Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study.

OBJECTIVES: To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. METHODS: In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. RESULTS: The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. CONCLUSION: Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Brain Temporal-Spectral Functional Variability Reveals Neural Improvements of DBS Treatment for Disorders of Consciousness.

Deep brain stimulation (DBS) is establishing itself as a promising treatment for disorders of consciousness (DOC). Measuring consciousness changes is crucial in the optimization of DBS therapy for DOC patients. However, conventional measures use subjective metrics that limit the investigations of treatment-induced neural improvements. The focus of this study is to analyze the regulatory effects of DBS and explain the regulatory mechanism at the brain functional level for DOC patients. Specifically, this paper proposed a dynamic brain temporal-spectral analysis method to quantify DBS-induced brain functional variations in DOC patients. Functional near-infrared spectroscopy (fNIRS) that promised to evaluate consciousness levels was used to monitor brain variations of DOC patients. Specifically, a fNIRS-based experimental procedure with auditory stimuli was developed, and the brain activities during the procedure from thirteen DOC patients before and after the DBS treatment were recorded. Then, dynamic brain functional networks were formulated with a sliding-window correlation analysis of phase lag index. Afterwards, with respect to the temporal variations of global and regional networks, the variability of global efficiency, local efficiency, and clustering coefficient were extracted. Further, dynamic networks were converted into spectral representations by graph Fourier transform, and graph energy and diversity were formulated to assess the spectral global and regional variability. The results showed that DOC patients under DBS treatment exhibited increased global and regional functional variability that was significantly associated with consciousness improvements. Moreover, the functional variability in the right brain regions had a stronger correlation with consciousness enhancements than that in the left brain regions. Therefore, the proposed method well signifies DBS-induced brain functional variations in DOC patients, and the functional variability may serve as promising biomarkers for consciousness evaluations in DOC patients.

Neuro-orthopaedic assessment and management in patients with prolonged disorders of consciousness: A review.

BACKGROUND: Following a severe acquired brain injury, neuro-orthopaedic disorders are commonplace. While these disorders can impact patients' functional recovery and quality of life, little is known regarding the assessment, management and treatment of neuro-orthopaedic disorders in patients with disorders of consciousness (DoC). OBJECTIVE: To describe neuro-orthopaedic disorders in the context of DoC and provide insights on their management and treatment. METHODS: A review of the literature was conducted focusing on neuro-orthopaedic disorders in patients with prolonged DoC. RESULTS: Few studies have investigated the prevalence of spastic paresis in patients with prolonged DoC, which is extremely high, as well as its correlation with pain. Pilot studies exploring the effects of pharmacological treatments and physical therapy show encouraging results yet have limited efficacy. Other neuro-orthopaedic disorders, such as heterotopic ossification, are still poorly investigated. CONCLUSION: The literature of neuro-orthopaedic disorders in patients with prolonged DoC remains scarce, mainly focusing on spastic paresis. We recommend treating neuro-orthopaedic disorders in their early phases to prevent complications such as pain and improve patients' recovery. Additionally, this approach could enhance patients' ability to behaviourally demonstrate signs of consciousness, especially in the context of covert awareness.

Music, occupational, physical, and speech therapy interventions for patients in disorders of consciousness: An umbrella review.

BACKGROUND: Current clinical guidelines recommend that a multidisciplinary team inclusive of allied healthcare practitioners deliver assessment and intervention for disorders of consciousness. Allied health professionals include music, occupational, physical, and speech therapists. These allied health clinicians are challenged to select interventions due to a lack of evidence-based recommendations regarding rehabilitation interventions that support recovery of consciousness. This umbrella review synthesizes available systematic reviews (SRs) that describe occupational, speech and language, physical and/or musical therapeutic interventions for people with disorders of consciousness. OBJECTIVES: Identify and summarize evidence from systematic reviews (SRs) that examine allied healthcare interventions for patients with disorders of consciousness. Additionally, this umbrella review aims to evaluate the impact of allied health interventions on recovery of consciousness, methodological quality and risk of bias for the included systematic reviews. METHODS: An umbrella review was completed. The review was reported according to the Preferred Reporting Items for Overview of Reviews (PRIOR) guidance. Five academic databases (PubMed, CINAHL, PsycInfo, Web of Science, and the Cochrane Library) were searched for SRs and/or meta-analyses of allied health (i.e., music, occupational, physical, and speech therapy) interventions for disorders of consciousness. For included studies, data were extracted and quality of the SRs appraised using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2 checklist. Data extracted from each SR identified the authors and years of primary studies, interventions, comparators, and outcomes related to recovery of consciousness (i.e., neurobehavioral/cognitive), functional status, physiological response pain, and adverse events. Rehabilitation interventions were categorized and described. RESULTS: Fifteen SRs were included and three of these reviews conducted meta-analyses. Identified rehabilitation interventions included: 1) sensory stimulation, 2) median nerve stimulation, 3) communication/environmental control through assistive technology, 4) mobilization, and 5) music-based therapy. SRs were published between 2002 and 2022 and included 2286 participants. Using the AMSTAR 2, the quality of reviews was critically low (k = 6), low (k = 3), moderate (k = 4), and high (k = 2). SRs within this umbrella review demonstrated significant heterogeneity in research methods and use of outcome measures to evaluate the recovery of consciousness within the primary studies. These factors influenced the ability to conduct meta-analyses. CONCLUSIONS: Sensory stimulation, median nerve stimulation, music therapy and mobilization are all interventions that demonstrate some level of benefit, but current SRs fail to prove benefit through high-level quality evidence. There is an indisputable need for continued rehabilitation research to expand options for treatment modalities and to ensure that the interventions being applied to DoC rehabilitation are evidence-based to improve consciousness and recovery.

Swallowing dysfunctions in patients with disorders of consciousness: Evidence from neuroimaging data, assessment, and management.

Following severe brain injuries, a subset of patients may remain in an altered state of consciousness; most of these patients require artificial feeding. Currently, a functional oral phase and the presence of exclusive oral feeding may constitute signs of consciousness. Additionally, the presence of pharyngo-laryngeal secretions, saliva aspiration, cough reflex and tracheostomy are related to the level of consciousness. However, the link between swallowing and consciousness is yet to be fully understood. The primary aim of this review is to establish a comprehensive overview of the relationship between an individual's conscious behaviour and swallowing (reflexive and voluntary). Previous studies of brain activation during volitional and non-volitional swallowing tasks in healthy subjects are also reviewed. We demonstrate that the areas activated by voluntary swallowing tasks (primary sensorimotor, cingulate, insula, premotor, supplementary motor, cerebellum, and operculum) are not specific to deglutitive function but are shared with other motor tasks and brain networks involved in consciousness. This review also outlines suitable assessment and treatment methods for dysphagic patients with disorders of consciousness. Finally, we propose that markers of swallowing could contribute to the development of novel diagnostic guidelines for patients with disorders of consciousness.

Pediatric disorders of consciousness: Considerations, controversies, and caveats.

Pediatric disorders of consciousness (PedDOC) encompass conditions that may occur following very severe traumatic or other forms of acquired brain injury sustained during childhood. As in adults, PedDOC is described as a disturbance of awareness and/or responsiveness. PedDOC is a complex condition that requires specialized care, infrastructures, and technologies. PedDOC poses many challenges to healthcare providers and caregivers during recovery and throughout development. In this commentary, we intend to highlight some considerations, controversies, and caveats on the diagnosis, prognosis and treatment of PedDOC.

Long-term HD-tDCS modulates dynamic changes of brain activity on patients with disorders of consciousness: A resting-state EEG study.

OBJECTIVE: High-definition transcranial direct current stimulation (HD-tDCS) has been an effective neurostimulation method in the treatment of disorders of consciousness (DOC). However, the effects and mechanism of HD-tDCS are still unclear. METHODS: This study recruited 8 DOC patients and applied 20-min sessions of 2 mA HD-tDCS (central anode electrode at Pz) for 14 consecutive days. We record DOC patients' EEG data and Coma Recovery Scale-Revised (CRS-R) values at four time point: baseline (T0), after 1 day's and 7,14 days' parietal HD-tDCS treatment (T1, T2, T3). Power spectral density (PSD), relative power (RP), spectral entropy and spectral exponent were calculated to evaluate the EEG dynamic changes of DOC patients during long-term parietal HD-tDCS. At last, we calculated the correlation between changes of EEG features and changes of CRS-R values. RESULT: After 1 day's parietal HD-tDCS, DOC patients' CRS-R value had not changed (8.25 ± 1.91). HD-tDCS improved DOC patients' CRS-R value at T2 (9.75 ± 1.91, p < 0.05) and at T3 (11.38 ± 2.77, p < 0.05), compared with that at T0 (8.25 ± 1.91). As the treatment time increased, the EEG PSD decayed more slowly. Specifically, the delta frequency band RP decreased, while the alpha, beta, and gamma frequency bands RP increased. EEG oscillation characteristics changed but not significant at T1 (p > 0.05), and showed significant changes at T2 and T3 (p < 0.05). The spectral entropy continuously increased and the spectral exponent continuously decreased from T0 to T3. Specifically, the spectral entropy and spectral exponent of the parietal and occipital regions were significantly higher at T2 and T3 than that at T0 (p < 0.05). In addition, The changes in EEG features of the parietal and occipital lobes were correlated with changes in CRS-R value, especially between T2 and T0. CONCLUSION: Long-term parietal HD-tDCS can improve the consciousness level and brain activity in DOC patients. Resting-state EEG can evaluate the dynamic changes of brain activity in DOC patients during HD-tDCS. EEG oscillation and non-oscillatory activity might be used to explain the mechanism of HD-tDCS on DOC patients.

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.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group in the Pediatric Population.

BACKGROUND: The fundamental gap obstructing forward progress of evidenced-based care in pediatric and neonatal disorders of consciousness (DoC) is the lack of defining consensus-based terminology to perform comparative research. This lack of shared nomenclature in pediatric DoC stems from the inherently recursive dilemma of the inability to reliably measure consciousness in the very young. However, recent advancements in validated clinical examinations and technologically sophisticated biomarkers of brain activity linked to future abilities are unlocking this previously formidable challenge to understanding the DoC in the developing brain. METHODS: To address this need, the first of its kind international convergence of an interdisciplinary team of pediatric DoC experts was organized by the Neurocritical Care Society's Curing Coma Campaign. The multidisciplinary panel of pediatric DoC experts proposed pediatric-tailored common data elements (CDEs) covering each of the CDE working groups including behavioral phenotyping, biospecimens, electrophysiology, family and goals of care, neuroimaging, outcome and endpoints, physiology and big Data, therapies, and pediatrics. RESULTS: We report the working groups' pediatric-focused DoC CDE recommendations and disseminate CDEs to be used in studies of pediatric patients with DoC. CONCLUSIONS: The CDEs recommended support the vision of progressing collaborative and successful internationally collaborative pediatric coma research.

Optimal Design of Clinical Trials Involving Persons with Disorders of Consciousness.

BACKGROUND: Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC. METHODS: The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC. RESULTS: There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC. CONCLUSIONS: Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care.

International survey on the implementation of the European and American guidelines on disorders of consciousness.

Diagnostic, prognostic, and therapeutic procedures for patients with prolonged disorders of consciousness (pDoCs) vary significantly across countries and clinical settings, likely due to organizational factors (e.g., research vs. non-academic hospitals), expertise and availability of resources (e.g., financial and human). Two international guidelines, one from the European Academy of Neurology (EAN) and one from the American Academy of Neurology (AAN) in collaboration with the American Congress of Rehabilitation Medicine (ACRM) and the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), were developed to facilitate consistent practice among professionals working with this challenging patient population. While the recommendations of both guidelines agree in principle, it remains an open issue how to implement them into clinical practice in the care pathway for patients with pDoCs. We conducted an online survey to explore health professional clinical practices related to the management of patients with pDoCs, and compare said practices with selected recommendations from both the guidelines. The survey revealed that while some recommendations are being followed, others are not and/or may require more honing/specificity to enhance their clinical utility. Particular attention should be given to the implementation of a multimodal assessment of residual consciousness, to the detection and treatment of pain, and to the impact of restrictions imposed by COVID-19 pandemics on the involvement of patients' families/representatives.

Common Data Element for Disorders of Consciousness: Recommendations from the Working Group on Therapeutic Interventions.

BACKGROUND: Over the past 30 years, there have been significant advances in the understanding of the mechanisms associated with loss and recovery of consciousness following severe brain injury. This work has provided a strong grounding for the development of novel restorative therapeutic interventions. Although all interventions are aimed at modulating and thereby restoring brain function, the landscape of existing interventions encompasses a very wide scope of techniques and protocols. Despite vigorous research efforts, few approaches have been assessed with rigorous, high-quality randomized controlled trials. As a growing number of exploratory interventions emerge, it is paramount to develop standardized approaches to reporting results. The successful evaluation of novel interventions depends on implementation of shared nomenclature and infrastructure. To address this gap, the Neurocritical Care Society's Curing Coma Campaign convened nine working groups and charged them with developing common data elements (CDEs). Here, we report the work of the Therapeutic Interventions Working Group. METHODS: The working group reviewed existing CDEs relevant to therapeutic interventions within the National Institutes of Health National Institute of Neurological Disorders and Stroke database and reviewed the literature for assessing key areas of research in the intervention space. CDEs were then proposed, iteratively discussed and reviewed, classified, and organized in a case report form (CRF). RESULTS: We developed a unified CRF, including CDEs and key design elements (i.e., methodological or protocol parameters), divided into five sections: (1) patient information, (2) general study information, (3) behavioral interventions, (4) pharmacological interventions, and (5) device interventions. CONCLUSIONS: The newly created CRF enhances systematization of future work by proposing a portfolio of measures that should be collected in the development and implementation of studies assessing novel interventions intended to increase the level of consciousness or rate of recovery of consciousness in patients with disorders of consciousness.

The effects of non-invasive brain stimulation on disorder of consciousness in patients with brain injury: A systematic review and meta-analysis of randomized controlled trial.

INTRODUCTION: Disorders of consciousness (DOC) result from neural system injury and manifest as changes in arousal or awareness. This systematic review and meta-analysis aimed to investigate the therapeutic effects of non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), on consciousness dysfunction in patients with brain disorders. METHODS: Literature was systematically searched in Medline, Embase, Cochrane database, Web of Science, EBSCO from inception to May 2023. Only randomized controlled trial with NIBS as an intervention and participants with DOC were included. RESULTS: A total of 7 studies with 313 participants were included for meta-analysis. Compared with sham- or placebo-stimulation, NIBS can improve the Coma Recovery Scale-Revised scores significantly (mean difference [MD] = 1.96, 95 % confidence interval [CI] = [1.49; 2.43], P <.0001). CONCLUSION: NIBS has a significant positive effect in enhancing the symptoms of DOC. Nevertheless, it is imperative for further investigations comprising high-quality research designs and larger sample sizes in order to comprehensively elucidate the effects of NIBS techniques on diverse targets of stimulation within the population of individuals suffering from DOC.

Effective DBS treatment improves neural information transmission of patients with disorders of consciousness: an fNIRS study.

Objective.Deep brain stimulation (DBS) is a potential treatment that promotes the recovery of patients with disorders of consciousness (DOC). This study quantified the changes in consciousness and the neuromodulation effect of DBS on patients with DOC.Approach.Eleven patients were recruited for this study which consists of three conditions: 'Pre' (two days before DBS surgery), 'Post-On' (one month after surgery with stimulation), and 'Post-Off' (one month after surgery without stimulation). Functional near-infrared spectroscopy (fNIRS) was recorded from the frontal lobe, parietal lobe, and occipital lobe of patients during the experiment of auditory stimuli paradigm, in parallel with the coma recovery scale-revised (CRS-R) assessment. The brain hemodynamic states were defined and state transition acceleration was taken to quantify the information transmission strength of the brain network. Linear regression analysis was conducted between the changes in regional and global indicators and the changes in the CRS-R index.Main results.Significant correlation was observed between the changes in the global transition acceleration indicator and the changes in the CRS-R index (slope = 55.910,p< 0.001,R2= 0.732). For the regional indicators, similar correlations were found between the changes in the frontal lobe and parietal lobe indicators and the changes in the CRS-R index (slope = 46.612,p< 0.01,R2= 0.694; slope = 47.491,p< 0.01,R2= 0.676).Significance.Our study suggests that fNIRS-based brain hemodynamics transition analysis can signify the neuromodulation effect of DBS treatment on patients with DOC, and the transition acceleration indicator is a promising brain functional marker for DOC.

Deep brain stimulation in disorders of consciousness: 10 years of a single center experience.

Disorders of consciousness (DoC), namely unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), represent severe conditions with significant consequences for patients and their families. Several studies have reported the regaining of consciousness in such patients using deep brain stimulation (DBS) of subcortical structures or brainstem nuclei. Our study aims to present the 10 years' experience of a single center using DBS as a therapy on a cohort of patients with DoC. Eighty Three consecutive patients were evaluated between 2011 and 2022; entry criteria consisted of neurophysiological and neurological evaluations and neuroimaging examinations. Out of 83, 36 patients were considered candidates for DBS implantation, and 32 patients were implanted: 27 patients had UWS, and five had MCS. The stimulation target was the centromedian-parafascicular complex in the left hemisphere in hypoxic brain lesion or the one better preserved in patients with traumatic brain injury. The level of consciousness was improved in seven patients. Three out of five MCS patients emerged to full awareness, with the ability to interact and communicate. Two of them can live largely independently. Four out of 27 UWS patients showed consciousness improvement with two patients emerging to full awareness, and the other two reaching MCS. In patients with DoC lasting longer than 12 months following traumatic brain injury or 6 months following anoxic-ischemic brain lesion, spontaneous recovery is rare. Thus, DBS of certain thalamic nuclei could be recommended as a treatment option for patients who meet neurological, neurophysiological and neuroimaging criteria, especially in earlier phases, before occurrence of irreversible musculoskeletal changes. Furthermore, we emphasize the importance of cooperation between centers worldwide in studies on the potentials of DBS in treating patients with DoC.

Clinical application of neuromodulation therapy in patients with disorder of consciousness: A pooled analysis of 544 participants.

BACKGROUND: The number of patients with disorders of consciousness (DoC) has increased dramatically with the advancement of intensive care and emergency medicine, which brings tremendous economic burdens and even ethical issues to families and society. OBJECTIVE: To evaluate the effectiveness of neuromodulation therapy for patients with DoC. METHODS: First, we conducted a literature review of individual patient data (IPD) on PubMed, EMBASE, and Cochrane-controlled trials following PRISMA guidelines. Then, we collected neuromodulation cases from our institution. Finally, we conducted a pooled analysis using the participants from the medical literature (n = 522) and our local institutions (n = 22). RESULTS: In this pooled analysis of 544 patients with DoC with a mean age of 46.33 years, our results revealed that patients have improved CRS-R scores [1.0 points (95% CI, 0.57-1.42)] after neuromodulation. Among them, patients have better effectiveness in traumatic than non-traumatic etiology (P < 0.05). The effectiveness of consciousness improvement could be affected by the age, baseline consciousness state, and duration of stimulation. Compared with non-invasive intervention, an invasive intervention can bring more behavioral improvement (P < 0.0001) to MCS rather than UWS/VS patients. Importantly, neuromodulation is a valuable therapy even years after the onset of DoC. CONCLUSION: This pooled analysis spotlights that the application of neuromodulation can improve the behavioral performance of patients with DoC. A preliminary trend is that age, etiology, baseline consciousness state, and stimulation duration could impact its effectiveness.

Review of spinal cord stimulation for disorders of consciousness.

PURPOSE OF REVIEW: High-cervical spinal cord stimulation can alter cortical activity and cerebral metabolism. These effects are potentially beneficial for disorders of consciousness. A better understanding of the effects of clinical application of stimulation is needed. We aimed to evaluate the existing literature to determine the state of available knowledge. We performed a literature review of clinical studies assessing cervical spinal cord epidural stimulation for disorders of consciousness. Only peer-reviewed articles reporting preoperative and postoperative clinical status were included. RECENT FINDINGS: Nineteen studies were included. A total of 532 cases were reported, and 255 patients were considered responsive (47.9%). Considering only studies published after the definition of minimally conscious state (MCS) as an entity, 402 individuals in unresponsive wakefulness syndrome (UWS) and 113 in MCS were reported. Responsiveness to SCS was reported in 170 UWS patients (42.3%) and in 78 MCS cases (69.0%), although the criteria for responsiveness and outcome measures varied among publications. SUMMARY: Cervical SCS yielded encouraging results in patients with disorders of consciousness and seems to be more effective in MCS. More extensive investigation is needed to understand its potential role in clinical practice.

Electrophysiological characteristics of CM-pf in diagnosis and outcome of patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. OBJECTIVE: To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. METHODS: We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. RESULTS: 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. CONCLUSION: We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Physiology and Big Data.

BACKGROUND: The implementation of multimodality monitoring in the clinical management of patients with disorders of consciousness (DoC) results in physiological measurements that can be collected in a continuous and regular fashion or even at waveform resolution. Such data are considered part of the "Big Data" available in intensive care units and are potentially suitable for health care-focused artificial intelligence research. Despite the richness in content of the physiological measurements, and the clinical implications shown by derived metrics based on those measurements, they have been largely neglected from previous attempts in harmonizing data collection and standardizing reporting of results as part of common data elements (CDEs) efforts. CDEs aim to provide a framework for unifying data in clinical research and help in implementing a systematic approach that can facilitate reliable comparison of results from clinical studies in DoC as well in international research collaborations. METHODS: To address this need, the Neurocritical Care Society's Curing Coma Campaign convened a multidisciplinary panel of DoC "Physiology and Big Data" experts to propose CDEs for data collection and reporting in this field. RESULTS: We report the recommendations of this CDE development panel and disseminate CDEs to be used in physiologic and big data studies of patients with DoC. CONCLUSIONS: These CDEs will support progress in the field of DoC physiologic and big data and facilitate international collaboration.