CONNECT-ME: CONsciousness in NEurocritical Care cohorT Study Using fMRI and EEG View Homepage


Ontology type: schema:MedicalStudy     


Clinical Trial Info

YEARS

2017-2022

ABSTRACT

Detecting preserved consciousness in brain-injured patients by traditional clinical means requires presence of motor function. Otherwise, patients may be erroneously classified as being in a vegetative state. In order to circumvent the need for motor function, paradigms using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have been developed. According to a recent meta-analysis, 15% of patients with a clinical diagnosis of vegetative state can follow commands by performing mental imaginary tasks, strongly suggesting they are indeed conscious. This is of utmost importance for prognosis, treatment, and resource allocation. However, consciousness paradigms are usually employed in rehabilitation medicine. Therefore, opportunities to optimize patient outcome at an early stage may be lost. As a novel approach, the CONsciousness in NEurocritical Care cohorT study using fMRI and EEG (CONNECT-ME) will import the full range of consciousness paradigms into neurocritical care. The investigators aim to assess patients with acute brain injury for preserved consciousness by serial multimodal evaluations using active, passive and resting state fMRI- and EEG-based paradigms. A prospective longitudinal database and a biobank for genomic and metabolomic research will be established. This approach will add essential clinical information, including detection of preserved consciousness in patients previously thought of as unconscious. Due to its complexity, this project is divided into nine work packages. Eventually, the investigators will have established a clinical service for the systematic assessment of covert consciousness, as well as an interdisciplinary research group dedicated to the neuronal mechanisms by which consciousness recovers after acute brain injury. Detailed Description Searching for consciousness in non-communicating brain-injured patients by clinical examination is essential, yet challenging. The origin of many clinical signs is not entirely clear and their significance as to whether or not the patient is conscious is even less certain. In addition, consciousness may wax and wane within seconds to hours and days to months. Indeed, as many as 40% of patients with disorders of consciousness (DoC) are misclassified as being in a vegetative state (VS). Although these patients may not show any signs of consciousness during clinical examination because of lost motor output, some are able to willfully modulate their brain activity on command, occasionally even answering yes or no questions by performing mental imagery tasks. For patients with acute brain injury and their caregivers, this has significant ethical and practical implications, not least for prognostication, treatment decisions, resource allocation and end-of-life considerations. Technologies based on functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG) have been developed during the last two decades to assist clinical evaluation of patients in VS and minimal conscious states (MCS). There are three main approaches to test for preserved consciousness: (i) Active paradigms in which patients are required to execute cognitive tasks, as outlined above, (ii) passive paradigms relying on the documentation of preserved large-scale functional cortical connectivity, following an external stimulus, and (iii) resting state conditions in which assumptions about the patient's conscious state are made by extrapolation from patterns of spontaneous brain activity. Consciousness paradigms offer exciting opportunities but so far they have been almost exclusively employed in rehabilitation medicine, addressing patients with chronic brain disorders, typically several years following onset of the injury. Moreover, these studies have mainly been restricted to spot assessments, not taking into account that consciousness fluctuates over time. In addition, important methodological issues remain, including uncertainties about the specificity and sensitivity of the different paradigms and about their applicability in brain disorders of various etiologies. Lastly, almost all studies until now have employed either fMRI- or EEG-based paradigms, although the two modalities do not necessarily yield identical results in a given patient but rather complement each other. As the investigators have recently pointed out in a review and meta-analysis, systematic evaluation of the similarities and differences of these technologies is essential, preferentially by multimodal serial assessments. In the present protocol, as a novel approach the investigators will focus on the evaluation of consciousness in patients in the acute phase of brain injury. The aim is to establish, validate and improve fMRI- and EEG-based consciousness paradigms in intensive care (ICU) and step down units. This will assist clinicians in more precisely estimating the level of consciousness in various acute disorders of the brain. The project will comprise a multidisciplinary approach including expertise from neurology, clinical neurophysiology, anesthesiology and functional neuroimaging. The investigators hypothesize that serial multimodal assessments better reflect changing levels of consciousness than single unimodal evaluations. Within the next two to three years, the investigators wish to establish a full clinical service and a fruitful research milieu covering the entire spectrum of fMRI- and EEG-based consciousness paradigms in acute brain injury. The ability to identify preserved cognitive abilities following acute brain injury is of utmost importance to improve diagnosis, to guide therapeutic decisions and to better predict outcome in non-responsive patients. Eventually, the present research project will lead to more efficient decision making in neurocritical care, thereby optimizing resource allocation and improving quality of life in survivors with acute brain injury. Study Design: Due to its complexity, this project is divided into 3 phases, including 9 work packages. - During the first phase of the project the investigators aim to set up the different parts of consciousness testing, that is, clinical rating scales; fMRI-based active, passive and resting state paradigms; and EEG-based active, passive and resting state paradigms. This will be done step by step and in a pragmatic manner according to local requirements and resources. To this end, a prospective, longitudinal database will be set up, collecting all relevant clinical, neurophysiological and imaging data, as well as a biobank for cerebrospinal fluid and blood samples (work packages 1-7). - During the second phase of the project the investigators wish to combine all diagnostic parts and to implement them simultaneously using a convenience sample of suitable non-communicating patients with acute brain injury (n=20) at the neurological and neurosurgical ICU and step down units, Rigshospitalet, Copenhagen University Hospital. These patients will be tested for the presence of preserved consciousness and cognitive abilities with the full range of fMRI- and EEG-based consciousness paradigms, as well as standardized bedside examination and clinical rating scales (work package 8). - In the third phase of the project the investigators wish to develop a full clinical service for the evaluation of patients with DoC following acute and sub-acute brain injury, including comprehensive neurological evaluation and fMRI- and EEG-based consciousness paradigms, and to build the infrastructure for a fruitful research activity in the future (work package 9). Detailed and regularly updated procedures for each work package are provided in the Amendments to the Study Protocol (see below). - Work package 1 (resting state fMRI; systematic clinical examination): The investigators will start by evaluating a convenience sample of DoC patients with acute brain injury (n=10), admitted to the ICU and/or neurological and neurosurgical step down units at Rigshospitalet, using resting state fMRI, since a relevant protocol is already available at the institution. A systems-level approach, including assessment of the auditory and default mode networks, will be used as described earlier. At the same time, the investigators will establish a systematic clinical examination protocol, including - but not limited to - the Full Outline of UnResponsiveness (FOUR) and Coma Recovery Scale-Revised (CRS-R). Exclusion criteria include contraindications for examination by MRI, severe cardiorespiratory compromise and similar acutely life-threatening conditions, evidence of severe pre-morbid neurological deficits such as aphasia or deafness, lack of Danish or English language proficiency, age less than 16 years, and patients without evidence of intact primary auditory and sensory cortex function as revealed by pretest screening with brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP). The investigators will aim for un-sedated patients; however, if patients cannot be weaned from sedation, the level of sedation will be lowered to the lowest possible level in order to maximize the chance of detecting the presence of consciousness. - Work package 2 (clinical database): In order to maximize the learning effect at the present institution and to facilitate research, all relevant clinical, neurophysiological and imaging data will be collected in a comprehensive longitudinal database. Clinical outcome data will be assessed, either by telephone interview or during follow up visits, using established rating scales (e.g. modified Rankin Scale (mRS), Barthel index) at hospital discharge and at 3, respectively, 12 months. Approval to establish this database and to distribute information derived from it by means of scientific publication will be obtained according to current legislation from the Danish authorities Datatilsynet (The Danish Data Protection Agency) and Sundhedsstyrelsen (The National Board of Health). - Work package 3 (active fMRI paradigms): The investigators will establish an active fMRI paradigm by means of visual imaginary tasks (playing tennis, navigating in a familiar surrounding) as described earlier, using a similar convenience sample (n=5-10) as in work package 1. Patients will be clinically evaluated on a daily basis, including 30 min prior to and after each fMRI assessment, in order to capture fluctuations in consciousness levels as accurately as possible. Prior to inclusion, patients will be examined by brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP) in order to ensure intact primary auditory and sensory cortex integrity. - Work package 4 (passive fMRI paradigms): The investigators wish to set up a passive fMRI paradigm using two oddball paradigms ("subject's own name", respectively, semantic ambiguity), and we will assess patients (n=5-10) clinically and neurophysiologically (BAEP, SSEP) as outlined above. - Work package 5 (resting state EEG): In order to correlate resting state EEG with clinical outcome data, the investigators will assess a historical EEG database, available at the Department of Clinical Neurophysiology, Rigshospitalet, for EEG complexity and other advanced EEG measures following acute brain injury 18. - Work package 6 (active EEG paradigms): Similar to fMRI, the investigators will establish an active EEG paradigm using visual imaginary tasks (playing tennis, navigating in a familiar surrounding) as described earlier (Cruse et al. 2011). Clinical evaluation of patients (n=5-10) will be performed as outlined previously. - Work package 7 (passive EEG paradigms): The investigators will set up passive EEG paradigms using oddball paradigms ("subject's own name", respectively, semantic ambiguity) as described previously. As cognitive correlates we will accept P300 and more prolonged evoked potentials, as well as more elaborate measures such as EEG complexity. Clinical evaluation of patients (n=5-10) will be performed as previously described. - Work package 8 (consecutive sample assessed by full range of fMRI- and EEG-paradigms): In this work package, corresponding to the second phase of the project, the investigators wish to combine all consciousness measures in order to systematically and comprehensively evaluate consciousness in each acute brain injury patient, using the full range of clinical assessments as well as active, passive and resting state fMRI- and EEG-based paradigms. The investigators aim for 20 consecutive TBI and/or non-TBI non-communicating DoC patients admitted to the neurological and neurosurgical ICU or step down units (inclusion criteria). Prior to inclusion, primary auditory and sensory cortex integrity will be verified using BAEP and SSEP. Exclusion criteria will include those referred to in work package 1. - Work package 9 (full clinical service; biobank): Once the investigators have shown that comprehensive fMRI- and EEG-based consciousness paradigms are feasible in patients with acute brain injury in the ICU and intermediate care units, they wish to establish a full clinical service and a national referral center for the evaluation of DoC patients following acute brain injury. In addition, the investigators will set up a biobank for cerebrospinal fluid and blood samples for potential future studies related to genomics and metabolomics. Together this will lay the foundation for a fruitful research milieu (phase 3). More... »

URL

https://clinicaltrials.gov/show/NCT02644265

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    "description": "Detecting preserved consciousness in brain-injured patients by traditional clinical means requires presence of motor function. Otherwise, patients may be erroneously classified as being in a vegetative state. In order to circumvent the need for motor function, paradigms using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have been developed. According to a recent meta-analysis, 15% of patients with a clinical diagnosis of vegetative state can follow commands by performing mental imaginary tasks, strongly suggesting they are indeed conscious. This is of utmost importance for prognosis, treatment, and resource allocation. However, consciousness paradigms are usually employed in rehabilitation medicine. Therefore, opportunities to optimize patient outcome at an early stage may be lost. 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There are three main approaches to test for preserved consciousness: (i) Active paradigms in which patients are required to execute cognitive tasks, as outlined above, (ii) passive paradigms relying on the documentation of preserved large-scale functional cortical connectivity, following an external stimulus, and (iii) resting state conditions in which assumptions about the patient's conscious state are made by extrapolation from patterns of spontaneous brain activity. Consciousness paradigms offer exciting opportunities but so far they have been almost exclusively employed in rehabilitation medicine, addressing patients with chronic brain disorders, typically several years following onset of the injury. Moreover, these studies have mainly been restricted to spot assessments, not taking into account that consciousness fluctuates over time. In addition, important methodological issues remain, including uncertainties about the specificity and sensitivity of the different paradigms and about their applicability in brain disorders of various etiologies. Lastly, almost all studies until now have employed either fMRI- or EEG-based paradigms, although the two modalities do not necessarily yield identical results in a given patient but rather complement each other. As the investigators have recently pointed out in a review and meta-analysis, systematic evaluation of the similarities and differences of these technologies is essential, preferentially by multimodal serial assessments. In the present protocol, as a novel approach the investigators will focus on the evaluation of consciousness in patients in the acute phase of brain injury. The aim is to establish, validate and improve fMRI- and EEG-based consciousness paradigms in intensive care (ICU) and step down units. This will assist clinicians in more precisely estimating the level of consciousness in various acute disorders of the brain. The project will comprise a multidisciplinary approach including expertise from neurology, clinical neurophysiology, anesthesiology and functional neuroimaging. The investigators hypothesize that serial multimodal assessments better reflect changing levels of consciousness than single unimodal evaluations. Within the next two to three years, the investigators wish to establish a full clinical service and a fruitful research milieu covering the entire spectrum of fMRI- and EEG-based consciousness paradigms in acute brain injury. The ability to identify preserved cognitive abilities following acute brain injury is of utmost importance to improve diagnosis, to guide therapeutic decisions and to better predict outcome in non-responsive patients. Eventually, the present research project will lead to more efficient decision making in neurocritical care, thereby optimizing resource allocation and improving quality of life in survivors with acute brain injury. Study Design: Due to its complexity, this project is divided into 3 phases, including 9 work packages. - During the first phase of the project the investigators aim to set up the different parts of consciousness testing, that is, clinical rating scales; fMRI-based active, passive and resting state paradigms; and EEG-based active, passive and resting state paradigms. This will be done step by step and in a pragmatic manner according to local requirements and resources. To this end, a prospective, longitudinal database will be set up, collecting all relevant clinical, neurophysiological and imaging data, as well as a biobank for cerebrospinal fluid and blood samples (work packages 1-7). - During the second phase of the project the investigators wish to combine all diagnostic parts and to implement them simultaneously using a convenience sample of suitable non-communicating patients with acute brain injury (n=20) at the neurological and neurosurgical ICU and step down units, Rigshospitalet, Copenhagen University Hospital. These patients will be tested for the presence of preserved consciousness and cognitive abilities with the full range of fMRI- and EEG-based consciousness paradigms, as well as standardized bedside examination and clinical rating scales (work package 8). - In the third phase of the project the investigators wish to develop a full clinical service for the evaluation of patients with DoC following acute and sub-acute brain injury, including comprehensive neurological evaluation and fMRI- and EEG-based consciousness paradigms, and to build the infrastructure for a fruitful research activity in the future (work package 9). Detailed and regularly updated procedures for each work package are provided in the Amendments to the Study Protocol (see below). - Work package 1 (resting state fMRI; systematic clinical examination): The investigators will start by evaluating a convenience sample of DoC patients with acute brain injury (n=10), admitted to the ICU and/or neurological and neurosurgical step down units at Rigshospitalet, using resting state fMRI, since a relevant protocol is already available at the institution. A systems-level approach, including assessment of the auditory and default mode networks, will be used as described earlier. At the same time, the investigators will establish a systematic clinical examination protocol, including - but not limited to - the Full Outline of UnResponsiveness (FOUR) and Coma Recovery Scale-Revised (CRS-R). Exclusion criteria include contraindications for examination by MRI, severe cardiorespiratory compromise and similar acutely life-threatening conditions, evidence of severe pre-morbid neurological deficits such as aphasia or deafness, lack of Danish or English language proficiency, age less than 16 years, and patients without evidence of intact primary auditory and sensory cortex function as revealed by pretest screening with brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP). The investigators will aim for un-sedated patients; however, if patients cannot be weaned from sedation, the level of sedation will be lowered to the lowest possible level in order to maximize the chance of detecting the presence of consciousness. - Work package 2 (clinical database): In order to maximize the learning effect at the present institution and to facilitate research, all relevant clinical, neurophysiological and imaging data will be collected in a comprehensive longitudinal database. Clinical outcome data will be assessed, either by telephone interview or during follow up visits, using established rating scales (e.g. modified Rankin Scale (mRS), Barthel index) at hospital discharge and at 3, respectively, 12 months. Approval to establish this database and to distribute information derived from it by means of scientific publication will be obtained according to current legislation from the Danish authorities Datatilsynet (The Danish Data Protection Agency) and Sundhedsstyrelsen (The National Board of Health). - Work package 3 (active fMRI paradigms): The investigators will establish an active fMRI paradigm by means of visual imaginary tasks (playing tennis, navigating in a familiar surrounding) as described earlier, using a similar convenience sample (n=5-10) as in work package 1. Patients will be clinically evaluated on a daily basis, including 30 min prior to and after each fMRI assessment, in order to capture fluctuations in consciousness levels as accurately as possible. Prior to inclusion, patients will be examined by brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP) in order to ensure intact primary auditory and sensory cortex integrity. - Work package 4 (passive fMRI paradigms): The investigators wish to set up a passive fMRI paradigm using two oddball paradigms (\"subject's own name\", respectively, semantic ambiguity), and we will assess patients (n=5-10) clinically and neurophysiologically (BAEP, SSEP) as outlined above. - Work package 5 (resting state EEG): In order to correlate resting state EEG with clinical outcome data, the investigators will assess a historical EEG database, available at the Department of Clinical Neurophysiology, Rigshospitalet, for EEG complexity and other advanced EEG measures following acute brain injury 18. - Work package 6 (active EEG paradigms): Similar to fMRI, the investigators will establish an active EEG paradigm using visual imaginary tasks (playing tennis, navigating in a familiar surrounding) as described earlier (Cruse et al. 2011). 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3 schema:description Detecting preserved consciousness in brain-injured patients by traditional clinical means requires presence of motor function. Otherwise, patients may be erroneously classified as being in a vegetative state. In order to circumvent the need for motor function, paradigms using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have been developed. According to a recent meta-analysis, 15% of patients with a clinical diagnosis of vegetative state can follow commands by performing mental imaginary tasks, strongly suggesting they are indeed conscious. This is of utmost importance for prognosis, treatment, and resource allocation. However, consciousness paradigms are usually employed in rehabilitation medicine. Therefore, opportunities to optimize patient outcome at an early stage may be lost. As a novel approach, the CONsciousness in NEurocritical Care cohorT study using fMRI and EEG (CONNECT-ME) will import the full range of consciousness paradigms into neurocritical care. The investigators aim to assess patients with acute brain injury for preserved consciousness by serial multimodal evaluations using active, passive and resting state fMRI- and EEG-based paradigms. A prospective longitudinal database and a biobank for genomic and metabolomic research will be established. This approach will add essential clinical information, including detection of preserved consciousness in patients previously thought of as unconscious. Due to its complexity, this project is divided into nine work packages. Eventually, the investigators will have established a clinical service for the systematic assessment of covert consciousness, as well as an interdisciplinary research group dedicated to the neuronal mechanisms by which consciousness recovers after acute brain injury. Detailed Description Searching for consciousness in non-communicating brain-injured patients by clinical examination is essential, yet challenging. The origin of many clinical signs is not entirely clear and their significance as to whether or not the patient is conscious is even less certain. In addition, consciousness may wax and wane within seconds to hours and days to months. Indeed, as many as 40% of patients with disorders of consciousness (DoC) are misclassified as being in a vegetative state (VS). Although these patients may not show any signs of consciousness during clinical examination because of lost motor output, some are able to willfully modulate their brain activity on command, occasionally even answering yes or no questions by performing mental imagery tasks. For patients with acute brain injury and their caregivers, this has significant ethical and practical implications, not least for prognostication, treatment decisions, resource allocation and end-of-life considerations. Technologies based on functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG) have been developed during the last two decades to assist clinical evaluation of patients in VS and minimal conscious states (MCS). There are three main approaches to test for preserved consciousness: (i) Active paradigms in which patients are required to execute cognitive tasks, as outlined above, (ii) passive paradigms relying on the documentation of preserved large-scale functional cortical connectivity, following an external stimulus, and (iii) resting state conditions in which assumptions about the patient's conscious state are made by extrapolation from patterns of spontaneous brain activity. Consciousness paradigms offer exciting opportunities but so far they have been almost exclusively employed in rehabilitation medicine, addressing patients with chronic brain disorders, typically several years following onset of the injury. Moreover, these studies have mainly been restricted to spot assessments, not taking into account that consciousness fluctuates over time. In addition, important methodological issues remain, including uncertainties about the specificity and sensitivity of the different paradigms and about their applicability in brain disorders of various etiologies. Lastly, almost all studies until now have employed either fMRI- or EEG-based paradigms, although the two modalities do not necessarily yield identical results in a given patient but rather complement each other. As the investigators have recently pointed out in a review and meta-analysis, systematic evaluation of the similarities and differences of these technologies is essential, preferentially by multimodal serial assessments. In the present protocol, as a novel approach the investigators will focus on the evaluation of consciousness in patients in the acute phase of brain injury. The aim is to establish, validate and improve fMRI- and EEG-based consciousness paradigms in intensive care (ICU) and step down units. This will assist clinicians in more precisely estimating the level of consciousness in various acute disorders of the brain. The project will comprise a multidisciplinary approach including expertise from neurology, clinical neurophysiology, anesthesiology and functional neuroimaging. The investigators hypothesize that serial multimodal assessments better reflect changing levels of consciousness than single unimodal evaluations. Within the next two to three years, the investigators wish to establish a full clinical service and a fruitful research milieu covering the entire spectrum of fMRI- and EEG-based consciousness paradigms in acute brain injury. The ability to identify preserved cognitive abilities following acute brain injury is of utmost importance to improve diagnosis, to guide therapeutic decisions and to better predict outcome in non-responsive patients. Eventually, the present research project will lead to more efficient decision making in neurocritical care, thereby optimizing resource allocation and improving quality of life in survivors with acute brain injury. Study Design: Due to its complexity, this project is divided into 3 phases, including 9 work packages. - During the first phase of the project the investigators aim to set up the different parts of consciousness testing, that is, clinical rating scales; fMRI-based active, passive and resting state paradigms; and EEG-based active, passive and resting state paradigms. This will be done step by step and in a pragmatic manner according to local requirements and resources. To this end, a prospective, longitudinal database will be set up, collecting all relevant clinical, neurophysiological and imaging data, as well as a biobank for cerebrospinal fluid and blood samples (work packages 1-7). - During the second phase of the project the investigators wish to combine all diagnostic parts and to implement them simultaneously using a convenience sample of suitable non-communicating patients with acute brain injury (n=20) at the neurological and neurosurgical ICU and step down units, Rigshospitalet, Copenhagen University Hospital. These patients will be tested for the presence of preserved consciousness and cognitive abilities with the full range of fMRI- and EEG-based consciousness paradigms, as well as standardized bedside examination and clinical rating scales (work package 8). - In the third phase of the project the investigators wish to develop a full clinical service for the evaluation of patients with DoC following acute and sub-acute brain injury, including comprehensive neurological evaluation and fMRI- and EEG-based consciousness paradigms, and to build the infrastructure for a fruitful research activity in the future (work package 9). Detailed and regularly updated procedures for each work package are provided in the Amendments to the Study Protocol (see below). - Work package 1 (resting state fMRI; systematic clinical examination): The investigators will start by evaluating a convenience sample of DoC patients with acute brain injury (n=10), admitted to the ICU and/or neurological and neurosurgical step down units at Rigshospitalet, using resting state fMRI, since a relevant protocol is already available at the institution. A systems-level approach, including assessment of the auditory and default mode networks, will be used as described earlier. At the same time, the investigators will establish a systematic clinical examination protocol, including - but not limited to - the Full Outline of UnResponsiveness (FOUR) and Coma Recovery Scale-Revised (CRS-R). Exclusion criteria include contraindications for examination by MRI, severe cardiorespiratory compromise and similar acutely life-threatening conditions, evidence of severe pre-morbid neurological deficits such as aphasia or deafness, lack of Danish or English language proficiency, age less than 16 years, and patients without evidence of intact primary auditory and sensory cortex function as revealed by pretest screening with brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP). The investigators will aim for un-sedated patients; however, if patients cannot be weaned from sedation, the level of sedation will be lowered to the lowest possible level in order to maximize the chance of detecting the presence of consciousness. - Work package 2 (clinical database): In order to maximize the learning effect at the present institution and to facilitate research, all relevant clinical, neurophysiological and imaging data will be collected in a comprehensive longitudinal database. Clinical outcome data will be assessed, either by telephone interview or during follow up visits, using established rating scales (e.g. modified Rankin Scale (mRS), Barthel index) at hospital discharge and at 3, respectively, 12 months. Approval to establish this database and to distribute information derived from it by means of scientific publication will be obtained according to current legislation from the Danish authorities Datatilsynet (The Danish Data Protection Agency) and Sundhedsstyrelsen (The National Board of Health). - Work package 3 (active fMRI paradigms): The investigators will establish an active fMRI paradigm by means of visual imaginary tasks (playing tennis, navigating in a familiar surrounding) as described earlier, using a similar convenience sample (n=5-10) as in work package 1. Patients will be clinically evaluated on a daily basis, including 30 min prior to and after each fMRI assessment, in order to capture fluctuations in consciousness levels as accurately as possible. Prior to inclusion, patients will be examined by brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP) in order to ensure intact primary auditory and sensory cortex integrity. - Work package 4 (passive fMRI paradigms): The investigators wish to set up a passive fMRI paradigm using two oddball paradigms ("subject's own name", respectively, semantic ambiguity), and we will assess patients (n=5-10) clinically and neurophysiologically (BAEP, SSEP) as outlined above. - Work package 5 (resting state EEG): In order to correlate resting state EEG with clinical outcome data, the investigators will assess a historical EEG database, available at the Department of Clinical Neurophysiology, Rigshospitalet, for EEG complexity and other advanced EEG measures following acute brain injury 18. - Work package 6 (active EEG paradigms): Similar to fMRI, the investigators will establish an active EEG paradigm using visual imaginary tasks (playing tennis, navigating in a familiar surrounding) as described earlier (Cruse et al. 2011). Clinical evaluation of patients (n=5-10) will be performed as outlined previously. - Work package 7 (passive EEG paradigms): The investigators will set up passive EEG paradigms using oddball paradigms ("subject's own name", respectively, semantic ambiguity) as described previously. As cognitive correlates we will accept P300 and more prolonged evoked potentials, as well as more elaborate measures such as EEG complexity. Clinical evaluation of patients (n=5-10) will be performed as previously described. - Work package 8 (consecutive sample assessed by full range of fMRI- and EEG-paradigms): In this work package, corresponding to the second phase of the project, the investigators wish to combine all consciousness measures in order to systematically and comprehensively evaluate consciousness in each acute brain injury patient, using the full range of clinical assessments as well as active, passive and resting state fMRI- and EEG-based paradigms. The investigators aim for 20 consecutive TBI and/or non-TBI non-communicating DoC patients admitted to the neurological and neurosurgical ICU or step down units (inclusion criteria). Prior to inclusion, primary auditory and sensory cortex integrity will be verified using BAEP and SSEP. Exclusion criteria will include those referred to in work package 1. - Work package 9 (full clinical service; biobank): Once the investigators have shown that comprehensive fMRI- and EEG-based consciousness paradigms are feasible in patients with acute brain injury in the ICU and intermediate care units, they wish to establish a full clinical service and a national referral center for the evaluation of DoC patients following acute brain injury. In addition, the investigators will set up a biobank for cerebrospinal fluid and blood samples for potential future studies related to genomics and metabolomics. Together this will lay the foundation for a fruitful research milieu (phase 3).
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