Table 2.
Transcrania lmagnetic stimulation studies in DoC patients.
| Study | Design/Control | Population | Target/Stimulation parameters | Behavioral effects | Electrophysiological effects | Side effects |
|---|---|---|---|---|---|---|
| Louise-Bender Pape et al., 2009 | Case report/None | 1 VS/UWS patient | Right DLPFC/30 sessions over 6 weeks of 10 Hz rTMS (300 paired-pulse) at 110% RMT | No significant (trend) improvement of DOC Scale | Improvement of latencies of auditory brainstem evoked potentials | None |
| Piccione et al., 2011 | Case report/Median nerve stimulation | 1 MCS patient | Left M1/2 sessions of 20 Hz rTMS (10 trains of 100 stimuli) at 90% RMT | Increased CRS-R score lasting 6 h after stimulation | Increase of absolute and relative power in delta, alpha and gamma band | None |
| Manganotti et al., 2013 | Open-label/None | 6 patients (3 VS/UWS and 3 MCS) | Left or right M1/1 session of 20 Hz rTMS (10 trains of 100 stimuli) at 120% RMT | Improvement of consciousness in only 1 patient | Increase of absolute and relative power in delta, alpha and gamma band and reactivity in the responding patient | None |
| Pape et al., 2014 | Open-label/None | 2 patients | Right DLPFC/30 sessions over 6 weeks of 10 Hz rTMS (300 paired-pulse) at 110% RMT | Not assessed | Not assessed | One epileptic seizure |
| Xie et al., 2015 | Open-label/Case-control | 20 patients (2 coma, 11 VS/UWS, 7 MCS) of which 10 were stimulated | Right DLPFC/28 sessions over 28 days of 5 Hz rTMS | 6 out of 10 patients stimulated showed CRS-R improvement persisting at 4 weeks | Increase of alpha power and decrease of delta power | Not reported |
| Naro et al., 2015a | Not randomized/Sham | 10 patients (all VS/UWS) and 10 healthy controls | Right DLPFC/1 session of 10 Hz rTMS (1000 pulses) at 90% RMT | No significant group effect but small short-lasting improvement in 3 patients on the motor subscale of the CRS-R | No significant effect at the group level, but some short-lasting modulation of motor evoked potentials in the 3 responding patients | None |
| Cincotta et al., 2015 | Cross-over RCT/Sham | 11 patients (all VS/UWS) | Left M1/5 sessions over 5 days of 20 Hz rTMS (1000 pulses) at 90% RMT | No significant differences in CRS-R scores between stimulation and sham | No significant changes on EEG (Synek classification) | None |
| Liu et al., 2016 | Cross-over RCT/Sham | 10 patients (5 VS/UWS, 5 MCS) | Left M1/1 session of 20 Hz rTMS (1000 pulses) at 100% RMT | No behavioral effect | Significant changes in hemodynamic parameters (mean and peak velocity of middle cerebral artery) on transcranial doppler only in MCS | None |
| Bai et al., 2017 | Case report/None | 1 MCS patient | Left DLPFC/20 sessions over 20 days of 10 Hz rTMS (1000 pulses) at 90% RMT | Improvement of CRS-R after 20 sessions | Concomitant improvement of perturbational complexity index, global mean field power and motor evoked potential. | None |
| Xia et al., 2017 | Prospective/Not controlled | 16 patients (11 VS/UWS and 5 MCS) | Left DLPFC/20 sessions over 20 days of 10 Hz rTMS (1000 pulses) at 90% RMT | Improvement of CRS-R score in all MCS patients and 4/11 VS/UWS persisting 10 days after stimulation. | None | None |
| Xia et al., 2017 | Prospective/Not controlled | 18 patients (12 had repeated sessions for 20 days) | Left DLPFC/20 sessions over 20 days of 10 Hz rTMS (1000 pulses) at 90% RMT | Overlapping population with the previous study. No statistical testing. | Decreased low-frequency band power and increased high-frequency band power, especially in MCS | None |
| He et al., 2018 | Cross-over RCT/Sham | 6 patients (3 VS/UWS, 2 MCS and 1 EMCS) | Left M1/5 sessions over 5 days of 20 Hz rTMS (1000 pulses) at 100% RMT | No significant differences in CRS-R. One patient improved after real stimulation. | Increase delta, theta, alpha and beta power spectra in the responding patient. | Not reported |
| Liu et al., 2018 | Cross-over RCT/Sham | 7 patients (2 VS/UWS and 5 MCS) | Left M1/5 sessions over 5 days of 20 Hz rTMS (1000 pulses) at 100% RMT | No significant changes of CRS-R scores | No significant changes in functional connectivity on EEG | None |
CRS-R, Coma Recovery Scale – Revised; DLPFC, dorsolateral prefrontal cortex; DoC, disorders of consciousness; EEG, electroencephalogram; EMCS, Emergence from Minimally Conscious State; M1, primary motor cortex; MCS, Minimally Conscious State; RCT, randomized controlled trial; RMT, resting motor threshold; rTMS, repetitive transcranial magnetic stimulation; VS/UWS, vegetative state/unresponsive wakefulness syndrome.