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At least one in three women experience intimate partner violence (IPV) in their lifetime. The most commonly sustained IPV-related brain injuries include strangulation-related alterations in consciousness (S-AICs) and traumatic brain injuries (TBIs). Moreover, survivors of IPV-related S-AICs and/or TBIs often demonstrate psychological distress such as depression, anxiety, and post-traumatic stress. However, the co-occurrence of S-AICs and TBIs, and whether such TBIs may be moderate to severe, has not been systematically examined, and most data have been collected from women in North America. The purpose of this study was to examine the co-occurrence of IPV-related S-AICs and TBIs across a range of geographical locations and to determine the extent to which these S-AICs are related to psychological distress. Women who had experienced physical IPV ( n = 213) were included in this secondary analysis of retrospectively collected data across four countries (Canada, the United States, Spain, and Colombia). The Brain Injury Severity Assessment (BISA) was used to assess IPV-related BI across all sites. Because various questionnaires were employed to assess levels of depression, anxiety, and post-traumatic stress disorder at each site, we created a standardized composite score by converting raw scores into Z -scores for analysis. Mann-Whitney U tests and chi-square tests were conducted to examine differences between women with and without experience of S-AICs and to discover if there was a relationship between the occurrence of S-AICs and TBIs. Analysis of variance and analysis of covariance (to control for the potential confounding effects of age, education, and non IPV-related TBI) were used to compare levels of psychological distress in women who had or had not experienced S-AICs. Approximately, 67% of women sustained at least one IPV-related BI (i.e., TBI and/or S-AIC). In a subsample of women who sustained at least one IPV-related BI, approximately 37% sustained both S-AICs and TBIs, 2% sustained only S-AICs (with no TBIs), and 61% sustained TBIs exclusively (with no S-AICs). Furthermore, women who had sustained S-AICs (with or without a TBI) were more likely to have experienced a moderate-to-severe BI than those who had not sustained an S-AIC (BISA severity subscale: U = 3939, p = 0.006). In addition, women who experienced S-AICs (with or without a TBI) reported higher levels of psychological distress compared with women who never experienced S-AICs, irrespective of whether they occurred once or multiple times. These data underscore the importance of assessing for S-AIC in women who have experienced IPV and when present, to also assess for TBIs and the presence of psychological distress. Unfortunately, there were methodological differences across sites precluding cross-site comparisons. Nonetheless, data were collected across four culturally and geographically diverse countries and, therefore, highlight IPV-related BIs as a global issue that needs to be aggressively studied with policies established and then implemented to address findings.

The overt or covert ability to follow commands in patients with disorders of consciousness is considered a sign of awareness and has recently been defined as cortically mediated behaviour. Despite its clinical relevance, the brain signatures of the perceptual processing supporting command following have been elusive. This multimodal study investigates the temporal spectral pattern of electrical brain activity to identify features that differentiated healthy controls from patients both able and unable to follow commands. We combined evidence from behavioural assessment, functional neuroimaging during mental imagery and high-density electroencephalography collected during auditory prediction, from 21 patients and 10 controls. We used a penalised regression model to identify command following using features from electroencephalography. We identified seven well-defined spatiotemporal signatures in the delta, theta and alpha bands that together contribute to identify DoC subjects with and without the ability to follow command, and further distinguished these groups of patients from controls. A fine-grained analysis of these seven signatures enabled us to determine that increased delta modulation at the frontal sensors was the main feature in command following patients. In contrast, higher frequency theta and alpha modulations differentiated controls from both groups of patients. Our findings highlight a key role of spatiotemporally specific delta modulation in supporting cortically mediated behaviour including the ability to follow command. However, patients able to follow commands nevertheless have marked differences in brain activity in comparison with healthy volunteers., (© 2021. The Author(s).)

Background: Lysergic acid diethylamide (LSD) and 3,4-methylenedioxymethamphetamine (MDMA) were used in psychotherapy in the 1960s-1980s, and are currently being re-investigated as treatments for several psychiatric disorders. In Switzerland, limited medical use of these substances is possible in patients not responding to other treatments (compassionate use)., Methods: This study aimed to describe patient characteristics, treatment indications and acute alterations of mind in patients receiving LSD (100-200 µg) and/or MDMA (100-175 mg) within the Swiss compassionate use programme from 2014-2018. Acute effects were assessed using the 5 Dimensions of Altered States of Consciousness scale and the Mystical Experience Questionnaire, and compared with those in healthy volunteers administered with LSD or MDMA and patients treated alone with LSD in clinical trials., Results: Eighteen patients (including 12 women and six men, aged 29-77 years) were treated in group settings. Indications mostly included posttraumatic stress disorder and major depression. Generally, a drug-assisted session was conducted every 3.5 months after 3-10 psychotherapy sessions. LSD induced pronounced alterations of consciousness on the 5 Dimensions of Altered States of Consciousness scale, and mystical-type experiences with increases in all scales on the Mystical Experience Questionnaire. Effects were largely comparable between patients in the compassionate use programme and patients or healthy subjects treated alone in a research setting., Conclusion: LSD and MDMA are currently used medically in Switzerland mainly in patients with posttraumatic stress disorder and depression in group settings, producing similar acute responses as in research subjects. The data may serve as a basis for further controlled studies of substance-assisted psychotherapy.

Background: Psilocybin is the psychoactive component in Psilocybe mushrooms ('magic mushrooms'). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies., Aim: Establishing dose-response relationships of the subjective experiences induced by psilocybin in healthy study participants and a comparison of patient groups., Method: We applied a linear meta-regression approach, based on the robust variance estimation framework, to obtain linear dose-response relationship estimates on questionnaire ratings after oral psilocybin administration. Data were obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale., Results: Psilocybin dose positively correlated with ratings on most factors and scales, mainly those referring to perceptual alterations and positively experienced ego dissolution. Measures referring to challenging experiences exhibited small effects and were barely modulated by dose., Conclusion: Psilocybin intensified almost all characteristics of altered states of consciousness assessed with the given questionnaires. Because subjective experiences are not only determined by dose, but also by individual and environmental factors, the results may only apply to controlled laboratory experiments and not to recreational use. This paper may serve as a general literature citation for the use of psilocybin in experimental and clinical research, to compare expected and observed subjective experiences.

Objective: This systematic review analysed the evidence for the effect of head-up tilt (passive-standing) on consciousness among persons in prolonged disorders of consciousness., Data Sources: Articles were identified through primary database searching (Medline, CINAHL, AMED, The Cochrane Library) and post-citation searching (Scopus)., Review Methods: This review followed the PRISMA statement. The search strategy was created to find articles that combined any conceivable passive standing device, any measure of consciousness and disorders of consciousness of any origin. Inclusion criteria were any papers that evaluated the use of head-up tilt in adults in defined disorders of consciousness. Exclusion criteria included active stand studies, paediatric studies and animal studies.The search was completed independently by two researchers. Data collection and risk of bias assessment was completed using the Downs and Black tool., Results: 6867 titles were retrieved (last search completed 21/6/20). Ten papers met the inclusion criteria: five examined the effects of a single head-up tilt treatment, and five the effects of head-up tilt regimes. Eighty-seven participants were randomised in three randomised controlled trials. In the remaining preliminary studies or case series, 233 participants were analysed. Quality was low, with only two high-quality studies available. Four studies were suitable for effect size analysis, where medium to large effect sizes were found. The two high-quality studies found head-up tilt had a large effect on consciousness., Conclusion: Overall there is some evidence that repeated passive standing on a tilt-table can improve consciousness, but the relevant studies provoke further questions.

In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Exertional heat illness (EHI) is recognised as a significant problem for fit young individuals taking part in strenuous activity in temperate climates. The aim of this research was to relate episodes of reported EHI against known risk factors for heat illness and determine whether modification of the training programme had an effect on the number of cases reported. Publication was not possible when the work was originally conducted in 2000 because of barriers within Royal Military Academy Sandhurst (RMAS) at the time., Methods: A retrospective study examined the medical data for Officer Cadets in training at the RMAS for a 2-year period ending April 2000., Results: 60 cases were initially reported as EHI, in 58 individuals. Using the following criteria; dizziness, collapse, reduced conscious level, headache, nausea, vomiting, elevated core (rectal) temperature and the results of urine and blood tests, 35 cases were diagnosed as EHI and 25 cases had other diagnoses recorded after investigation. Minority of cases (n=12) had an identifiable risk factor but the majority appeared to be fit young individuals who were susceptible to EHI in conditions where the rest of the population was unaffected., Discussion: Further work is planned to study individuals during strenuous activity events in the hope of accurately identifying those at risk and further reducing the incidence of EHI. EHI is common, case definition is poor, risk factors are not present in all individuals but modification of training programmes is effective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

We provide here the first systematic review on the studies dealing with repetitive transcranial magnetic stimulation (rTMS) for traumatic brain injury (TBI) in animals and humans. Several experimental studies in animal models have explored with promising results the use of rTMS to enhance neuroprotection and recovery after TBI. However, there are surprisingly few studies that have obtained substantial evidence regarding effects of rTMS in humans with TBI, many of them are case reports investigating the heterogeneous conditions linked to TBI. The most studies have investigated the effects of rTMS in subjects with post-traumatic depression and variable effects have been observed. rTMS has been proposed as an experimental approach for the treatment of disorders of consciousness (DOC), but in subjects with TBI therapeutic effects on DOC have also been variously documented. Beneficial effects have been reported in subjects with cognitive/emotional disturbances and auditory dysfunction (tinnitus and hallucinations), although the results are somewhat conflicting. rTMS applied over the left prefrontal cortex may relieve, at least transiently, post-traumatic headache. Isolated rTMS studies have been performed in TBI patients with motor impairment, chronic dizziness or pain. Especially whether provided in combination, rTMS and neurorehabilitation may be synergistic in the potential to translate experimental findings in the clinical practice. In order to reach definitive conclusions, well-designed randomized controlled studies with larger patient samples, improved design and optimized rTMS setup, are warranted to verify and corroborate the initial promising findings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To generate foundational knowledge in the creation of a quality-of-life instrument for patients who are clinically diagnosed as being in a vegetative or minimally conscious state but are able to communicate by modulating their brain activity (i.e., behaviourally nonresponsive and covertly aware). The study aimed to identify a short list of key domains that could be used to formulate questions for an instrument that determines their self-reported quality of life., Methods: A novel two-pronged strategy was employed: (i) a scoping review of quality-of-life instruments created for patient populations sharing some characteristics with patients who are behaviourally nonresponsive and covertly aware was done to compile a set of potentially relevant domains of quality of life; and (ii) a three-round Delphi consensus process with a multidisciplinary panel of experts was done to determine which of the identified domains of quality of life are most important to those who are behaviourally nonresponsive and covertly aware. Five expert groups were recruited for this study including healthcare workers, neuroscientists, bioethicists, quality-of-life methodologists, and patient advocates., Results: Thirty-five individuals participated in the study with an average response rate of 95% per round. Over the three rounds, experts reached consensus on 34 of 44 domains (42 domains were identified in the scoping review and two new domains were added based on suggestions by experts). 22 domains were rated as being important for inclusion in a quality-of-life instrument and 12 domains were deemed to be of less importance. Participants agreed that domains related to physical pain, communication, and personal relationships were of primary importance. Based on subgroup analyses, there was a high degree of consistency among expert groups., Conclusions: Quality of life should be a central patient-reported outcome in all patient populations regardless of patients' ability to communicate. It remains to be determined how covertly aware patients perceive their circumstances and quality of life after suffering a life-altering injury. Nonetheless, it is important that any further dialogue on what constitutes a life worth living should not occur without direct patient input.

Purpose of Review: Consciousness disorders occurring during seizures are a major source of disability in people with epilepsy. The purpose of this review is to show recent developments in the assessment and understanding of consciousness disorders in epilepsy., Recent Findings: The most frequent alterations in consciousness are alterations in the level of awareness. They are linked to disruptions on a large-scale network of fronto-parietal associative systems in different forms of focal seizures or in absences. Different theories account for these alterations., Summary: Although there is no specific treatment for 'consciousness,' high expectations are placed on brain stimulation techniques, which need to be better defined in the future in terms of targets and parameters.

Severe brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.

Objective : To explore the ways in which health care professionals and families understand terms and concepts associated with disorders of consciousness. Methods : Open-ended, semi-structured interviews were conducted with 20 health care professionals and 18 family caregivers affiliated with a disorders of consciousness program within a nationally ranked rehabilitation facility in the United States. Results : Analysis revealed that: (1) disagreement between some health care professionals and family caregivers regarding the presence of consciousness can arise due to differing beliefs about a patient experiencing pain, and differences in the length of time family caregivers spend with patients relative to clinical staff; (2) some health care professionals and family caregivers use nonclinical terms and concepts to describe consciousness; and (3) some family caregivers might attribute complex mental capacities to patients, which extend beyond the clinical evidence. Conclusion : The beliefs of health care professionals and families regarding disorders of consciousness are complex and could be influenced by broader psychological proclivities to "see minds" in patients who have a liminal neurological status. Awareness of these dynamics may assist health care professionals when interacting with family caregivers.

Purpose of Review: Diagnostic classification of patients with disorders of consciousness (DoC) is based on clinician's observation of volitional behaviours. However, patients' caregivers often report higher levels of responsiveness with respect to those observed during the clinical assessment. Thus, increasing efforts have been aimed at comprehending the effects of self-referential and emotional stimuli on patients' responsiveness. Here we systematically reviewed the original experimental studies that compared behavioural and electrophysiological responses with salient vs. neutral material in patients in vegetative state/unresponsive wakefulness syndrome or in minimally conscious state., Recent Findings: Most of the reviewed studies showed that salient stimuli (i.e. patient's own or familiar faces, patient's own name, and familiar voices) seem to elicit a higher amount of behavioural or electrophysiological responses with respect to neutral pictures or sounds. Importantly, a quite high percentage of patients seem to respond to salient stimuli only. The present review could foster use of personally salient stimuli in assessing DoC. However, the low overall quality of evidence and some limitations in the general reviewing process might induce caution in transferring these suggestions into clinical practice.

Background: Disorders of consciousness (DOC) after traumatic brain injury (TBI) raise the mortality of patients, restrict the rehabilitation of patients with TBI, and increase the physical and economic burden that TBI imposes on patients and their families. Thus, treatment to promote early awakening in DOC after TBI is of vital importance. Various treatments have been reported, but there is no advanced evidence base to support them. Transcranial direct current stimulation (tDCS) has shown great potential in promoting neuroelectrochemical effects. This protocol is for a double-blind, randomized, controlled, clinical trial aiming to research the effects and safety of conventional rehabilitation combined with tDCS therapy in patients with DOC after TBI., Methods/design: Eighty patients with DOC after TBI will be randomized into one of two groups receiving conventional rehabilitation combined with sham tDCS or conventional rehabilitation combined with active tDCS. The intervention period in each of the two groups will last 4 weeks (20 min per day, 6 days per week). Primary outcomes (Glasgow Outcome Scale (GOS)) will be measured at baseline and the end of every week from the first to the fourth week. Secondary outcomes will be measured at baseline and the end of the fourth week. Adverse events and untoward effects will be measured during each treatment., Discussion: Patients with central nervous system lesions have received tDCS as a painless, non-invasive, easily applied and effective therapy for several decades, and there has been some evidence in recent years showing partial improvement on the level of consciousness of partial patients with DOC. However, reports mainly focus on the patients in a minimally conscious state (MCS), and there is a lack of large-sample clinical trials. This protocol presents an objective design for a randomized controlled trial that aims to study the effectiveness of conventional rehabilitation combined with tDCS therapy for DOC after TBI, to evaluate its safety, and to explore effective and economical therapeutic methods., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800014808 . Registered on 7 February 2018.

Objective: Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL use., Method: We performed a secondary analysis of the Euro-DEN Plus Registry (14 countries, 22 EDs) which includes 17,371 consecutive patients presenting to the ED with acute recreational drug toxicity over 39 consecutive months (October 2013 - December 2016). We compared the epidemiological and clinical characteristics and ED management of patients identified as presenting with acute toxicity related to lone GHB/GBL (Group A) or GHB/GBL combined with ethanol (Group B) without other concomitant drugs., Results: A total of 609 patients were included (age 32 (8) years; 116 women (19%); Group A: 183 patients and Group B: 426). The most common features were reduction in consciousness (defined as Glasgow Coma Score <13 points: 56.1%) and agitation/aggressiveness (33.6%). Those with ethanol co-ingestion were younger patients (Group A/B: 31.5/33.1 years, p = 0.029) and ethanol co-ingestion was associated with a lower frequency of bradycardia (23.5%/15.7%, p = 0.027) and more frequent arrival at the ED by ambulance (68.3/86.6%; p < 0.001), reduction in consciousness (58.9%/49.1%; p = 0.031), need for treatment in the ED (49.2%/60.4%; p = 0.011), use of sedatives (20.1%/12.8%; p = 0.034), admission to critical care units (22.4%/55.3%; p < 0.001), and longer hospital stay (stay longer than 6 h: 16.9%/28.4%; p = 0.003)., Conclusions: Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL, leading to greater depression of consciousness, need for treatment, admission to the ICU and longer hospital stay., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Increasing evidence from studies of brain responses to subject's own name (SON) indicates that residual consciousness is preserved in patients with disorders of consciousness (DOC) and that specific network activation might provide evidence of consciousness. However, it remains unclear whether SON is suitable for detection of emotional consciousness; moreover, the particular aspects of brain network organization that are critical for consciousness are unknown. The present study used an innovative approach to explore affective consciousness in patients with DOC during emotional stimuli. EEG data were acquired from 15 patients and 15 healthy volunteers. We analyzed brain potentials and functional network connectivity with a passive emotional paradigm based on graph theoretical methods. Larger N1 or P3a was detected in patients upon exposure to emotional sound, relative to neutral stimuli. Brain topology revealed that emotional sound evoked significantly stronger network linkages in healthy controls; additionally, it evoked several connectivity changes in patients with DOC. In conclusion, emotional consciousness might be partially preserved in patients with DOC; moreover, EEG network patterns could provide new insights into the neural activity of emotional perception in these patients.

Consciousness disturbances are the most common posttraumatic complications. The purpose of this study was to compare the single and combined effects of nature sounds and foot sole reflexology massage on level of consciousness in traumatic comatose patients. This randomized controlled clinical trial was conducted in 2 teaching hospitals in an urban area of Iran. Samples were 120 traumatic comatose patients who were randomly assigned into control, nature sounds, foot reflexology massage, and nature sounds plus foot sole reflexology massage groups. Patients in all groups received routine care. Interventions were performed twice a day for 2 weeks, each time for 30 minutes. The patients' level of consciousness was assessed using the Glasgow Coma Scale before, 1 week, and 2 weeks after the intervention. The groups had no significant differences in the mean scores of the consciousness level before, 1 week after, and the last day of the intervention. Also, there was a significant difference in the number of patients who regained full consciousness (P = .001) in the intervention groups compared with the control group. Significant differences in the number of days of consciousness were reported in at least one of the groups compared with other groups (P = .001). This difference was significant in the control group compared with the foot reflexology massage group (P = .032), as well as the nature sounds plus foot sole reflexology massage group (P = .001). Single or combined interventions can increase the level of consciousness in comatose patients and reduce the duration of coma.

Background and Purpose: Patients with acute ischemic stroke (AIS) may display prolonged neurological deficits and conscious disturbance even after successful endovascular thrombectomy. We hypothesized that hemodynamic change after reperfusion might influence outcomes. This study investigated the factors causing hyperperfusion and outcomes., Methods: We retrospectively analyzed 27 patients with AIS who underwent successful acute revascularization (TICI: Thrombolysis in Cerebral Infarction 2b + 3). Changes of the neurological status were precisely assessed by using the National Institutes of Health Stroke Scale (NIHSS). Ischemic lesions were scored by MRI with diffusion-weighted imaging (DWI), and blood flow in the middle cerebral artery territory was assessed by MRI with arterial spin labeling. Univariate analysis was performed to investigate correlations between hyperperfusion and demographic factors or the functional prognosis., Results: Thirteen of the 27 (48%) patients developed hyperperfusion after reperfusion. A significant correlation was seen between hyperperfusion and the improvement of NIHSS at 24 hours (P < .0001), the duration of disturbance of consciousness (days) (P < .0001), DWI-ASPECTS (P = .001), hemorrhagic transformation (P = .007), and mRS less than or equal to 2 at 90 days (P = .007)., Conclusions: The present findings suggested that some patients with AIS will develop hyperperfusion after successful acute revascularization. The status of hyperperfusion could prolong conscious disturbance and affect outcomes. Since the mechanism of hyperperfusion after revascularization depends on stroke etiology, diagnosing the type of ischemic stroke in the acute stage is important for managing postoperative treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To investigate behavioral and demographic features of levels of consciousness in young children with brain injury, including the classifications of consciousness: conscious state (CS), minimally conscious state (MCS), and vegetative state (VS), and to investigate the course of recovery in children with disorders of consciousness (DOC)., Design: Retrospective chart review and post hoc analysis., Setting: Pediatric inpatient rehabilitation unit., Participants: Children aged 6 months to 5 years (N=54) admitted for inpatient rehabilitation directly from an acute care hospital following new neurologic injury from 2011 to 2016., Interventions: Not applicable., Main Outcome Measures: Clinically abstracted behavioral features of DOC and levels of consciousness at admission and discharge, based on established guidelines from the Aspen Neurobehavioral Conference Workgroup., Results: Children in MCS were younger than children in CS. Commonly observed behaviors in children in VS were mouth movements or vocalizations, flexion withdrawal or motor posturing, visual or auditory startle, and localization to sound. Common features of MCS were contingent affect, visual fixation or pursuit, automatic motor behavior, and contingent communicative intent. No children in MCS showed command following or intelligible verbalizations. All children in CS showed functional object use, while functional communication was observed in a subset. By discharge, more than half of children in VS emerged to MCS, and a third emerged from MCS to CS. No child emerged from VS to CS., Conclusions: Visual and motor skills may be most applicable, and language-based skills may be least applicable for the assessment of DOC in very young children. Accurate classifications of consciousness may have important prognostic implications, and additional research is needed to develop clear guidelines for assessment of DOC in this population., (Copyright © 2019 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

The coma recovery scale-revised (CRS-R) behavioral scale is commonly used for the clinical evaluation of patients with disorders of consciousness (DOC). However, since DOC patients generally cannot supply stable and efficient behavioral responses to external stimulation, evaluation results based on behavioral scales are not sufficiently accurate. In this paper, we proposed a novel brain-computer interface (BCI) based on 3D stereo audiovisual stimuli to supplement object recognition evaluation in the CRS-R. During the experiment, subjects needed to follow the instructions and to focus on the target object on the screen, whereas EEG data were recorded and analyzed in real time to determine the object of focus, and the detection result was output as feedback. Thirteen DOC patients participated in the object recognition assessments using the 3D audiovisual BCI and CRS-R. None of the patients showed object recognition function in the CRS-R assessment before the BCI experiment. However, six of these DOC patients achieved accuracies that were significantly higher than the chance level in the BCI-based assessment, indicating the successful detection of object recognition function in these six patients using our 3D audiovisual BCI system. These results suggest that the BCI method may provide a more sensitive object recognition evaluation compared with CRS-R and may be used to assist clinical CRS-R for DOC patients.

Objective: Quantification of signatures of conscious processing in children with disorders of consciousness (DoC) using odd-ball paradigms in multiple modalities., Method: We review the diagnostic approaches available in the field, from clinical scales to neuroimaging methods, and concentrate upon measures derived from electroencephalographic event related potentials., Results: Evoked potentials were recorded in five procedures, encompassing visual, auditory and tactile modalities, from ten pediatric DoC patients-six in a minimally conscious state (MCS), three in unresponsive wakefulness syndrome (UWS) and one who emerged from MCS (eMCS)-and the control group of 10 healthy children. In almost all the eMCS and MCS patients, higher amplitude of P300 was observed and the effect was statistically significant in at least one out of the five performed procedures. Additionally, signs of conscious information processing were detected in one UWS patient., Conclusion: The presented results provide a proof of concept for the possibility of applying ERP-derived electrophysiological measures as an aid in the assessment of children and adolescents in DoC.

Primary Objective: Only a few objective prognostic markers are available for patients with disorders of consciousness (DoC). We assessed whether the magnitude of short-latency afferent inhibition (SAI) might be a useful predictor of responsiveness recovery and functional outcome in patients with DoC., Research Design: We enrolled 40 patients with prolonged Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) in a longitudinal, observational study., Methods and Procedures: Clinical features (including Coma Recovery Scale-Revised, CRS-R, and Glasgow Outcome Scale, GOS) and SAI were collected at the study entry and after 18 months from study inclusion, to assess a correlation between SAI and the clinical outcome., Main Outcomes and Results: At the follow-up, 19 patients remained in their baseline condition, whereas 7 UWS evolved into MCS or emerged-from-MCS (EMCS), eight MCS evolved into EMCS, and two MCS- evolved into MCS+. Two UWS and one MCS+ died for cardiopulmonary complications. The patients who showed the highest GOS, the highest CRS-R and the lowest SAI strength at study entry, improved at the follow-up., Conclusions: Our findings suggest that an objective and simple neurophysiologic measure as SAI strength could provide useful information to predict the outcome and the behavioral responsiveness of patients with DoC.

Primary Objective : The aim of this study was to demonstrate the clinical outcomes of long-term multidisciplinary attentive treatment (MAT) in patients with chronic disorders of consciousness (DOC) due to severe traumatic brain injury (TBI) following automotive accidents. Research Design : Five hundred and ten patients (mean age: 40.4 years) were enrolled in this retrospective study. Methods and Procedures : Patients were provided MAT for one to several years in the eight medical facilities of the National Agency for Automotive Safety and Victims' Aid (NASVA) in Japan. Clinical status for consciousness, communication, and activities of daily living were evaluated using the NASVA grading system. Outcomes and results : Following MAT, NASVA scores at discharge were significantly improved compared to those at admission in every patient subgroup including sex, age, NASVA score, and association with/without hypoxic encephalopathy at admission. Younger age, shorter interval between injury and admission, and better neurocognitive function at admission were found to be significant and independent factors for a good prognosis. Conclusions : MAT can partially improve the cognitive and physical abilities of patients with chronic DOC. From the perspective of not only restoring a patient's daily life, but also reducing the caregiver's burden, this type of treatment program warrants more public attention.

In order to demonstrate emergence from a disorder of consciousness (DoC) an individual is currently required to demonstrate functional object use of two objects, or functional communication defined as accurately answering six yes/no questions on two consecutive occasions (Giacino et al., 2002). In practice, experienced speech and language therapists (SLTs) working with this group often focus on facilitating object use or employ other language tasks, since achieving a 100% accurate yes/no response can be difficult for patients following an extensive brain injury due to language and/or cognitive impairments. There is an increasing awareness of this issue in the literature and in practice and there is discussion about reviewing the current definition of emergence. This paper outlines the traditional definition of emergence and recent updates, discusses some of the problems and implications associated with current assessment, highlights the importance of getting it right, explores potential other ways to determine emergence, and suggests further areas for research.

Instruments for assessing people with disorders of consciousness have been developed over the last 15 years, but there remains a dearth of suitable assessment paradigms for those who have emerged from disorders of consciousness. This paper presents a pilot study for the development of the Cognitive Assessment by Visual Election (CAVE), a short assessment designed to investigate a number of cognitive domains in very severely brain injured patients who are in or have emerged from minimally conscious states (EMCS). Reliability and validity data are presented. The challenge of determining neuropsychological profiles of EMCS patients is discussed, current published assessments are briefly reviewed and suggestions for a wider assessment framework are made.

Objectives: After a coma, one major challenge is the detection of awareness in patients with disorders of consciousness. In some patients, the only manifestation indicative of awareness is an appropriate emotional response. Preferred music is a powerful medium to elicit emotions and autobiographical memory. Furthermore, music has been shown to improve cognitive functions both in healthy subjects and patients with neurological impairment. We hypothesized that signs of awareness could be enhanced in some patients with disorders of consciousness under appropriate emotional stimulation such as preferred music and also probably preferred odors., Methods: To investigate an objective, easily recordable marker of emotions at the patients' bedside, electrodermal activity (skin conductance level, SCL) was assessed with stimulations in auditory and olfactory modalities, notably with preferred music, neutral sound, preferred odors, and neutral odors. The study was conducted in 11 patients with disorders of consciousness (DOC) and 7 healthy participants., Results: In healthy subjects, the mean amplitude of the SCL was increased during exposure to preferred music as compared to neutral sounds (respectively: 0.00037±0.0004 vs. - 0.00004±0.00019μS). No significant difference between conditions was detected in patients., Conclusion: The results of this study suggest that electrodermal activity could be a useful marker of emotions induced by music in healthy controls. However, it failed to show any significant difference between conditions in patients with DOC., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: To detect any improvement of awareness in prolonged disorders of consciousness in the long term., Methods: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21-73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2-16 years later using Coma Recovery Scale-Revised., Results: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean = 45, SD = 11.4) and non-recovery group (Mean = 43, SD = 15.5) were not statistically different (p = 0.76)., Conclusions: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered. Implications for rehabilitation Long-term regular follow-up of people with prolonged disorders of consciousness is important. Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases. Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered.

Objective: The management of patients with disorders of consciousness (DOC) has raised several important ethical, social, and medical issues. It is also known that families and caregivers are subjected to physical and emotional load due to their assistance activity. The aim of this observational study was to compare distress and coping strategies used among caregivers of two kinds of DOC: vegetative state (VS) and minimally conscious state (MCS)., Methods: We have enrolled 80 caregivers (mean age 47.87 ± 11-28 years) that were tested with self-administered measures of distress and coping to individuate which coping strategies were adopted by caregivers of DOC patients and to analyze how these have influenced the degree of distress., Results: Data showed that the reaction to stress was different between two groups of caregivers (VS and MCS); moreover, it may vary according to the coping strategies used., Conclusion: Results showed the importance to develop effective coping strategies aimed to reduce psychological distress and improving caregiver's well-being.

Evidence suggests that disruptions of the posteromedial cortex (PMC) and posteromedial corticothalamic connectivity contribute to disorders of consciousness (DOCs). While most previous studies treated the PMC as a whole, this structure is functionally heterogeneous. The present study investigated whether particular subdivisions of the PMC are specifically associated with DOCs. Participants were DOC patients, 21 vegetative state/unresponsive wakefulness syndrome (VS/UWS), 12 minimally conscious state (MCS), and 29 healthy controls. Individual PMC and thalamus were divided into distinct subdivisions by their fiber tractograpy to each other and default mode regions, and white matter integrity and brain activity between/within subdivisions were assessed. The thalamus was represented mainly in the dorsal and posterior portions of the PMC, and the white matter tracts connecting these subdivisions to the thalamus had less integrity in VS/UWS patients than in MCS patients and healthy controls. In addition, these tracts had less integrity in DOC patients who did not recover after 12 months than in patients who did. The structural substrates were validated by resting state fMRI finding impaired functional activity within these PMC subdivisions. This study is the first to show that tracts from dorsal and posterior subdivisions of the PMC to the thalamus contribute to DOCs.

Visual pursuit assessment is extensively applied in the behavioral scale-based clinical examination of patients with disorders of consciousness (DOC). However, this assessment is challenging because it relies on behavioral markers, and these patients severely lack behavioral responses. Brain-computer interfaces (BCIs) may provide a potential solution to detect brain responses to external stimuli without requiring behavioral expressions. A BCI system was designed to simulate visual pursuit detection in the coma recovery scale-revised (CRS-R). The graphical user interface included four buttons, one that moved on the screen and three that did not. These buttons flashed in a random order. The patients were prompted to follow the moving button. Based on the collected electroencephalography data, the algorithm determined whether the patient focused on the moving target. Among the 14 DOC patients who participated in the assessments based on the BCI system and the CRS-R, four patients exhibited visual pursuit, and three were nonresponsive in both assessments. More importantly, seven patients who did not exhibit visual pursuit in CRS-R were detected to be responsive to the moving target stimuli in the BCI assessment. Furthermore, five out of seven recovered consciousness to some degree and showed visual pursuit in the second CRS-R assessment. The proposed BCI system is better able to detect visual pursuit than the behavioral scale-based assessment and thus can assist in clinically evaluating the challenging population of DOC patients.

Background: Traumatic brain injury (TBI) has become a leading cause of death among young people worldwide. Survivors may live with a long-term TBI-related disability or even develop a disorder of consciousness resulting in poor life quality and shortened life expectancy. Thus far, very few approaches have been found to be effective in the consciousness recovery of these patients. Acupuncture has long been used in the treatment of neurological disorders in China. However, its efficacy and safety in consciousness recovery remain to be proved., Methods: Here, we present a study design and protocol of a randomized, blinded, controlled study to evaluate the efficacy and safety of electro-acupuncture in the consciousness recovery of patients with TBI. A total of 150 patients with initial Glasgow coma scale score of less than 8 points will be recruited in the trial and randomized into acupuncture or control groups. Patients in the control group will receive routine pharmacological treatment alone while patients in the acupuncture group will receive electro-acupuncture treatment for 10 days in addition to routine treatment. The efficacy will be assessed with the changes in Glasgow coma scale score and mismatch negativity of event-related brain potentials before and after treatment. Moreover, Glasgow outcome scale and Barthel index of activities of daily living will be compared between the two groups at 3 months after treatment. The secondary outcome measures are the length of stay in ICU and hospital, expenses in ICU and hospital, as well as the incidence of coma-related complications. The safety of electro-acupuncture will be assessed by monitoring the incidence of adverse events and changes in vital signs during the study., Discussion: Results from this trial will significantly add to the current body of evidence on the role of electro-acupuncture in the consciousness recovery of patients with severe TBI. In addition, a more convenient and consistent electro-acupuncture method can be set up for clinical practice. If found to be effective and safe, electro-acupuncture will be a valuable complementary option for comatose patients with TBI., Trial Registration: Chinese Clinical Trial Registry: ChiCTR-INR-17011674 . Registered on 16 June 2016.

How consciousness (experience) arises from and relates to material brain processes (the "mind-body problem") has been pondered by thinkers for centuries, and is regarded as among the deepest unsolved problems in science, with wide-ranging theoretical, clinical, and ethical implications. Until the last few decades, this was largely seen as a philosophical topic, but not widely accepted in mainstream neuroscience. Since the 1980s, however, novel methods and theoretical advances have yielded remarkable results, opening up the field for scientific and clinical progress. Since a seminal paper by Crick and Koch (1998) claimed that a science of consciousness should first search for its neural correlates (NCC), a variety of correlates have been suggested, including both content-specific NCCs, determining particular phenomenal components within an experience, and the full NCC, the neural substrates supporting entire conscious experiences. In this review, we present recent progress on theoretical, experimental, and clinical issues. Specifically, we (1) review methodological advances that are important for dissociating conscious experience from related enabling and executive functions, (2) suggest how critically reconsidering the role of the frontal cortex may further delineate NCCs, (3) advocate the need for general, objective, brain-based measures of the capacity for consciousness that are independent of sensory processing and executive functions, and (4) show how animal studies can reveal population and network phenomena of relevance for understanding mechanisms of consciousness., (Copyright © 2017 the authors 0270-6474/17/3710882-12$15.00/0.)

Background: This paper considers the pleasures of psychedelic drugs and proposes a Deleuzian understanding of drugged pleasures as affects. In spite of a large body of work on psychedelics, not least on their therapeutic potentials, the literature is almost completely devoid of discussions of the recreational practices and pleasures of entheogenic drugs. Yet, most people do not use psychedelics because of their curative powers, but because they are fun and enjoyable ways to alter the experience of reality., Methods: In the analytical part of the paper, I examine 100 trip reports from an internet forum in order to explore the pleasures of tripping., Results: The analyses map out how drugs such as LSD and mushrooms - in combination with contextual factors such as other people, music and nature - give rise to a set of affective modifications of the drug user's capacities to feel, sense and act., Conclusion: In conclusion it is argued that taking seriously the large group of recreational users of hallucinogens is important not only because it broadens our understanding of how entheogenic drugs work in different bodies and settings, but also because it may enable a more productive and harm reductive transmission of knowledge between the scientific and recreational psychedelic communities., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Systematic review of the nature, frequency and severity of psychological experiences of people who have a close relationship with a person with a prolonged disorder of consciousness., Data Sources: Cochrane Library, Web of Science, PsycINFO, PubMed, Embase ® , MEDLINE ® , Allied and Complementary Medicine™, were searched from inceptions until December 2016 with additional hand searching of reference lists of included articles., Review Methods: Studies were included that used quantitative methodologies and psychological measures to investigate experiences. The PRISMA statement was followed with inclusion criteria set a priori. A data synthesis summarized psychological constructs studied., Results: A total of 18 studies (ranging between n = 16-487 participants) met the inclusion criteria with 15 of 18 studies focused on the primary caregiver. A total of 23 standardized psychological measures were identified to assess four primary psychological constructs: Loss and grief, psychological wellbeing changes, burden and use of coping strategies., Conclusions: Small sample sizes, limited variables and reliance on observational methods affected quality. Caregivers do find ways to manage independently, but some exhibit clinically significant psychological distress that does not change over time alone and may get worse.

Introduction: Nonconvulsive seizures (NCS) are frequent in hospitalized patients and may further aggravate injury in the already damaged brain, potentially worsening outcomes in encephalopathic patients. Therefore, both early seizure recognition and treatment have been advocated to prevent further neurological damage., Objective: Evaluate the main EEG patterns seen in patients with impaired consciousness and address the effect of treatment with antiepileptic drugs (AEDs), continuous intravenous anesthetic drugs (IVADs), or the combination of both, on outcomes., Methods: This was a single center retrospective cohort study conducted in a private, tertiary care hospital. Consecutive adult patients with altered consciousness submitted to a routine EEG between January 2008 and February 2011 were included in this study. Based on EEG pattern, patients were assigned to one of three groups: Group Interictal Patterns (IP; EEG showing only interictal epileptiform discharges or triphasic waves), Group Rhythmic and Periodic Patterns (RPP; at least one EEG with rhythmic or periodic patterns), and Group Ictal (Ictal; at least one EEG showing ictal pattern). Groups were compared in terms of administered antiepileptic treatment and frequency of unfavorable outcomes (modified Rankin scale ≥3 and in-hospital mortality)., Results: Two hundred and six patients (475 EEGs) were included in this analysis. Interictal pattern was observed in 35.4% (73/206) of patients, RPP in 53.4% (110/206) and ictal in 11.2% (23/206) of patients. Treatment with AEDs, IVADs or a combination of both was administered in half of the patients. While all Ictal group patients received treatment (AEDs or IVADs), only 24/73 (32.9%) IP group patients and 55/108 (50.9%) RPP group patients were treated (p<0.001). Hospital length of stay (LOS) and frequency of unfavorable outcomes did not differ among the groups. In-hospital mortality was higher in IVADs treated RPP patients compared to AEDs treated RPP patients [11/19 (57.9%) vs. 11/36 (30.6%) patients, respectively, p = 0.049]. Hospital LOS, in-hospital mortality and frequency of unfavorable outcomes did not differ between Ictal patients treated exclusively with AEDs or IVADs., Conclusion: In patients with acute altered consciousness and abnormal routine EEG, antiepileptic treatment did not improve outcomes regardless of the presence of periodic, rhythmic or ictal EEG patterns.

Purpose/objective: The psychologist in an inpatient pediatric neurorehabilitation setting provides a vital role in the assessment, treatment, and management of pediatric patients with disorders of consciousness (DoC). Competencies are drawn from several specialty areas of professional psychology, including rehabilitation psychology, pediatric neuropsychology, and pediatric psychology. This specialized knowledge forms the basis for tailoring assessment and treatment plans specific to the individual brain injury profile, with the goals of enhancing diagnosis, prognosis, and care transition decision., Aim: To describe the role of the psychologist in the differential diagnosis and treatment of pediatric patients with severe brain injury and DoC during inpatient rehabilitation. Research Method/Design: Three pediatric cases admitted to inpatient rehabilitation with suspected DoC illustrate the psychologist's role in diagnostics, case conceptualization, assessment design, and data collection based on patient-specific brain injury profiles. Customized data collection informs diagnostic decisions and treatment planning, with the goal of improved of care and resource utilization. The psychologist also provides ongoing psychoeducation, psychotherapy, and supportive interventions to the patient's family and caregivers to facilitate family adjustment to disability and promote long-term adaptation and adjustment., Conclusions/implications: This case series illustrates the role of the psychologist in the use of individual brain injury profiles to coordinate assessment, diagnosis, and care for children with severe brain injury. Implications include the need for focused research to demonstrate the value-added role of the psychologist on the interdisciplinary team working in the neurorehabilitation of this complex patient population. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Objectives: To assess family caregivers' opinions about level of interaction with the environment in their relatives with disorders of consciousness (DOCs) and to explore psychological features of caregivers whose opinions diverge from clinicians' diagnosis., Method: Forty-five family caregivers of 38 DOC inpatients without communication abilities answered 2 questions assessing their opinion about level of interaction with the environment in their relatives. Self-report questionnaires were used to evaluate caregivers' depression, anxiety, psychophysiological disturbances, prolonged grief disorder, coping strategies, quality of perceived needs and social support., Results: Fifteen caregivers (5 relatives of patients in vegetative state and 10 of patients in minimally conscious state) considered their relatives able to communicate, in contrast with clinical diagnosis. These caregivers had significantly higher depressive symptoms, and higher worries about possible death of their relatives with respect to the remaining caregivers., Conclusions: Caregivers of DOC patients detected some interaction with the environment in their relatives more often than care professionals. This is likely related to caregivers' beliefs and expectations, but is also based on observations closer and longer than those possible for physicians. These considerations are important to build a therapeutic alliance with caregivers and to involve them in the diagnostic process and rehabilitative program. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Rationale: Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking., Methods: We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg., Results: On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg., Conclusions: Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

Examining task-free functional connectivity (FC) in the human brain offers insights on how spontaneous integration and segregation of information relate to human cognition, and how this organization may be altered in different conditions, and neurological disorders. This is particularly relevant for patients in disorders of consciousness (DOC) following severe acquired brain damage and coma, one of the most devastating conditions in modern medical care. We present a novel data-driven methodology, connICA, which implements Independent Component Analysis (ICA) for the extraction of robust independent FC patterns (FC-traits) from a set of individual functional connectomes, without imposing any a priori data stratification into groups. We here apply connICA to investigate associations between network traits derived from task-free FC and cognitive/clinical features that define levels of consciousness. Three main independent FC-traits were identified and linked to consciousness-related clinical features. The first one represents the functional configuration of a "resting" human brain, and it is associated to a sedative (sevoflurane), the overall effect of the pathology and the level of arousal. The second FC-trait reflects the disconnection of the visual and sensory-motor connectivity patterns. It also relates to the time since the insult and to the ability of communicating with the external environment. The third FC-trait isolates the connectivity pattern encompassing the fronto-parietal and the default-mode network areas as well as the interaction between left and right hemispheres, which are also associated to the awareness of the self and its surroundings. Each FC-trait represents a distinct functional process with a role in the degradation of conscious states of functional brain networks, shedding further light on the functional sub-circuits that get disrupted in severe brain-damage., (Copyright © 2017. Published by Elsevier Inc.)

Background: Consciousness, the medium of sentient thought, requires integrity of functional networks and their connectivity. In health, they function as a co-operative but mutually exclusive paradigm of introspection versus external awareness subserved via the Default Mode Network and Task Positive State, respectively. Higher thinking in the conscious state is then segregated according to need. There is research evidence to suggest that functional networks may be impacted in disorders of consciousness and conceptual support for a mechanistic role in delirium. This potentially central aspect of delirium manifestation is relatively unexplored., Objective: This article describes the role of disrupted functional networks in delirium. How this relates to current understanding of delirium neurobiology and the ramifications for clinical diagnosis is discussed., Method: A review of the role of functional networks, particularly DMN and TPN, has been undertaken with respect to health and delirium. An exploration of how symptoms of delirium may be related to functional network aberrancy has been undertaken. Implications for research and clinical practice in delirium have been presented., Results: In delirium, a disturbance of consciousness, the DMN is pathologically co-activated and functional cortical connectivity is compromised. The clinical correlate is of an experiential singularity where internal and external drivers become indistinguishable, reality and delusion merge and the notion of self is effaced. Our group propose that functional network disruption in conjunction with cortical disconnectivity is central to the mechanism of delirium. Clinical tools may exploit the neurobiology of delirium to improve its diagnosis and an example of such a simple screening instrument (SQeeC) is provided., Conclusion: Functional networks are critically disrupted in delirium and may be central to clinical features. A better understanding of the neurobiology of delirium will generate research opportunities with potential for therapeutic gains in detection, diagnosis, and management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Reliable evaluation of patients with unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS) remains a major challenge. It has been suggested that the expression of residual cerebral function could be improved by allowing patients to listen to their favourite music. However, the potential effect of music on behavioural responsiveness, as well as the effect of preferred stimuli in other sensory modalities (e.g. olfaction), remain poorly understood., Objective: The aim of our study was to investigate the effect of sensory modality (auditory versus olfactory) and preference (preferred versus neutral) of the test stimuli on patients' subsequent performance on the Coma Recovery Scale-Revised (CRS-R)., Research Design: Within-subject design because of inter-individual differences between patients., Methods and Procedures: We studied four items from the CRS-R (visual pursuit using a mirror, auditory localization of the own name and two movements to command) in 13 patients (7 MCS; 6 UWS)., Main Outcomes and Results: Auditory stimuli triggered higher responsiveness compared to olfactory stimuli, and preferred stimuli were followed by higher scores than did neutral stimuli., Conclusions: Findings suggest that preferred auditory stimuli at the bedside contribute to the expression of residual function and could improve the diagnostic assessment.

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

Decoding the contents of consciousness from brain activity is one of most challenging frontiers of cognitive neuroscience. The ability to interpret mental content without recourse to behavior is most relevant for understanding patients who may be demonstrably conscious, but entirely unable to speak or move willfully in any way, precluding any systematic investigation of their conscious experience. Until recently, patient studies have used structured instructions to elicit willful modulation of brain activity according to command. Recent work has used a different approach, where the similarity of any given patient's brain activity to that of healthy controls during naturalistic paradigms can help detect high-level cognition and consciousness. This approach is easy to administer, brief, and does not require compliance with arbitrary task instructions. Therefore, it is suited to probing consciousness and revealing residual cognition in highly impaired comatose patients, thus helping to improve diagnosis and prognostication for this vulnerable patient group.

Objective: To examine whether emotional functioning can be observed in patients who are behaviourally non-responsive using peripheral markers of emotional functioning., Method: We tested two patients, both diagnosed as being in a vegetative state (VS) following hypoxia secondary to cardiac arrest. Thirty-seven healthy participants with no history of neurological illness served as a control group. The activity of two facial muscles (zygomaticus major, corrugator supercilii) was measured using facial electromyography (EMG) to probe for patterned responses that differentiate between auditorily presented joke and non-joke stimuli in VS patients., Results: One of the two VS patients we tested demonstrated greater zygomatic and reduced corrugator activity in response to jokes compared with non-jokes. Critically, these responses followed the pattern and temporal profile of muscle activity observed in our healthy control sample., Conclusions: Despite their behaviorally non-responsive profile, some patients diagnosed as VS appear to retain some aspects of emotional experience., Significance: Our findings represent, to our knowledge, the first demonstration that a patient diagnosed as VS can exhibit intact emotional responses to humor as assessed by facial EMG. Therefore, our approach may constitute a feasible bedside tool capable of providing novel insight into the mental and emotional lives of patients who are behaviourally non-responsive., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Disorders of consciousness (DOCs) cause great human suffering and material costs for society. Understanding of these disorders has advanced remarkably in recent years, but uncertainty remains with respect to the diagnostic criteria and standards of care. One of the most serious problems concerns misdiagnoses, their impact on medical decision-making, and on patients' well-being. Recent studies use neurotechnology to assess residual consciousness in DOC patients that traditional behavioral diagnostic criteria are unable to detect. The results show an urgent need to strengthen the development of new diagnostic tools and more refined diagnostic criteria. If residual consciousness may be inferred from robust and reproducible results from neurotechnological communication with DOC patients, this also raises ethical challenges. With reference to the moral notions of beneficence and fundamental rights, five ethical imperatives are here suggested in terms of diagnosis, communication, interpretation of subjective states, adaptation of living conditions, and care.

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)