Waking up the brain: a case study of stimulation-induced wakeful unawareness during anaesthesia.

Hitherto, little is known about the specific functional contributions of extrathalamic arousal systems to the regulation of wakefulness in humans. Here, we describe a 42-year-old woman with treatment resistant tremulous cervical dystonia who underwent microelectrode-guided stereotactic implantation of deep brain stimulation (DBS) electrodes in the internal segment of the globus pallidus internus (GPi) under general anaesthesia. Acute unilateral DBS of circumscribed sites within the subpallidal fibre-field with 130 Hz caused a transient state of wakefulness with an increased responsiveness to external stimuli but without detectable signs of conscious awareness. The extent of behavioural arousal could be titrated as a function of stimulus intensity. At lower stimulation intensities, bilateral eye opening occurred in response to verbal commands or tactile stimulation. At suprathreshold intensities, the patient's eyes remained open and conjugated throughout the stimulation period. The arousal effect ceased abruptly when DBS was discontinued. Behavioural arousal was accompanied by global cortical EEG activation in the gamma-frequency range (40-120 Hz) and by autonomic activation as evidenced by increased heart rate. The observed effect was reproducible in both hemispheres and topographically restricted to 6 out of 15 tested sites in the fibre-field between the GPi and the posterior aspect of the basal nucleus of Meynert. We conclude that the stimulated neural substrate in the subpallidal basal forebrain is involved in the premotor control of lid and eye position and the control of the activation state of the human neocortex. It may thus be important for the induction and maintenance of anaesthesia-induced unconsciousness in humans. It is suggested that subpallidal DBS released a downstream arousal circuit from anaesthesia-related inhibitory modulation either by direct excitation of an arousal nucleus or by inhibition of a sleep-promoting centre in the basal forebrain.