Phenomenological memory characteristics and impact of near-death experience in critically ill survivors: Observations at discharge and after a 1-year follow-up.

Background: It is not rare that intensive care unit (ICU) patients report unusual subjective experiences, ranging from a feeling of harmony with the environment to complex phenomena such as near-death experience (NDE). This 1-year follow-up study investigates the characteristics and potential global impact of the NDE memories recalled by ICU survivors. Method: We prospectively enrolled 126 adult survivors of a prolonged (>7days) ICU stay (all etiologies), including 19 (15 %) who reported a NDE as identified by the Greyson NDE scale. The NDE group underwent a semi-structured interview one month later evaluating their memory characteristics and the associated life-threatening situation. One year after inclusion, all patients (regardless of whether they recalled an NDE) were contacted for a follow-up Greyson NDE scale assessment and questions about their ICU experience and opinions on death since discharge. Results: The Greyson NDE scale revealed that the most frequently reported features were altered time perception, heightened senses and life review, and the Greyson total scores did not evolve over time. NDE memories persisted, with a consequent number of phenomenological characteristics (e.g., visual details, emotions). One year post-ICU, two patients (18 %) of the NDE group and 12 (24 %) of the non-NDE group were less afraid of death. Conclusions: Results emphasize the clinical importance of interviewing all ICU patients to explore any memory after an ICU stay.

Lateral frontoparietal effective connectivity differentiates and predicts state of consciousness in a cohort of patients with traumatic disorders of consciousness.

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.

Automatic Sleep Stage Classification Using Nasal Pressure Decoding Based on a Multi-Kernel Convolutional BiLSTM Network.

Sleep quality is an essential parameter of a healthy human life, while sleep disorders such as sleep apnea are abundant. In the investigation of sleep and its malfunction, the gold-standard is polysomnography, which utilizes an extensive range of variables for sleep stage classification. However, undergoing full polysomnography, which requires many sensors that are directly connected to the heaviness of the setup and the discomfort of sleep, brings a significant burden. In this study, sleep stage classification was performed using the single dimension of nasal pressure, dramatically decreasing the complexity of the process. In turn, such improvements could increase the much needed clinical applicability. Specifically, we propose a deep learning structure consisting of multi-kernel convolutional neural networks and bidirectional long short-term memory for sleep stage classification. Sleep stages of 25 healthy subjects were classified into 3-class (wake, rapid eye movement (REM), and non-REM) and 4-class (wake, REM, light, and deep sleep) based on nasal pressure. Following a leave-one-subject-out cross-validation, in the 3-class the accuracy was 0.704, the F1-score was 0.490, and the kappa value was 0.283 for the overall metrics. In the 4-class, the accuracy was 0.604, the F1-score was 0.349, and the kappa value was 0.217 for the overall metrics. This was higher than the four comparative models, including the class-wise F1-score. This result demonstrates the possibility of a sleep stage classification model only using easily applicable and highly practical nasal pressure recordings. This is also likely to be used with interventions that could help treat sleep-related diseases.

Psychedelics and disorders of consciousness: the current landscape and the path forward.

Modern medicine has been shaken by the surge of psychedelic science that proposes a new approach to mitigate mental disorders, such as depression and post-traumatic stress disorder. Clinical trials to investigate whether psychedelic substances can treat psychiatric conditions are now underway, yet less discussion gravitates around their use in neurological disorders due to brain injury. One suggested implementation of brain-complexity enhancing psychedelics is to treat people with post-comatose disorders of consciousness (DoC). In this article, we discuss the rationale of this endeavour, examining possible outcomes of such experiments by postulating the existence of an optimal level of complexity. We consider the possible counterintuitive effects of both psychedelics and DoC on the functional connectivity of the default mode network and its possible impact on selfhood. We also elaborate on the role of computational modelling in providing complementary information to experimental studies, both contributing to our understanding of the treatment mechanisms and providing a path towards personalized medicine. Finally, we update the discourse surrounding the ethical considerations, encompassing clinical and scientific values.

Swallowing Assessment in Post-Comatose Patients: A Feasibility Study on the SWADOC Tool.

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.

Re-awakening the brain: Forcing transitions in disorders of consciousness by external in silico perturbation.

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.

Phenomenological characteristics of auto-induced cognitive trance and Mahorikatan® trance.

Trance states include various practices characterized by a modulation of consciousness, but with their own specific characteristics and induction techniques. They have been very seldom scientifically studied, and their phenomenological similarities and differences are poorly documented. This paper will focus on two types of Western trances developed after the leaders were trained in traditional shamanic communities: the auto-induced cognitive trance (AICT) and the Mahorikatan® trance (MT). Twenty-five AICT and 26 MT participants who were able to self-induce the trance state completed questionnaires about their trance practice (e.g. context of the first trance episode, frequency of practice, and consequences on personal life) and the phenomenological characteristics (i.e. emotional, physical, and cognitive) of the trance episodes they experienced. These characteristics were compared to explore similarities and differences between the two trance states. AICT and MT are characterized by the expression of different emotions, modification of various perceptions, a feeling of unicity (i.e. being completely oneself), and an expansion of consciousness. AICT participants commonly reported body movements, vocalizations, as well as increased creativity, visions of entities and/or places, and feeling of interaction with the environment. MT participants commonly reported a feeling of body dissolution. Most participants in both groups reported positive effects of their trance practice on their personal life. These results helped characterize AICT and MT, as well as their similarities and differences. Further studies should continue to explore the characteristics of such trance states, as well as their potential clinical applications.

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

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

Changes in high-order interaction measures of synergy and redundancy during non-ordinary states of consciousness induced by meditation, hypnosis, and auto-induced cognitive trance.

High-order interactions are required across brain regions to accomplish specific cognitive functions. These functional interdependencies are reflected by synergistic information that can be obtained by combining the information from all the sources considered and redundant information (i.e., common information provided by all the sources). However, electroencephalogram (EEG) functional connectivity is limited to pairwise interactions thereby precluding the estimation of high-order interactions. In this multicentric study, we used measures of synergistic and redundant information to study in parallel the high-order interactions between five EEG electrodes during three non-ordinary states of consciousness (NSCs): Rajyoga meditation (RM), hypnosis, and auto-induced cognitive trance (AICT). We analyzed EEG data from 22 long-term Rajyoga meditators, nine volunteers undergoing hypnosis, and 21 practitioners of AICT. We here report the within-group changes in synergy and redundancy for each NSC in comparison with their respective baseline. During RM, synergy increased at the whole brain level in the delta and theta bands. Redundancy decreased in frontal, right central, and posterior electrodes in delta, and frontal, central, and posterior electrodes in beta1 and beta2 bands. During hypnosis, synergy decreased in mid-frontal, temporal, and mid-centro-parietal electrodes in the delta band. The decrease was also observed in the beta2 band in the left frontal and right parietal electrodes. During AICT, synergy decreased in delta and theta bands in left-frontal, right-frontocentral, and posterior electrodes. The decrease was also observed at the whole brain level in the alpha band. However, redundancy changes during hypnosis and AICT were not significant. The subjective reports of absorption and dissociation during hypnosis and AICT, as well as the mystical experience questionnaires during AICT, showed no correlation with the high-order measures. The proposed study is the first exploratory attempt to utilize the concepts of synergy and redundancy in NSCs. The differences in synergy and redundancy during different NSCs warrant further studies to relate the extracted measures with the phenomenology of the NSCs.

Study protocol: Cerebral characterization of sensory gating in disconnected dreaming states during propofol anesthesia using fMRI.

Background: Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited. Methods: To overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity. Discussion: This study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness. Clinical trial registration: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

Swallowing dysfunctions in patients with disorders of consciousness: Evidence from neuroimaging data, assessment, and management.

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.

Brain-Computer Interfaces for Communication in Patients with Disorders of Consciousness: A Gap Analysis and Scientific Roadmap.

BACKGROUND: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment. METHODS: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question. RESULTS: We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed. CONCLUSIONS: We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care.

Mood assessments of family caregivers of patients with severe brain injury in China.

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.

International survey on the implementation of the European and American guidelines on disorders of consciousness.

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.

Cognitive Motor Dissociation: Gap Analysis and Future Directions.

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

Criticality of resting-state EEG predicts perturbational complexity and level of consciousness during anesthesia.

Consciousness has been proposed to be supported by electrophysiological patterns poised at criticality, a dynamical regime which exhibits adaptive computational properties, maximally complex patterns and divergent sensitivity to perturbation. Here, we investigated dynamical properties of the resting-state electroencephalogram of healthy subjects undergoing general anesthesia with propofol, xenon or ketamine. We then studied the relation of these dynamic properties with the perturbational complexity index (PCI), which has shown remarkably high sensitivity in detecting consciousness independent of behavior. All participants were unresponsive under anesthesia, while consciousness was retained only during ketamine anesthesia (in the form of vivid dreams)., enabling an experimental dissociation between unresponsiveness and unconsciousness. We estimated (i) avalanche criticality, (ii) chaoticity, and (iii) criticality-related measures, and found that states of unconsciousness were characterized by a distancing from both the edge of activity propagation and the edge of chaos. We were then able to predict individual subjects' PCI (i.e., PCImax) with a mean absolute error below 7%. Our results establish a firm link between the PCI and criticality and provide further evidence for the role of criticality in the emergence of consciousness.