ABSTRACT
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.
Subject(s)
Consciousness Disorders , Consciousness , Electroencephalography , Parietal Lobe , Humans , Male , Female , Adult , Electroencephalography/methods , Middle Aged , Parietal Lobe/physiopathology , Parietal Lobe/diagnostic imaging , Consciousness Disorders/physiopathology , Consciousness Disorders/diagnostic imaging , Consciousness/physiology , Positron-Emission Tomography , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Brain Injuries, Traumatic/physiopathology , Brain Injuries, Traumatic/diagnostic imaging , Persistent Vegetative State/physiopathology , Persistent Vegetative State/diagnostic imaging , Cohort Studies , Case-Control Studies , Young Adult , Nerve Net/physiopathology , Nerve Net/diagnostic imagingABSTRACT
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.
ABSTRACT
During fainting, disconnected consciousness may emerge in the form of dream-like experiences. Characterized by extra-ordinary and mystical features, these subjective experiences have been associated to near-death-like experiences (NDEs-like). We here aim to assess brain activity during syncope-induced disconnected consciousness by means of high-density EEG monitoring. Transient loss of consciousness and unresponsiveness were induced in 27 healthy volunteers through hyperventilation, orthostasis, and Valsalva maneuvers. Upon awakening, subjects were asked to report memories, if any. The Greyson NDE scale was used to evaluate the potential phenomenological content experienced during the syncope-induced periods of unresponsiveness. EEG source reconstruction assessed cortical activations during fainting, which were regressed out with subjective reports collected upon recovery of normal consciousness. We also conducted functional connectivity, graph-theoretic and complexity analyses. High quality high-density EEG data were obtained in 22 volunteers during syncope and unresponsiveness (lasting 22±8 s). NDE-like features (Greyson NDE scale total score ≥7/32) were apparent for eight volunteers and characterized by higher activity in delta, theta and beta2 bands in temporal and frontal regions. The richness of the NDE-like content was associated with delta, theta and beta2 bands cortical current densities, in temporal, parietal and frontal lobes, including insula, right temporoparietal junction, and cingulate cortex. Our analyses also revealed a higher complexity and that networks related to delta, theta, and beta2 bands were characterized by a higher overall connectivity paralleled by a higher segregation (i.e., local efficiency) and a higher integration (i.e., global efficiency) for the NDE-like group compared to the non-NDE-like group. Fainting-induced NDE-like episodes seem to be sustained by surges of neural activity representing promising markers of disconnected consciousness.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Consciousness , Electroencephalography , Hypnosis , Meditation , Humans , Male , Female , Adult , Consciousness/physiology , Middle Aged , Brain/physiology , Young AdultABSTRACT
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.
Subject(s)
Consciousness Disorders , Humans , Consciousness Disorders/diagnosis , Consciousness Disorders/physiopathology , Dissociative Disorders/diagnosis , Dissociative Disorders/physiopathology , PrognosisABSTRACT
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.
Subject(s)
Consciousness , Disabled Persons , Humans , United States , Consciousness Disorders/diagnosis , Consciousness Disorders/therapy , Rehabilitation Research/methods , PrognosisABSTRACT
Neuroscientists agree on the value of locating the source of consciousness within the brain. Anaesthesiologists are no exception, and have their own operational definition of consciousness based on phenomenological observations during anaesthesia. The full functional correlates of consciousness are yet to be precisely identified, however rapidly evolving progress in this scientific domain has yielded several theories that attempt to model the generation of consciousness. They have received variable support from experimental observations, including those involving anaesthesia and its ability to reversibly modulate different aspects of consciousness. Aside from the interest in a better understanding of the mechanisms of consciousness, exploring the functional tenets of the phenomenological consciousness states of general anaesthesia has the potential to ultimately improve patient management. It could facilitate the design of specific monitoring devices and approaches, aiming at reliably detecting each of the possible states of consciousness during an anaesthetic procedure, including total absence of mental content (unconsciousness), and internal awareness (sensation of self and internal thoughts) with or without conscious perception of the environment (connected or disconnected consciousness, respectively). Indeed, it must be noted that unresponsiveness is not sufficient to infer absence of connectedness or even absence of consciousness. This narrative review presents the current knowledge in this field from a system-level, underlining the contribution of anaesthesia studies in supporting theories of consciousness, and proposing directions for future research.
ABSTRACT
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.
Subject(s)
Consciousness , Hallucinogens , Humans , Autonomic Nervous System , Benchmarking , Discriminant AnalysisABSTRACT
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Anesthesia , Dexmedetomidine , Humans , Transcranial Magnetic Stimulation , Dexmedetomidine/pharmacology , Evoked Potentials , Frontal LobeABSTRACT
Lemon fragrance is known for its stimulating properties, but its mechanisms of action are not well known yet. This study aimed to examine the effect of lemon essential oil inhalation on healthy participants' alertness level and their neural correlates using magnetic resonance imaging (MRI). Twenty-one healthy men underwent functional MRI scans in different conditions: a resting state condition, a condition where they were exposed to passive lemon smelling (alternating exposure to lemon and breathing fresh air), and a control condition without lemon fragrance diffusion -the order of the last two conditions being randomized. Alertness levels were assessed immediately after each condition using the Karolinska Sleepiness Scale. Voxel-wise whole-brain global functional connectivity and graph theory analyses were computed to investigate brain functional connectivity and network topology alterations. After lemon fragrance inhalation, we observed a higher level of alertness as compared to resting state -but not compared to control condition. During lemon fragrance inhalation, we found increased global functional connectivity in the thalamus, paralleled by decreased global connectivity in several cortical regions such as precuneus, postcentral and precentral gyrus, lateral occipital cortex and paracingulate gyrus. Graph theory analysis revealed increased network integration in cortical regions typically involved in olfaction and emotion processing such as olfactory bulb, hypothalamus and thalamus, while decreased network segregation in several regions of the posterior part of the brain during olfaction as compared to resting state. The present findings suggest that lemon essential oil inhalation could increase the level of alertness.
Subject(s)
Brain Mapping , Brain , Male , Humans , Magnetic Resonance Imaging/methods , Attention , Thalamus/diagnostic imagingSubject(s)
Coma , Consciousness Disorders , Humans , Consciousness Disorders/diagnosis , Glasgow Coma ScaleABSTRACT
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.
Subject(s)
Electroencephalography , Virtual Reality , Humans , Emotions , TouchABSTRACT
Introduction: Little is known about the potential personality and psychological predictors of near-death experiences (NDEs), and fewer yet those of near-death-like experiences (NDEs-like; similar phenomenology reported after a non-life-threatening context). This study investigated whether personality traits (Openness, Extraversion, Pleasantness, Conscientiousness, and Neuroticism), dissociative experiences, Fantasy proneness, disposition toward auditory hallucinations, absorption trait, and endorsement of paranormal and spiritual beliefs could be associated with the recall of NDEs(-like). Methods: To this aim, we invited four groups of people to retrospectively fill in questionnaires assessing the following factors: NDE experiencers (n = 63), NDE(-like) experiencers (n = 31), controls with a life-threatening situation but no NDE(-like) (n = 43), and controls without a life-threatening situation or an NDE(-like) (n = 44). We carried out univariate analyses for each factor and then performed a multiple regression analysis and a discriminant analysis. Results: The multivariate logistic regression analysis revealed that the endorsement of spiritual beliefs was associated with the recall of NDEs-like while Openness and Fantasy proneness were associated with the recall of NDEs. The discriminant analysis showed that these variables produce 35% of correct classification. Discussion: Albeit retrospective, these results pave the way for future research on psychological predictors of NDEs(-like) by highlighting the influence of Spirituality, Openness, and Fantasy proneness on these phenomena.
ABSTRACT
Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unclear. We combine whole-brain modeling, data augmentation, and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to patients with brain injury is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, increasing alongside loss of consciousness. Finally, we investigate the effects of model perturbations, providing geometrical interpretation for the stability and reversibility of states. We conclude that conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.
Subject(s)
Brain Injuries , Consciousness , Humans , Brain , Wakefulness , Neural Pathways , Magnetic Resonance Imaging , Brain MappingABSTRACT
The assessment and management of pain and nociception is very challenging in patients unable to communicate functionally such as patients with disorders of consciousness (DoC) or in locked-in syndrome (LIS). In a clinical setting, the detection of signs of pain and nociception by the medical staff is therefore essential for the wellbeing and management of these patients. However, there is still a lot unknown and a lack of clear guidelines regarding the assessment, management and treatment of pain and nociception in these populations. The purpose of this narrative review is to examine the current knowledge regarding this issue by covering different topics such as: the neurophysiology of pain and nociception (in healthy subjects and patients), the source and impact of nociception and pain in DoC and LIS and, finally, the assessment and treatment of pain and nociception in these populations. In this review we will also give possible research directions that could help to improve the management of this specific population of severely brain damaged patients.
ABSTRACT
Background. Many patients with severe brain damage may survive and remain in a prolonged disorder of consciousness (PDoC), impacting the quality of life (QoL) and needs of their family caregivers. However, the current literature on the factors influencing these needs is contradictory. We aim to describe the needs, QoL, and emotional distress of caregivers of patients with PDoC. Methods. Questionnaires investigating the importance and satisfaction of six categories of needs (i.e., health information, emotional, instrumental, and professional supports, community support network, and involvement in care), QoL, and emotional distress were completed by the main caregivers of PDoC patients. Results. We analyzed 177 questionnaires. Seventy-nine percent of the needs were considered as important or very important, and 44% were partially met or unmet. The needs for health information and professional support were the most important, while the needs for involvement in care and for health information were the most satisfied. Mean QoL was low and emotional distress high. Variables such as care setting and time since brain injury affected the level of QoL and distress. Conclusion. The needs for health information and professional support should receive particular attention. Given their low QoL and high distress, adequate support structures should be provided to caregivers of PDoC patients.