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Background: Disorders of consciousness (DoC) represent a spectrum of neurological conditions that pose significant treatment challenges. Percutaneous short-term spinal cord stimulation (SCS) has emerged as a promising experimental diagnostic treatment to assess and potentially improve consciousness levels. However, the effectiveness of this intervention is frequently compromised by the shift of electrodes, particularly in the cervical region, which can negatively affect therapeutic outcomes., Methods: This retrospective study aimed to study if electrodes shift in percutaneous short-term SCS in patients with DoC would affect the outcome. We analyzed the relationship between electrode shift length and patient outcome, as well as the correlation with various anatomical parameters, including the actual length of the cervical spine, linear length, spinal canal transverse diameter, spinal canal diameter, and C2 cone height, in a cohort of patients undergoing the procedure., Results: Our findings revealed that in patients with better outcome, there are significant less patient with electrode shift ( p  = 0.019). Further, a linear correlation was found between the length of electrode shift and patients' outcome (Rho = 0.583, p  = 0.002), with longer shift lengths associated with poorer outcomes. Contrary to our expectations, there was no significant association between the measured anatomical parameters and the extent of electrode shift. However, a trend was found between the actual length of the cervical spine and the shift of the electrode ( p  = 0.098). Notably, the shorter spinal canal transverse diameter was found to be significantly associated with better outcome in patients with DoC receiving percutaneous short-term SCS ( p  = 0.033)., Conclusion: These results highlight the clinical importance of electrode stability in the cervical region during SCS treatment for patients with DoC. Ensuring secure placement of electrodes may play a crucial role in enhancing patients' outcome and minimize postoperative complications. Given the lack of association with expected anatomical parameters, future research should investigate other factors that could impact electrode stability to optimize this therapeutic intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Yang, Xu, Niu, Wu, Huang, Chai, Cao, Wang, Wong, He, Yang and Zhao.)

Background and Objectives: Initial shunt failure following ventriculoperitoneal (VP) shunt surgery has a significant impact on the working time of the shunt. However, there are few studies regarding factors affecting VP shunt longevity. Hence, in this study, we aimed to build a nomogram to predict the longevity of the replacement VP shunt in patients with initial shunt failure., Methods: From 2011 to 2021, 142 patients with initial VP failure who underwent VP shunt revision were enrolled and relevant clinical and demographic factors were analyzed. Univariate and multivariate Cox proportional hazard regression models were used to choose predictors, and a nomogram was constructed using nine independent prognostic variables: sex, age, hydrocephalus type, intensive care unit admission, tracheostomy, decompressive craniectomy, craniotomy, lumbar cisterna drainage, and ventricular drainage. The prediction models' discrimination, accuracy, calibration, and clinical value were evaluated using Harrell's C-index, a calibration plot, and decision curve analysis., Results: At 1 month, 3 months, and 5 years, the nomogram's C-index was 0.680, 0.708, and 0.694, respectively. The nomogram's calibration plot provided a good fit for the overall prediction over the course of 1 year. Decision curve analysis predicted that 1-3 months after surgery will yield good net benefits between 30 and 50% probability thresholds., Conclusion: A preoperative nomogram may be an effective tool for assessing VP shunt longevity after initial VP shunt placement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, He, Niu, Li, Geng, Cao, Wang, Lv, He, Zhao, Chen and Yang.)

Disordered Consciousness (DOC) is among neurological disorders for which there is currently no admitted treatment. The pathogenesis of DOC is still unclear, covering a variety of indistinguishable types of diseases, high misdiagnosis rate and poor prognosis. Most treatments remain to be clarified in the future to provide adequate evidence for clinical guidance. Neuromodulation technology aims to regulate neural circuits to promote awakening more directly. At present, it is confirmed that the potential of transcutaneous auricular vagus nerve stimulation (taVNS) as a therapeutic tool is worth exploring in the context of consciousness disorders, as previously proposed for invasive forms of VNS, in which the means of stimulating the vagus nerve to change the brain areas related to cosciousness have also received widespread attention. In this paper, we review the literature on taVNS and DOC to better understand the current status and development prospect of taVNS treament as a non-invasive neuromodulation method with sensitivity and/or specificity at the single subject., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zhang, Zhai, Wang, Li, Yang, Zheng, He and Rong.)

Background: Non-invasive brain stimulation (NIBS) techniques are now widely used in patients with disorders of consciousness (DOC) for accelerating their recovery of consciousness, especially minimally conscious state (MCS). However, the effectiveness of single NIBS techniques for consciousness rehabilitation needs further improvement. In this regard, we propose to enhance from bottom to top the thalamic-cortical connection by using transcutaneous auricular vagus nerve stimulation (taVNS) and increase from top to bottom cortical-cortical connections using simultaneous high-definition transcranial direct current stimulation (HD-tDCS) to reproduce the network of consciousness., Methods/design: The study will investigate the effect and safety of simultaneous joint stimulation (SJS) of taVNS and HD-tDCS for the recovery of consciousness. We will enroll 84 MCS patients and randomize them into two groups: a single stimulation group (taVNS and HD-tDCS) and a combined stimulation group (SJS and sham stimulation). All patients will undergo a 4-week treatment. The primary outcome will be assessed using the coma recovery scale-revised (CRS-R) at four time points to quantify the effect of treatment: before treatment (T0), after 1 week of treatment (T1), after 2 weeks of treatment (T2), and after 4 weeks of treatment (T3). At the same time, nociception coma scale-revised (NCS-R) and adverse effects (AEs) will be collected to verify the safety of the treatment. The secondary outcome will involve an analysis of electroencephalogram (EEG) microstates to assess the response mechanisms of dynamic brain networks to SJS. Additionally, CRS-R and AEs will continue to be obtained for a 3-month follow-up (T4) after the end of the treatment., Discussion: This study protocol aims to innovatively develop a full-time and multi-brain region combined neuromodulation paradigm based on the mesocircuit model to steadily promote consciousness recovery by restoring thalamocortical and cortical-cortical interconnections., Competing Interests: The authors declare that the research will be conducted in the absence of any commercial or financial relationships that will be construed as a potential conflict of interest., (Copyright © 2023 Zhuang, Zhai, Li, Jiao, Ge, Rong and He.)

Objectives: The pathological mechanism for a disorder of consciousness (DoC) is still not fully understood. Based on traditional behavioral scales, there is a high rate of misdiagnosis for subtypes of DoC. We aimed to explore whether topological characterization may explain the pathological mechanisms of DoC and be effective in diagnosing the subtypes of DoC., Methods: Using resting-state functional magnetic resonance imaging data, the weighted brain functional networks for normal control subjects and patients with vegetative state (VS) and minimally conscious state (MCS) were constructed. Global and local network characteristics of each group were analyzed. A support vector machine was employed to identify MCS and VS patients., Results: The average connection strength was reduced in DoC patients and roughly equivalent in MCS and VS groups. Global efficiency, local efficiency, and clustering coefficients were reduced, and characteristic path length was increased in DoC patients ( p < 0.05). For patients of both groups, global network measures were not significantly different ( p > 0.05). Nodal efficiency, nodal local efficiency, and nodal clustering coefficient were reduced in frontoparietal brain areas, limbic structures, and occipital and temporal brain areas ( p < 0.05). The comparison of nodal centrality suggested that DoC causes reorganization of the network structure on a large scale, especially the thalamus. Lobal network measures emphasized that the differences between the two groups of patients mainly involved frontoparietal brain areas. The accuracy, sensitivity, and specificity of the classifier for identifying MCS and VS patients were 89.83, 78.95, and 95%, respectively., Conclusion: There is an association between altered network structures and clinical symptoms of DoC. With the help of network metrics, it is feasible to differentiate MCS and VS patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Dai, He, Wang, Chen, Geng, He and Duan.)

Hyperbaric oxygen (HBO) therapy is an effective treatment for patients with disorders of consciousness (DOC). In this study, real-time electroencephalogram (EEG) recordings were obtained from patients with DOC during HBO therapy. EEG microstate indicators including mean microstate duration (MMD), ratio of total time covered (RTT), global explained variance (GEV), transition probability, mean occurrence, and mean global field power (GFP) were compared before and during HBO therapy. The results showed that the duration of microstate C in all patients with DOC increased after 20 min of HBO therapy ( p  < 0.05). Further statistical analysis found that the duration of microstate C was longer in the higher CRS-R group (≥8, 17 cases) than in the lower group (<8, 24 cases) during HBO treatment. In the higher CRS-R group, the transition probabilities from microstate A to microstate C and from microstate C to microstate A also increased significantly compared with the probability before treatment ( p  < 0.05). Microstate C is generally considered to be related to a salience network; an increase in the transition probability between microstate A and microstate C indicates increased information exchange between the auditory network and the salience network. The results of this study show that HBO therapy has a specific activating effect on attention and cognitive control in patients and causes increased activity in the primary sensory cortex (temporal lobe and occipital lobe). This study demonstrates that real-time EEG detection and analysis during HBO is a clinically feasible method for assessing brain function in patients with DOC. During HBO therapy, some EEG microstate indicators show significant changes related to the state of consciousness in patients with chronic DOC. This will be complementary to important electrophysiological indicators for assessing consciousness and may also provide an objective foundation for the precise treatment of patients with DOC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Xu, Ge, Xue, Liu, Wang, Wu, Liu, Chen, Zhuang, Geng, Chen, Wang, Yu, He and Zhao.)

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique. Several studies have reported the effectiveness of taVNS in patients with disorders of consciousness (DOC); however, differences in the modulation paradigm have led to inconsistent treatment outcomes., Methods/design: This prospective exploratory trial will include 15 patients with a minimally conscious state (MCS) recruited according to the coma recovery scale-revised (CRS-R). Each patient will receive 5 different frequencies of taVNS (1, 10, 25, 50, and 100 Hz); sham stimulation will be used as a blank control. The order of stimulation will be randomized, and the patients' CRS-R scores and resting electroencephalography (EEG) before and after stimulation will be recorded., Discussion: The overall study of taVNS used in treating patients with DOC is still in the preliminary stage of exploration. Through this experiment, we aim to explore the optimal stimulation frequency parameters of taVNS for the treatment of DOC patients. Furthermore, we expect to achieve a stable improvement of consciousness in DOC patients by continuously optimizing the neuromodulation paradigm of taVNS for the treatment of DOC patients., Clinical Trial Registration: https://www.chictr.org.cn/index.aspx, identifier ChiCTR 2200063828., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhai, Jiao, Zhuang, Yang, Zhang, Wang, Wang, Zhao, Zhang, He and Rong.)

Introduction: Effective treatment to facilitate recovery from prolonged disorders of consciousness is a complex topic for the medical community. In clinical practice, we have found that a subset of patients has a short-term improvement of consciousness after general anesthesia., Methods: To determine the clinical factors responsible for the consciousness improvement, we enrolled 50 patients with disorders of consciousness who underwent surgery from October 2021 to June 2022. Their states of consciousness were evaluated before surgery, within 48 h after surgery, and 3 months after surgery. Clinical-related factors and intraoperative anesthetic drug doses were collected and compared between patients with and without consciousness improvement. Independent associations between selected factors and postoperative improvement were assessed using multivariate logistical regression analyses., Results: Postoperative short-term consciousness improvement was found in 44% (22/50) of patients, with significantly increased scores of auditory and visual subscales. Patients with traumatic etiology, a preoperative diagnosis of minimally conscious state, and higher scores in the auditory, visual, and motor subscales were more likely to have postoperative improvement. This short-term increase in consciousness after surgery correlated with patients' abilities to communicate in the long term. Furthermore, the amount of opioid analgesic used was significantly different between the improved and non-improved groups. Finally, analgesic dose, etiology, and preoperative diagnosis were independently associated with postoperative consciousness improvement., Discussion: In conclusion, postoperative consciousness improvement is related to the residual consciousness of the patient and can be used to evaluate prognosis. Administration of opioids may be responsible for this short-term improvement in consciousness, providing a potential therapeutic approach for disorders of consciousness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ge, Wang, Zhuang, Li, Han, Guo and He.)

Background: Spinal cord stimulation (SCS) is a promising treatment for patients with disorders of consciousness (DoC); however, the laboratory examinations and different electrodes (permanent #39286 vs. temporary percutaneous #3777, Medtronic, USA) that are associated with postoperative outcomes are unclear. The study aims to study the association between the change in postoperative cerebrospinal fluid (CSF) protein level and improvement in consciousness after SCS in DoC patients and to explore whether different electrodes were associated with elevated CSF protein levels., Materials and Methods: A total of 66 DoC patients who received SCS treatment from December 2019 to December 2021 were retrospectively analyzed. Patients were grouped according to their elevated CSF protein level. The clinical characteristics of the patients and SCS stimulation parameters were compared. The preoperative sagittal diameter of the spinal canal is the distance from the midpoint of the posterior border of the vertebral body to the midpoint of the posterior wall of the spinal canal at the level of the superior border of C3. The postoperative sagittal diameter of the spinal canal is the distance from the midpoint of the posterior edge of the vertebral body to the anterior edge of the stimulation electrode. Patients with improved postoperative CRS-R scores greater than 3 or who progressed to the MCS + /eMCS were classified as the improved group and otherwise regarded as poor outcome., Results: We found that more DoC patients had elevated CSF protein levels among those receiving SCS treatment with permanent electrodes than temporary percutaneous electrodes ( P = 0.001), and elevated CSF protein levels were significantly associated with a reduced sagittal diameter ( P = 0.044). In DoC patients receiving SCS treatment, we found that elevated CSF protein levels ( P = 0.022) and preoperative diagnosis ( P = 0.003) were significantly associated with poor outcomes at 3 months. Logistic regression analysis showed that elevated CSF protein levels were significantly associated with poor outcomes (OR 1.008, 95% CI 1.001-1.016, P = 0.032)., Conclusion: The results suggest that reducing the effect of electrode pads on anatomical changes may help improve the outcomes of DoC patients receiving SCS treatment. CSF protein levels are associated with poor postoperative outcomes and whether they are potential biomarkers in DoC patients receiving SCS treatment remain further exploration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Li, Xiong, Xia, Dang, Chen, Geng, He, Yang and Zhao.)

Background: Spinal cord stimulation (SCS) can improve the level of awareness of prolonged disorder of consciousness (pDOC), but its application is restricted due to damage of invasive operation. Short-term spinal cord stimulation (st-SCS) in a minimally invasive manner will better balance the benefits and risks., Objectives: This study focuses on the safety and efficacy of st-SCS for pDOC and reveals the modulation characteristics of different frequencies of SCS., Methods: 31 patients received 2-week st-SCS treatment and 3-months follow-up. All patients were divided into two types of frequency treatment groups of 5 Hz and 70 Hz according to the postoperative electroencephalography (EEG) test. The efficacy was assessed based on the revised coma recovery scale (CRS-R)., Results: The results showed a significant increase in CRS-R scores after treatment (Z = -3.668, p < 0.001) without significant adverse effects. Univariate analysis showed that the minimally conscious state minus (MCS-) benefits most from treatment. Furthermore, two frequency have a difference in the time-point of the CRS-R score increase. 5 Hz mainly showed a significant increase in CRS-R score at 2 weeks of treatment ( p = 0.027), and 70 Hz additionally showed a delayed effect of a continued significant increase at 1 week after treatment ( p = 0.004)., Conclusion: st-SCS was safe and effective in improving patients with pDOC levels of consciousness, and was most effective for MCS-. Both 5 Hz and 70 Hz st-SCS can promote consciousness recovery, with 70 Hz showing a delayed effect in particular., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhuang, Yang, Xu, Chen, Geng, Zhao and He.)

Background and Purpose: Spinal cord stimulation (SCS) has been reported to be a promising neuromodulation method for patients with disorders of consciousness (DOC). Our previous studies found that clinical characteristics of patients and SCS stimulation parameters could affect the therapeutic effects of SCS, while surgical-related factors remain unknown. Through the improvement of surgical procedures, most of the SCS electrodes are implanted in the middle, while a small number of electrodes have still deviated., Methods: A total of 137 patients received SCS treatment in our institutions from 1 January 2010 to 31 December 2020. Among them, 27 patients were found with electrode deviation and met the inclusion criteria. Patients were grouped according to whether the electrode deviation angle (EDA) is >30°, respectively. Clinical characteristics of patients and SCS stimulation parameters were compared. Potential related factors and outcomes were evaluated by Chi-square test or two-way repeated measures analysis., Results: Twenty seven patients receiving cervical SCS treatment were found to have electrode deviation postoperatively. Among them, 12 patients were classified into the more deviation group. No significant difference was found among age, sex, pathogeny, course of DOC, C2-C5 distance, spinal cord to spinal canal ratio at C2 level, and preoperative JFK Coma Recovery Scale-Revised (CRS-R) scores. We found that the electrode direction significantly deviated to the contralateral side in the lateral decubitus position ( P = 0.025). The maximum tolerant stimulation intensity in the less deviation group (1.70 ± 0.41) was significantly higher than that in the more deviation group (1.25 ± 0.34) ( P = 0.006). Under the strongest stimulation, less unilateral limb tremor ( P = 0.049) and paroxysmal sympathetic hyperactivity (PSH) episodes ( P = 0.030) were found. EDA had a significant effect on postoperative CRS-R in patients, and patients in the less deviation group had significantly higher postoperative CRS-R ( P < 0.01). There was also an interaction effect between EDA and postoperative time. With the prolonged postoperative time, the CRS-R improvement rate of patients with different EDA was different, and the CRS-R improved faster in patients with less EDA ( P < 0.05)., Conclusions: Electrode deviation will affect the outcome of patients receiving cervical SCS treatment. The intraoperative surgical position is associated with postoperative electrode deviation direction. The reduction of EDA under 30° can increase maximum tolerant stimulation intensity, reduce complications, and further improve patients' outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Han, Xia, Dang, Chen, He and Yang.)

CD146 is cell adhesion molecule and is implicated in a variety of physiological and pathological processes. However, the involvement of CD146 in peripheral nerve regeneration has not been studied yet. Here, we examine the spatial and temporal expression pattern of CD146 in injured mouse sciatic nerve via high-throughput data analysis, RT-PCR and immunostaining. By microarray data analysis and RT-PCR validation, we show that CD146 mRNA is significantly up-regulated in the nerve bridge and in the distal nerve stump following mouse sciatic nerve transection injury. By single cell sequencing data analysis and immunostaining, we demonstrate that CD146 is up-regulated in Schwann cells and cells associated with blood vessels following mouse peripheral nerve injury. Bioinformatic analysis revealed that CD146 not only has a key role in promoting of blood vessel regeneration but also regulates cell migration. The biological function of CD146 in Schwann cells was further investigated by knockdown of CD146 in rat primary Schwann cells. Functional assessments showed that knockdown of CD146 decreases viability and proliferation of Schwann cells but increases Schwann cell migration. Collectively, our findings imply that CD146 could be a key cell adhesion molecule that is up-regulated in injured peripheral nerves to regulate peripheral nerve regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shen, Zhu, Liu, Ding, Dun and He.)

Recent advances in neuroimaging technologies have provided insights into detecting residual consciousness and assessing cognitive abilities in patients with disorders of consciousness (DOC). Functional near-infrared spectroscopy (fNIRS) is non-invasive and portable and can be used for longitudinal bedside monitoring, making it uniquely suited for evaluating brain function in patients with DOC at appropriate spatiotemporal resolutions. In this pilot study, an active command-driven motor imagery (MI) paradigm based on fNIRS was used to detect residual consciousness in patients with prolonged DOC. A support vector machine (SVM) classifier was used to classify yes-or-no responses. The results showed that relatively reliable responses were detected from three out of five patients in a minimally consciousness state (MCS). One of the patients answered all the questions accurately when assessed according to this method. This study confirmed the feasibility of using portable fNIRS technology to detect residual cognitive ability in patients with prolonged DOC by active command-driven motor imagery. We hope to detect the exact level of consciousness in DOC patients who may have a higher level of consciousness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Yang, Zhang, Gao, Jing, Dang, Chen, He and Si.)

This study aimed to preliminarily illustrate the cerebral hemodynamic correlates of transcutaneous auricular vagal nerve stimulation (taVNS) in consciousness restoration. Arterial spin labeling (ASL) was adopted with functional magnetic resonance imaging (fMRI) to measure cerebral blood flow (CBF) changes before and after taVNS in 10 qualified patients with disorders of consciousness (DOC). Before taVNS, five patients responded to auditory stimuli (RtAS), and five did not respond to auditory stimuli (nRtAS). The RtAS DOC patients obtained favorable prognoses after the 4-week taVNS treatment, whereas the nRtAS ones did not. Simultaneously, taVNS increased CBF of multiple brain regions in the RtAS DOC patients, but hardly in the nRtAS ones. In conclusion, the preserved auditory function might be the prior key factor of the taVNS responders in DOC patients, and taVNS might alleviate RtAS DOC by activating the salience network, the limbic system, and the interoceptive system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Yang, Gan, Guo, Fang, Wang, Tang, Bai, He and Rong.)

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., (Copyright © 2020 Wang, Guo, Zhang, Li, Gao, Li, Zhou, Zhang, He and Cong.)

Transcranial direct current stimulation (tDCS) recently was shown to benefit rehabilitation of patients with disorders of consciousness (DOC). However, high-Definition tDCS (HD-tDCS) has not been applied in DOC. In this study, we tried to use HD-tDCS protocol (2 mA, 20 min, the precuneus, and sustaining 14 days) to rehabilitate 11 patients with DOC. Electroencephalography (EEG) and Coma Recovery Scale-Revised (CRS-R) scores were recorded at before (T0), after a single session (T1), after 7 days' (T2), and 14 days' HD-tDCS (T3) to assess the modulation effects. EEG coherence was measured to evaluate functional connectivity during the experiment. It showed that 9 patients' scores increased compared with the baseline. The central-parietal coherence significantly decreased in the delta band in patients with DOC. EEG coherence might be useful for assessing the effect of HD-tDCS in patients with DOC. Long-lasting HD-tDCS over the precuneus is promising for the treatment of patients with DOC.

Spinal cord stimulation (SCS) has been shown to improve the consciousness levels of patients with disorder of consciousness (DOC). However, the underlying mechanisms of SCS remain poorly understood. This study recorded resting-state electroencephalograms (EEG) from 16 patients with minimally conscious state (MCS), before and after SCS, and investigated the mechanisms of SCS on the neuronal dynamics in MCS patients. Detrended fluctuation analysis (DFA), combined with surrogate data method, was employed to measure the long-range temporal correlations (LRTCs) of the EEG signals. A surrogate data method was utilized to acquire the genuine DFA exponents (GDFAE) reflecting the genuine LRTCs of brain activity. We analyzed the GDFAE in four brain regions (frontal, central, posterior, and occipital) at five EEG frequency bands [delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-45 Hz)]. The GDFAE values ranged from 0.5 to 1, and showed temporal and spatial variation between the pre-SCS and the post-SCS states. We found that the channels with GDFAE spread wider after SCS. This phenomenon may indicate that more cortical areas were engaged in the information integration after SCS. In addition, the GDFAE values increased significantly in the frontal area at delta, theta, and alpha bands after SCS. At the theta band, a significant increase in GDFAE was observed in the occipital area. No significant change was found at beta or gamma bands in any brain region. These findings show that the enhanced LRTCs after SCS occurred primarily at low-frequency bands in the frontal and occipital regions. As the LRTCs reflect the long-range temporal integration of EEG signals, our results indicate that information integration became more "complex" after SCS. We concluded that the brain activities at low-frequency oscillations, particularly in the frontal and occipital regions, were improved by SCS.

Purpose: Diagnostic error is common among patients with vegetative state (VS) and minimally conscious state (MCS). The purpose of this article is to use three-dimensional pseudo-continuous arterial spin labeling (pcASL) to compare cerebral blood flow (CBF) patterns in patients in MCS with those in VS., Methods: Patients meeting MCS and VS criteria were identified. Two post-labeling delay (PLD) time pcASL on 3.0-Tesla magnetic resonance imaging scanner system were performed with patients in the resting awake state. After registration to T1WI structure imaging, multiple brain regions of interest of ASL CBF map were automatically separated. The average CBF value of every brain region was calculated and compared between the MCS and VS groups with t -tests., Results: Fifteen patients with VS were identified, with ages ranging from 33 to 71 years. Eight patients who met the MCS criteria ranged in age from 23 to 61 years. Compared with VS, the regional CBF for MCS had a pattern of significantly increased CBF in the regions including the putamen, anterior cingulate gyrus, and medial frontal cortex. A left-lateralized pattern was observed to differentiate MCS from VS. CBF with PLD 2.5 s could find more regions of pattern differentiating MCS from VS than with PLD 1.5 s, except for the pallidum., Conclusion: MCS might be differentiated from VS by different ranges of regional CBF as measured by ASL. Multi-PLD ASL may serve as an adjunct method to separate MCS from VS and assess functional reserve in patients recovering from severe brain injuries.

Spinal cord stimulation (SCS) has become a valuable brain-intervention technique used to rehabilitate patients with disorders of consciousness (DOC). To explore how the SCS affects the cerebral cortex and what possible electrophysiological mechanism of SCS effects on the cortex, the present study investigated the functional connectivity and network properties during SCS in minimally conscious state (MCS) patients. MCS patients received both SCS and sham sessions. Functional connectivity of the phase lock value (PLV) in the gamma band (30-45 Hz) was investigated at the pre-, on- and post-SCS stages. In addition, to evaluate global network properties, complex network parameters, including average path length, cluster coefficient and small-world, were measured. When SCS was turned on, significantly decreased connectivity was noted in the local scale of the frontal-frontal region and in the large scales of the frontal-parietal and frontal-occipital regions. The global network showed fewer small-world properties, average path lengths increased and cluster coefficients decreased. When SCS was turned off, the large-scale connectivity and global network returned to its pre-SCS level, but the local scale of frontal-frontal connectivity remained significantly lower than its pre-SCS level. Sham sessions produced no significant changes in either functional connectivity or network. The findings directly showed that SCS could effectively intervene cortical gamma activity, and the intervention included immediate global effects (large scale connectivity and network alteration only occurred in stimulation period) and long-lasting local effects (local scale connectivity alteration persist beyond stimulation period). Moreover, considering the mechanism and propagation of gamma activity, it indicates that the frontal cortex plays a crucial role in the SCS effects on the cerebral cortex.

Background: While repetitive transcranial magnetic stimulation (rTMS) has been applied in treatment of patients with disorders of consciousness (DOC), a standardized stimulation protocol has not been proposed, and its therapeutic effects are inconsistently documented., Objectives: To assess the efficacy of rTMS in improving consciousness in patients with persistent minimally conscious state (MCS) or unresponsive wakefulness syndrome (UWS), previously known as vegetative state (VS)., Method: A prospective single-blinded study, with selected subjects, was carried out. In total, 16 patients (5 MCS and 11 VS/UWS) with chronic DOC were included. All patients received active 10 Hz rTMS at the left dorsolateral prefrontal cortex (DLPFC), at one session per day, for 20 consecutive days. A single daily session of stimulation consisted of 1,000 pulses (10 s of 10 Hz trains; repeated 10 times with an inter-train interval of 60 s; and 11 min and 40 s for total session). The main outcome measures were changes in the total score on the JFK Coma Recovery Scale-Revised (CRS-R) scale. Additional measures were the impressions of caregivers after the conclusion of the interventions, which were assessed using the Clinical Global Impression-Improvement (CGI-I) scale., Results: The CRS-R scores were increased in all 5 MCS patients and 4 of 11 VS/UWS patients, while a significant enhancement of CRS-R scores was observed compared to the baseline in all participants ( p  = 0.007). However, the improvement was more notable in MCS patients ( p  = 0.042) than their VS/UWS counterparts ( p  = 0.066). Based on the CGI-I scores, two patients improved considerably, two improved, six minimally improved, six experienced no change, and none deteriorated. Good concordance was seen between the CGI-I result and the increases in CRS-R scores., Conclusion: Treatment of 10 Hz multisession rTMS applied to the left DLPFC is promising for the rehabilitation of DOC patients, especially those in MCS. Further validation with a cohort of a larger sample size is required.