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.

Validation of the Music Therapy Assessment Tool for Awareness in Disorders of Consciousness With the Coma Recovery Scale-Revised.

OBJECTIVE: To examine (1) the concurrent validity of the Music Therapy Assessment Tool for Awareness in Disorders of Consciousness (MATADOC) with the criterion standard Coma Recovery Scale-Revised (CRS-R) for outcomes of awareness in patients with prolonged disorders of consciousness (PDoC), (2) the relationship between MATADOC items and CRS-R function subscales in similar domains, and (3) determine if items/function subscales measure different constructs. DESIGN: A prospective multicentric blinded study with repeated concurrent measures. SETTING: Three inpatient rehabilitation units. PARTICIPANTS: Convenience sample of 74 adults with PDoC (N=74). MAIN OUTCOME MEASURES: The MATADOC protocol elicits behavioral responsiveness using live music in 5 tasks. A total score ranges 0-10 scoring behaviors across 14-items. The CRS-R uses a language-based protocol and scores observed responses ranging from 0-23 in 6 function subscales. Both measures were delivered at 4 concurrent time points over 2 weeks. RESULTS: Fair (κ=0.238, P=.006) ranging to moderate (κ=0.419, P<.001) significant agreement was found between CRS-R and MATADOC diagnostic outcomes. Fair-borderline moderate significant agreement was found for overall diagnostic outcomes across all diagnostic categories (κ=0.397, P=.001). There was moderate significant agreement between measures for motor scores (0.551≤κ≤0.571, P<.001) and visual outcomes (0.192≤κ≤0.415, .001≤P<.005) but no agreement for item/function subscale outcomes assessing auditory responsiveness. Exploratory factor analysis of all items showed 2 factors, suggesting that MATADOC and CRS-R measure the same underlying latent variable (awareness) in different ways and could complement each other for diagnosis and intervention purposes. This was supported by scale analysis, which showed increased reliability when the 2 scales are used together rather than separately. CONCLUSIONS: Unlike the CRS-R, the music-based MATADOC scores auditory localization for complexity of response and categorizes these behaviors as conscious rather than reflexive. The MATADOC may supplement the CRS-R, having a particular role in interdisciplinary programming for providing a more robust assessment of auditory responsiveness because of using nonverbal musical stimuli.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Behavioral Phenotyping.

BACKGROUND: The recent publication of practice guidelines for management of patients with disorders of consciousness (DoC) in the United States and Europe was a major step forward in improving the accuracy and consistency of terminology, diagnostic criteria, and prognostication in this population. There remains a pressing need for a more precise brain injury classification system that combines clinical semiology with neuroimaging, electrophysiologic, and other biomarker data. To address this need, the National Institute of Neurological Disorders and Stroke launched the Common Data Elements (CDEs) initiative to facilitate systematic collection of high-quality research data in studies involving patients with neurological disease. The Neurocritical Care Society's Curing Coma Campaign expanded this effort in 2018 to develop CDEs for DoC. Herein, we present CDE recommendations for behavioral phenotyping of patients with DoC. METHODS: The Behavioral Phenotyping Workgroup used a preestablished, five-step process to identify and select candidate CDEs that included review of existing National Institute of Neurological Disorders and Stroke CDEs, nomination and systematic vetting of new CDEs, CDE classification, iterative review, and approval of panel recommendations and development of corresponding case review forms. RESULTS: We identified a slate of existing and newly proposed basic, supplemental, and exploratory CDEs that can be used for behavioral phenotyping of adult and pediatric patients with DoC. CONCLUSIONS: The proposed behavioral phenotyping CDEs will assist with international harmonization of DoC studies and allow for more precise characterization of study cohorts, favorably impacting observational studies and clinical trials aimed at improving outcome in this population.

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.

Language Assessment in Patients with Disorders of Consciousness.

The assessment of residual language abilities in patients with disorders of consciousness (DoC) after severe brain injury is particularly challenging due to their limited behavioral repertoire. Moreover, associated language impairment such as receptive aphasia may lead to an underestimation of actual consciousness levels. In this review, we examine past research on the assessment of residual language processing in DoC patients, and we discuss currently available tools for identifying language-specific abilities and their prognostic value. We first highlight the need for validated and sensitive bedside behavioral assessment tools for residual language abilities in DoC patients. As regards neuroimaging and electrophysiological methods, the tasks involving higher level linguistic commands appear to be the most informative about level of consciousness and have the best prognostic value. Neuroimaging methods should be combined with the most appropriate behavioral tools in multimodal assessment protocols to assess receptive language abilities in DoC patients in the most complete and sensitive manner.

Sociodemographic, geographic and clinical factors associated with functional outcome and discharge location in US inpatient rehabilitation settings.

OBJECTIVE: To assess the impact of sociodemographic factors, clinical factors and regional differences on both patients' functional outcome and discharge location in U.S. inpatient rehabilitation settings. METHODS: Using eRehabData, 536,453 admissions was used for functional outcome analyses (based on FIM gain) while 259,308 admissions was used for the discharge location analyses. Regression models were used to look at both outcomes. RESULTS: Having private insurance and being young and male was associated with the higher FIM gains while being African American, widowed, and living in the Midwest was associated with the lower FIM gains. Furthermore, having private insurance, being young, male, married and African American or Hispanic was associated with the lower odds of being discharged to a skilled nursing facility while living in the Midwest was associated with the greatest odds of being discharged to a skilled nursing facility. Clinical factors such as days from onset and length of stay also had a significant effect on both outcomes. CONCLUSION: Our findings suggest that, in the U.S., one of the challenges to successful recovery in the inpatient rehabilitation setting includes insurance status (Medicare/Medicaid), race (African American) but also regional differences (Midwest) and length of stay.

Longitudinal changes in blood-based biomarkers in chronic moderate to severe traumatic brain injury: preliminary findings.

Objectives: This longitudinal study aims at 1) providing preliminary evidence of changes in blood-based biomarkers across time in chronic TBI and 2) relating these changes to outcome measures and cerebral structure and activity.Methods: Eight patients with moderate-to-severe TBI (7 males, 35 ± 7.6 years old, 5 severe TBI, 17.52 ± 3.84 months post-injury) were evaluated at monthly intervals across 6 time-points using: a) Blood-based biomarkers (GFAP, NSE, S100A12, SDBP145, UCH-L1, T-tau, P-tau, P-tau/T-tau ratio); b) Magnetic Resonance Imaging to evaluate changes in brain structure; c) Resting-state electroencephalograms to evaluate changes in brain function; and d) Outcome measures to assess cognition, emotion, and functional recovery (MOCA, RBANS, BDI-II, and DRS).Results: Changes in P-tau levels were found across time [p = .007]. P-tau was positively related to functional [p < .001] and cognitive [p = .006] outcomes, and negatively related to the severity of depression, 6 months later [R = -0.901; p =.006]. P-tau and P-tau/T-tau ratio were also positively correlated to shape change in subcortical areas such as brainstem [T(7) = 4.71, p = .008] and putamen [T(7) = 3.25, p = .012].Conclusions: Our study provides preliminary findings that suggest a positive relationship between P-tau and the recovery of patients with chronic TBI.

International survey on diagnostic and prognostic procedures in pediatric disorders of consciousness.

AIMS: 1. to investigate diagnostic and prognostic procedures routinely used by international professionals to assess children with disorders of consciousness (DoC); 2. to explore use and availability of internal and national guidelines for pediatric DoC; 3. to identify international differences in diagnostic/prognostic protocols. METHODS: The International Brain Injury Association DoC Special Interest Group emailed a survey link to 43,469 professionals. The survey included questions on diagnostic/prognostic procedures and guidelines for children with DoC. RESULTS: Data on 82 respondents [(50% physicians) primarily from Europe (43.9%)and North America (37.8%)] were analyzed. Common diagnostic tools included the Glasgow Coma Scale for clinical assessment (94%), the Coma Recovery Scale-Revised for outcome measurement (57%), and cerebral MRI (94%). Clinical features used most frequently to inform prognosis varied with patient age. Few respondents used national (28%) admission protocols for children with DoC, and most were unaware of published national guidelines for diagnostic (72%) and prognostic (85%) procedures. Compared to North American respondents, more European respondents were physicians and used neurophysiological data for prognosis. CONCLUSIONS: This international survey provides useful information about diagnostic and prognostic procedures currently used for children with DoC and highlights the need for guidelines to promote best practices for diagnosis/prognosis in pediatric DoC.

An International survey on diagnostic and prognostic protocols in patients with disorder of consciousness.

To date, no international guidelines or recommendations for diagnosis or prognosis of patients with disorders of consciousness (DoC) have been established. The International Brain Injury Association's (IBIA) Special Interest Group on Disorders of Consciousness (DoC-SIG) launched an international multicenter survey to compare diagnostic and prognostic procedures across countries and clinical settings. Objectives: To explore which specific diagnostic protocols and prognostic indices were utilized in the care for persons with DoC in different countries and to determine the usage, if any, of national guidelines in the care of such patients. Methods: The questionnaire included 17 questions in two distinct sections (I - clinical and instrumental tools and involvement of caregivers and II - clinical, anamnestic and instrumental markers). Results: Physicians composed 50% of the survey respondents (120) and were all involved in post-acute rehabilitation care. In the majority of countries, respondents reported that there were no national guidelines or recommendations for DoC care. The Glasgow Coma Scale (GCS) and the Coma Recovery Scale-Revised (CRS-R) were the most frequently used clinical scales for diagnostic purposes. The majority of respondents reported the involvement of caregivers in the evaluation of behavioral responsiveness of patient with DoC. The survey indicated that only a few centers performed neurophysiological investigations routinely as diagnostic instrumental procedures. Our results suggest that international guidelines and recommendations for the care of persons with DoC still need to be formulated and ideally agreed to by consensus.

Validation of the Chinese version of the Coma Recovery Scale-Revised (CRS-R).

PRIMARY OBJECTIVE: This study aims to validate the Chinese version of the Coma Recovery Scale-Revised (CRS-R). METHODS: One hundred sixty-nine patients were assessed with both the CRS-R and the Glasgow Coma Scale (GCS), diagnosed as being in unresponsive wakefulness syndrome (UWS, formerly known as vegetative state), minimally conscious state (MCS), or emergence from MCS (EMCS). A subgroup of 50 patients has been assessed twice by the same rater, within 24 h. Patient outcome was documented six months after assessment. RESULTS: The internal consistency for the CRS-R total score was excellent (Cronbach's α = 0.84). Good test-retest reliability was obtained for CRS-R total score and subscale scores (intra-class correlation coefficient [ICC] = 0.87 and ICC = 0.66-0.84, respectively). Inter-rater reliability was high (ICC = 0.719; p < 0.01). Concurrent validity was good between CRS-R total scale and GCS total scale. Diagnostic validity was excellent compared with GCS (emerged from UWS: 24%; emerged from MCS: 28%). When considering patient outcome, diagnostic validity was good. In addition, false-positive rates have been detected for both diagnoses. CONCLUSION: The Chinese version of the CRS-R is a reliable and sensitive tool and can discriminate patients in UWS, MCS, and EMCS successfully.

Brain networks predict metabolism, diagnosis and prognosis at the bedside in disorders of consciousness.

Recent advances in functional neuroimaging have demonstrated novel potential for informing diagnosis and prognosis in the unresponsive wakeful syndrome and minimally conscious states. However, these technologies come with considerable expense and difficulty, limiting the possibility of wider clinical application in patients. Here, we show that high density electroencephalography, collected from 104 patients measured at rest, can provide valuable information about brain connectivity that correlates with behaviour and functional neuroimaging. Using graph theory, we visualize and quantify spectral connectivity estimated from electroencephalography as a dense brain network. Our findings demonstrate that key quantitative metrics of these networks correlate with the continuum of behavioural recovery in patients, ranging from those diagnosed as unresponsive, through those who have emerged from minimally conscious, to the fully conscious locked-in syndrome. In particular, a network metric indexing the presence of densely interconnected central hubs of connectivity discriminated behavioural consciousness with accuracy comparable to that achieved by expert assessment with positron emission tomography. We also show that this metric correlates strongly with brain metabolism. Further, with classification analysis, we predict the behavioural diagnosis, brain metabolism and 1-year clinical outcome of individual patients. Finally, we demonstrate that assessments of brain networks show robust connectivity in patients diagnosed as unresponsive by clinical consensus, but later rediagnosed as minimally conscious with the Coma Recovery Scale-Revised. Classification analysis of their brain network identified each of these misdiagnosed patients as minimally conscious, corroborating their behavioural diagnoses. If deployed at the bedside in the clinical context, such network measurements could complement systematic behavioural assessment and help reduce the high misdiagnosis rate reported in these patients. These metrics could also identify patients in whom further assessment is warranted using neuroimaging or conventional clinical evaluation. Finally, by providing objective characterization of states of consciousness, repeated assessments of network metrics could help track individual patients longitudinally, and also assess their neural responses to therapeutic and pharmacological interventions.

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.

Evidence of altered pressure pain thresholds in persons with disorders of consciousness as measured by the Nociception Coma Scale-Italian version.

Pain assessment in patients with disorders of consciousness (DoC) is a controversial issue for clinicians, who require tools and standardised procedures for testing nociception in non-communicative patients. The aims of the present study were, first, to analyse the psychometric properties of the Italian version of the Nociception Coma Scale and, second, to evaluate pressure pain thresholds in a group of patients with DoC. The authors conducted a multi-centre study on 40 healthy participants and 60 DoC patients enrolled from six hospitals in Italy. For each group an electronic algometer was used to apply all nociceptive pressure stimuli. Our results show that the Italian version of the NCS retains the good psychometric properties of the original version and is therefore suitable for standardised pain assessment in clinical practice. In our study, pressure pain thresholds measured in a group of patients in vegetative and minimally conscious state were relatively lower than pain threshold values found in a group of healthy participants. Such findings motivate additional investigation on possible pain sensitisation in patients with severe brain injury and multiple co-morbidities, and on application of tailored therapeutic approaches useful for pain management in patients unable verbally to communicate their feelings.

Disorders of consciousness after severe brain injury: therapeutic options.

PURPOSE OF REVIEW: Very few options exist for patients who survive severe traumatic brain injury but fail to fully recover and develop a disorder of consciousness (e.g. vegetative state, minimally conscious state). RECENT FINDINGS: Among pharmacological approaches, Amantadine has shown the ability to accelerate functional recovery. Although with very low frequency, Zolpidem has shown the ability to improve the level of consciousness transiently and, possibly, also in a sustained fashion. Among neuromodulatory approaches, transcranial direct current stimulation has been shown to transiently improve behavioral responsiveness, but mostly in minimally conscious patients. New evidence for thalamic deep brain stimulation calls into question its cost/benefit trade-off. SUMMARY: The growing understanding of the biology of disorders of consciousness has led to a renaissance in the development of therapeutic interventions for patients with disorders of consciousness. High-quality evidence is emerging for pharmacological (i.e. Amantadine) and neurostimulatory (i.e. transcranial direct current stimulation) interventions, although further studies are needed to delineate preconditions, optimal dosages, and timing of administration. Other exciting new approaches (e.g. low intensity focused ultrasound) still await systematic assessment. A crucial future direction should be the use of neuroimaging measures of functional and structural impairment as a means of tailoring patient-specific interventions.

Chinese translation of the Coma Recovery Scale-Revised.

BACKGROUND: Misdiagnosis rate is high in patients with disorders of consciousness, potentially leading to an inappropriate clinical management of these patients. Sensitive standardised rating scales offer some protections from these diagnostic errors. In this context, the use of the Coma Recovery Scale-Revised (CRS-R) has strongly been recommended by the American Congress of Rehabilitation Medicine. OBJECTIVE: Here, we present the work that has been performed to translate this important diagnostic tool in Chinese. METHODS: The scale has been translated from its original English version to Chinese by a team of native Chinese speakers in agreement with an expert highly trained in the use of the original version of the CRS-R and, then, back-translated to English by four independent translators blinded to the original version. The resulting translation has been sent to the original author for final approval. RESULTS AND CONCLUSION: The Chinese version of the CRS-R is now available for use in clinical practise. Further investigations will nevertheless be needed in order to show that its psychometric properties are identical to the original English version.

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.

Cerebral response to subject's own name showed high prognostic value in traumatic vegetative state.

BACKGROUND: Previous studies have shown the prognostic value of stimulation elicited blood-oxygen-level-dependent (BOLD) signal in traumatic patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS). However, to the best of our knowledge, no studies have focused on the relevance of etiology and level of consciousness in patients with disorders of consciousness (DOC) when explaining the relationship between BOLD signal and both outcome and signal variability. We herein propose a study in a large sample of traumatic and non-traumatic DOC patients in order to ascertain the relevance of etiology and level of consciousness in the variability and prognostic value of a stimulation-elicited BOLD signal. METHODS: 66 patients were included, and the response of each subject to his/her own name said by a familiar voice (SON-FV) was recorded using fMRI; 13 patients were scanned twice in the same day, respecting the exact same conditions in both cases. A behavioral follow-up program was carried out at 3, 6, and 12 months after scanning. RESULTS: Of the 39 VS/UWS patients, 12 (75%) out of 16 patients with higher level activation patterns recovered to minimally conscious state (MCS) or emergence from MCS (EMCS) and 17 (74%) out of 23 patients with lower level activation patterns or no activation had a negative outcome. Taking etiology into account for VS/UWS patients, a higher positive predictive value was assigned to traumatic patients, i.e., up to 92% (12/13) patients with higher level activation pattern achieved good recovery whereas 11 out of 13 (85%) non-traumatic patients with lower level activation or without activation had a negative clinical outcome. The reported data from visual analysis of fMRI activation patterns were corroborated using ROC curve analysis, which supported the correlation between auditory cortex activation volume and VS/UWS patients' recovery. The average brain activity overlap in primary and secondary auditory cortices in patients scanned twice was 52%. CONCLUSIONS: The activation type and volume in auditory cortex elicited by SON-FV significantly correlated with VS/UWS patients' prognosis, particularly in patients with traumatic etiology, however, this could not be established in MCS patients. Repeated use of this simple fMRI task might help obtain more reliable prognostic information.