy awake subjects. Longitudinal measurements in subjects who gradually recovered consciousness showed that this change in the brain’s capacity for internal communication occurred at an early stage before reliable communication could be established with the subject and before the spontaneous EEG showed significant modifications. Altogether, the results of these experiments help linking theoretical notions of consciousness to the practical aspects of bedside assessment in brain-injured patients, and suggest that detecting consciousness may rely not only on a subject’s ability to communicate with the external environment, but also on the brain’s capacity for internal communication (effective connectivity).