Background: With the improvement of emergency techniques, the survival rate of patients with severe brain injury has increased. However, this has also led to an annual increase in the number of patients with prolonged disorders of consciousness (pDoC). Hence, recovery of consciousness is an important part of treatment. With advancing techniques, noninvasive neuromodulation seems a promising intervention. The objective of this review was to summarize the latest techniques and provide the basis for protocols of noninvasive neuromodulations in pDoC.Methods: This review summarized the advances in noninvasive neuromodulation in the treatment of pDoC in the last 5 years.Results: Variable techniques of neuromodulation are used in pDoC. Transcranial ultrasonic stimulation (TUS) and transcutaneous auricular vagus nerve stimulation (taVNS) are very new techniques, while transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are still the hotspots in pDoC. Median nerve electrical stimulation (MNS) has received little attention in the last 5 years.Conclusions: Noninvasive neuromodulation is a valuable and promising technique to treat pDoC. Further studies are needed to determine a unified stimulus protocol to achieve optimal effects as well as safety.

Although the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Twenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. After the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. Parietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal–parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.

Frontal transcranial direct current stimulation (tDCS) and parietal tDCS are effective for treating disorders of consciousness (DoC); however, the relative efficacies of these techniques have yet to be determined. This paper compares the neuromodulation effects of frontal and parietal tDCS on DoC. Twenty patients with DoC were recruited and randomly assigned to two groups. One group received single-session frontal tDCS and single-session sham tDCS. The other group received single-session parietal tDCS and single-session sham tDCS. Before and after every tDCS session, we recorded coma recovery scale-revised (CRS-R) values and an electroencephalogram. CRS-R was also used to evaluate the state of consciousness at 9–12-month follow-up. Both single-session frontal and parietal tDCS caused significant changes in the genuine permutation cross-mutual information (G_PCMI) of local frontal and across brain regions (p < 0.05). Furthermore, the changes in G_PCMI values were significantly correlated to the CRS-R scores at 9–12-month follow-up after frontal and parietal tDCS (p < 0.05). The changes in G_PCMI and CRS-R scores were also correlated (p < 0.05). Both frontal tDCS and parietal tDCS exert neuromodulatory effects in DoC and induce significant changes in electrophysiology. G_PCMI can be used to evaluate the neuromodulation effects of tDCS.

The basis of disorders of consciousness is the destruction of brain functional connectivity, and the restoration of damaged connectivity is considered as an indicator of consciousness recovery. The purpose of this study is to explore the effect of parietal repetitive transcranial magnetic stimulation (rTMS) on the changes of brain functional connectivity and consciousness recovery in patients with minimal conscious state (MCS) by electrophysiological (EEG) functional connectivity analysis, and to further explore the potential mechanism of consciousness recovery. In this study, 24 patients with MCS were randomly assigned to either real or sham rTMS group. The real rTMS group was applied to the parietal cortex at 10 Hz with 90% of the rest motor threshold, while the sham group underwent a similar procedure without cortical stimulation. Resting-state EEG and Coma Recovery Scale-Revised (CRS-R) scores were obtained before and after treatment. The Phase Locking Value (PLV) was calculated for the region of interest to assess the effect of parietal rTMS on functional brain connectivity. The CRS-R scores significantly improved after treatment in the real rTMS group, accompanied by increases in PLV, the default mode network (DMN), the frontoparietal network (FPN), and FPN-DMN connectivity. In contrast, the sham rTMS group showed no significant changes in CRS-R scores or EEG results. Moreover, alterations in FPN networks were positively correlated with changes in CRS-R scores. Parietal rTMS promotes the recovery of consciousness by fortifying large-scale brain connections and activating neural networks. In particular, FPN functional connections are closely linked to the early recovery of consciousness.