Clinical application of neuromodulation therapy in patients with disorder of consciousness: A pooled analysis of 544 participants.

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

Doing what matters in times of stress: No-nonsense meditation and occupational well-being in COVID-19.

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

Electrophysiological characteristics of CM-pf in diagnosis and outcome of patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. OBJECTIVE: To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. METHODS: We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. RESULTS: 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. CONCLUSION: We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

Autonomic nervous system modulation during self-induced non-ordinary states of consciousness.

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

From nose to brain: The effect of lemon inhalation observed by whole brain voxel to voxel functional connectivity.

Lemon fragrance is known for its stimulating properties, but its mechanisms of action are not well known yet. This study aimed to examine the effect of lemon essential oil inhalation on healthy participants' alertness level and their neural correlates using magnetic resonance imaging (MRI). Twenty-one healthy men underwent functional MRI scans in different conditions: a resting state condition, a condition where they were exposed to passive lemon smelling (alternating exposure to lemon and breathing fresh air), and a control condition without lemon fragrance diffusion -the order of the last two conditions being randomized. Alertness levels were assessed immediately after each condition using the Karolinska Sleepiness Scale. Voxel-wise whole-brain global functional connectivity and graph theory analyses were computed to investigate brain functional connectivity and network topology alterations. After lemon fragrance inhalation, we observed a higher level of alertness as compared to resting state -but not compared to control condition. During lemon fragrance inhalation, we found increased global functional connectivity in the thalamus, paralleled by decreased global connectivity in several cortical regions such as precuneus, postcentral and precentral gyrus, lateral occipital cortex and paracingulate gyrus. Graph theory analysis revealed increased network integration in cortical regions typically involved in olfaction and emotion processing such as olfactory bulb, hypothalamus and thalamus, while decreased network segregation in several regions of the posterior part of the brain during olfaction as compared to resting state. The present findings suggest that lemon essential oil inhalation could increase the level of alertness.

Altered Brain Connectivity and Network Topological Organization in a Non-ordinary State of Consciousness Induced by Hypnosis.

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

A neurophenomenological approach to non-ordinary states of consciousness: hypnosis, meditation, and psychedelics.

No contemporary unifying framework has been provided for the study of non-ordinary states of consciousness (NSCs) despite increased interest in hypnosis, meditation, and psychedelics. NSCs induce shifts in experiential contents (what appears to the experiencer) and/or structure (how it appears). This can allow the investigation of the plastic and dynamic nature of experience from a multiscale perspective that includes mind, brain, body, and context. We propose a neurophenomenological (NP) approach to the study of NSCs which highlights their role as catalysts of transformation in clinical practice by refining our understanding of the relationships between experiential (subjective) and neural dynamics. We outline the ethical implications of the NP approach for standard conceptions of health and pathology as well as the crucial role of experience-based know-how in NSC-related research and application.

Virtual reality hypnosis in the management of pain: Self-reported and neurophysiological measures in healthy subjects.

BACKGROUND: Virtual reality hypnosis (VRH) has emerged as a new and promising option for pain management. Nonetheless, neural dynamics of pain modulation during VRH have not been investigated yet. The aim of this study was to measure the effects of VRH on pain, combining neurophysiological and self-reported measurements. METHODS: Eighteen healthy subjects underwent noxious electrical stimulations in both normal wakefulness and VRH conditions. Dissociation, absorption, time perception, anxiety, pain intensity and unpleasantness, heart rate variability and breathing were reported for each condition. EEG signals were analysed using event-related potentials (ERP) and time-frequency response (TFR) time-locked to stimuli. Neurophysiological features were correlated with self-reported data. RESULTS: VRH condition was associated with lower pain and higher dissociation. VRH significantly decreased amplitudes of N100 and P200 ERP components, reduced EEG power between 1 and 5 Hz from 100 to 560 ms, and increased EEG power from 5 to 11 Hz from 340 to 800 ms. These findings were observed at frontal, central and posterior electrodes. Heart rate variability was significantly higher and breathing frequency reduced with VRH. Correlations were found between the self-reported level of pain and ERP components. CONCLUSION: VRH modulates cerebral pain processes and body physiology, leading to reduced pain levels. These findings offer a first insight on the analgesic mechanisms of VRH and suggest that VRH is an effective approach to reduce experimental pain. SIGNIFICANCE: VRH decreases experimental pain perception, increases subject level of dissociation and modulates cerebral pain processing mechanisms. Pain can be managed with analgesic medication but also through complementary interventions. Among these, hypnosis and virtual reality (VR) are known to reduce pain for patients and healthy individuals. In recent years, an innovative technique combining hypnosis and VR has been proposed to help patients in managing pain. However, to our knowledge, no study has focused on the underlying mechanisms of this VR/hypnosis combination. We showed that VR combined with hypnosis decreases experimental pain, increases dissociation and influences EEG modulation.

Hypnosis, Meditation, and Self-Induced Cognitive Trance to Improve Post-treatment Oncological Patients' Quality of Life: Study Protocol.

INTRODUCTION: A symptom cluster is very common among oncological patients: cancer-related fatigue (CRF), emotional distress, sleep difficulties, pain, and cognitive difficulties. Clinical applications of interventions based on non-ordinary states of consciousness, mostly hypnosis and meditation, are starting to be investigated in oncology settings. They revealed encouraging results in terms of improvements of these symptoms. However, these studies often focused on breast cancer patients, with methodological limitations (e.g., small sample size, no control group, and no follow-up). Another non-ordinary state of consciousness may also have therapeutic applications in oncology: self-induced cognitive trance (SICT). It seems to differ from hypnosis and meditation, as it involves the body more directly. Thus, investigating its clinical applications, along with hypnosis and meditation interventions, could improve available therapeutic options in oncology. This article details the study protocol of a preference-based longitudinal controlled superiority trial aiming to assess the effectiveness of 3 group interventions (hypnosis, meditation, and SICT) to improve oncological patients' quality of life, and more specifically CRF, emotional distress, sleep, pain, and cognitive difficulties (primary outcomes). METHODS AND ANALYSIS: A power analysis required a total sample of 160 patients. Main inclusion criteria are: cancer diagnosis, active treatments completed for less than a year, no practice of hypnosis, meditation, or SICT, and presence of at least one of these four symptoms: fatigue, sleep difficulties, depression, or anxiety. Each participant will choose the intervention in which they want to participate (hypnosis, mindful self-compassion meditation, SICT, or no intervention-control group). To test the effectiveness of the interventions, data will be collected by questionnaires and neurobiological measures and directly from the medical record at four time points: before inclusion in the study (baseline); immediately after the intervention; and at 3- and 12-month follow-up. The longitudinal data in each group will then be measured. DISCUSSION: In addition to standard cancer therapies, there is a growing interest from patients in complementary approaches, such as hypnosis, meditation, and SICT. The results of this study will be useful to increase knowledge about short- and long-term effectiveness of 3 group interventions for CRF, emotional distress, sleep, pain, and cognitive difficulties in patients with different cancers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov/ (NCT04873661). Retrospectively registered on the 29th of April 2021. url: https://clinicaltrials.gov/ct2/show/NCT04873661.

Hypnosis Associated with 3D Immersive Virtual Reality Technology in the Management of Pain: A Review of the Literature.

Hypnosis is well documented in the literature in the management of acute and chronic pain. Virtual reality (VR) is currently gaining credibility in the same fields as hypnosis for medical applications. Lately, the combination of hypnosis and VR was considered. The aim of this scoping review is to understand the current studied contexts and effects of virtual reality hypnosis (VRH) for the management of pain. We searched on PubMed, Taylor & Francis Online, and ProQuest databases with the following terms: "virtual reality," "3D," "hypnosis," and "pain". We included 8 studies that combined hypnosis and VR. All articles are in English. Two included healthy volunteers and six are clinical studies. Short-term results indicated significant decreases in pain intensity, pain unpleasantness, time spent thinking about pain, anxiety, and levels of opioids. However, results are not consistent for all patients all the days. VR alone seems to reduce pain independently of the hypnotizability level. One study claimed that VR and hypnosis could alter each other's effects and another argued that VR did not inhibit the hypnotic process and may even facilitate it by employing visual imagery. We cannot affirm that VR added value to hypnosis when they are combined. These trials and case series gave us indications about the possible applications of VRH in different contexts. Additional randomized clinical trials on VRH in the future will have to test this technique in clinical practice and help define guidelines for VRH utilization in pain management.

Mental imagery for brain-computer interface control and communication in non-responsive individuals.

BACKGROUND: People who survive severe brain damage may eventually develop a prolonged consciousness disorder. Others can regain full consciousness but remain unable to speak or move because of the severity of the lesions, as for those with locked-in syndrome (LIS). Brain-computer interface techniques can be useful to disentangle these states by detecting neurophysiological correlates of conscious processing of information to enable communication with these individuals after the diagnosis. OBJECTIVE: The goal of our study was to evaluate with a user-centered design approach the usability of a mental imagery task to detect signs of voluntary information processing and enabling communication in a group of severely disabled individuals. METHODS: Five individuals with LIS participated in the study. Participants were instructed to imagine hand, arm or feet movements during electroencephalography (EEG) to detect patterns of event-related synchronization/desynchronization associated with each task. After the user-centered design, usability was evaluated (i.e., efficiency, effectiveness and satisfaction). RESULTS: Two participants achieved significant levels of accuracy in 2 different tasks. The associated workload and levels of satisfaction perceived by the users were moderate and were mainly related to the time demand of the task. CONCLUSION: Results showed lack of effectiveness of the task to detect voluntary brain activity and thus detect consciousness or communicate with non-responsive individuals. The application must be modified to be sufficiently satisfying for the intended end-users and suggestions are made in this regard.

Neurophenomenology of near-death experience memory in hypnotic recall: a within-subject EEG study.

The neurobiological basis of near-death experiences (NDEs) is unknown, but a few studies attempted to investigate it by reproducing in laboratory settings phenomenological experiences that seem to closely resemble NDEs. So far, no study has induced NDE-like features via hypnotic modulation while simultaneously measuring changes in brain activity using high-density EEG. Five volunteers who previously had experienced a pleasant NDE were invited to re-experience the NDE memory and another pleasant autobiographical memory (dating to the same time period), in normal consciousness and with hypnosis. We compared the hypnosis-induced subjective experience with the one of the genuine experience memory. Continuous high-density EEG was recorded throughout. At a phenomenological level, we succeeded in recreating NDE-like features without any adverse effects. Absorption and dissociation levels were reported as higher during all hypnosis conditions as compared to normal consciousness conditions, suggesting that our hypnosis-based protocol increased the felt subjective experience in the recall of both memories. The recall of a NDE phenomenology was related to an increase of alpha activity in frontal and posterior regions. This study provides a proof-of-concept methodology for studying the phenomenon, enabling to prospectively explore the NDE-like features and associated EEG changes in controlled settings.

CAN SUBJECTIVE RATINGS OF ABSORPTION, DISSOCIATION, AND TIME PERCEPTION DURING "NEUTRAL HYPNOSIS" PREDICT HYPNOTIZABILITY?: An exploratory study.

This study explored absorption, dissociation, and time perception on visual analogue scales (VAS) after a neutral hypnosis session to predict hypnotizability. Sixty-two subjects completed the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) and, during a neutral hypnosis session, VAS ratings of absorption, dissociation, and time perception. The findings indicated that 44% of subjects scored high, 35% medium, and 21% low on hypnotizability, as determined by scores on the SHSS:C. Dissociation VAS ratings significantly differed when comparing low to high and medium to high hypnotizable subjects. However, ratings were not significantly different between medium and low subjects. Significant positive correlation was found between dissociation VAS ratings and SHSS:C total scores. Future research is needed to validate this proof-of-concept study.

Enhancing clinical communication assessments using an audiovisual BCI for patients with disorders of consciousness.

OBJECTIVE: The JFK coma recovery scale-revised (JFK CRS-R), a behavioral observation scale, is widely used in the clinical diagnosis/assessment of patients with disorders of consciousness (DOC). However, the JFK CRS-R is associated with a high rate of misdiagnosis (approximately 40%) because DOC patients cannot provide sufficient behavioral responses. A brain-computer interface (BCI) that detects command/intention-specific changes in electroencephalography (EEG) signals without the need for behavioral expression may provide an alternative method. APPROACH: In this paper, we proposed an audiovisual BCI communication system based on audiovisual 'yes' and 'no' stimuli to supplement the JFK CRS-R for assessing the communication ability of DOC patients. Specifically, patients were given situation-orientation questions as in the JFK CRS-R and instructed to select the answers using the BCI. MAIN RESULTS: Thirteen patients (eight vegetative state (VS) and five minimally conscious state (MCS)) participated in our experiments involving both the BCI- and JFK CRS-R-based assessments. One MCS patient who received a score of 1 in the JFK CRS-R achieved an accuracy of 86.5% in the BCI-based assessment. Seven patients (four VS and three MCS) obtained unresponsive results in the JFK CRS-R-based assessment but responsive results in the BCI-based assessment, and 4 of those later improved scores in the JFK CRS-R-based assessment. Five patients (four VS and one MCS) obtained usresponsive results in both assessments. SIGNIFICANCE: The experimental results indicated that the audiovisual BCI could provide more sensitive results than the JFK CRS-R and therefore supplement the JFK CRS-R.

Brain plasticity after implanted peroneal nerve electrical stimulation to improve gait in chronic stroke patients: Two case reports.

BACKGROUND: Recent studies have shown that stimulation of the peroneal nerve using an implantable 4-channel peroneal nerve stimulator could improve gait in stroke patients. OBJECTIVES: To assess structural cortical and regional cerebral metabolism changes associated with an implanted peroneal nerve electrical stimulator to correct foot drop related to a central nervous system lesion. METHODS: Two stroke patients presenting a foot drop related to a central nervous system lesion were implanted with an implanted peroneal nerve electrical stimulator. Both patients underwent clinical evaluations before implantation and one year after the activation of the stimulator. Structural magnetic resonance imaging (MRI) and [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) were acquired before and one year after the activation of the stimulator. RESULTS: Foot drop was corrected for both patients after the implantation of the stimulator. After one year of treatment, patient 1 improved in three major clinical tests, while patient 2 only improved in one test. Prior to treatment, FDG-PET showed a significant hypometabolism in premotor, primary and supplementary motor areas in both patients as compared to controls, with patient 2 presenting more widespread hypometabolism. One year after the activation of the stimulator, both patients showed significantly less hypometabolism in the damaged motor cortex. No difference was observed on the structural MRI. CONCLUSION: Clinical improvement of gait under peroneal nerve electrical stimulation in chronic stroke patients presenting foot drop was paralleled to metabolic changes in the damaged motor cortex.

Sedation of Patients With Disorders of Consciousness During Neuroimaging: Effects on Resting State Functional Brain Connectivity.

BACKGROUND: To reduce head movement during resting state functional magnetic resonance imaging, post-coma patients with disorders of consciousness (DOC) are frequently sedated with propofol. However, little is known about the effects of this sedation on the brain connectivity patterns in the damaged brain essential for differential diagnosis. In this study, we aimed to assess these effects. METHODS: Using resting state functional magnetic resonance imaging 3T data obtained over several years of scanning patients for diagnostic and research purposes, we employed a seed-based approach to examine resting state connectivity in higher-order (default mode, bilateral external control, and salience) and lower-order (auditory, sensorimotor, and visual) resting state networks and connectivity with the thalamus, in 20 healthy unsedated controls, 8 unsedated patients with DOC, and 8 patients with DOC sedated with propofol. The DOC groups were matched for age at onset, etiology, time spent in DOC, diagnosis, standardized behavioral assessment scores, movement intensities, and pattern of structural brain injury (as assessed with T1-based voxel-based morphometry). RESULTS: DOC were associated with severely impaired resting state network connectivity in all but the visual network. Thalamic connectivity to higher-order network regions was also reduced. Propofol administration to patients was associated with minor further decreases in thalamic and insular connectivity. CONCLUSIONS: Our findings indicate that connectivity decreases associated with propofol sedation, involving the thalamus and insula, are relatively small compared with those already caused by DOC-associated structural brain injury. Nonetheless, given the known importance of the thalamus in brain arousal, its disruption could well reflect the diminished movement obtained in these patients. However, more research is needed on this topic to fully address the research question.

Cerebral metabolism before and after external trigeminal nerve stimulation in episodic migraine.

Background and aim A recent sham-controlled trial showed that external trigeminal nerve stimulation (eTNS) is effective in episodic migraine (MO) prevention. However, its mechanism of action remains unknown. We performed 18-fluorodeoxyglucose positron emission tomography (FDG-PET) to evaluate brain metabolic changes before and after eTNS in episodic migraineurs. Methods Twenty-eight individuals were recruited: 14 with MO and 20 healthy volunteers (HVs). HVs underwent a single FDG-PET, whereas patients were scanned at baseline, directly after a first prolonged session of eTNS (Cefaly®) and after three months of treatment (uncontrolled study). Results The frequency of migraine attacks significantly decreased in compliant patients ( N = 10). Baseline FDG-PET revealed a significant hypometabolism in fronto-temporal areas, especially in the orbitofrontal (OFC) and rostral anterior cingulate cortices (rACC) in MO patients. This hypometabolism was reduced after three months of eTNS treatment. Conclusion Our study shows that metabolic activity of OFC and rACC, which are pivotal areas in central pain and behaviour control, is decreased in migraine. This hypometabolism is reduced after three months of eTNS. eTNS might thus exert its beneficial effects via slow neuromodulation of central pain-controlling areas, a mechanism also previously reported in chronic migraine and cluster headache after percutaneous occipital nerve stimulation. However, this finding needs to be confirmed by further studies using a sham condition.

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study.

MAIN OBJECTIVE: Disorders of consciousness (DOC; encompassing coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state minus/plus (MCS-/+)) are associated with structural brain injury. The extent of this damage remains poorly understood and merits a detailed examination using novel analysis techniques. Research design/methods and procedures: This study used voxel-based morphometry (VBM) on structural magnetic resonance imaging scans of 61 patients with DOC to examine grey and white matter injury associated with DOC, time spent in DOC, aetiology and diagnosis. MAIN OUTCOMES AND RESULTS: DOC and time spent in DOC were found to be associated with widespread structural brain injury, although the latter did not correlate strongly with injury in the right cerebral hemisphere. Traumatic, as compared to non-traumatic aetiology, was related to more injury in the brainstem, midbrain, thalamus, hypothalamus, basal forebrain, cerebellum, and posterior corpus callosum. Potential structural differences were found between VS/UWS and MCS and between MCS- and MCS+, but need further examination. CONCLUSIONS: The findings indicate that both traumatic and non-traumatic DOC are associated with widespread structural brain injury, although differences exist that could lead to aetiology-specific treatment strategies. Furthermore, the high degree of atrophy occurring after initial brain injury prompts the development and use of neuroprotective techniques to potentially increase patients' chances of recovery.

Cortical reorganization in an astronaut's brain after long-duration spaceflight.

To date, hampered physiological function after exposure to microgravity has been primarily attributed to deprived peripheral neuro-sensory systems. For the first time, this study elucidates alterations in human brain function after long-duration spaceflight. More specifically, we found significant differences in resting-state functional connectivity between motor cortex and cerebellum, as well as changes within the default mode network. In addition, the cosmonaut showed changes in the supplementary motor areas during a motor imagery task. These results highlight the underlying neural basis for the observed physiological deconditioning due to spaceflight and are relevant for future interplanetary missions and vestibular patients.