Cognitive Motor Dissociation in Disorders of Consciousness.

BACKGROUND: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness. METHODS: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R). RESULTS: Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands. CONCLUSIONS: Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.).

Exploring the Significance of Cognitive Motor Dissociation on Patient Outcome in Acute Disorders of Consciousness.

Cognitive motor dissociation (CMD) is characterized by a dissociation between volitional brain responses and motor control, detectable only through techniques such as electroencephalography (EEG) and functional magnetic resonance imaging. Hence, it has recently emerged as a major challenge in the assessment of patients with disorders of consciousness. Specifically, this review focuses on the prognostic implications of CMD detection during the acute stage of brain injury. CMD patients were identified in each diagnostic category (coma, unresponsive wakefulness syndrome/vegetative state, minimally conscious state minus) with a relatively similar prevalence of around 20%. Current knowledge tends to indicate that the diagnosis of CMD in the acute phase often predicts a more favorable clinical outcome compared with other unresponsive non-CMD patients. Nevertheless, the review underscores the limited research in this domain, probably at least partially explained by its nascent nature and the lack of uniformity in the nomenclature for CMD-related disorders, hindering the impact of the literature in the field.

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.

Cognitive Motor Dissociation: Gap Analysis and Future Directions.

BACKGROUND: Patients with disorders of consciousness who are behaviorally unresponsive may demonstrate volitional brain responses to motor imagery or motor commands detectable on functional magnetic resonance imaging or electroencephalography. This state of cognitive motor dissociation (CMD) may have prognostic significance. METHODS: The Neurocritical Care Society's Curing Coma Campaign identified an international group of experts who convened in a series of monthly online meetings between September 2021 and April 2023 to examine the science of CMD and identify key knowledge gaps and unmet needs. RESULTS: The group identified major knowledge gaps in CMD research: (1) lack of information about patient experiences and caregiver accounts of CMD, (2) limited epidemiological data on CMD, (3) uncertainty about underlying mechanisms of CMD, (4) methodological variability that limits testing of CMD as a biomarker for prognostication and treatment trials, (5) educational gaps for health care personnel about the incidence and potential prognostic relevance of CMD, and (6) challenges related to identification of patients with CMD who may be able to communicate using brain-computer interfaces. CONCLUSIONS: To improve the management of patients with disorders of consciousness, research efforts should address these mechanistic, epidemiological, bioengineering, and educational gaps to enable large-scale implementation of CMD assessment in clinical practice.

Whole-brain analyses indicate the impairment of posterior integration and thalamo-frontotemporal broadcasting in disorders of consciousness.

The study of the brain's dynamical activity is opening a window to help the clinical assessment of patients with disorders of consciousness. For example, glucose uptake and the dysfunctional spread of naturalistic and synthetic stimuli has proven useful to characterize hampered consciousness. However, understanding of the mechanisms behind loss of consciousness following brain injury is still missing. Here, we study the propagation of endogenous and in-silico exogenous perturbations in patients with disorders of consciousness, based upon directed and causal interactions estimated from resting-state fMRI data, fitted to a linear model of activity propagation. We found that patients with disorders of consciousness suffer decreased capacity for neural propagation and responsiveness to events, and that this can be related to severe reduction of glucose metabolism as measured with [18 F]FDG-PET. In particular, we show that loss of consciousness is related to the malfunctioning of two neural circuits: the posterior cortical regions failing to convey information, in conjunction with reduced broadcasting of information from subcortical, temporal, parietal and frontal regions. These results shed light on the mechanisms behind disorders of consciousness, triangulating network function with basic measures of brain integrity and behavior.

What lies underneath: Precise classification of brain states using time-dependent topological structure of dynamics.

The self-organising global dynamics underlying brain states emerge from complex recursive nonlinear interactions between interconnected brain regions. Until now, most efforts of capturing the causal mechanistic generating principles have supposed underlying stationarity, being unable to describe the non-stationarity of brain dynamics, i.e. time-dependent changes. Here, we present a novel framework able to characterise brain states with high specificity, precisely by modelling the time-dependent dynamics. Through describing a topological structure associated to the brain state at each moment in time (its attractor or 'information structure'), we are able to classify different brain states by using the statistics across time of these structures hitherto hidden in the neuroimaging dynamics. Proving the strong potential of this framework, we were able to classify resting-state BOLD fMRI signals from two classes of post-comatose patients (minimally conscious state and unresponsive wakefulness syndrome) compared with healthy controls with very high precision.

Sham-controlled randomized multicentre trial of transcranial direct current stimulation for prolonged disorders of consciousness.

BACKGROUND AND PURPOSE: Transcranial direct current stimulation (tDCS) has been shown to improve signs of consciousness in a subset of patients with disorders of consciousness (DoC). However, no multicentre study confirmed its efficacy when applied during rehabilitation. In this randomized controlled double-blind study, the effects of tDCS whilst patients were in rehabilitation were tested at the group level and according to their diagnosis and aetiology to better target DoC patients who might repond to tDCS. METHODS: Patients received 2 mA tDCS or sham applied over the left prefrontal cortex for 4 weeks. Behavioural assessments were performed weekly and up to 3 months' follow-up. Analyses were conducted at the group and subgroup levels based on the diagnosis (minimally conscious state [MCS] and unresponsive wakefulness syndrome) and the aetiology (traumatic or non-traumatic). Interim analyses were planned to continue or stop the trial. RESULTS: The trial was stopped for futility when 62 patients from 10 centres were enrolled (44 ± 14 years, 37 ± 24.5 weeks post-injury, 18 women, 32 MCS, 39 non-traumatic). Whilst, at the group level, no treatment effect was found, the subgroup analyses at 3 months' follow-up revealed a significant improvement for patients in MCS and with traumatic aetiology. CONCLUSIONS: Transcranial direct current stimulation during rehabilitation does not seem to enhance patients' recovery. However, diagnosis and aetiology appear to be important factors leading to a response to the treatment. These findings bring novel insights into possible cortical plasticity changes in DoC patients given these differential results according to the subgroups of patients.

What is the nutritional status of patients with prolonged disorders of consciousness? A retrospective cross-sectional study.

BACKGROUND: Nutritional status of patients with disorders of consciousness (DoC) is poorly studied. OBJECTIVES: To evaluate the relationship between nutritional status (body mass index, daily calories intake) and clinical variables (level of consciousness, time since injury, diagnosis, etiology and spastic muscle overactivity; SMO,) in patients with prolonged DoCor emerging. Our main hypotheses are i) patients with lower level of consciousness (UWS) have worse nutritional status compared to patients in minimally conscious state (MCS) and ii) SMO could influence nutritional status. METHODS AND RESULTS: Among the 80 patients included in the study (19 UWS, 47 MCS, 14 emerging MCS; 43 ± 15 yo; 3 ± 4 years post-injury, 35 traumatic etiology, 34 females), 9% were at risk to be undernourished, with no differences between UWS and MCS. Patients without SMO had a higher BMI compared to patients with severe SMO. Compared to the recommended daily calories intake, patients with the highest BMI received less calories and patients with the lowest BMI received more calories. We observed a negative correlation between SMO (in lower limbs) and BMI. CONCLUSION: Our study shows that most patients are well nourished, independently from the level of consciousness. SMO may require additional calories in patients' daily needs; however, longitudinal studies are needed to explore the causal relationship between these variables.

Neural Responses to Heartbeats Detect Residual Signs of Consciousness during Resting State in Postcomatose Patients.

The neural monitoring of visceral inputs might play a role in first-person perspective (i.e., the unified viewpoint of subjective experience). In healthy participants, how the brain responds to heartbeats, measured as the heartbeat-evoked response (HER), correlates with perceptual, bodily, and self-consciousness. Here we show that HERs in resting-state EEG data distinguishes between postcomatose male and female human patients (n = 68, split into training and validation samples) with the unresponsive wakefulness syndrome and in patients in a minimally conscious state with high accuracy (random forest classifier, 87% accuracy, 96% sensitivity, and 50% specificity in the validation sample). Random EEG segments not locked to heartbeats were useful to predict unconsciousness/consciousness, but HERs were more accurate, indicating that HERs provide specific information on consciousness. HERs also led to more accurate classification than heart rate variability. HER-based consciousness scores correlate with glucose metabolism in the default-mode network node located in the right superior temporal sulcus, as well as with the right ventral occipitotemporal cortex. These results were obtained when consciousness was inferred from brain glucose met`abolism measured with positron emission topography. HERs reflected the consciousness diagnosis based on brain metabolism better than the consciousness diagnosis based on behavior (Coma Recovery Scale-Revised, 77% validation accuracy). HERs thus seem to capture a capacity for consciousness that does not necessarily translate into intentional overt behavior. These results confirm the role of HERs in consciousness, offer new leads for future bedside testing, and highlight the importance of defining consciousness and its neural mechanisms independently from behavior.

Preservation of Brain Activity in Unresponsive Patients Identifies MCS Star.

OBJECTIVE: Brain-injured patients who are unresponsive at the bedside (ie, vegetative state/unresponsive wakefulness syndrome - VS/UWS) may present brain activity similar to patients in minimally conscious state (MCS). This peculiar condition has been termed "non-behavioural MCS" or "MCS*". In the present study we aimed to investigate the proportion and underlying brain characteristics of patients in MCS*. METHODS: Brain 18 F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) was acquired on 135 brain-injured patients diagnosed in prolonged VS/UWS (n = 48) or MCS (n = 87). From an existing database, relative metabolic preservation in the fronto-parietal network (measured with standardized uptake value) was visually inspected by three experts. Patients with hypometabolism of the fronto-parietal network were labelled "VS/UWS", while its (partial) preservation either confirmed the behavioural diagnosis of "MCS" or, in absence of behavioural signs of consciousness, suggested a diagnosis of "MCS*". Clinical outcome at 1-year follow-up, functional connectivity, grey matter atrophy, and regional brain metabolic patterns were investigated in the three groups (VS/UWS, MCS* and MCS). RESULTS: 67% of behavioural VS/UWS presented a partial preservation of brain metabolism (ie, MCS*). Compared to VS/UWS patients, MCS* patients demonstrated a better outcome, global functional connectivity and grey matter preservation more compatible with the diagnosis of MCS. MCS* patients presented lower brain metabolism mostly in the posterior brain regions compared to MCS patients. INTERPRETATION: MCS* is a frequent phenomenon that is associated with better outcome and better brain preservation than the diagnosis of VS/UWS. Complementary exams should be provided to all unresponsive patients before taking medical decisions. ANN NEUROL 2021;90:89-100.

Risk factors for 2-year mortality in patients with prolonged disorders of consciousness: An international multicentre study.

BACKGROUND AND PURPOSE: Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Because an accurate prognosis is essential for decision-making on patients' management, we analysed data from an international multicentre prospective cohort study to evaluate 2-year mortality rate and bedside predictors of mortality. METHODS: We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and nontraumatic brain injury within 3 months postinjury. At enrolment, we collected demographic (age, sex), anamnestic (aetiology, time postinjury), clinical (Coma Recovery Scale-Revised [CRS-R], Disability Rating Scale, Nociception Coma Scale-Revised), and neurophysiologic (electroencephalogram [EEG], somatosensory evoked and event-related potentials) data. Patients were followed up to gather data on mortality up to 24 months postinjury. RESULTS: Among 143 traumatic (n = 55) and nontraumatic (n = 88) patients (VS/UWS, n = 68, 19 females; MCS, n = 75, 22 females), 41 (28.7%) died within 24 months postinjury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p < 0.001). Multivariate regression in VS/UWS showed that significant predictors of mortality were older age and lower CRS-R total score, whereas in MCS female sex and absence of alpha rhythm on EEG at study entry were significant predictors. CONCLUSIONS: This study demonstrated that a feasible multimodal assessment in the postacute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients' families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC.

Noninvasive Brain Stimulation Therapies to Promote Recovery of Consciousness: Where We Are and Where We Should Go.

Therapeutic options for patients with disorders of consciousness (DoC) are still underexplored. Noninvasive brain stimulation (NIBS) techniques modulate neural activity of targeted brain areas and hold promise for the treatment of patients with DoC. In this review, we provide a summary of published research using NIBS as therapeutic intervention for DoC patients, with a focus on (but not limited to) randomized controlled trials (RCT). We aim to identify current challenges and knowledge gaps specific to NIBS research in DoC. Furthermore, we propose possible solutions and perspectives for this field. Thus far, the most studied technique remains transcranial electrical stimulation; however, its effect remains moderate. The identified key points that NIBS researchers should focus on in future studies are (1) the lack of large-scale RCTs; (2) the importance of identifying the endotypes of responders; and (3) the optimization of stimulation parameters to maximize the benefits of NIBS.

Neuroimaging and neurophysiological diagnosis and prognosis in paediatric disorders of consciousness.

The diagnosis and prognosis of disorders of consciousness (DOC) such as coma, unresponsive wakefulness syndrome, or minimally conscious state are especially challenging in children. In some paediatric patients with severe acquired brain injury, medical comorbidities or developmental factors may obscure the detection of signs of consciousness via clinical assessments, thus leading to misdiagnosis. To circumvent these biases, patients benefit from multimodal assessments that combine behavioural, neuroimaging, and neurophysiological measures. In this review, we provide original data for such diagnostic procedures in children. Neuroimaging is largely underdocumented in children and most neurophysiological research consists of a cohort study design aimed at providing prognostic markers for clinical outcomes. The scarcity of available data on complementary diagnostic approaches in children makes it difficult to establish clear paediatric guidelines. Although there is preliminary evidence for the applicability of paradigms involving event-related potentials as support for diagnosis in children, more well-designed studies need to be conducted to promote evidence-based practices in paediatric DOC.

Neurorehabilitation for people with disorders of consciousness: an international survey of health-care structures and access to treatment, (Part 1).

AIMS: The provision of rehabilitation services for people with disorders of consciousness (DoC) may vary due to geographical, financial, and political factors. The extent of this variability and the implementation of treatment standards across countries is unknown. This study explored international neurorehabilitation systems for people with DoC. METHODS: An online survey (SurveyMonkey®) was disseminated to all members of the International Brain Injury Association (IBIA) DoC Special Interest Group (SIG) examining existing rehabilitation systems and access to them. RESULTS: Respondents (n = 35) were from 14 countries. Specialized neurorehabilitation was available with varying degrees of access and duration. Commencement of specialized neurorehabilitation averaged 3-4 weeks for traumatic brain injury (TBI) and 5-8 weeks for non-traumatic brain injury (nTBI) etiologies. Length of stay in inpatient rehabilitation was 1-3 months for TBI and 4-6 months for nTBI. There were major differences in access to services and funding across countries. The majority of respondents felt there were not enough resources in place to provide appropriate neurorehabilitation. CONCLUSIONS: There exists inter-country differences for DoC neurorehabilitation after severe acquired brain injury. Further work is needed to implement DoC treatment standards at an international level.

Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness.

This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

Update on neuroimaging in disorders of consciousness.

PURPOSE OF REVIEW: Neuroimaging has acquired a prominent place in the assessment of disorders of consciousness (DoC). Rapidly evolving technologies combined with state-of-the-art data analyses open new horizons to probe brain activity, but selecting appropriate imaging modalities from the plethora of available techniques can be challenging for clinicians. This update reviews selected advances in neuroimaging that demonstrate clinical relevance and translational potential in the assessment of severely brain-injured patients with DoC. RECENT FINDINGS: Magnetic resonance imaging and high-density electroencephalography provide measurements of brain connectivity between functional networks, assessments of language function, detection of covert consciousness, and prognostic markers of recovery. Positron emission tomography can identify patients with preserved brain metabolism despite clinical unresponsiveness and can measure glucose consumption rates in targeted brain regions. Transcranial magnetic stimulation and near-infrared spectroscopy are noninvasive and practical tools with promising clinical applications. SUMMARY: Each neuroimaging technique conveys advantages and pitfalls to assess consciousness. We recommend a multimodal approach in which complementary techniques provide diagnostic and prognostic information about brain function. Patients demonstrating neuroimaging evidence of covert consciousness may benefit from early adapted rehabilitation. Translating methodological advances to clinical care will require the implementation of recently published international guidelines and the integration of neuroimaging techniques into patient-centered decision-making algorithms.

Epilepsy in prolonged disorders of consciousness: a systematic review.

To date, no guideline exists for the management of epilepsy in patients with prolonged Disorders of Consciousness (DoC). This review aimed to assess the occurrence of epilepsy and epileptic abnormalities (EA) in these patients, to determine their impact on recovery; and to review the effect of antiepileptic drugs (AED) and therapeutic interventions on seizure occurrence and consciousness recovery. A structured search for studies on prolonged DoC and epilepsy was undertaken following PRISMA guidelines. From an initial search resulting in 5,775 titles, twelve studies met inclusion criteria. The occurrence of epilepsy and EA in DoC was poorly and inconsistently reported across studies. The results estimated a seizure prevalence of 27% in DoC. No conclusive data were found for the effects of AED on recovery nor on the influence of any therapeutic interventions on seizure occurrence. Given the scarcity of data, it is premature to make evidence-based recommendations on epilepsy in prolonged DoC. Based on this review and current clinical practices the following are recommended: (1) repeated standard EEG for detecting seizures and EA; (2) treating epilepsy while avoiding AEDs with sedating or cognitive side-effects. Future research should use standardized classification systems for seizures and EA.

Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions.

BACKGROUND/OBJECTIVE: For patients with disorders of consciousness (DoC) and their families, the search for new therapies has been a source of hope and frustration. Almost all clinical trials in patients with DoC have been limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use; amantadine is the only therapy recommended by current clinical guidelines, specifically for patients with DoC caused by severe traumatic brain injury. To foster and advance development of consciousness-promoting therapies for patients with DoC, the Curing Coma Campaign convened a Coma Science Work Group to perform a gap analysis. METHODS: We consider five classes of therapies: (1) pharmacologic; (2) electromagnetic; (3) mechanical; (4) sensory; and (5) regenerative. For each class of therapy, we summarize the state of the science, identify gaps in knowledge, and suggest future directions for therapy development. RESULTS: Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials. To address these gaps, we propose a precision medicine approach in which clinical trials selectively enroll patients based upon their physiological receptivity to targeted therapies, and therapeutic effects are measured by complementary behavioral, neuroimaging, and electrophysiologic endpoints. CONCLUSIONS: This personalized approach can be realized through rigorous clinical trial design and international collaboration, both of which will be essential for advancing the development of new therapies and ultimately improving the lives of patients with DoC.

Can the Nociception Coma Scale-Revised Be Used in Patients With a Tracheostomy?

OBJECTIVE: To investigate the influence of the presence of a tracheostomy tube to assess pain with the Nociception Coma Scale-Revised (NCS-R) in patients with disorders of consciousness (DOC). DESIGN: A cohort study in which patients were evaluated at a single time point. SETTING: Patients were evaluated in a tertiary care hospital. PARTICIPANTS: Patients (N=125) (unresponsive wakefulness syndrome [UWS]: 46 patients, minimally conscious state [MCS]: 74 patients, emerging from MCS [eMCS]: 5 patients, mean age: 46±16y, time since injury: 817±1280d) in a convenience sample were evaluated with the NCS-R after noxious stimulation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We compared the NCS-R scores of patients with and without tracheostomy with a Mann-Whitney U test. A secondary outcome was to evaluate the influence of the presence of a tracheostomy on the previously described cutoff score of 2. RESULTS: The presence of a tracheostomy was associated with lower verbal subscores (P=.002) as well as total scores (P=.039). The cutoff score of 2 remained valid for the group of patients with tracheostomy with a high sensitivity (71.43%) and specificity (89.29%), as well as when we excluded the verbal subscore of the NCS-R (sensitivity=83.2% and specificity=92.4%). CONCLUSION: Our study confirms the validity of the NCS-R in DOC patients with a tracheostomy. However, the presence of a nonspeaking tracheostomy should be clearly mentioned when applying the NCS-R, because it significantly lowers the verbal subscore.

Single tDCS session of motor cortex in patients with disorders of consciousness: a pilot study.

Primary Objective: Patients with disorders of consciousness (DOC) face a lack of treatments and risk of misdiagnosis, potentially due to motor impairment. Transcranial direct current stimulation (tDCS) showed promising results over the prefrontal cortex in DOC and over the primary motor cortex (M1) in stroke. Tis pilot study aimed at evaluating the behavioral effects of M1 tDCS in patients with DOC.Research Design: In this randomized double-blind sham-controlled crossover trial, we included 10 patients (49 ± 22 years, 7 ± 13 months since injury, 4 unresponsive wakefulness syndrome, 6 minimally conscious state, 5 traumatic etiologies).Methods and Procedures: One session of tDCS (2 mA for 20 min) and one session of sham tDCS were applied over M1 in a randomized order with a washout period of minimum 24 h and behavioral effects were assessed using the CRS-R. At the group level, no treatment effect was identified on the total score (p = .55) and on the motor subscale (p = .75). Two patients responded to tDCS by showing a new sign of consciousness (visual pursuit and object localization).Conclusions: One session of M1 tDCS failed to improve behavioral responsiveness in patients with DOC. Other application strategies should be tested.