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Future studies should also assess the view of the most important stakeholder, next to the patient, and that is the (pediatric) patient's parent. Physicians' attitudes towards ethical issues and end-of-life decision-making for pediatric patients with unresponsive wakefulness syndrome: An international survey. [Extracted from the article]

Introduction: In case of untreatable suffering at the end of life, continuous sedation until death (CSD) may be the only treatment option left. Because these patients cannot communicate anymore, caregivers have to rely on behavioral observation to assess the patient's comfort. Recently, however, a number of studies from the neurosciences have shown that sometimes consciousness and pain are undetectable with these traditional behavioral methods. The aim of this study was to find out if subjective caregiver assessments of consciousness and pain would be confirmed by objective neurophysiological measures. Methods: In this prospective observational study, we observed patients from the start of palliative sedation until death. Subjective caregiver assessments of level of consciousness and pain based on behavioral observations were compared with objective measures from neurophysiological monitoring devices. Results: We collected and analyzed 108 subjective caregiver assessments in a sample of 12 patients and 32 assessments by traditionally used observational scales. We compared these with objective neurophysiological measures. Sensitivity and specificity of caregivers' subjective assessments of consciousness was 23.6 and 91.1% respectively, with an accuracy of 54.0% and interrater reliability (κ) of 0.13. For pain, this was 0 and 94.79%, respectively, an accuracy of 88%, and an inter-rater reliability (κ) of − 0.063. Agreement between caregivers' subjective assessments and objective neurophysiological measures of consciousness and pain was very poor. Conclusions: Caregivers' subjective assessment of level of consciousness and pain during CSD is unreliable compared with objective neurophysiological monitoring. Our results suggest that assessments of patient comfort during CSD could have been improved substantially by including objective monitoring of level of consciousness and pain. Trial Registration: The protocol for this observational study has been registered retrospectively at Clinical-Trials.gov (ID NCT03273244). [ABSTRACT FROM AUTHOR]

Background: Awareness and pain during palliative sedation is typically assessed by observational scales, but the use of such scales has been put into question. Case presentation: A woman in her mid-80s was admitted to a palliative care unit, presenting with chronic lymphatic leukemia, depression, and a cerebrovascular accident, with right-sided hemiplegia and aphasia. The patient was unable to eat and was suffering from nausea and vomiting. Before admission, the patient had expressed her desire to discontinue treatment on several occasions. Case management: The decision was made to initiate palliative sedation. The patient consented to take part in a study to assess level of comfort and pain using two monitoring devices (NeuroSense monitor and Analgesia Nociception Index monitor). Case outcome: The patient died 90 h after initiation of palliative sedation. Titration of the medication was challenging and sedation was not deep enough during the first 2 days. Thirteen assessments made with the Ramsay Sedation Scale showed that the patient was considered to be in a deep sleep, while in fact the NeuroSense monitor indicated otherwise. Conclusion: This case demonstrates the feasibility and potential advantages of using monitoring devices to objectify assessments of pain and discomfort in palliatively sedated patients. [ABSTRACT FROM AUTHOR]

Spasticity is a motor disorder frequently encountered after a lesion involving the central nervous system. It is hypothesized to arise from an anarchic reorganization of the pyramidal and parapyramidal fibers and leads to hypertonia and hyperreflexia of the affected muscular groups. While this symptom and its management is well-known in patients suffering from stroke, multiple sclerosis or spinal cord lesion, little is known regarding its appropriate management in patients presenting disorders of consciousness after brain damage. Objectives: Our aim was to review the occurrence of spasticity in patients with disorders of consciousness and the therapeutic interventions used to treat it. Methods: We conducted a systematic review using the PubMed online database. It returned 157 articles. After applying our inclusion criteria (i.e., studies about patients in coma, unresponsive wakefulness syndrome or minimally conscious state, with spasticity objectively reported as a primary or secondary outcome), 18 studies were fully reviewed. Results: The prevalence of spasticity in patients with disorders of consciousness ranged from 59% to 89%. Current treatment options include intrathecal baclofen and soft splints. Several treatment options still need further investigation; including acupuncture, botulin toxin or cortical activation by thalamic stimulation. Conclusion: The small number of articles available in the current literature highlights that spasticity is poorly studied in patients with disorders of consciousness although it is one of the most common motor disorders. While treatments such as intrathecal baclofen and soft splints seem effective, large randomized controlled trials have to be done and new therapeutic options should be explored. [ABSTRACT FROM AUTHOR]

The article focuses on the attitudes of the healthcare providers towards the medico-ethical issues associated with non-communicating patients. Topics discussed include the healthcare providers' attitude towards the end-of-life and pain management of patients with consciousness disorder and locked-in syndrome, the taxonomy of consciousness disorders, and the technology-based detection of awareness.

Keywords: consciousness; islands of awareness; cortical complexity EN consciousness islands of awareness cortical complexity 545 546 2 07/25/20 20200801 NES 200801 Bayne et al. (2020) [1] envision the fascinating possibility that disconnected hemispheres (through hemispherotomy), ex cranio brains, and cerebral organoids may be islands of awareness (IOAs). Perhaps Bayne et al.[1] do not refer to subjective experience when speaking about consciousness in IOAs. Even if we accept the possibility of reducing consciousness to a certain measure of cortical complexity, we are still faced with the problem of defining a set of values consistent with consciousness. [Extracted from the article]

Recently, neuroscientists and clinicians have seen the rapid evolution of diagnoses in disorders of consciousness. The unresponsive wakefulness syndrome--vegetative state, the minimally conscious state plus and minus, and the functional locked-in syndrome have been defined using new neuroimaging techniques. Diffusion tensor imaging, positron emission tomography, functional magnetic resonance imaging, electroen- cephalography, and transcranial magnetic stimulation techniques have all promoted important discoveries in the field of disorders of consciousness. This has led to a better understanding of these patients' condition and to the development of new prognosis, therapeutic, and communication tools. However, low sensitivity and artifacts problems need to be solved to bring these new technologies to the single-patient level; they also need to be studied in larger scale and randomized control trials. In addition, new ethics questions have arisen and need to be investigated. [ABSTRACT FROM AUTHOR]

Abstract: The past 15years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behavioral evidence of conscious awareness may retain critical cognitive capacities and the first scientific demonstrations that some patients, with severely injured brains and very longstanding conditions of limited behavioral responsiveness, may nonetheless harbor latent capacities for significant recovery. Included among such capacities are particularly human functions of language and higher-level cognition that either spontaneously or through direct interventions may reemerge even at long time intervals or remain unrecognized. Collectively, these observations have reframed scientific inquiry and further led to important new insights into mechanisms underlying consciousness in the human brain. These studies support a model of consciousness as the emergent property of the collective behavior of widespread frontoparietal network connectivity modulated by specific forebrain circuit mechanisms. We here review these advances in measurement and the scientific and broader implications of this rapidly progressing field of research. [Copyright &y& Elsevier]

The article presents a clinical review of the condition called vegetative state. The causes of the condition include traumatic or non-traumatic brain injury and Alzheimer's disease. It is characterised by an apparent dissociation between awareness and wakefulness, which are the two major elements of consciousness. The three main clinical features of vegetative state are cited, as well as its causes. Information is also presented on the factors that affect prognosis in patients with a diagnosis of vegetative state and the occurrence of misdiagnosis.

Background: Some patients awaken from coma (that is, open the eyes) but remain unresponsive (that is, only showing reflex movements without response to command). This syndrome has been coined vegetative state. We here present a new name for this challenging neurological condition: unresponsive wakefulness syndrome (abbreviated UWS). Discussion: Many clinicians feel uncomfortable when referring to patients as vegetative. Indeed, to most of the lay public and media vegetative state has a pejorative connotation and seems inappropriately to refer to these patients as being vegetable-like. Some political and religious groups have hence felt the need to emphasize these vulnerable patients' rights as human beings. Moreover, since its first description over 35 years ago, an increasing number of functional neuroimaging and cognitive evoked potential studies have shown that physicians should be cautious to make strong claims about awareness in some patients without behavioral responses to command. Given these concerns regarding the negative associations intrinsic to the term vegetative state as well as the diagnostic errors and their potential effect on the treatment and care for these patients (who sometimes never recover behavioral signs of consciousness but often recover to what was recently coined a minimally conscious state) we here propose to replace the name. Conclusion: Since after 35 years the medical community has been unsuccessful in changing the pejorative image associated with the words vegetative state, we think it would be better to change the term itself. We here offer physicians the possibility to refer to this condition as unresponsive wakefulness syndrome or UWS. As this neutral descriptive term indicates, it refers to patients showing a number of clinical signs (hence syndrome) of unresponsiveness (that is, without response to commands) in the presence of wakefulness (that is, eye opening). [ABSTRACT FROM AUTHOR]

Abstract: The clinical and para-clinical examination of residual self-consciousness in non-communicative severely brain damaged patients (i.e., coma, vegetative state and minimally conscious state) remains exceptionally challenging. Passive presentation of the patient’s own name and own face are known to be effective attention-grabbing stimuli when clinically assessing consciousness at the patient’s bedside. Event-related potential and functional neuroimaging studies using such self-referential stimuli are currently being used to disentangle the cognitive hierarchy of self-processing. We here review neuropsychological, neuropathological, electrophysiological and neuroimaging studies using the own name and own face paradigm obtained in conscious waking, sleep, pharmacological coma, pathological coma and related disorders of consciousness. Based on these results we discuss what we currently do and do not know about the functional significance of the neural network involved in “automatic” and “conscious” self-referential processing. [Copyright &y& Elsevier]

Consciousness has two main components: wakefulness and awareness. The vegetative state is characterized by wakefulness without awareness. Recent functional neuroimaging results have shown that some parts of the cortex are still functioning in ‘vegetative’ patients. External stimulation, such as a painful stimulus, still activates ‘primary’ sensory cortices in these patients but these areas are functionally disconnected from ‘higher order’ associative areas needed for awareness. Such studies are disentangling the neural correlates of the vegetative state from the minimally conscious state, and have major clinical consequences in addition to empirical importance for the understanding of consciousness. [Copyright &y& Elsevier]

The concept of death has evolved as technology has progressed. This has forced medicine and society to redefine its ancient cardiorespiratory centred diagnosis to a neurocentric diagnosis of death. The apparent consensus about the definition of death has not yet appeased all controversy. Ethical, moral and religious concerns continue to surface and include a prevailing malaise about possible expansions of the definition of death to encompass the vegetative state or about the feared bias of formulating criteria so as to facilitate organ transplantation. [ABSTRACT FROM AUTHOR]

The interest of functional imaging in patients in a vegetative state is twofold. First, the vegetative state continues to represent a major clinical and ethical problem, in terms of diagnosis, prognosis, treatment, everyday management and end-of-life decisions. Second, it offers a lesional approach to the study of human consciousness and adds to the international research effort on identifying the neural correlate of consciousness. Cerebral metabolism has been shown to be massively reduced in the vegetative state. However, recovery of consciousness from vegetative state seems not always associated with substantial changes in global metabolism. Recent PET data indicate that some vegetative patients are unconscious not just because of a global loss of neuronal function, but due to an altered activity in a critical fronto-parietal cortical network and to abolished functional connections within this network and with non-specific thalamic nuclei. Recovery of consciousness was shown to be paralleled by a restoration of this cortico-thalamo-cortical interaction. Despite the metabolic impairment, external stimulation still induces neuronal activation as shown by both auditory and noxious stimuli. However, this activation is limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. [ABSTRACT FROM AUTHOR]

In rats, the firing sequences observed in hippocampal ensembles during spatial learning are replayed during subsequent sleep, suggesting a role for posttraining sleep periods in the offline processing of spatial memories. Here, using regional cerebral blood flow measurements, we show that, in humans, hippocampal areas that are activated during route learning in a virtual town are likewise activated during subsequent slow wave sleep. Most importantly, we found that the amount of hippocampal activity expressed during slow wave sleep positively correlates with the improvement of performance in route retrieval on the next day. These findings suggest that learning-dependent modulation in hippocampal activity during human sleep reflects the offline processing of recent episodic and spatial memory traces, which eventually leads to the plastic changes underlying the subsequent improvement in performance. [Copyright &y& Elsevier]

We review the nosological criteria and functional neuroanatomical basis for brain death, coma, vegetative state, minimally conscious state, and the locked-in state. Functional neuroimaging is providing new insights into cerebral activity in patients with severe brain damage. Measurements of cerebral metabolism and brain activations in response to sensory stimuli with PET, fMRI, and electrophysiological methods can provide information on the presence, degree, and location of any residual brain function. However, use of these techniques in people with severe brain damage is methodologically complex and needs careful quantitative analysis and interpretation. In addition, ethical frameworks to guide research in these patients must be further developed. At present, clinical examinations identify nosological distinctions needed for accurate diagnosis and prognosis. Neuroimaging techniques remain important tools for clinical research that will extend our understanding of the underlying mechanisms of these disorders. [Copyright &y& Elsevier]

We have previously shown that several brain areas are activated both during sequence learning at wake and during subsequent rapid-eye-movements (REM) sleep (Nat. Neurosci. 3 (2000) 831–836), suggesting that REM sleep participates in the reprocessing of recent memory traces in humans. However, the nature of the reprocessed information remains open. Here, we show that regional cerebral reactivation during posttraining REM sleep is not merely related to the acquisition of basic visuomotor skills during prior practice of the serial reaction time task, but rather to the implicit acquisition of the probabilistic rules that defined stimulus sequences. Moreover, functional connections between the reactivated cuneus and the striatum—the latter being critical for implicit sequence learning—are reinforced during REM sleep after practice on a probabilistic rather than on a random sequence of stimuli. Our results therefore support the hypothesis that REM sleep is deeply involved in the reprocessing and optimization of the high-order information contained in the material to be learned. In addition, we show that the level of acquisition of probabilistic rules attained prior to sleep is correlated to the increase in regional cerebral blood flow during subsequent REM sleep. This suggests that posttraining cerebral reactivation is modulated by the strength of the memory traces developed during the learning episode. Our data provide the first experimental evidence for a link between behavioral performance and cerebral reactivation during REM sleep. [Copyright &y& Elsevier]

The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans. [ABSTRACT FROM AUTHOR]

Neuroimaging studies have suggested an important role for the default mode network (DMN) in disorders of consciousness (DoC). However, the extent to which DMN connectivity can discriminate DoC states–unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS)–is less evident. Particularly, it is unclear whether effective DMN connectivity, as measured indirectly with dynamic causal modelling (DCM) of resting EEG can disentangle UWS from healthy controls and from patients considered conscious (MCS+). Crucially, this extends to UWS patients with potentially "covert" awareness (minimally conscious star, MCS*) indexed by voluntary brain activity in conjunction with partially preserved frontoparietal metabolism as measured with positron emission tomography (PET+ diagnosis; in contrast to PET- diagnosis with complete frontoparietal hypometabolism). Here, we address this gap by using DCM of EEG data acquired from patients with traumatic brain injury in 11 UWS (6 PET- and 5 PET+) and in 12 MCS+ (11 PET+ and 1 PET-), alongside with 11 healthy controls. We provide evidence for a key difference in left frontoparietal connectivity when contrasting UWS PET- with MCS+ patients and healthy controls. Next, in a leave-one-subject-out cross-validation, we tested the classification performance of the DCM models demonstrating that connectivity between medial prefrontal and left parietal sources reliably discriminates UWS PET- from MCS+ patients and controls. Finally, we illustrate that these models generalize to an unseen dataset: models trained to discriminate UWS PET- from MCS+ and controls, classify MCS* patients as conscious subjects with high posterior probability (pp >.92). These results identify specific alterations in the DMN after severe brain injury and highlight the clinical utility of EEG-based effective connectivity for identifying patients with potential covert awareness. [ABSTRACT FROM AUTHOR]

Objectives: Surrogate decision-making by family caregivers for patients with severe brain injury is influenced by the availability and understanding of relevant information and expectations for future rehabilitation. We aimed to compare the consistency of family caregivers' perceptions with clinical diagnoses and to inform their expectation of prognosis in the future. Methods: The Coma Recovery Scale-Revised was used to assess the diagnosis of inpatients with severe brain injury between February 2019 and February 2020. A main family caregiver was included per patient. The family caregiver's perception of the patient's consciousness and expectations of future recovery were collected through questionnaires and compared consistently with the clinical diagnosis. Results: The final sample included 101 main family caregivers of patients (57 UWS, unresponsive wakefulness syndrome, 37 MCS, minimally conscious state, 7 EMCS, emergence from MCS) with severe brain injury. Only 57 family caregivers correctly assessed the level of consciousness as indicated by the CRS-R, showing weak consistency (Kappa = 0.217, P = 0.002). Family caregivers' demographic characteristics and CRS-R diagnosis influenced the consistency between perception and clinical diagnosis. Family caregivers who provided hands-on care to patients showed higher levels of consistent perception (AOR = 12.24, 95% CI = 2.06-73.00, P = 0.006). Compared to UWS, the family caregivers of MCS patients were more likely to have a correct perception (OR = 7.68, 95% CI = 1.34–44.06). Family caregivers had positive expectations for patients' recovery in terms of both communication and returning to normal life. Conclusion: Nearly half of family caregivers have inadequate understanding of their relative's level of consciousness, and most of them report overly optimistic expectations that do not align with clinical diagnosis. Providing more medical information to family caregivers to support their surrogate decision-making process is essential. [ABSTRACT FROM AUTHOR]

Background: After a severe brain injury and a coma, patients may develop disorders of consciousness (DoC), frequently accompanied by severe dysphagia. The evaluation and therapy of swallowing are therefore essential aspects of their management. Objectives: This study aims to evaluate the SWallowing Assessment in Disorders of Consciousness (SWADOC) tool in the assessment of swallowing in post-comatose patients. Here, we validate its quantitative items, describe preliminary results and identify limitations. Methods: Fourteen post-comatose patients were repeatedly evaluated with the Simplified Evaluation of CONsciousness Disorders (SECONDs) and with the SWADOC. Results: The internal consistency of the oral and pharyngeal subscales of the SWADOC was good. The test–retest reliability showed that all items, all subscores and the total score were stable except for two items (endo-buccal secretions and bronchial congestion). A comparison to the Facial Oral Tract Therapy Swallowing Assessment of Saliva (F.O.T.T-SAS) confirmed that scoring with the SWADOC offers a greater potential for quantitative observations in assessing swallowing abilities among patients with DoC. The SECONDs scores and SWADOC total scores showed a significant positive correlation (τ = 0.78, p < 0.001). Conclusions: This study provides preliminary but encouraging results on the psychometric properties of the SWADOC tool. It shows that this tool is relevant and feasible as a bedside assessment of dysphagia in patients with DoC. [ABSTRACT FROM AUTHOR]

A fundamental challenge in neuroscience is accurately defining brain states and predicting how and where to perturb the brain to force a transition. Here, we investigated resting-state fMRI data of patients suffering from disorders of consciousness (DoC) after coma (minimally conscious and unresponsive wakefulness states) and healthy controls. We applied model-free and model-based approaches to help elucidate the underlying brain mechanisms of patients with DoC. The model-free approach allowed us to characterize brain states in DoC and healthy controls as a probabilistic metastable substate (PMS) space. The PMS of each group was defined by a repertoire of unique patterns (i.e., metastable substates) with different probabilities of occurrence. In the model-based approach, we adjusted the PMS of each DoC group to a causal whole-brain model. This allowed us to explore optimal strategies for promoting transitions by applying off-line in silico probing. Furthermore, this approach enabled us to evaluate the impact of local perturbations in terms of their global effects and sensitivity to stimulation, which is a model-based biomarker providing a deeper understanding of the mechanisms underlying DoC. Our results show that transitions were obtained in a synchronous protocol, in which the somatomotor network, thalamus, precuneus and insula were the most sensitive areas to perturbation. This motivates further work to continue understanding brain function and treatments of disorders of consciousness. Author summary: We studied disorders of consciousness (DoC) by defining a brain state as a repertoire of metastable substates with different probabilities of occurrence. We created whole-brain computational models of DoC to uncover the causal mechanisms underlying recovery. These models allowed us to simulate transitions by studying the effects of artificial individual local perturbations under different protocol regimes. We demonstrated successful transitions in the synchronization protocol and showed that the most sensitive areas were located in the somatomotor network, thalamus, precuneus and insula. In the long-term, this could bring valuable insights for understanding DoC and open new avenues for future clinical therapies. [ABSTRACT FROM AUTHOR]

Keywords: Continuous sedation until death; Pain assessment; Palliative medicine; Unconsciousness; Comfort assessment; Palliative sedation; Neurophysiological monitoring; Wavelet anesthetic value; Analgesia Nociception Index EN Continuous sedation until death Pain assessment Palliative medicine Unconsciousness Comfort assessment Palliative sedation Neurophysiological monitoring Wavelet anesthetic value Analgesia Nociception Index 743 746 4 05/16/22 20220601 NES 220601 To the Editor, We would like to thank Prod'homme and colleagues for their thoughtful comments on our publication [[1]]. Continuous sedation until death, Pain assessment, Palliative medicine, Unconsciousness, Comfort assessment, Palliative sedation, Neurophysiological monitoring, Wavelet anesthetic value, Analgesia Nociception Index. [Extracted from the article]

Neuroimaging techniques Diffusion tensor imaging Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique employed to estimate the axonal organization of the brain. The underdocumentation of imaging studies in children may be explained by the fact that MRI and other neuroimaging tools often require sedation in younger patients and in patients with DOC in general. Abbreviations CRS-R Coma Recovery Scale-Revised DOC disorders of consciousness DTI diffusion tensor imaging ERP event-related potential MCS minimally conscious state SEP somatosensory evoked potential SWA slow-wave activity UWS unresponsive wakefulness syndrome What this paper adds Neuroimaging and neurophysiological tools that complement clinical assessment of disorders of consciousness in children are scarce. Among these 167 children, 151 were patients meeting the criteria for DOC: 70 were in a comatose state, 51 with UWS, 29 in MCS, and one patient did not receive any clear diagnosis. [Extracted from the article]

The article discusses various reports published within the issue, including one by Athena Demertzi and colleagues on the relationship between mind and brain, another by Edward Jones on the role of thalamo-cortico-thalamic networks and assessments of coma and related disorders by Bryan Young.

Predicting the chances of recovery of consciousness and communication in patients who survive their coma but transit in a vegetative state or minimally conscious state (MCS) remains a major challenge for their medical caregivers. Very few studies have examined the slow neuronal changes underlying functional recovery of consciousness from severe chronic brain damage. A case study in this issue of the JCI reports an extraordinary recovery of functional verbal communication and motor function in a patient who remained in MCS for 19 years (see the related article beginning on page 2005). Diffusion tensor MRI showed increased fractional anisotropy (assumed to reflect myelinated fiber density) in posteromedial cortices, encompassing cuneus and precuneus. These same areas showed increased glucose metabolism as studied by PET scanning, likely reflecting the neuronal regrowth paralleling the patient's clinical recovery. This case shows that old dogmas need to be oppugned, as recovery with meaningful reduction in disability continued in this case for nearly 2 decades after extremely severe traumatic brain injury. [ABSTRACT FROM AUTHOR]

The improvement of a perceptual or motor skill continues after training has ended. The central question is whether this improvement is just a function of time or whether sleep, a certain circadian phase, or their interaction (sleep occurring in a particular circadian phase) is favorable to the reprocessing of recent memory traces. In this issue of Neuron, provide behavioral evidence that most of the improvement of a motor skill depends on nocturnal sleep. [Copyright &y& Elsevier]

Objectives: Long-term care of severe brain injury patients places a significant mental burden on family caregivers, yet few studies have reported the situation in China. We aimed to describe the mood states of family caregivers of patients with severe brain injury and examine the influencing factors that affect caregivers' moods. Methods: Cross-sectional survey was used to assess the mood profiles of Chinese family caregivers between February 2019 and February 2020. Demographic data of caregivers and patients, the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7) were used to assess the level of depressive and anxiety symptoms. The quality of life score was also assessed by a visual analog scale, and the Coma Recovery Scale-Revised was used to assess the patient's consciousness. Result: One hundred and one patients with severe brain injury (57 unresponsive wakefulness syndrome, UWS) between the age of 14 and 70 and their main family caregivers were enrolled in the study. Most caregivers displayed depressive (n = 62) and anxiety symptoms (n = 65), with 17 and 20 of these family caregivers reporting (moderately) severe depressive symptom and severe anxiety symptom, respectively. The caregiver's depressive symptom level significantly decreased as the patient's injury lasted longer (r = – 0.208, P = 0.037). Moreover, the age of the patient negatively related to the levels of depressive (r = – 0.310, P = 0.002) and anxiety symptoms (r = – 0.289, P = 0.003) in caregivers. There was a significant positive correlation between anxiety and depressive symptoms scores in family caregivers (r = 0.838, P < 0.001). The higher the level of anxiety (r = – 0.273, P = 0.006) and depressive symptoms (r = – 0.265, P = 0.007), the worse the quality of life. Conclusion: Many family caregivers of patients with severe brain injury experience various levels of anxiety and depressive symptoms in China. Tailor-made psychological help seems imperative. Researchers and doctors can provide information about patient's conditions to assist family members in discussing rehabilitation options for patients in different states of consciousness will help to ease anxiety of family caregivers. [ABSTRACT FROM AUTHOR]

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

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

Background: Over the past 5 decades, advances in neuroimaging have yielded insights into the pathophysiologic mechanisms that cause disorders of consciousness (DoC) in patients with severe brain injuries. Structural, functional, metabolic, and perfusion imaging studies have revealed specific neuroanatomic regions, such as the brainstem tegmentum, thalamus, posterior cingulate cortex, medial prefrontal cortex, and occipital cortex, where lesions correlate with the current or future state of consciousness. Advanced imaging modalities, such as diffusion tensor imaging, resting-state functional magnetic resonance imaging (fMRI), and task-based fMRI, have been used to improve the accuracy of diagnosis and long-term prognosis, culminating in the endorsement of fMRI for the clinical evaluation of patients with DoC in the 2018 US (task-based fMRI) and 2020 European (task-based and resting-state fMRI) guidelines. As diverse neuroimaging techniques are increasingly used for patients with DoC in research and clinical settings, the need for a standardized approach to reporting results is clear. The success of future multicenter collaborations and international trials fundamentally depends on the implementation of a shared nomenclature and infrastructure. Methods: To address this need, the Neurocritical Care Society's Curing Coma Campaign convened an international panel of DoC neuroimaging experts to propose common data elements (CDEs) for data collection and reporting in this field. Results: We report the recommendations of this CDE development panel and disseminate CDEs to be used in neuroimaging studies of patients with DoC. Conclusions: These CDEs will support progress in the field of DoC neuroimaging and facilitate international collaboration. [ABSTRACT FROM AUTHOR]

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

While the COVID-19 pandemic challenged the general public's health and well-being, it exacerbated the pre-existing well-being issues in the educational sector in many countries. Mindfulness-based interventions are often applied to protect and promote occupational well-being. To investigate how the well-being benefits of these interventions arise, we selected one accessible technique that is used in most of them: focused attention meditation. In the middle of the COVID-19 pandemic, 199 teachers voluntarily practiced five to ten minutes of meditation together with their pupils, every morning for six months. We employed a three-wave longitudinal design to follow any changes in the meditating teachers' well-being and compared these changes to a waitlist control condition of 42 teachers. Three dimensions of well-being were measured at baseline, half-time, and post-intervention: emotional, cognitive, and physical well-being. Latent growth curve models revealed that the meditation technique not only improves well-being but also prevents the development of well-being problems. The practice of focused attention meditation resulted in improvements in emotional and physical well-being and prevented the development of cognitive well-being problems that were observed within the control condition. The effects were strongest for emotional and cognitive well-being and followed a linear trend. This paper shows that the well-being effects of mindfulness-based interventions are at least in part due to the focused attention meditation that is practiced in them. Occupational groups that experience emotional, cognitive, or physical well-being issues can benefit from a few minutes of focused attention meditation per day. [ABSTRACT FROM AUTHOR]

Background: In case of untreatable suffering at the end of life, palliative sedation may be chosen to assure comfort by reducing the patient's level of consciousness. An important question here is whether such sedated patients are completely free of pain. Because these patients cannot communicate anymore, caregivers have to rely on observation to assess the patient's comfort. Recently however, more sophisticated techniques from the neurosciences have shown that sometimes consciousness and pain are undetectable with these traditional behavioral methods. The aim of this study is to better understand how unconscious palliative sedated patients experience the last days of their life and to find out if they are really free of pain. Methods: In this study we will observe 40 patients starting with initiation of palliative sedation until death. Assessment of comfort based on behavioral observations will be related with the results from a NeuroSense monitor, an EEG-based monitor used for evaluation of the adequacy of anesthesia and sedation in the operating room and an ECG-based Analgesia Nociception Index (ANI) monitor, which informs about comfort or discomfort condition, based on the parasympathetic tone. An innovative and challenging aspect of this study is its qualitative approach; "objective" and "subjective" data will be linked to achieve a holistic understanding of the study topic. The following data will be collected: assessment of pain/comfort by the patients themselves (if possible) by scoring a Visual Analogue Scale (VAS); brain function monitoring; monitoring of parasympathetic tone; caregivers' assessment (pain, awareness, communication); relatives' perception of the quality of the dying process; assessment by 2 trained investigators using observational scales; video and audio registration. Discussion: Measuring pain and awareness in non-communicative dying patients is both technically and ethically challenging. ANI and EEG have shown to be promising technologies to detect pain that otherwise cannot be detected with the "traditional" methods. Although these technologies have the potential to provide objective quantifiable indicators for distress and awareness in non-communicative patients, strikingly they have not yet been used to check whether the current assessments for non-communicative patients are reliable. Trial registration: The study is registered on ClinicalTrials.gov (Identifier: NCT03273244; registration date: 7.9.2017). [ABSTRACT FROM AUTHOR]

The article discusses various reports within the issue, including one by Gosseries et al. on advances in the diagnosis of disorders of consciousness, one by Kotchoubey et al. on patients in minimally conscious states and one by Habbal et al. on the use of electromyography to detect consciousness in patients with brain injury.

Following electronic publication of the above-referenced manuscript, we discovered that one of the three criteria we proposed to establish command-following in the MCS+ syndrome was inadvertently omitted in some parts of the manuscript. [ABSTRACT FROM AUTHOR]

Background: We investigated the relationship between three language-dependent behaviors (i.e., command-following, intelligible verbalization, and intentional communication) and the functional status of patients with disorders of consciousness (DoC). We hypothesized that patients in minimally conscious state (MCS) who retain behavioral evidence of preserved language function would have similar levels of functional disability, while patients who lack these behaviors would demonstrate significantly greater disability. We reasoned that these results could then be used to establish empirically-based diagnostic criteria for MCS+. Methods: In this retrospective cohort study we included rehabilitation inpatients diagnosed with DoC following severe-acquired brain injury (MCS = 57; vegetative state/unresponsive wakefulness syndrome [VS/UWS] = 63); women: 46; mean age: 47 ± 19 years; traumatic etiology: 68; time post-injury: 40 ± 23 days). We compared the scores of the Disability Rating Scale score (DRS) at time of transition from VS/UWS to MCS or from MCS– to MCS+, and at discharge between groups. Results: Level of disability on the DRS was similar in patients with any combination of the three language-related behaviors. MCS patients with no behavioral evidence of language function (i.e., MCS–) were more functionally impaired than patients with MCS+ at time of transition and at discharge. Conclusions: Command-following, intelligible verbalization, and intentional communication are not associated with different levels of functional disability. Thus, the MCS+ syndrome can be diagnosed based on the presence of any one of these language-related behaviors. Patients in MCS+ may evidence less functional disability compared to those in MCS who fail to demonstrate language function (i.e., MCS–). [ABSTRACT FROM AUTHOR]

Forty-five years ago, the first evidence of near-death experience (NDE) during comatose state was provided, setting the stage for a new paradigm for studying the neural basis of consciousness in unresponsive states. At present, the state of consciousness associated with NDEs remains an open question. In the common view, consciousness is said to disappear in a coma with the brain shutting down, but this is an oversimplification. We argue that a novel framework distinguishing awareness, wakefulness, and connectedness is needed to comprehend the phenomenon. Classical NDEs correspond to internal awareness experienced in unresponsive conditions, thereby corresponding to an episode of disconnected consciousness. Our proposal suggests new directions for NDE research, and more broadly, consciousness science. Scientific investigation of NDEs has accelerated in part because of the improvement of resuscitation techniques over the past decades, and because these memories have been more openly reported. This has allowed progress in the understanding of NDEs, but there has been little conceptual analysis of the state of consciousness associated with NDEs. The scientific investigation of NDEs challenges our current concepts about consciousness, and its relationship to brain functioning. We suggest that a detailed approach distinguishing wakefulness, connectedness, and internal awareness can be used to properly investigate the NDE phenomenon. We think that adopting this theoretical conceptualization will increase methodological and conceptual clarity and will permit connections between NDEs and related phenomena, and encourage a more fine-grained and precise understanding of NDEs. [ABSTRACT FROM AUTHOR]

Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in response to dexmedetomidine, the effects of which are not fully known. We recorded transcranial magnetic stimulation (TMS) and EEG in frontal and parietal cortex of 20 healthy subjects undergoing dexmedetomidine sedation in four conditions (baseline, light sedation, deep sedation, recovery). We used the first component (0–30 ms) of the TMS-evoked potential (TEP) to measure cortical excitability (amplitude), slope, and positive and negative peak latencies (collectively, TEP indices). We used generalised linear mixed models to test the effect of condition, brain region, and responsiveness on TEP indices. Compared with baseline, amplitude in the frontal cortex increased by 6.52 μV (P <0.001) in light sedation, 4.55 μV (P =0.003) in deep sedation, and 5.03 μV (P <0.001) in recovery. Amplitude did not change in the parietal cortex. Compared with baseline, slope increased in all conditions (P <0.02) in the frontal but not parietal cortex. The frontal cortex showed 5.73 μV higher amplitude (P <0.001), 0.63 μV ms−1 higher slope (P <0.001), and 2.2 ms shorter negative peak latency (P =0.001) than parietal areas. Interactions between dexmedetomidine and region had effects over amplitude (P =0.004) and slope (P =0.009), with both being higher in light sedation, deep sedation, and recovery compared with baseline. Transcranial magnetic stimulation-evoked potential amplitude changes non-linearly as a function of depth of sedation by dexmedetomidine, with a region-specific paradoxical increase. Future research should investigate other anaesthetics to elucidate the link between cortical excitability and depth of sedation. [ABSTRACT FROM AUTHOR]

Self-induced cognitive trance (SICT) is a voluntary non-ordinary state of consciousness characterized by a lucid yet narrowed awareness of the external surroundings. It involves a hyper-focused immersive experience of flow, expanded inner imagery, modified somatosensory processing, and an altered perception of self and time. SICT is gaining attention due to its potential clinical applications. Similar states of non-ordinary state of consciousness, such as meditation, hypnosis, and psychedelic experiences, have been reported to induce changes in the autonomic nervous system. However, the functioning of the autonomic nervous system during SICT remains poorly understood. In this study, we aimed to investigate the impact of SICT on the cardiac and respiratory signals of 25 participants proficient in SICT. To accomplish this, we measured various metrics of heart rate variability (HRV) and respiration rate variability (RRV) in three conditions: resting state, SICT, and a mental imagery task. Subsequently, we employed a machine learning framework utilizing a linear discriminant analysis classifier and a cross-validation scheme to identify the features that exhibited the best discrimination between these three conditions. The results revealed that during SICT, participants experienced an increased heart rate and a decreased level of high-frequency (HF) HRV compared to the control conditions. Additionally, specific increases in respiratory amplitude, phase ratio, and RRV were observed during SICT in comparison to the other conditions. These findings suggest that SICT is associated with a reduction in parasympathetic activity, indicative of a hyperarousal state of the autonomic nervous system during SICT. [ABSTRACT FROM AUTHOR]

Hypnosis has been shown to be of clinical utility; however, its underlying neural mechanisms remain unclear. This study aims to investigate altered brain dynamics during the non-ordinary state of consciousness induced by hypnosis. We studied high-density EEG in 9 healthy participants during eyes-closed wakefulness and during hypnosis, induced by a muscle relaxation and eyes fixation procedure. Using hypotheses based on internal and external awareness brain networks, we assessed region-wise brain connectivity between six ROIs (right and left frontal, right and left parietal, upper and lower midline regions) at the scalp level and compared across conditions. Data-driven, graph-theory analyses were also carried out to characterize brain network topology in terms of brain network segregation and integration. During hypnosis, we observed (1) increased delta connectivity between left and right frontal, as well as between right frontal and parietal regions; (2) decreased connectivity for alpha (between right frontal and parietal and between upper and lower midline regions) and beta-2 bands (between upper midline and right frontal, frontal and parietal, also between upper and lower midline regions); and (3) increased network segregation (short-range connections) in delta and alpha bands, and increased integration (long-range connections) in beta-2 band. This higher network integration and segregation was measured bilaterally in frontal and right parietal electrodes, which were identified as central hub regions during hypnosis. This modified connectivity and increased network integration–segregation properties suggest a modification of the internal and external awareness brain networks that may reflect efficient cognitive-processing and lower incidences of mind-wandering during hypnosis. [ABSTRACT FROM AUTHOR]

Out-of-body experiences (OBEs) are subjective experiences of seeing one's own body and the environment from a location outside the physical body. They can arise spontaneously or in specific conditions, such as during the intake of dissociative drug. Given its unpredictable occurrence, one way to empirically study it is to induce subjective experiences resembling an OBE using technology such as virtual reality. We employed a complex multisensory method of virtual embodiment in a virtual reality scenario with seven healthy participants to induce virtual OBE-like experiences. Participants performed two conditions in a randomly determined order. For both conditions, the participant's viewpoint was lifted out of the virtual body toward the ceiling of the virtual room, and real body movements were (visuo-tactile ON condition) or were not (visuo-tactile OFF condition) translated into movements on the virtual body below—the latter aiming to maintain a feeling of connection with the virtual body. A continuous 128-electrode EEG was recorded. Participants reported subjective experiences of floating in the air and of feeling high up in the virtual room at a strong intensity, but a weak to moderate feeling of being "out of their body" in both conditions. The EEG analysis revealed that this subjective experience was associated with a power shift that manifested in an increase of delta and a decrease of alpha relative power. A reduction of theta complexity and an increase of beta-2 connectivity were also found. This supports the growing body of evidence revealing a prominent role of delta activity during particular conscious states. [ABSTRACT FROM AUTHOR]

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