Table 3.
Studies were reviewed and included in the review.
| Electrophysiological methods | ||||||
|---|---|---|---|---|---|---|
| No | References | Sample | Method | Clinical rating | Task | Result |
| Resting-state/Sleep and qEEG | ||||||
| 1 | Lehembre et al. (21) | 31 DOC patients (10 VS/UWS, 21MCS) |
EEG (power spectrum) |
CRS-R | Resting state | Increases in delta and alpha power were observed in VS/UWS subjects with respect to MCS. Moreover, a connectivity reduction particularly, in alpha and theta bands, was also observed |
| 2 | Bagnato et al. (53) | 46 DOC patients (25 VS/UWS, 21 MCS) |
EEG (SYNEK scale) 21 electrodes |
LCF | Resting-state | A correlation between the SYNEK score and the LCF scale was observed in patients with non-traumatic brain injuries but not in those with traumatic brain injuries |
| 3 | Fingelkurts et al. (54) | 21 DOC patients (14 VS/UWS, 7 MCS) |
EEG (duration & oscillatory) 21 electrodes |
ANA | Resting-state | A relation between the level of consciousness and the dynamic parameters of EEG microstates such as the duration and oscillation were observed Oscillation was reduced by 50% compared to normal subjects The reduction in the number of alpha rhythm spectral patterns was 37% for MCS and 26% for VS/UWS |
| 4 | Lechinger et al. (55) | 17 DOC patients (8 VS/UWS, 9 MCS) |
EEG (power spectrum) 19 electrodes |
CRS-R | Resting-state | VS/UWS patients showed higher values in both theta and delta average relative resting amplitude, while no difference has been shown between controls and MCS patients |
| 5 | Bonfiglio et al. (56) | 9 DOC patients (4 VS/UWS, 5 MCS) 12 healthy participants |
EEG 19 electrodes |
CRS-R | Resting-state | Reduction in the intensity of the Blink-Related Synchronization/Desynchronization (nBRS/BRD), particularly on the inferior and temporo-occipital junction, was observed in VS/UWS patients with respect to the control group. MCS patients showed intermediate intensity |
| 6 | Schnakers et al. (57) | 43 DOC patients (13 VS/UWS, 30 MCS) |
EEG (BIS) |
GCS, CRS-R | Resting-state | The Bispectral index (BIS) showed the highest correlation with the level of consciousness. Moreover, the BIS was able to predict the probability the patients recovering |
| 7 | Engemann et al. (58) | 327 DOC patients (148 VS/UWS, 179 MCS) 66 healthy participants |
EEG (power spectrum & more) |
CRS-R | Resting-state and “Local-Global” Protocol | A broad machine-learning classification analysis showed that several EEG-derived features can accurately discriminate MCS and VS/UWS patients in a robust manner (different acquisition methodologies, clinical settings) |
| 8 | Gosseries et al. (59) | 56 DOC patients (24 VS/UWS, 26 MCS, 6 coma) |
EEG (Entropy) 3 electrodes |
CRS-R | Resting-state | VS/UWS patients showed higher response entropy (73 ± 19) with respect to MCS patients (45 ± 28) |
| 9 | Piarulli et al. (60) | 12 DOC patients (6 VS/UWS, 6 MCS) |
EEG (spectral entropy) 12 electrodes |
CRS-R | Resting-state | Lower delta, higher theta and alpha power, and higher spectral entropy was observed in MCS (0.68) with respect to VS/UWS patients (0.59). Moreover, periodicity was absent in VS/UWS while MCS patients showed periodicity similar to healthy subjects |
| 10 | Marinazzo et al. (61) | 26 DOC patients (11 VS/UWS, 5 MCS, 5 EMCS) 10 healthy participants |
EEG (transfer entropy) 19 electrodes |
CRS-R | Resting-state | Transfer entropy was able to indicate EMCS easily among DOC patients, but the procedure was not as useful for other patient classifications It was also found that information transfer increased for DOC patients in centrals region but decreased in the lateral regions |
| Event-Related potential ERP | ||||||
| 11 | Cavinato et al. (62) | 17 DOC patients (6 VS/UWS, 11 MCS) 10 healthy people |
ERP (P300) |
CRS-R | Auditory | Cortical response was detected in the MCS patients due to the stimulation. The increase of P300 latency was observed only in MCS patients and healthy controls |
| 12 | King et al. (22) | 181 DOC patients (75 VS/UWS, 68 MCS, 24 Coma) 14 healthy participants |
EEG WSMI | CRS-R | Auditory | A novel metric called Weighted Symbolic Mutual Information (WSMI) was employed. WSMI across distant cortical and thalamic areas showed a correlation with the level of consciousness. For VS patients, WSMI in the frontal area was less impaired than in the posterior regions |
| 13 | Wang et al. (63) | 11 DOC patients (6 VS/UWS, 5 MCS) 5 healthy participants |
ERP (P300, MMN) |
CRS-R | Auditory | MMN and P300 were observed in all MCS patients and in 5/6 VS/UWS patients. P300 was observed in 4/6 VS/UWS patients |
| 14 | Calabrò et al. (64) | 21 DOC patients (11VS, 10MCS) |
ERP (LORETA) 19 electrodes |
CRS-R | Heat stimuli | Partially preserved gamma band ERP activation was observed in MCS patients, and in only 2/11 VS/UWS patients |
| 15 | Leo et al. (65) | 22 DOC patients (10VS, 12MCS) |
ERP 6 electrodes |
CRS-R | Heat stimuli | Changes in the HRV and oxygen saturation in response to stimulation were observed in MCS patients, while no change was observed in VS/UWS patients (with the exception of two such individuals) |
| 16 | Boly et al. (66) | 21 DOC patients (8 VS, 13MCS) |
ERP MMN 60 electrodes |
CRS-R | Auditory | Significant impairments of backward connectivity (from frontal to temporal) during a mismatch negativity paradigm was observed in VS/UWS patients |
| 17 | Sitt et al. (67) | 167 DOC patients (75 VS/UWS, 68 MCS, 24 coma) 24 healthy people |
ERP (P300, MMN) 56-electrode geodesic sensor net (EGI) |
CRS-R | Auditory | P300 and MMN were found to differentiate between patients and healthy controls but not between DOC groups with acceptable accuracy, while EEG complexity could be the most acceptable indicator |
| 18 | Raimondo et al. (68) | 127 DOC patients (70 VS/UWS, 50 MCS) |
ERP Correlate with HR |
CRS-R | Auditory | Only MCS patients showed a phase shift in a cardiac cycle after auditory stimulation, represented by a significant short interval between the auditory stimulation and the following R peak |
| 19 | De Biase et al. (69) | 62 DOC patients (57 VS/UWS, 5 MCS) |
ERP (REM) 19 electrodes |
CRS-R and GCS | Polysomnography (PSG) Somatosensory Auditory Visual |
Patients who showed all sleep elements had higher CRS-R value (7/62) Polysomnography recordings have confirmed to be a reliable tool in the neurophysiologic assessment of patients suffering from prolonged DOCs (more adequately than EPs) |
| 20 | Faugeras et al. (70) | 49 DOC patients (22 VS/UWS, 19 MCS, 8coma) 10 healthy people |
ERP (MMN, global and local effect) 256 electrodes |
CRS-R | Auditory | 13/19 MCS patients showed a response to P3a and P3b (global effect) while only 2/22 VS/UWS patients showed the same global effect |
| 21 | Kotchoubey et al. (71) | 98 DOC patients (60 PVS, 38 MCS) |
ERP (MMN, P300, N1) 9 electrodes |
CRS-R | Auditory | MCS and VS/UWS showed a significant difference only in MMN frequency (p < 0.05) while no difference was observed for N1 and P300 |
| 22 | Rohaut et al. (72) | 30 DOC patients (15 VS/UWS, 15 MCS) 20 healthy participants |
ERP (LPC, N400) 256 electrodes |
CRS-R | Auditory | The LPC (late positive components) response was only observed in MCS and healthy groups. The LPC was proposed to be an indicator of a potential specific marker of conscious semantic processing. The only DOC patients (3/30) who showed significant LPC and N400 components were MCS |
| 23 | Rivera-Lillo et al. (73) | 13 DOC patients (VS/UWS & MCS) 10 healthy participants |
ERP (P300) 24 electrodes |
CRS-R | Auditory | A correlation between the strength of the P300 and the percentage of epochs with delta event-related synchronization (ERS) was found |
| 24 | Balconi et al. (74) | 18 patients (10 VS/UWS, 8 MCS) 20 healthy participants |
ERP (N400) 64 electrodes |
GSC | Auditory | Increasing peak amplitude of N400 within the fronto-central cortical areas was found in reaction to incongruous sequences for both controls and DOC patients. Thus, semantic processing was partially preserved in both MCS and VS/UWS patients |
| 25 | Braiman et al. (75) | 21 DOC patients (3 VS/UWS, 12 MCS, 6 EMCS) healthy people |
ERP natural speech envelope correlates (NSE) |
CRS-R | Auditory | The earliest NSE reactions was observed in healthy controls, while delayed latency reaction was observed in the VS/UWS and MCS patient groups |
| 26 | Estraneo et al. (76) | 143 DOC patients (70 VS, 73MCS) |
P300 19 electrodes |
CRS-R | Eye opening and closing, tactile, noxious, acoustic, and Intermittent photic stimuli | The patients who showed response to auditory stimuli and forced eye closing tasks had a higher probability of showing improvement of their condition. The other tasks failed to predict future improvement |
| 27 | Annen et al. (77) | 40 DOC patients (15 VS, 23 MCS, 2 EMCS) 12 healthy participants |
P300 EEG based BCI system |
CRS-R | Auditory and somato-sensory stimulation | P300 did not show a significant difference between VS and MCS patients. Also, multimodal recordings showed better performance than unimodal assessments in BCI application |
| 28 | Binder et al. (78) | 15 DOC patients (No information on severity level) |
Low and high gamma frequencies (64 electrodes) |
CRS-R | Auditory | A strong correlation was found between low gamma range frequencies and CRS-R score. There was also evidence of differences in phase locking indices between VS and MCS in the frequency range between 36 and 47 Hz |
| 29 | Risetti et al. (79) | 14 DOC patients (7 VS, 7 MCS) |
N100, MMN, and P300 10 electrodes (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, and Oz) |
CRS-R | Auditory | N100 was delayed in VS compared to MCS patients. However, the presence of brain lesions might have accounted for the N100 latency delay observed in VS patients The MMN component of ERPs did not show significant differences in mean latencies and amplitudes between the two groups of patients P300 showed a significant delay in the VS compared to MCS patients. aHowever, P300 latency in VS with respect to MCS might be due to the different brain lesion between the two groups |
| Concurrent EEG-TMS | ||||||
| 30 | Ragazzoni et al. (80) | 13 DOC patients (8 VS/UWS, 5 MCS) 5 healthy participants |
EEG-TMS 19 electrodes |
CRS-R | Resting-State | The occurrence of TEPs in both ipsilateral and contralateral was observed in healthy control and MCS patients, but with a reduction of amplitudes for the MCS group. TEPs were restricted in the ipsilateral part in 3 of VS/UWS patients and absent in the other 5 |
| 31 | Casali et al. (81) | 12 DOC patients (6 VS/UWS, 6 MCS) |
EEG-TMS perturbation complexity index | CRS-R | Resting-State | The perturbation complexity index during TMS was significantly lower for unconscious patients with respect to normal subjects |
| 32 | Gosseries et al. (82) | 17 DOC patients (VS/UWS & MCS) |
EEG-TMS high-density EEG | CRS-R | Resting-State | Distant waves with high frequency and low amplitude were observed in MCS patients after TMS, whereas adjacent waves with low frequency were observed in VS/UWS |
| 33 | Manganotti et al. (83) | 6 DOC patients (3 VS/UWS, 3 MCS) |
EEG-TMS 21 electrodes |
CRS-R | Resting-State | Only one MCS patient showed long-lasting neurophysiological and behavioral modification during rTMS over the stimulated area |
| 34 | Bai et al. (84) | 18 DOC patients (9 VS/UWS, 9 MCS) |
EEG-TMS 62 electrodes |
CRS-R | Resting-State | The excitability time in temporal and spatial domains increased between was significantly different between VS/UWS and MCS patients |
| 35 | Casarotto et al. (85) | 81 DOC patients (43 VS/UWS 38 MCS) 150 healthy participants |
EEG-TMS 60 electrodes |
CRS-R | Resting-State & fractal dimension | Despite the ability to fully discriminate between consciousness and unconsciousness, no significant differences were found between VS and MCS cohorts |
The table shows the main results reported in the literature reviewed for the electrophysiological methods.