Delta band activity contributes to the identification of command following in disorder of consciousness.

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.

Acute subjective effects in LSD- and MDMA-assisted psychotherapy.

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.

Dose-response relationships of psilocybin-induced subjective experiences in humans.

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.

A systematic review of head-up tilt to improve consciousness in people with a prolonged disorder of consciousness.

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.

Post-traumatic Confusional State: A Case Definition and Diagnostic Criteria.

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.

Heat illness during initial military training.

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.

Repetitive transcranial magnetic stimulation in traumatic brain injury: Evidence from animal and human studies.

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.

Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness.

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.

Why do seizures impair consciousness and how can we reverse this?

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.

Conciencia de déficit como proceso clave en la rehabilitación de pacientes con daño cerebral adquirido: revisión sistemática / Self-awareness as a key process for rehabilitation of patients with acquired brain injury: a systematic review

Introducción: La afectación de la conciencia de déficit es un síntoma habitual de los pacientes que sufren una lesión cerebral, que afecta al proceso rehabilitador y a los logros en términos de independencia funcional del paciente. Pacientes y métodos: Se realizó una revisión sistemática en las bases bibliográficas Scopus y PubMed de los trabajos científicos que han abordado la conciencia de déficit en pacientes con daño cerebral entre 2000 y 2019. Finalmente se revisaron 65 artículos. Resultados: La conciencia de déficit como proceso metacognitivo está ligada a otros procesos cognitivos de orden superior, como las funciones ejecutivas y la memoria. En los últimos años, se han diseñado e implementado programas de intervención específicos sobre conciencia de déficit que han demostrado su eficacia mediante la incorporación de diferentes técnicas (por ejemplo, psicoeducación y feedback). Ante la necesidad de evaluar el éxito de la intervención sobre la conciencia de déficit en términos de mejora funcional, algunos trabajos han estudiado la generalización y la trasferencia de los resultados de la intervención sobre la conciencia de déficit a las actividades de la vida diaria. Conclusiones: La investigación en conciencia de déficit en pacientes con daño cerebral se ha desarrollado de forma significativa en los últimos años, considerando los factores neuropsicológicos, psicológicos y sociales de este fenómeno. Su futuro prometedor apunta hacia su incorporación como cribado en los protocolos de evaluación y, en su caso, su intervención de forma específica, lo que contribuirá a una rehabilitación eficaz que repercuta en la calidad de vida de los pacientes

Introduction: Self-awareness impairment is a common symptom of patients after suffering acquired brain injury, affecting the rehabilitation process and achievements in terms of patients’s daily living functionality. Patients and methods: A systematic review was performed using Scopus and PubMed databases of scientific articles that address self-awareness in patients with brain injury between 2000 and 2019. Finally, 65 articles were reviewed. Results. As a metacognitive process, self-awareness is linked to other higher order cognitive domains such an executive functions and memory. In recent years, specific intervention programs for self-awareness have been developed and implemented, and have proved their effectiveness, by using different techniques (i.e. psychoeducation and feedback). Considering the importance of assessing the success of the self-awareness interventions in terms of functional improvement, some studies have explored the generalization and transfer of results from those interventions to activities of daily living. Conclusions: Research in self-awareness in patients with acquired brain injury has developed significantly in recent years, considering the neuropsychological, psychological and social factors of this phenomenon. The promising future of research in this field points at its inclusion as screening tool in the assessment protocols and, if applicable, its individualized intervention, contributing to an effective global rehabilitation that affects patient's quality of life

Towards the assessment of quality of life in patients with disorders of consciousness.

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.

Seeing minds in patients with disorders of 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.

Can Salient Stimuli Enhance Responses in Disorders of Consciousness? A Systematic Review.

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.

Effects of transcranial direct current stimulation on patients with disorders of consciousness after traumatic brain injury: study protocol for a randomized, double-blind controlled trial.

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.

Multidisciplinary attentive treatment for patients with chronic disorders of consciousness following severe traumatic brain injury in the NASVA of Japan.

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.

Clinical relevance of ethanol coingestion in patients with GHB/GBL intoxication.

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.

Emotional consciousness preserved in patients with disorders of consciousness?

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.

Comparison of Single and Combined Effects of Nature Sounds and Foot Sole Reflexology Massage on the Level of Consciousness in Traumatic Comatose Patients: A Randomized Controlled Clinical Trial.

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.