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Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome.

ABSTRACT: Up to 40% of individuals with unresponsive wakefulness syndrome (UWS) actually might be conscious. Recent attempts to detect covert consciousness in behaviorally unresponsive patients via neurophysiological patterns are limited by the need to compare data from brain-injured patients to healthy controls. In this report, we pilot an alternative within-subject approach by using propofol to perturb the brain state of a patient diagnosed with UWS. An auditory stimulation series was presented to the patient before, during, and after exposure to propofol while high-density electroencephalograph (EEG) was recorded. Baseline analysis revealed residual markers in the continuous EEG and event-related potentials (ERPs) that have been associated with conscious processing. However, these markers were significantly distorted by the patient's pathology, challenging the interpretation of their functional significance. Upon exposure to propofol, changes in EEG characteristics were similar to what is seen in healthy individuals and ERPs associated with conscious processing disappeared. At the 1-month follow up, the patient had regained consciousness. We offer three alternative explanations for these results: (1) the patient was covertly consciousness, and was anesthetized by propofol administration; (2) the patient was unconscious, and the observed EEG changes were a propofol-specific phenomenon; and (3) the patient was unconscious, but his brain networks responded normally in a way that heralded the possibility of recovery. These alternatives will be tested in a larger study, and raise the intriguing possibility of using a general anesthetic as a probe of brain states in behaviorally unresponsive patients.

SUBMITTER: Blain-Moraes S

PROVIDER: S-EPMC4889589 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome.

Blain-Moraes Stefanie S Boshra Rober R Ma Heung Kan HK Mah Richard R Ruiter Kyle K Avidan Michael M Connolly John F JF Mashour George A GA

Frontiers in human neuroscience 20160602

Up to 40% of individuals with unresponsive wakefulness syndrome (UWS) actually might be conscious. Recent attempts to detect covert consciousness in behaviorally unresponsive patients via neurophysiological patterns are limited by the need to compare data from brain-injured patients to healthy controls. In this report, we pilot an alternative within-subject approach by using propofol to perturb the brain state of a patient diagnosed with UWS. An auditory stimulation series was presented to the p ...[more]

PMID: 27313518

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Project description:IntroductionBehavioral and cerebral dissociation has been now clearly established in some patients with acquired disorders of consciousness (DoC). Altogether, these studies mainly focused on the preservation of high-level cognitive markers in prolonged DoC, but did not specifically investigate lower but key-cognitive functions to consciousness emergence, such as the ability to take a first-person perspective, notably at the acute stage of coma. We made the hypothesis that the preservation of self-recognition (i) is independent of the behavioral impairment of consciousness, and (ii) can reflect the ability to recover consciousness.MethodsHence, using bedside Electroencephalography (EEG) recordings, we acquired, in a large cohort of 129 severely brain damaged patients, the brain response to the passive listening of the subject's own name (SON) and unfamiliar other first names (OFN). One hundred and twelve of them (mean age ± SD = 46 ± 18.3 years, sex ratio M/F: 71/41) could be analyzed for the detection of an individual and significant discriminative P3 event-related brain response to the SON as compared to OFN ('SON effect', primary endpoint assessed by temporal clustering permutation tests).ResultsPatients were either coma (n = 38), unresponsive wakefulness syndrome (UWS, n = 30) or minimally conscious state (MCS, n = 44), according to the revised version of the Coma Recovery Scale (CRS-R). Overall, 33 DoC patients (29%) evoked a 'SON effect'. This electrophysiological index was similar between coma (29%), MCS (23%) and UWS (34%) patients (p = 0.61). MCS patients at the time of enrolment were more likely to emerged from MCS (EMCS) at 6 months than coma and UWS patients (p = 0.013 for comparison between groups). Among the 72 survivors' patients with event-related responses recorded within 3 months after brain injury, 75% of the 16 patients with a SON effect were EMCS at 6 months, while 59% of the 56 patients without a SON effect evolved to this favorable behavioral outcome.DiscussionAbout 30% of severely brain-damaged patients suffering from DoC are capable to process salient self-referential auditory stimuli, even in case of absence of behavioral detection of self-conscious processing. We suggest that self-recognition covert brain ability could be an index of consciousness recovery, and thus could help to predict good outcome.

Project description:Background:Determining the early changes of brain structure that occur from vegetative state/unresponsive wakefulness syndrome (VS/UWS) to a minimally conscious state (MCS) is important for developing our understanding of the processes underlying disorders of consciousness (DOC), particularly during spontaneous recovery from severe brain damage. Objective:This study used a multi-modal neuroimaging approach to investigate early structural changes during spontaneous recovery from VS/UWS to MCS. Methods:The Coma Recovery Scale-Revised (CRS-R) score, 24-h electroencephalography (EEG), and ultra-high field 7-T magnetic resonance imaging were used to investigate a male patient with severe brain injury when he was in VS/UWS compared to MCS. Using white matter connectometry analysis, fibers in MCS were compared with the same fibers in VS/UWS. Whole-brain analysis was used to compare all fibers showing a 10% increase in density with each other as a population. Results:Based on connectometry analysis, the number of fibers with increased density, and the magnitude of increase in MCS compared to VS/UWS, was greatest in the area of the temporoparietal junction (TPJ), and was mostly located in the right hemisphere. These results are in accordance with the active areas observed on 24-h EEG recordings. Moreover, analysis of different fibers across the brain, showing at least a 10% increase in density, revealed that altered white matter connections with higher discriminative weights were located within or across visual-related areas, including the cuneus_R, calcarine_R, occipital_sup_R, and occipital_mid_R. Furthermore, the temporal_mid_R, which is related to the auditory cortex, showed the highest increase in connectivity to other areas. This was consistent with improvements in the visual and auditory components of the CRS-R, which were greater than other improvements. Conclusion:These results provide evidence to support the important roles for the TPJ and the visual and auditory sensory systems in the early recovery of a patient with severe brain injury. Our findings may facilitate a much deeper understanding of the mechanisms underlying conscious-related processes and enlighten treatment strategies for patients with DOC.

Project description:The extent to which people ascribe mind to others has been shown to predict the extent to which human rights are conferred. Therefore, in the context of disorders of consciousness (DOC), mind ascription can influence end of life decisions. A previous US-American study indicated that participants ascribed even less mind to patients with unresponsive-wakefulness-syndrome (UWS) than to the dead. Results were explained in terms of implicit dualism and religious beliefs, as highly religious people ascribed least mind to UWS. Here, we addresses mind ascription to UWS patients in Germany.We investigate the perception of UWS patients in a large German sample (N?=?910) and compare the results to the previous US data, addressing possible cultural differences. We further assess effects of medical expertise, age, gender, socio-economic status and subjective knowledge about UWS in the German sample.Unlike the US sample, German participants did not perceive UWS patients as "more dead than dead", ascribing either equal (on 3 of 5 items) or more (on 2 items) mental abilities to UWS patients than to the dead. Likewise, an effect of implicit dualism was not replicated and German medically trained participants ascribed more capabilities to UWS patients than did a non-medical sample. Within the German sample, age, gender, religiosity and socio-economic status explained about 15% of the variability of mind ascription. Age and religiosity were individually significant predictors, younger and more religious people ascribing more mind. Gender had no effect.Results are consistent with cross-cultural differences in the perception of UWS between Germany and the USA, Germans ascribing more mind to UWS patients. The German sample ascribed as much or more but not less mind to a UWS patient than to a deceased, although within group variance was large, calling for further research. Mind ascription is vital, because, in times of declining resources for healthcare systems, and an increasing legalization of euthanasia, public opinion will influence UWS patients' rights and whether 'the right to die' will be the only right conceded to them.

Dataset Information

Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome.

Publications

Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome.

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