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Spontaneous Recovery from Unresponsive Wakefulness Syndrome to a Minimally Conscious State: Early Structural Changes Revealed by 7-T Magnetic Resonance Imaging.

ABSTRACT: 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.

SUBMITTER: Tan X

PROVIDER: S-EPMC5776100 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Spontaneous Recovery from Unresponsive Wakefulness Syndrome to a Minimally Conscious State: Early Structural Changes Revealed by 7-T Magnetic Resonance Imaging.

Tan Xufei X Gao Jian J Zhou Zhen Z Wei Ruili R Gong Ting T Wu Yuqin Y Liu Kehong K He Fangping F Wang Junyang J Li Jingqi J Zhang Xiaotong X Pan Gang G Luo Benyan B

Frontiers in neurology 20180117

<h4>Background</h4>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.<h4>Objective</h4>This study used a multi-modal neuroimaging approach to investigate early structural changes during spontaneous recovery from VS ...[more]

PMID: 29387037

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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:Recently, the cortical source of blink-related delta oscillations (delta BROs) in resting healthy subjects has been localized in the posterior cingulate cortex/precuneus (PCC/PCu), one of the main core-hubs of the default-mode network. This has been interpreted as the electrophysiological signature of the automatic monitoring of the surrounding environment while subjects are immersed in self-reflecting mental activities. Although delta BROs were directly correlated to the degree of consciousness impairment in patients with disorders of consciousness, they failed to differentiate vegetative state/unresponsive wakefulness syndrome (VS/UWS) from minimally conscious state (MCS). In the present study, we have extended the analysis of BROs to frequency bands other than delta in the attempt to find a biological marker that could support the differential diagnosis between VS/UWS and MCS. Four patients with VS/UWS, 5 patients with MCS, and 12 healthy matched controls (CTRL) underwent standard 19-channels EEG recordings during resting conditions. Three-second-lasting EEG epochs centred on each blink instance were submitted to time-frequency analyses in order to extract the normalized Blink-Related Synchronization/Desynchronization (nBRS/BRD) of three bands of interest (low-alpha, high-alpha and low-beta) in the time-window of 50-550 ms after the blink-peak and to estimate the corresponding cortical sources of electrical activity. VS/UWS nBRS/BRD levels of all three bands were lower than those related to both CTRL and MCS, thus enabling the differential diagnosis between MCS and VS/UWS. Furthermore, MCS showed an intermediate signal intensity on PCC/PCu between CTRL and VS/UWS and a higher signal intensity on the left temporo-parieto-occipital junction and inferior occipito-temporal regions when compared to VS/UWS. This peculiar pattern of activation leads us to hypothesize that resting MCS patients have a bottom-up driven activation of the task positive network and thus are tendentially prone to respond to environmental stimuli, even though in an almost unintentional way.

Project description:ObjectiveA minimally conscious state (MCS) is characterized by discernible behavioral evidence of consciousness that cannot be reproduced consistently. This condition is highly challenging to treat. Recent studies have demonstrated the potential therapeutic effect of non-invasive brain stimulation in patients with MCS. In one patient in an MCS, we delivered simultaneous transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) based on an individual brain network analysis and evaluated the therapeutic effect.MethodsThe directional transfer function (DTF) was calculated based on electroencephalograph (EEG) analysis. Global brain connectivity was calculated based on functional magnetic resonance imaging (fMRI) analysis. By referring to the EEG and fMRI results, we identified inferior parietal lobes (IPLs) as targets. In the 2-week treatment period, 14 sessions were applied to the identified bilateral parietal regions. Simultaneous 1.5-mA anodal tDCS and 5-Hz rTMS were delivered for 20 min per hemisphere in each session. Clinical evaluation scores were recorded weekly throughout the treatment. A second patient given the routine treatment was evaluated as a control.ResultsThe clinical scores of patient 1 with MCS improved after 2 weeks of stimulation treatment, and the effect lasted for up to 1 month. EEG analysis showed a significant increase (p < 0.001) in the DTF value in the gamma band in a bilateral set of posterior regions, and fMRI showed a trend toward normalized activity in the IPLs. The clinical scores of patient 2 with coma did not improve much after 2 weeks of routine treatment. The EEG analysis showed a significant increase (p = 0.021) in the DTF value in the gamma band in a bilateral set of posterior regions.ConclusionThe application of EEG and fMRI to characterize the functional connectivity features of the network in an MCS patient provided a reasonable and accurate stimulation target and verified the changes in functional connectivity resulting from stimulation.

Project description:The existence of normal sleep in patients in a vegetative state is still a matter of debate. Previous electrophysiological sleep studies in patients with disorders of consciousness did not differentiate patients in a vegetative state from patients in a minimally conscious state. Using high-density electroencephalographic sleep recordings, 11 patients with disorders of consciousness (six in a minimally conscious state, five in a vegetative state) were studied to correlate the electrophysiological changes associated with sleep to behavioural changes in vigilance (sustained eye closure and muscle inactivity). All minimally conscious patients showed clear electroencephalographic changes associated with decreases in behavioural vigilance. In the five minimally conscious patients showing sustained behavioural sleep periods, we identified several electrophysiological characteristics typical of normal sleep. In particular, all minimally conscious patients showed an alternating non-rapid eye movement/rapid eye movement sleep pattern and a homoeostatic decline of electroencephalographic slow wave activity through the night. In contrast, for most patients in a vegetative state, while preserved behavioural sleep was observed, the electroencephalographic patterns remained virtually unchanged during periods with the eyes closed compared to periods of behavioural wakefulness (eyes open and muscle activity). No slow wave sleep or rapid eye movement sleep stages could be identified and no homoeostatic regulation of sleep-related slow wave activity was observed over the night-time period. In conclusion, we observed behavioural, but no electrophysiological, sleep wake patterns in patients in a vegetative state, while there were near-to-normal patterns of sleep in patients in a minimally conscious state. These results shed light on the relationship between sleep electrophysiology and the level of consciousness in severely brain-damaged patients. We suggest that the study of sleep and homoeostatic regulation of slow wave activity may provide a complementary tool for the assessment of brain function in minimally conscious state and vegetative state patients.

Dataset Information

Spontaneous Recovery from Unresponsive Wakefulness Syndrome to a Minimally Conscious State: Early Structural Changes Revealed by 7-T Magnetic Resonance Imaging.

Publications

Spontaneous Recovery from Unresponsive Wakefulness Syndrome to a Minimally Conscious State: Early Structural Changes Revealed by 7-T Magnetic Resonance Imaging.

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