Circ_BLNK is a Unique Molecular Marker in Non-small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) patients are characterized by distant metastasis and poor prognosis. Growing evidence has implied that circular RNAs (circRNAs) are involved in multiple tumor progression, including NSCLC. The objective of the present study was to functionally dissect the role and mechanism of circ_BLNK in NSCLC development and progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of circ_BLNK, miR-942-5p, and forkhead box protein O1 (FOXO1) in NSCLC tissues and cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay detected cell proliferation; the protein expression levels were tested by western blot assay; cell apoptosis was measured by flow cytometry, and transwell assay detected cell migration and invasion. The molecular targeting relationship was determined by dual-luciferase reporter assay. The effect of circ_BLNK overexpression on tumor growth was detected by in vivo experiments and immunohistochemistry. Circ_BLNK was dramatically decreased in NSCLC, and overexpression of circ_BLNK inhibited proliferation, migration, and invasion of NSCLC cells and promoted cell apoptosis. Circ_BLNK level was negatively correlated with miR-942-5p expression and positively correlated with FOXO1 expression. Moreover, circ_BLNK acted as a sponge for miR-942-5p, which targeted FOXO1. Rescue assays presented that miR-942-5p reversed the anticancer action of circ_BLNK in NSCLC. Besides that, miR-942-5p inhibition suppressed the oncogenic behaviors, which were attenuated by FOXO1 knockdown. Animal experiments exhibited that circ_BLNK upregulation repressed tumor growth in vivo. Our study demonstrated a novel regulatory mechanism that circ_BLNK/miR-942-5p/FOXO1 axis adjusted non-small cell lung cancer development.

EEG complexity correlates with residual consciousness level of disorders of consciousness.

BACKGROUND AND OBJECTIVE: Electroencephalography (EEG) and neuroimaging measurements have been highly encouraged to be applied in clinics of disorders of consciousness (DOC) to improve consciousness detection. We tested the relationships between neural complexity measured on EEG and residual consciousness levels in DOC patients. METHODS: Resting-state EEG was recorded from twenty-five patients with DOC. Lempel-Ziv complexity (LZC) and permutation Lempel-Ziv complexity (PLZC) were measured on the EEG, and their relationships were analyzed with the consciousness levels of the patients. RESULTS: PLZC and LZC values significantly distinguished patients with a minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS), and healthy controls. PLZC was significantly correlated with the Coma Recovery Scale-Revised (CRS-R) scores of DOC patients in the global brain, particularly in electrodes locating in the anterior and posterior brain regions. Patients with higher CRS-R scores showed higher PLZC values. The significant difference in PLZC values between MCS and VS/UWS was mainly located in the bilateral frontal and right hemisphere regions. CONCLUSION: Neural complexity measured on EEG correlates with residual consciousness levels of DOC patients. PLZC showed higher sensitivity than LZC in the classification of consciousness levels.

Proposal of a Novel Procedure for C2-4 Cervical Spinal Cord Stimulator Implantation to Improve Complete Midline Coverage via Electrode Array in Patients with Disorders of Consciousness: A Retrospective Single-Center Study.

BACKGROUND: Deviation of electrode array from the midline of spinal cords affects the therapeutic outcomes of C2-4 cervical spinal cord stimulation (SCS) in patients with disorders of consciousness (DOC). This study proposed the implementation of a novel C2-3 dural exposure procedure and investigated its efficacy compared to conventional surgery. METHODS: Surgical and postoperative imaging data from 69 patients with DOC who underwent SCS in the lateral decubitus position were retrospectively assessed. The C2-3 dural exposure procedure was performed in 16 patients while the rest underwent conventional surgery. The incidence of electrode deviation was compared, and factors associated with the deviation were investigated. RESULTS: The rate of complete midline coverage by the electrodes in the C2-3 dural exposure group was significantly higher than the conventional group (93.8% vs. 54.7%, p = 0.004). Exposure of the dura between C2-3 was a significant favorable factor for complete midline coverage by the electrode array (odds ratio [OR]: 0.091; 95% confidence interval [CI]: 0.011-0.757; p = 0.027). Electrode positioned ≥5 cm above the lower edge of the C2 vertebra was a significant risk factor for incomplete midline coverage (OR: 1.126; 95% CI: 1.016-1.248; p = 0.023). No difference in operation time, intraoperative bleeding, or surgical site infection was observed between the 2 groups. CONCLUSIONS: The C2-3 dural exposure procedure, performed in the lateral decubitus position, was safe and had higher complete midline coverage than conventional surgery.

Spontaneous transient brain states in EEG source space in disorders of consciousness.

Spontaneous transient states were recently identified by functional magnetic resonance imaging and magnetoencephalography in healthy subjects. They organize and coordinate neural activity in brain networks. How spontaneous transient states are altered in abnormal brain conditions is unknown. Here, we conducted a transient state analysis on resting-state electroencephalography (EEG) source space and developed a state transfer analysis to patients with disorders of consciousness (DOC). They uncovered different neural coordination patterns, including spatial power patterns, temporal dynamics, spectral shifts, and connectivity construction varies at potentially very fast (millisecond) time scales, in groups with different consciousness levels: healthy subjects, patients in minimally conscious state (MCS), and patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Machine learning based on transient state features reveal high classification accuracy between MCS and VS/UWS. This study developed methodology of transient states analysis on EEG source space and abnormal brain conditions. Findings correlate spontaneous transient states with human consciousness and suggest potential roles of transient states in brain disease assessment.

Prognostic models for prolonged disorders of consciousness: an integrative review.

Disorders of consciousness (DoC) are acquired conditions of severe altered consciousness. During the past decades, some prognostic models for DoC have been explored on the basis of a variety of predictors, including demographics, neurological examinations, clinical diagnosis, neurophysiology and brain images. In this article, a systematic review of pertinent literature was conducted. We identified and evaluated 21 prognostic models involving a total of 1201 DoC patients. In terms of the reported accuracies of predicting the prognosis of DoC, these 21 models vary widely, ranging from 60 to 90%. Using improvement of consciousness level as favorable outcome criteria, we performed a quantitative meta-analysis, and found that the pooled sensitivity and specificity of the hybrid model that combined more than one technique were both superior to those of any single technique, including EEG and fMRI at the tasks and resting state. These results support the view that any single technique has its own advantages and limitations; and the integrations of multiple techniques, including diverse brain images and different paradigms, have the potential to improve predictive accuracy for DoC. Then, we provide methodological points of view and some prospects about future research. Totally, in comparison to a great many diagnostic methods for the DoC, the research of prognostic models is sparse and preliminary, still largely in its infancy with many challenges and opportunities.

Protein phosphorylation profiling of peripheral nerve regeneration after autologous nerve grafting.

Autologous nerve grafting is the golden standard therapeutic approach of peripheral nerve injury. However, the clinical effect of autologous nerve grafting is still unsatisfying. To achieve better clinical functional recovery, it is of an impending need to expand our understanding of the dynamic cellular and molecular changes after nerve transection and autologous nerve transplantation. To address this aim, in the current study, rats were subjected to sciatic nerve transection and autologous nerve grafting. Rat sciatic nerve segments were collected at 4, 7, and 14 days after surgery and subjected to antibody array analysis to determine phosphoprotein profiling patterns. Compared with rats that underwent sham surgery, a total of 48, 19, and 75 differentially expressed phosphoproteins with fold changes > 2 or < -2 were identified at 4, 7, and 14 days after autologous nerve grafting, respectively. Several phosphoproteins, including STAM2 (Phospho-Tyr192) and Tau (Phospho-Ser422), were found to be differentially expressed at multiple time points, suggesting the importance of the phosphorylation of these proteins. Western blot validation of the expression patterns of STAM2 (Phospho-Tyr192) indicated the accuracy of antibody array assay. Bioinformatic analysis of these differentially expressed proteins suggested that cellular behavior and organ morphology were significantly involved biological functions while cell behavior and immune response-related signaling pathways were significantly involved canonical signaling pathways. These outcomes contributed to the illumination of the molecular mechanisms underlying autologous nerve grafting from the phosphoprotein profiling perspective.

Spinal cord stimulation modulates complexity of neural activities in patients with disorders of consciousness.

Objective: Spinal cord stimulation (SCS) is a valuable treatment for patients with disorders of consciousness (DOC). This study used permutation entropy (PeEn) of neural activities to quantify brain responses to SCS.Method: We recruited 14 patients with DOC, including seven patients in minimally conscious state (MCS) and seven patients in vegetative state/unawareness state (VS/UWS). All patients received a single session of 20 min' continuous SCS. We recorded resting state EEG before, during and after SCS. In this study, PeEn was first calculated to describe overall neural activities changes in SCS. The brain was then divided into frontal, central, parietal and occipital regions to explore spatial SCS modulation effects. Finally, a correlation analysis was conducted between CRS-R values and changes in PeEn on each of the four regions.Results: SCS was associated with short-term changes in neural activities in DOC. When SCS was on, PeEn increased as compared to the baseline. When SCS was shut off, PeEn decreased. The PeEn of all patients after SCS was higher than before SCS, and changes of PeEn for MCS were more significant than those for VS, especially in the frontal region.Conclusion: PeEn from EEG data could be used to evaluate SCS modulation effects, and EEG complexity might be a critical index to describe brain responses to SCS in DOC.

miR-3075 Inhibited the Migration of Schwann Cells by Targeting Cntn2.

Peripheral nerve injury is a complex biological process that involves the expression changes of various coding and non-coding RNAs. Previously, a number of novel miRNAs that were dysregulated in rat sciatic nerve stumps after peripheral nerve injury were identified and functionally annotated by Solexa sequencing. In the current study, we studied one of these identified novel miRNAs, miR-3075, in depth. Results of transwell-based cell migration assay showed that increased expression of miR-3075 suppressed the migration rate of Schwann cells while decreased expression of miR-3075 elevated the migration rate of Schwann cells, demonstrating that miR-3075 inhibited Schwann cell migration. Results of BrdU cell proliferation assay showed that neither miR-3075 mimic nor miR-3075 inhibitor would affect Schwann cell proliferation. We further studied candidate target genes of miR-3075 by using bioinformatic tools and analyzing gene expression patterns and found that miR-3075 might target contactin 2 (Cntn2). Previous study showed that Cntn2 regulated cell migration and myelination. Our current observation suggested that the biological effects of miR-3075 on Schwann cell phenotype might by through the negative regulation of Cntn2. Overall, our study revealed the function of a novel miRNA, miR-3075, and expanded our current understanding of the molecular mechanisms underlying peripheral nerve injury and regeneration.

Fronto-parietal coherence response to tDCS modulation in patients with disorders of consciousness.

AIM OF THE STUDY: A transcranial direct current stimulation (tDCS) protocol (20 min, 2 mA, anodal electrode at the left dorsolateral prefrontal cortex and cathodal electrode at the right supraorbital area) was applied in patients with different degrees of disorders of consciousness (DoC). Although previous research indicates that it could improve patients' coma recovery scale-revised (CRS-R) scores, the brain's electrophysiological responses to tDCS are still unclear. Therefore, the present study was performed to explore the underlying brain responses of patients in a minimally conscious state (MCS) and an unresponsive wakefulness syndrome (UWS) to tDCS modulation. MATERIALS AND METHODS: Seventeen patients with DoC were recruited in a sham controlled crossover study receiving real and sham tDCS. EEG coherence was used to measure functional connectivity changes induced by the tDCS modulation. RESULTS: After real tDCS modulation, the fronto-parietal coherence significantly increased in the theta band and decreased in the gamma band in the MCS group. No significant changes were found in the UWS group. The coherence responses significantly correlated with the patients' baseline CRS-R scores. No distinct alteration occurred in the sham session for either the MCS or UWS patients. CONCLUSIONS: The coherence responses to the present tDCS protocol may be a tool for diagnosing MCS versus UWS, as they may be a crucial cause of the different clinical effects in the two states.

Quantitative research into the deconditioning of hemodynamic to disorder of consciousness carried out using transcranial Doppler ultrasonography and photoplethysmography obtained via finger-transmissive absorption.

In this study, transcranial Doppler ultrasonography (TCD) and photoplethysmography (PPG) have been utilized, through the observation of peripheral and cerebrovascular hemodynamic changes of the disorder of consciousness (DOC) patients, measured on clinical behavior scale of Coma Recovery Score-Revised (CRS-R) to obesrve their diagnostic value in evaluation of DOC patients. TCD ultrasound was used to evaluate the flow velocity and waveform patterns of middle cerebral artery (MCA), while PPG infrared signals were utilized to assess the peripheral circulation as a mean of measuring cardiovascular activities. The research was carried out on a sample of 36 individuals, of which 16 met the DOC criteria and 20 were healthy individuals. Each person in the patients groups was assessed by the CRS-R. The velocity of middle cerebral artery in tested patients in a whole cardiac cycle, detected by TCD, decreased comparing with normal values. The values of pulsatility index (PI) of the MCA increased in patients groups comparing with normal. Through binary variables correlation analysis, we found that the PI of the left MCA of TCD of the patients significantly inversely correlated with their motor subscore, included in their CRS-R in the level of α = 0.05 (Pearson's product-moment correlation coefficient = -0.556, p = 0.025). The values of photoplethysmographic augmentation index (PAI) that were detected by PPG increased comparing with normal. Finally, using binary variables correlation analysis we found the significant inverse correlation between the PAI of PPG and the mean velocity of the left MCA of the TCD in the level of α = 0.05 (Pearson's product-moment correlation coefficient = -0.377, p = 0.022) in all the groups. The results of this study revealed a specific relationship between PI and PAI in the DOC patients. That relationship can potentially be exploited to enhance the capabilities in early assessment of the deconditioning of the DOC patients' cardiovascular system and its influence on their cerebral vascular system. Ultimately, the dependency discovered can assist in predicting the tendency of the prognosis of the DOC patients in clinic.

Hyperactive external awareness against hypoactive internal awareness in disorders of consciousness using resting-state functional MRI: highlighting the involvement of visuo-motor modulation.

Resting-state functional MRI (fMRI) has emerged as a valuable tool to characterize the complex states encompassing disorders of consciousness (DOC). Awareness appears to comprise two coexistent, anticorrelated components named the external and internal awareness networks. The present study hypothesizes that DOC interrupts the balance between the internal and external awareness networks. To gain more understanding of this phenomenon, the present study analyzed resting-state fMRI data from 12 patients with DOC versus 12 healthy age-matched controls. The data were explored using independent component analysis and amplitude of low-frequency fluctuation (ALFF) analysis. The results indicated that DOC deactivated midline areas associated with internal awareness. In addition, external awareness was strengthened in DOC because of increased activation in the insula, lingual gyrus, paracentral and supplementary motor area. The activity patterns suggested strengthened external awareness against weakened internal awareness in DOC. In particular, increased activity found in the insula, lingual gyrus, paracentral and supplementary motor area of patients with DOC implied possible involvement of augmented visuo-motor modulation in these patients. DOC is probably related to hyperactive external awareness opposing hypoactive internal awareness. This unique pattern of brain activity may potentially be a prognostic marker for DOC.

Combined behavioral and EEG evidence for the 70 Hz frequency selection of short-term spinal cord stimulation in disorders of consciousness.

OBJECTIVES: This study investigated the prognostic effect of electroencephalography (EEG) instant effects of single spinal cord stimulation (SCS) on clinical outcome in disorders of consciousness (DOC) and the time-dependent brain response during the recovery of consciousness prompted by SCS. METHODS: Twenty three patients with DOC underwent short-term SCS (stSCS) implantation operation. Then, all patients received the postoperative EEG test including EEG record before (T1) and after (T2) single SCS session. Subsequently, 2 weeks stSCS treatment was performed and revised coma recovery scale (CRS-R) and EEG data were collected. Finally, they were classified into effective and ineffective groups at 3-month follow-up (T6). RESULTS: The parietal-occipital (PO) connectivity and clustering coefficients (CC) in the beta band of the effective group at the 1 week after the treatment (T5) were found to be higher than preoperative assessment (T0). Correlation analysis showed that the change in beta CC at T1/T2 was correlated with the change in CRS-R at T0/T6. In addition, the change in PO connectivity and CC in the beta at T0/T5 were also correlated with the change in CRS-R at T0/T5. CONCLUSION: SCS may facilitate the recovery of consciousness by enhancing local information interaction in posterior brain regions. And the recovery can be predicted by beta CC in the EEG test.

Global Field Time-Frequency Representation-Based Discriminative Similarity Analysis of Passive Auditory ERPs for Diagnosis of Disorders of Consciousness.

Behavioural diagnosis of patients with disorders of consciousness (DOC) is challenging and prone to inaccuracies. Consequently, there have been increased efforts to develop bedside assessment based on EEG and event-related potentials (ERPs) that are more sensitive to the neural factors supporting conscious awareness. However, individual detection of residual consciousness using these techniques is less established. Here, we hypothesize that the cross-state similarity (defined as the similarity between healthy and impaired conscious states) of passive brain responses to auditory stimuli can index the level of awareness in individual DOC patients. To this end, we introduce the global field time-frequency representation-based discriminative similarity analysis (GFTFR-DSA). This method quantifies the average cross-state similarity index between an individual patient and our constructed healthy templates using the GFTFR as an EEG feature. We demonstrate that the proposed GFTFR feature exhibits superior within-group consistency in 34 healthy controls over traditional EEG features such as temporal waveforms. Second, we observed the GFTFR-based similarity index was significantly higher in patients with a minimally conscious state (MCS, 40 patients) than those with unresponsive wakefulness syndrome (UWS, 54 patients), supporting our hypothesis. Finally, applying a linear support vector machine classifier for individual MCS/UWS classification, the model achieved a balanced accuracy and F1 score of 0.77. Overall, our findings indicate that combining discriminative and interpretable markers, along with automatic machine learning algorithms, is effective for the differential diagnosis in patients with DOC. Importantly, this approach can, in principle, be transferred into any ERP of interest to better inform DOC diagnoses.

Temporal and spatial variability of dynamic microstate brain network in disorders of consciousness.

BACKGROUND: Accurately diagnosing patients with the vegetative state (VS) and the minimally conscious state (MCS) reached a misdiagnosis of approximately 40%. METHODS: A method combined microstate and dynamic functional connectivity (dFC) to study the spatiotemporal variability of the brain in disorders of consciousness (DOC) patients was proposed. Resting-state EEG data were obtained from 16 patients with MCS and 16 patients with VS. Mutual information (MI) was used to assess the EEG connectivity in each microstate. MI-based features with statistical differences were selected as the total feature subset (TFS), then the TFS was utilized to feature selection and fed into the classifier, obtaining the optimal feature subsets (OFS) in each microstate. Subsequently, an OFS-based MI functional connectivity network (MIFCN) was constructed in the cortex. RESULTS: The group-average MI connectivity matrix focused on all channels revealed that all five microstates exhibited stronger information interaction in the MCS when comparing with the VS. While OFS-based MIFCN, which only focused on a few channels, revealed greater MI flow in VS patients than in MCS patients under microstates A, B, C, and E, except for microstate D. Additionally, the average classification accuracy of OFS in the five microstates was 96.2%. CONCLUSION: Constructing features based on microstates to distinguish between two categories of DOC patients had effectiveness.

Clinical neuromodulatory effects of deep brain stimulation in disorder of consciousness: A literature review.

BACKGROUND: The management of patients with disorders of consciousness (DOC) presents substantial challenges in clinical practice. Deep brain stimulation (DBS) has emerged as a potential therapeutic approach, but the lack of standardized regulatory parameters for DBS in DOC hinders definitive conclusions. OBJECTIVE: This comprehensive review aims to provide a detailed summary of the current issues concerning patient selection, target setting, and modulation parameters in clinical studies investigating the application of DBS for DOC patients. METHODS: A meticulous systematic analysis of the literatures was conducted, encompassing articles published from 1968 to April 2023, retrieved from reputable databases (PubMed, Embase, Medline, and Web of Science). RESULTS: The systematic analysis of 21 eligible articles, involving 146 patients with DOC resulting from acquired brain injury or other disorders, revealed significant insights. The most frequently targeted regions were the Centromedian-parafascicular complex (CM-pf) nuclei and central thalamus (CT), both recognized for their role in regulating consciousness. However, other targets have also been explored in different studies. The stimulation frequency was predominantly set at 25 or 100 Hz, with pulse width of 120 µs, and voltages ranged from 0 to 4 V. These parameters were customized based on individual patient responses and evaluations. The overall clinical efficacy rate in all included studies was 39.7%, indicating a positive effect of DBS in a subset of DOC patients. Nonetheless, the assessment methods, follow-up durations, and outcome measures varied across studies, potentially contributing to the variability in reported efficacy rates. CONCLUSION: Despite the challenges arising from the lack of standardized parameters, DBS shows promising potential as a therapeutic option for patients with DOC. However, there still remains the need for standardized protocols and assessment methods, which are crucial to deepen the understanding and optimizing the therapeutic potential of DBS in this specific patient population.

Serum metabolism alteration behind different etiology, diagnosis, and prognosis of disorders of consciousness.

BACKGROUND: Patients with disorders of consciousness (DoC) exhibit varied revival outcomes based on different etiologies and diagnoses, the mechanisms of which remain largely unknown. The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses, often leading to misdiagnoses. There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment guidance. METHODS: To explore biomarkers and understand the biological processes, we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC. Patients were categorized based on etiology (TBI vs. non-TBI), CRS-R scores, and prognosis. Advanced analytical techniques, including PCA and OPLS-DA models, were employed to identify differential metabolites. RESULTS: Our analysis revealed a distinct separation in metabolomic profiles among the different groups. The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids, with a notable decrease in glycerophospholipids observed in the TBI group. Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism. Notably, serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes, suggesting their potential as prognostic biomarkers. CONCLUSIONS: Our study underscores the critical role of phospholipid metabolism in the brain's metabolic alterations in patients with DoC. It identifies key biomarkers for diagnosis and prognosis, offering insights that could lead to novel therapeutic targets. These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.

The temporal dynamics of Large-Scale brain network changes in disorders of consciousness: A Microstate-Based study.

BACKGROUND AND OBJECTIVES: The resting-state brain is composed of several discrete networks, which remain stable for 10-100 ms. These functional microstates are considered the building blocks of spontaneous consciousness. Electroencephalography (EEG) microstate analysis may provide insight into the altered brain dynamics underlying consciousness recovery in patients with disorders of consciousness (DOC). We aimed to analyze microstates in the resting-state EEG source space in patients with DOC, the relationship between state-specific features and consciousness levels, and the corresponding patterns of microstates and functional networks. METHODS: We obtained resting-state EEG data from 84 patients with DOC (27 in a minimally conscious state [MCS] and 57 in a vegetative state [VS] or with unresponsive wakefulness syndrome). We conducted a microstate analysis of the resting-state (EEG) source space and developed a state-transition analysis protocol for patients with DOC. RESULTS: We identified seven microstates with distinct spatial distributions of cortical activation. Multivariate pattern analyses revealed that different functional connectivity patterns were associated with source-level microstates. There were significant differences in the microstate properties, including spatial activation patterns, temporal dynamics, state shifts, and connectivity construction, between the MCS and VS groups. DISCUSSION: Our findings suggest that consciousness depends on complex dynamics within the brain and may originate from the anterior cortex.

Deep brain stimulation improves electroencephalogram functional connectivity of patients with minimally conscious state.

AIM: Deep brain stimulation (DBS) is a potential neuromodulatory therapy that enhances recovery from disorders of consciousness, especially minimally conscious state (MCS). This study measured the effects of DBS on the brain and explored the underlying mechanisms of DBS on MCS. METHODS: Nine patients with MCS were recruited for this study. The neuromodulation effects of 100 Hz DBS were explored via cross-control experiments. Coma Recovery Scale-Revised (CRS-R) and EEG were recorded, and corresponding functional connectivity and network parameters were calculated. RESULTS: Our results showed that 100 Hz DBS could improve the functional connectivity of the whole, local and local-local brain regions, while no significant change in EEG functional connectivity was observed in sham DBS. The whole brain's network parameters (clustering coefficient, path length, and small world characteristic) were significantly improved. In addition, a significant increase in the CRS-R and functional connectivity of three MCS patients who received 100 Hz DBS for 6 months were observed. CONCLUSION: This study showed that DBS improved EEG functional connectivity and brain networks, indicating that the long-term use of DBS could improve the level of consciousness of MCS patients.

Long-term functional outcomes improved with deep brain stimulation in patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) has been preliminarily applied to treat patients with disorders of consciousness (DoCs). The study aimed to determine whether DBS was effective for treating patients with DoC and identify factors related to patients' outcomes. METHODS: Data from 365 patients with DoCs who were consecutively admitted from 15 July 2011 to 31 December 2021 were retrospectively analysed. Multivariate regression and subgroup analysis were performed to adjust for potential confounders. The primary outcome was improvement in consciousness at 1 year. RESULTS: An overall improvement in consciousness at 1 year was achieved in 32.4% (12/37) of the DBS group compared with 4.3% (14/328) of the conservative group. After full adjustment, DBS significantly improved consciousness at 1 year (adjusted OR 11.90, 95% CI 3.65-38.46, p<0.001). There was a significant treatment×follow up interaction (H=14.99, p<0.001). DBS had significantly better effects in patients with minimally conscious state (MCS) compared with patients with vegetative state/unresponsive wakefulness syndrome (p for interaction <0.001). A nomogram based on age, state of consciousness, pathogeny and duration of DoCs indicated excellent predictive performance (c-index=0.882). CONCLUSIONS: DBS was associated with better outcomes in patients with DoC, and the effect was likely to be significantly greater in patients with MCS. DBS should be cautiously evaluated by nomogram preoperatively, and randomised controlled trials are still needed.

Altered brain functional connectivity in vegetative state and minimally conscious state.

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.