Objective: To evaluate the effects of long-term High-definition transcranial direct current stimulation (HD-tDCS) over precuneus on the level of consciousness (LOC) and the relationship between Mismatch negativity (MMN) and the LOC over the therapy period in patients with Disorders of consciousness (DOCs). Methods: We employed a with-in group repeated measures design with an anode HD-tDCS protocol (2 mA, 20 min, the precuneus) on 11 (2 vegetative state and nine minimally conscious state) patients with DOCs. MMN and Coma Recovery Scale-Revised (CRS-R) scores were measured at four time points: before the treatment of HD-tDCS (T0), after a single session of HD-tDCS (T1), after the treatment of 7 days (T2) and 14 days (T3). A frequency-deviant oddball paradigm with two deviation magnitudes (standard stimulus: 1000 Hz, small deviant stimuli: 1050 Hz, large deviant stimuli: 1200 Hz) was adopted to elicit MMN. Results: Significant improvements of CRS-R score were found after 7-day (T2) and 14-day (T3) treatment compared with baseline (T0). Regarding the MMN, significant improvements of MMN amplitudes were observed after a single session of stimulation (T1), 7-day (T2) and 14-day treatment (T3) compared with baseline (T0). Additionally, there were significant negative correlations between CRS-R scores and MMN amplitudes elicited by both large and small deviant stimuli. Conclusion: Long-term HD-tDCS over precuneus might improve signs of consciousness in patients with DOCs as measured by CRS-R total scores, and MMN could be an assistant assessment in the course of tDCS treatment.

In the present study, we aimed to elucidate changes in electroencephalography (EEG) metrics during recovery of consciousness and to identify possible clinical markers thereof. More specifically, in order to assess changes in multidimensional EEG metrics during neuromodulation, we performed repeated stimulation using a high-density transcranial direct current stimulation (HD-tDCS) protocol in 42 patients with disorders of consciousness (DOC). Coma Recovery Scale-Revised (CRS-R) scores and EEG metrics [brain network indicators, spectral energy, and normalized spatial complexity (NSC)] were obtained before as well as fourteen days after undergoing HD-tDCS stimulation. CRS-R scores increased in the responders (R +) group after HD-tDCS stimulation. The R + group also showed increased spectral energy in the alpha2 and beta1 bands, mainly at the frontal and parietal electrodes. Increased graphical metrics in the alpha1, alpha2, and beta1 bands combined with increased NSC in the beta2 band in the R + group suggested that improved consciousness was associated with a tendency toward stronger integration in the alpha1 band and greater isolation in the beta2 band. Following this, using NSC as a feature to predict responsiveness through machine learning, which yielded a prediction accuracy of 0.929, demonstrated that the NSC of the alpha and gamma bands at baseline successfully predicted improvement in consciousness. According to our findings reported herein, we conclude that neuromodulation of the posterior lobe can lead to an EEG response related to consciousness in DOC, and that the posterior cortex may be one of the key brain areas involved in the formation or maintenance of consciousness.

Introduction: The mismatch negativity (MMN) index has been used to evaluate consciousness levels in patients with disorders of consciousness (DoC). Indeed, MMN has been validated for the diagnosis of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS). In this study, we evaluated the accuracy of different MMN amplitude representations in predicting levels of consciousness.Methods: Task-state electroencephalography (EEG) data were obtained from 67 patients with DoC (35 VS and 32 MCS). We performed a microstate analysis of the task-state EEG and used four different representations (the peak amplitude of MMN at electrode Fz (Peak), the average amplitude within a time window −25– 25 ms entered on the latency of peak MMN component (Avg for peak ± 25 ms), the average amplitude of averaged difference wave for 100–250 ms (Avg for 100–250 ms), and the average amplitude difference between the standard stimulus (“S”) and the deviant stimulus (“D”) at the time corresponding to Microstate 1 (MS1) (Avg for MS1) of the MMN amplitude to predict the levels of consciousness.Results: The results showed that among the four microstates clustered, MS1 showed statistical significance in terms of time proportion during the 100–250 ms period. Our results confirmed the activation patterns of MMN through functional connectivity analysis. Among the four MMN amplitude representations, the microstate-based representation showed the highest accuracy in distinguishing different levels of consciousness in patients with DoC (AUC = 0.89).Conclusion: We discovered a prediction model based on microstate calculation of MMN amplitude can accurately distinguish between MCS and VS states. And the functional connection of the MS1 is consistent with the activation mode of MMN.