Neuromodulation of the conscious state following severe brain injuries

•A common mesocircuit mechanism is proposed underlying disorders of consciousness.•Reduction of central thalamic activity downregulates frontostriatal activity.•Catecholamine depletion via selective injuries may add to this downregulation.•A wide range of medications can act directly to mitigate mesocircuit dysfunction.•Recovery is linked to reactivation of central thalamic outflow.

Disorders of consciousness (DOC) following severe structural brain injuries globally affect the conscious state and the expression of goal-directed behaviors. In some subjects, neuromodulation with medications or electrical stimulation can markedly improve the impaired conscious state present in DOC. We briefly review recent studies and provide an organizing framework for considering the apparently widely disparate collection of medications and approaches that may modulate the conscious state in subjects with DOC. We focus on neuromodulation of the anterior forebrain mesocircuit in DOC and briefly compare mechanisms supporting recovery from structural brain injuries to those underlying facilitated emergence from unconsciousness produced by anesthesia. We derive some general principles for approaching the problem of restoration of consciousness after severe structural brain injuries, and suggest directions for future research.