Patients lying in a vegetative state present severe impairments of consciousness [1] caused by lesions in the cortex, the brainstem, the thalamus and the white matter [2]. There is agreement that this condition may involve disconnections in long-range cortico-cortical and thalamo-cortical pathways [3]. Hence, in the vegetative state cortical activity is 'deafferented' from subcortical modulation and/or principally disrupted between fronto-parietal regions. Some patients in a vegetative state recover while others persistently remain in such a state. The neural signature of spontaneous recovery is linked to increased thalamo-cortical activity and improved fronto-parietal functional connectivity [3]. The likelihood of consciousness recovery depends on the extent of brain damage and patients' etiology, but after one year of unresponsive behavior, chances become low [1]. There is thus a need to explore novel ways of repairing lost consciousness. Here we report beneficial effects of vagus nerve stimulation on consciousness level of a single patient in a vegetative state, including improved behavioral responsiveness and enhanced brain connectivity patterns.

Response inhibition is commonly thought to rely on voluntary, reactive, selective, and relatively slow prefrontal mechanisms. In contrast, we suggest here that response inhibition is achieved automatically, nonselectively, within very short delays in uncertain environments. We modified a classical go/nogo protocol to probe context-dependent inhibitory mechanisms. Because no single neuroimaging method can definitely disentangle neural excitation and inhibition, we combined fMRI and EEG recordings in healthy humans. Any stimulus (go or nogo) presented in an uncertain context requiring action restraint was found to evoke activity changes in the supplementary motor complex (SMC) with respect to a control condition in which no response inhibition was required. These changes included: (1) An increase in event-related BOLD activity, (2) an attenuation of the early (170 ms) event related potential generated by a single, consistent source isolated by advanced blind source separation, and (3) an increase in the evoked-EEG Alpha power of this source. Considered together, these results suggest that the BOLD signal evoked by any stimulus in the SMC when the situation is unpredictable can be driven by automatic, nonselective, context-dependent inhibitory activities. This finding reveals the paradoxical mechanisms by which voluntary control of action may be achieved. The ability to provide controlled responses in unpredictable environments would require setting-up the automatic self-inhibitory circuitry within the SMC. Conversely, enabling automatic behavior when the environment becomes predictable would require top-down control to deactivate anticipatorily and temporarily the inhibitory set.