Table 1.

Deep brain stimulation studies in DoC patients.

Study	Design/Control	Population	Target/Stimulation parameters	Behavioral effects	Electrophysiological/metabolic effects	Side effects
McLardy et al., 1968	Case report/None	1 (considered as) VS/UWS	Left thalamus; midbrain (intralaminar nuclei/reticular formation) / 250Hz, 1ms	No modifications of consciousness, left hand spontaneous movement	No post procedure electrophysiological nor metabolic evaluation available	None
Hassler et al., 1969	Case report/None	1 (considered as) VS/UWS	Left ventral anterior thalamus; right pallidum / Left, 25-30Hz, 20V, 1-3ms; Right 8Hz, 30V, 1-3ms	“Improvement” of consciousness, vocalizations, left limbs spontaneous movement	EEG recordings showed a disappearance of a unilateral delta focus which is replaced by an alpha activity	None
Tsubokawa et al., 1990	Open-label/None	8 patients (VS/UWS)	Central thalamic nuclei; nucleus cuneiformis (reticular formation)/50 Hz, 0–10 V	4 recoveries (PCS 2–4 = > 8-9) 1 responder (PCS 2–4 = > 7) 3 failures (PCS 2–4 = > 3-5)	Increase of spectral power and desynchronization on EEG in the 4 patients who recovered/Increase on the brain perfusion on MRI in these patients	None
Cohadon and Richer, 1993	Open-label/None	25 patients (VS/UWS)	Central nucleus of the thalamus/50 Hz, 5–10 V, 5 ms	1 moderate disabilities (GOS) 10 severe disabilities (GOS) 12 no effect (2 patients died before the endpoint)	No post procedure electrophysiological nor metabolic evaluation available	2 died (unrelated to surgical procedure)
Schiff et al., 2007	Case report, Cross-over RCT/Sham	1 MCS	Anterior intralaminar thalamic nuclei / 100Hz, 4V	Fluctuant increase in CRS-R subscales, better feeding and motor behaviors, restoration of communication	No post procedure electrophysiological nor metabolic evaluation available	None
Yamamoto et al., 2010 (includes publications since 2002)	Open-label/None	21 patients (VS/UWS)	Centro-median nucleus of the thalamus; midbrain (reticular formation) / 25Hz, various intensities	8 became MCS or EMCS 13 remain VS/UWS	The 8 patients who recovered from VS showed desynchronization on continuous EEG frequency analysis/Increase on the brain perfusion on MRI in these patients	None
Wojtecki et al., 2014	Case report/None	1 MCS	Internal medullary lamina; nuclei reticularis thalami/70–250 Hz, various intensities	No modifications of consciousness	Modulation of oscillatory activity in the beta and theta band within the central thalamus accompanied by an increase in thalamocortical coherence in the theta band	None
Magrassi et al., 2016	Open-label/None	3 patients (1 MCS, 2 VS/UWS)	Anterior intralaminar nuclei; paralaminar Areas/80–110 Hz, various intensities	Increase of CRS-R in all of the 3 patients: 14 = > c15 8 = > 11 6 = > 9	Increase of theta and gamma power spectrum in EEG after 1 month of stimulation. No modifications of the evoked potentials.	1 postoperative intraparenchymal hematoma
Adams et al., 2016	Case report/None	1 MCS	Anterior intralaminar thalamic nuclei/100 Hz, 4 V	Variable increase of CRS-R (11–14)	Long term re-emergence of sleep patterns	None
Chudy et al., 2018	Open-label/None	14 patients (4 MCS, 10 VS/UWS)	Central thalamic nuclei / 25 Hz, 2.5–3.5 V, 90 μs	3 MCS became EMCS; 1 VS became MCS; 7 had no improvement of consciousness (3 patients died before the endpoint)	No post procedure electrophysiological nor metabolic evaluation available	3 died (unrelated to surgical procedure)
Lemaire et al., 2018	Cross-over RCT/Sham	5 patients (4 MCS, 1 VS/UWS)	Dual pallido-thalamic / 30-Hz, 6V, 60μs	1 VS/UWS and 1 MCS had an significant improvement of the CRS-R.	The metabolism of the medial cortices increased specifically in the two responders	1 postoperative bronchopulmonary infection

CRS-R, Coma Recovery Scale – Revised; DoC, disorders of consciousness; EEG, electroencephalogram; EMCS, Emergence from Minimally Conscious State; GOS, Glasgow Outcome Scale; MCS, Minimally Conscious State; PCS, Prolonged Coma Scale; RCT, randomized controlled trial; VS/UWS, vegetative state/unresponsive wakefulness syndrome.