EEG signature of near-death-like experiences during syncope-induced periods of unresponsiveness.

During fainting, disconnected consciousness may emerge in the form of dream-like experiences. Characterized by extra-ordinary and mystical features, these subjective experiences have been associated to near-death-like experiences (NDEs-like). We here aim to assess brain activity during syncope-induced disconnected consciousness by means of high-density EEG monitoring. Transient loss of consciousness and unresponsiveness were induced in 27 healthy volunteers through hyperventilation, orthostasis, and Valsalva maneuvers. Upon awakening, subjects were asked to report memories, if any. The Greyson NDE scale was used to evaluate the potential phenomenological content experienced during the syncope-induced periods of unresponsiveness. EEG source reconstruction assessed cortical activations during fainting, which were regressed out with subjective reports collected upon recovery of normal consciousness. We also conducted functional connectivity, graph-theoretic and complexity analyses. High quality high-density EEG data were obtained in 22 volunteers during syncope and unresponsiveness (lasting 22±8 s). NDE-like features (Greyson NDE scale total score ≥7/32) were apparent for eight volunteers and characterized by higher activity in delta, theta and beta2 bands in temporal and frontal regions. The richness of the NDE-like content was associated with delta, theta and beta2 bands cortical current densities, in temporal, parietal and frontal lobes, including insula, right temporoparietal junction, and cingulate cortex. Our analyses also revealed a higher complexity and that networks related to delta, theta, and beta2 bands were characterized by a higher overall connectivity paralleled by a higher segregation (i.e., local efficiency) and a higher integration (i.e., global efficiency) for the NDE-like group compared to the non-NDE-like group. Fainting-induced NDE-like episodes seem to be sustained by surges of neural activity representing promising markers of disconnected consciousness.

Effects of an intervention combining self-care and self-hypnosis on fatigue and associated symptoms in post-treatment cancer patients: A randomized-controlled trial.

OBJECTIVE: Cancer has a lot of consequences such as fatigue, sleep disturbances, emotional distress, cognitive impairment and reduced physical activity. Some hypnosis-based psychological interventions showed positive effects on fatigue, sleep and emotional distress, but generally focused on breast cancer patients. Our study aimed at assessing the effects of a group intervention combining self-care and self-hypnosis on quality of life of cancer patients. METHODS: Our longitudinal randomized-controlled trial assessed the benefits of the intervention first on fatigue and secondly on associated symptoms (sleep, emotional distress, cognitive impairment and reduced physical activity) of post-treatment cancer patients, and investigated predictors of the evolution of fatigue. All variables were measured with questionnaires and an actigraph (for sleep and physical activity). RESULTS: Ninety five women with different cancers were included in our study. Group-by-time effects were showed for fatigue, sleep, emotional distress and cognitive functioning: symptoms have improved in the intervention group compared to wait-list control group. Three predictors of the evolution of fatigue were revealed: depression, anxiety and worry. CONCLUSIONS: Our group intervention had benefits for post-treatment cancer patients' quality of life. Impacting emotional distress could be important in order to decrease fatigue. Further studies are needed to replicate our results. This intervention could be easily implemented to improve quality of life of cancer patients. Registration: ClinicalTrials.gov (NCT03144154). Retrospectively registered on the 1st of May, 2017.

The Near-Death Experience Content (NDE-C) scale: Development and psychometric validation.

As interest grows in near-death experiences (NDEs), it is increasingly important to accurately identify them to facilitate empirical research and reproducibility among assessors. We aimed (1) to reassess the psychometric properties of the NDE scale developed by Greyson (1983) and (2) to validate the Near-Death Experience Content (NDE-C) scale that quantifies NDEs in a more complete way. Internal consistency, construct and concurrent validity analyses were performed on the NDE scale. Based on those results and the most recent empirical evidence, we then developed a new 20-item scale. Internal consistency, explanatory and confirmatory factor, concurrent and discriminant validity analyses were conducted. Results revealed (1) a series of weaknesses in the NDE scale, (2) a 5-factor structure covering relevant dimensions and the very good psychometric properties of the NDE-C scale, including very good internal consistency (Cronbach α = 0.85) and concurrent validity (correlations above 0.76). This new reliable scale should facilitate future research.

Modulation of the spontaneous hemodynamic response function across levels of consciousness.

Functional imaging research has already contributed with several results to the study of neural correlates of consciousness. Apart from task-related activation derived in fMRI, PET based glucose metabolism rate or cerebral blood flow account for a considerable proportion of the study of brain activity under different levels of consciousness. Resting state functional connectivity MRI is playing a crucial role to explore the consciousness related functional integration, successfully complementing PET, another widely used neuroimaging technique. Here, spontaneous hemodynamic response is introduced to characterize resting state brain activity giving information on the local metabolism (neurovascular coupling), and useful to improve the time-resolved activity and connectivity measures based on BOLD fMRI. This voxel-wise measure is then used to investigate the loss of consciousness under Propofol anesthesia and unresponsive wakefulness syndrome. Changes in the hemodynamic response in precuneus and posterior cingulate are found to be a common principle underlying loss of consciousness in both conditions. The thalamus appears to be less obviously modulated by Propofol, compared with frontoparietal regions. However, a significant increase in spontaneous thalamic hemodynamic response was found in patients in unresponsive wakefulness syndrome compared with healthy controls. Our results ultimately show that anesthesia- or pathology-induced neurovascular coupling could be tracked by modulated spontaneous hemodynamic response derived from resting state fMRI.

Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports.

The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings of peace, bliss and timelessness, life review, the sensation of traveling through a tunnel and an irreversible threshold. Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism. Anecdotal accounts of the similarity between NDEs and certain drug-induced altered states of consciousness prompted us to perform a large-scale comparative analysis of these experiences. After assessing the semantic similarity between ≈15,000 reports linked to the use of 165 psychoactive substances and 625 NDE narratives, we determined that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine consistently resulted in reports most similar to those associated with NDEs. Ketamine was followed by Salvia divinorum (a plant containing a potent and selective κ receptor agonist) and a series of serotonergic psychedelics, including the endogenous serotonin 2A receptor agonist N,N-Dimethyltryptamine (DMT). This similarity was driven by semantic concepts related to consciousness of the self and the environment, but also by those associated with the therapeutic, ceremonial and religious aspects of drug use. Our analysis sheds light on the long-standing link between certain drugs and the experience of "dying", suggests that ketamine could be used as a safe and reversible experimental model for NDE phenomenology, and supports the speculation that endogenous NMDA antagonists with neuroprotective properties may be released in the proximity of death.

A systematic analysis of distressing near-death experience accounts.

Near-death experiences (NDEs) are usually associated with positive affect, however, a small proportion are considered distressing. We aimed to look into the proportion of distressing NDEs in a sample of NDE narratives, categorise distressing narratives according to Greyson and Bush's classification (inverse, void or hellish), and compare distressing and "classical" NDEs. Participants wrote down their experience, completed the Memory Characteristics Questionnaire (assessing the phenomenology of memories) and the Greyson scale (characterising content of NDEs). The proportion of suicidal attempts, content and intensity of distressing and classical NDEs were compared using frequentist and Bayesian statistics. Distressing NDEs represent 14% of our sample (n = 123). We identified 8 inverse, 8 hellish and 1 void accounts. The proportion of suicide survivors is higher in distressing NDEs as compared to classical ones. Finally, memories of distressing NDEs appear as phenomenologically detailed as classical ones. Distressing NDEs deserve careful consideration to ensure their integration into experiencers' identity.

Randomized controlled trial of an 8-week intervention combining self-care and hypnosis for post-treatment cancer patients: study protocol.

BACKGROUND: Cancer has a lot of consequences on patients' quality of life (such as cancer-related fatigue (CRF), sleep difficulties and emotional distress) and on patients' partners and their relationship, such as distress and communication difficulties. These consequences are undertreated, and interventions based on hypnosis often focus on breast cancer patients only. This paper describes the study protocol of a longitudinal randomized controlled trial aiming to assess the efficacy of an 8-week intervention combining hypnosis and self-care to improve cancer patients' CRF, sleep and emotional distress and to indirectly improve their partners' distress. METHODS: A power analysis required a total sample of 88 patients. To test the efficacy of the intervention, results of the experimental group receiving the intervention will be compared to those of the control group. Data will be collected by questionnaires, relaxation tasks, an attentional bias task, and everyday life assessments measured at four different times: 1.) before inclusion in the study (baseline); 2.) after the intervention; and 3.) at 4- and 12-month follow-up. Partners' symptoms will also be evaluated with questionnaires at the same measurement times. DISCUSSION: There is a growing interest in alternative approaches (such as hypnosis) in addition to standard therapies in oncology settings. The results of this study should be useful for improving knowledge about long-term efficacy of hypnosis-based group interventions for CRF, sleep and distress among all types of cancer patients and their partners, and to better understand the mechanisms of emotional regulation in cancer patients through the attentional bias task. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03144154). Retrospectively registered on the 1st of May, 2017.

False memory susceptibility in coma survivors with and without a near-death experience.

It has been postulated that memories of near-death experiences (NDEs) could be (at least in part) reconstructions based on experiencers' (NDErs) previous knowledge and could be built as a result of the individual's attempt to interpret the confusing experience. From the point of view of the experiencer, NDE memories are perceived as being unrivalled memories due to its associated rich phenomenology. However, the scientific literature devoted to the cognitive functioning of NDErs in general, and their memory performance in particular, is rather limited. This study examined NDErs' susceptibility to false memories using the Deese-Roediger-McDermott (DRM) paradigm. We included 20 NDErs who reported having had their experience in the context of a life-threatening event (Greyson NDE scale total score ≥7/32) and 20 volunteers (matched for age, gender, education level, and time since brain insult) who reported a life-threatening event but without a NDE. Both groups were presented with DRM lists for a recall task during which they were asked to assign "Remember/Know/Guess" judgements to any recalled response. In addition, they were later asked to complete a post-recall test designed to obtain estimates of activation and monitoring of critical lures. Results demonstrated that NDErs and volunteers were equally likely to produce false memories, but that NDErs recalled them more frequently associated with compelling illusory recollection. Of particular interest, analyses of activation and monitoring estimates suggest that NDErs and volunteers groups were equally likely to think of critical lures, but source monitoring was less successful in NDErs compared to volunteers.

Prevalence of coma-recovery scale-revised signs of consciousness in patients in minimally conscious state.

Different behavioural signs of consciousness can distinguish patients with an unresponsive wakefulness syndrome from patients in minimally conscious state (MCS). The Coma Recovery Scale-Revised (CRS-R) is the most sensitive scale to differentiate the different altered states of consciousness and eleven items detect the MCS. The aim of this study is to document the prevalence of these items. We analysed behavioural assessments of 282 patients diagnosed in MCS based on the CRS-R. Results showed that some items are particularly frequent among patients in MCS, namely fixation, visual pursuit, and reproducible movement to command, which were observed in more than 50% of patients. These responses were also the most probably observed items when the patients only showed one sign of consciousness. On the other hand, some items were rarely or never observed alone, e.g., object localisation (reaching), object manipulation, intelligible verbalisation, and object recognition. The results also showed that limiting the CRS-R assessment to the five most frequently observed items (i.e., fixation, visual pursuit, reproducible movement to command, automatic motor response and localisation to noxious stimulation) detected 99% of the patients in MCS. If clinicians have only limited time to assess patients with disorders of consciousness, we suggest to evaluate at least these five items of the CRS-R.

Intensity and memory characteristics of near-death experiences.

Memories of Near-Death Experiences (NDEs) seem to be very detailed and stable over time. At present, there is still no satisfactory explanation for the NDEs' rich phenomenology. Here we compared phenomenological characteristics of NDE memories with the reported experience's intensity. We included 152 individuals with a self-reported "classical" NDE (i.e. occurring in life-threatening conditions). All participants completed a mailed questionnaire that included a measure of phenomenological characteristics of memories (the Memory Characteristics Questionnaire; MCQ) and a measure of NDE's intensity (the Greyson NDE scale). Greyson NDE scale total score was positively correlated with MCQ total score, suggesting that participants who described more intense NDEs also reported more phenomenological memory characteristics of NDE. Using MCQ items, our study also showed that NDE's intensity is associated in particular with sensory details, personal importance and reactivation frequency variables.

Sedation of Patients With Disorders of Consciousness During Neuroimaging: Effects on Resting State Functional Brain Connectivity.

BACKGROUND: To reduce head movement during resting state functional magnetic resonance imaging, post-coma patients with disorders of consciousness (DOC) are frequently sedated with propofol. However, little is known about the effects of this sedation on the brain connectivity patterns in the damaged brain essential for differential diagnosis. In this study, we aimed to assess these effects. METHODS: Using resting state functional magnetic resonance imaging 3T data obtained over several years of scanning patients for diagnostic and research purposes, we employed a seed-based approach to examine resting state connectivity in higher-order (default mode, bilateral external control, and salience) and lower-order (auditory, sensorimotor, and visual) resting state networks and connectivity with the thalamus, in 20 healthy unsedated controls, 8 unsedated patients with DOC, and 8 patients with DOC sedated with propofol. The DOC groups were matched for age at onset, etiology, time spent in DOC, diagnosis, standardized behavioral assessment scores, movement intensities, and pattern of structural brain injury (as assessed with T1-based voxel-based morphometry). RESULTS: DOC were associated with severely impaired resting state network connectivity in all but the visual network. Thalamic connectivity to higher-order network regions was also reduced. Propofol administration to patients was associated with minor further decreases in thalamic and insular connectivity. CONCLUSIONS: Our findings indicate that connectivity decreases associated with propofol sedation, involving the thalamus and insula, are relatively small compared with those already caused by DOC-associated structural brain injury. Nonetheless, given the known importance of the thalamus in brain arousal, its disruption could well reflect the diminished movement obtained in these patients. However, more research is needed on this topic to fully address the research question.

Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients.

Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for separating patients in a minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Among them, the auditory network was ranked the most highly. The regions of the auditory network which were more functionally connected in patients in minimally conscious state compared to vegetative state/unresponsive wakefulness syndrome encompassed bilateral auditory and visual cortices. Connectivity values in these three regions discriminated congruently 20 of 22 independently assessed patients. Our findings point to the significance of preserved abilities for multisensory integration and top-down processing in minimal consciousness seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics.

Detection and Interpretation of Impossible and Improbable Coma Recovery Scale-Revised Scores.

OBJECTIVE: To determine the frequency with which specific Coma Recovery Scale-Revised (CRS-R) subscale scores co-occur as a means of providing clinicians and researchers with an empirical method of assessing CRS-R data quality. DESIGN: We retrospectively analyzed CRS-R subscale scores in hospital inpatients diagnosed with disorders of consciousness (DOCs) to identify impossible and improbable subscore combinations as a means of detecting inaccurate and unusual scores. Impossible subscore combinations were based on violations of CRS-R scoring guidelines. To determine improbable subscore combinations, we relied on the Mahalanobis distance, which detects outliers within a distribution of scores. Subscore pairs that were not observed at all in the database (ie, frequency of occurrence=0%) were also considered improbable. SETTING: Specialized DOC program and university hospital. PARTICIPANTS: Patients diagnosed with DOCs (N=1190; coma: n=76, vegetative state: n=464, minimally conscious state: n=586, emerged from minimally conscious state: n=64; 794 men; mean age, 43±20y; traumatic etiology: n=747; time postinjury, 162±568d). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Impossible and improbable CRS-R subscore combinations. RESULTS: Of the 1190 CRS-R profiles analyzed, 4.7% were excluded because they met scoring criteria for impossible co-occurrence. Among the 1137 remaining profiles, 12.2% (41/336) of possible subscore combinations were classified as improbable. CONCLUSIONS: Clinicians and researchers should take steps to ensure the accuracy of CRS-R scores. To minimize the risk of diagnostic error and erroneous research findings, we have identified 9 impossible and 36 improbable CRS-R subscore combinations. The presence of any one of these subscore combinations should trigger additional data quality review.

Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study.

BACKGROUND: Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI). METHODS: For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale-Revised (CRS-R), cerebral (18)F-fluorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS-R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale-Extended. FINDINGS: We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). (18)F-FDG PET had high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85-98) and high congruence (85%, 77-90) with behavioural CRS-R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30-61) and had lower overall congruence with behavioural scores (63%, 51-73) than PET imaging. (18)F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64-81), and fMRI in 36 of 65 patients (56%, 43-67). 13 of 41 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS-R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness. INTERPRETATION: Cerebral (18)F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for differential diagnosis, but seems to be less accurate. FUNDING: The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège.

Near-Death Experiences in patients with locked-in syndrome: Not always a blissful journey.

Memories of Near-Death Experiences (NDEs) most often are recounted as emotionally positive events. At present, no satisfactory explanatory model exists to fully account for the rich phenomenology of NDEs following a severe acute brain injury. The particular population of patients with locked-in syndrome (LIS) provides a unique opportunity to study NDEs following infratentorial brain lesions. We here retrospectively characterized the content of NDEs in 8 patients with LIS caused by an acute brainstem lesion (i.e., "LIS NDEs") and 23 NDE experiencers after coma with supratentorial lesions (i.e., "classical NDEs"). Compared to "classical NDEs", "LIS NDEs" less frequently experienced a feeling of peacefulness or well-being. It could be hypothesized that NDEs containing less positive emotions might have a specific neuroanatomical substrate related to impaired pontine/paralimbic connectivity or alternatively might be related to the emotional distress caused by the presence of conscious awareness in a paralyzed body.

Detection of visual pursuit in patients in minimally conscious state: a matter of stimuli and visual plane?

OBJECTIVES: The aim of this study was to determine whether the assessment of pursuit eye movements in patients in minimally conscious state (MCS) is influenced by the choice of the visual stimulus (study 1) and by the moving plane (study 2). METHODS: Patients with MCS (MCS- and MCS+) in the acute (<1 month post-injury) or chronic (>1 month) setting were assessed. The Coma Recovery Scale-Revised (CRS-R) procedure was used to test visual pursuit of a moving mirror, object and person (study 1, n = 88) and to test vertical and horizontal visual tracking (study 2, n = 94). RESULTS: Study 1: Patients with visual pursuit tracked preferentially the moving mirror over the moving person or object. Study 2: Patients displaying visual pursuit, especially in MCS- and in chronic setting, preferentially tracked on the horizontal rather than the vertical plane. CONCLUSION: The findings confirm the importance of using a mirror to assess visual pursuit in patients in MCS and of initiating testing using the horizontal plane, specifically in patients in MCS- and those in chronic setting. Assessment should then be done on the vertical plane if visual pursuit is not detected on the horizontal plane.

Needs and Quality of Life of Caregivers of Patients with Prolonged Disorders of Consciousness.

Background. Many patients with severe brain damage may survive and remain in a prolonged disorder of consciousness (PDoC), impacting the quality of life (QoL) and needs of their family caregivers. However, the current literature on the factors influencing these needs is contradictory. We aim to describe the needs, QoL, and emotional distress of caregivers of patients with PDoC. Methods. Questionnaires investigating the importance and satisfaction of six categories of needs (i.e., health information, emotional, instrumental, and professional supports, community support network, and involvement in care), QoL, and emotional distress were completed by the main caregivers of PDoC patients. Results. We analyzed 177 questionnaires. Seventy-nine percent of the needs were considered as important or very important, and 44% were partially met or unmet. The needs for health information and professional support were the most important, while the needs for involvement in care and for health information were the most satisfied. Mean QoL was low and emotional distress high. Variables such as care setting and time since brain injury affected the level of QoL and distress. Conclusion. The needs for health information and professional support should receive particular attention. Given their low QoL and high distress, adequate support structures should be provided to caregivers of PDoC patients.

Exploratory Controlled Study of the Impact of a Hypnosis-Based Intervention on the Couple's Communication and Coping in the Context of Cancer.

Emotional distress, communication, and dyadic coping difficulties are common among cancer patients and their partners. Hypnosis-based interventions can improve emotional distress in patients. We designed a group intervention combining self-hypnosis and self-care techniques. We hypothesized an effect of the intervention on emotional distress, conjugal communication, and dyadic coping, considered in patients and their partners. Our exploratory controlled study included 55 women with cancer and 55 partners. Participants completed questionnaires before and after the intervention, which was delivered to patients only. No significant effect of the intervention was revealed for patients or partners. Positive correlations between patients' and partners' communication and dyadic coping were revealed. However, to address couples' or partners' difficulties, interventions specifically designed for couples or partners must be tested.

Reconfiguration of large-scale functional connectivity in patients with disorders of consciousness.

INTRODUCTION: Functional connectivity alterations within individual resting state networks (RSNs) are linked to disorders of consciousness (DOC). If these alterations influence the interaction quality with other RNSs, then, brain alterations in patients with DOC would be characterized by connectivity changes in the large-scale model composed of RSNs. How are functional interactions between RSNs influenced by internal alterations of individual RSNs? Do the functional alterations induced by DOC change some key properties of the large-scale network, which have been suggested to be critical for the consciousness emergence? Here, we use network analysis to measure functional connectivity in patients with DOC and address these questions. We hypothesized that network properties provide descriptions of brain functional reconfiguration associated with consciousness alterations. METHODS: We apply nodal and global network measurements to study the reconfiguration linked with the disease severity. We study changes in integration, segregation, and centrality properties of the functional connectivity between the RSNs in subjects with different levels of consciousness. RESULTS: Our analysis indicates that nodal measurements are more sensitive to disease severity than global measurements, particularly, for functional connectivity of sensory and cognitively related RSNs. CONCLUSION: The network property alterations of functional connectivity in different consciousness levels suggest a whole-brain topological reorganization of the large-scale functional connectivity in patients with DOC.