Assessing consciousness in coma and related states using transcranial magnetic stimulation combined with electroencephalography.
Gosseries, Olivia ; Thibaut, Aurore ; Boly, Mélanie et al
in Annales Françaises d'Anesthésie et de Réanimation (2014)
Thanks to advances in medical care, an increased number of patients recover from coma. However, some remain in vegetative/unresponsive wakefulness syndrome or in a minimally conscious state. Detection of ... [more ▼]
Thanks to advances in medical care, an increased number of patients recover from coma. However, some remain in vegetative/unresponsive wakefulness syndrome or in a minimally conscious state. Detection of awareness in severely brain-injured patients is challenging because it relies on behavioral assessments, which can be affected by motor, sensory and cognitive impairments of the patients. Other means of evaluation are needed to improve the accuracy of the diagnosis in this challenging population. We will here review the different altered states of consciousness occurring after severe brain damage, and explain the difficulties associated with behavioral assessment of consciousness. We will then describe a non-invasive technique, transcranial magnetic stimulation combined with high-density electroencephalography (TMS-EEG), which has allowed us to detect the presence or absence of consciousness in different physiological, pathological and pharmacological states. Some potential underlying mechanisms of the loss of consciousness will then be discussed. In conclusion, TMS-EEG is highly promising in identifying markers of consciousness at the individual level and might be of great value for clinicians in the assessment of consciousness. [less ▲]Detailed reference viewed: 41 (7 ULg)
Quantifying cortical EEG responses to TMS in (un)consciousness
; ; et al
in Clinical EEG and Neuroscience : Official Journal of the EEG and Clinical Neuroscience Society (ENCS) (2014)
We normally assess another individual's level of consciousness based on her or his ability to interact with the surrounding environment and communicate. Usually, if we observe purposeful behavior ... [more ▼]
We normally assess another individual's level of consciousness based on her or his ability to interact with the surrounding environment and communicate. Usually, if we observe purposeful behavior, appropriate responses to sensory inputs, and, above all, appropriate answers to questions, we can be reasonably sure that the person is conscious. However, we know that consciousness can be entirely within the brain, even in the absence of any interaction with the external world; this happens almost every night, while we dream. Yet, to this day, we lack an objective, dependable measure of the level of consciousness that is independent of processing sensory inputs and producing appropriate motor outputs. Theoretically, consciousness is thought to require the joint presence of functional integration and functional differentiation, otherwise defined as brain complexity. Here we review a series of recent studies in which Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) has been employed to quantify brain complexity in wakefulness and during physiological (sleep), pharmacological (anesthesia) and pathological (brain injury) loss of consciousness. These studies invariably show that the complexity of the cortical response to TMS collapses when consciousness is lost during deep sleep, anesthesia and vegetative state following severe brain injury, while it recovers when consciousness resurges in wakefulness, during dreaming, in the minimally conscious state or locked-in syndrome. The present paper will also focus on how this approach may contribute to unveiling the pathophysiology of disorders of consciousness affecting brain-injured patients. Finally, we will underline some crucial methodological aspects concerning TMS/EEG measurements of brain complexity. [less ▲]Detailed reference viewed: 37 (4 ULg)
DIRECTED INFORMATION TRANSFER IN SCALP ELECTROENCEPHALOGRAPHIC RECORDINGS: INSIGHTS ON DISORDERS OF CONSCIOUSNESS
; Gosseries, Olivia ; Boly, Mélanie et al
in Clinical EEG and Neuroscience : Official Journal of the EEG and Clinical Neuroscience Society (ENCS) (2014)
Introduction: The neural mechanisms underlying electrophysiological changes observed in patients with disorders of consciousness following a coma remain poorly understood. The aim of this article is to ... [more ▼]
Introduction: The neural mechanisms underlying electrophysiological changes observed in patients with disorders of consciousness following a coma remain poorly understood. The aim of this article is to investigate the mechanisms underlying the differences in spontaneous electroencephalography between patients in vegetative/unresponsive wakefulness syndrome, minimally conscious state, emergence of the minimally conscious state and age-matched healthy control subjects. <br />Methods: Forty recording of spontaneous scalp electroencephalography were performed in 27 patients who were comatose on admission, and on healthy controls. Multivariate Granger Causality and Transfer Entropy were applied on the data. <br />Results: Distinctive patterns of putative bottlenecks of information were associated to each conscious state. Healthy controls are characterized by a greater amount of synergetic contributions from duplets of variables. <br />Conclusion: A novel set of measures was tested to get a novel insight on the pattern of information transfer in a network of scalp electrodes in patients with disorders of consciousness. [less ▲]Detailed reference viewed: 44 (7 ULg)
Dynamic change of global and local information processing in Propofol-induced loss and recovery of consciousness
; ; et al
in PLoS Computational Biology (2013), 9Detailed reference viewed: 108 (23 ULg)
Changes in Effective Connectivity by Propofol Sedation
Gomez Jaramillo, Francisco Albeiro ; Phillips, Christophe ; Soddu, Andrea et al
in PLoS ONE (2013), 8(8), 71370
Mechanisms of propofol-induced loss of consciousness remain poorly understood. Recent fMRI studies have shown decreases in functional connectivity during unconsciousness induced by this anesthetic agent ... [more ▼]
Mechanisms of propofol-induced loss of consciousness remain poorly understood. Recent fMRI studies have shown decreases in functional connectivity during unconsciousness induced by this anesthetic agent. Functional connectivity does not provide information of directional changes in the dynamics observed during unconsciousness. The aim of the present study was to investigate, in healthy humans during an auditory task, the changes in effective connectivity resulting from propofol induced loss of consciousness. We used Dynamic Causal Modeling for fMRI (fMRI-DCM) to assess how causal connectivity is influenced by the anesthetic agent in the auditory system. Our results suggest that the dynamic observed in the auditory system during unconsciousness induced by propofol, can result in a mixture of two effects: a local inhibitory connectivity increase and a decrease in the effective connectivity in sensory cortices. [less ▲]Detailed reference viewed: 312 (11 ULg)
Thalamus, Brainstem and Salience Network Connectivity Changes During Propofol-Induced Sedation and Unconsciousness
Guldenmund, Justus Pieter ; Demertzi, Athina ; BOVEROUX, Pierre et al
in Brain connectivity (2013), 3
In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based ... [more ▼]
In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based on independent component analysis and a classical seed-based analysis. Contrary to previous propofol research, which mainly emphasized the importance of connectivity in the default mode network (DMN) and external control network (ECN), we focused on the salience network, thalamus, and brainstem. The importance of these brain regions in brain arousal and organization merits a more detailed examination of their connectivity response to propofol. We found that the salience network disintegrated during propofol-induced unconsciousness. The thalamus decreased connectivity with the DMN, ECN, and salience network, while increasing connectivity with sensorimotor and auditory/insular cortices. Brainstem regions disconnected from the DMN with unconsciousness, while the pontine tegmental area increased connectivity with the insulae during mild sedation. These findings illustrate that loss of consciousness is associated with a wide variety of decreases and increases of both cortical and subcortical connectivity. It furthermore stresses the necessity of also examining resting state connectivity in networks representing arousal, not only those associated with awareness. [less ▲]Detailed reference viewed: 51 (12 ULg)
Interaction between hippocampal and striatal systems predicts subsequent consolidation of motor sequence memory.
; ; Vandewalle, Gilles et al
in PLoS ONE (2013), 8(3), 59490Detailed reference viewed: 15 (3 ULg)
Neural correlates of consciousness during general anesthesia using functional magnetic resonance imaging (fMRI).
BONHOMME, Vincent ; ; Brichant, Jean-François et al
in Archives italiennes de biologie (2012), 150(2-3), 155-63
This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose ... [more ▼]
This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose function is hierarchically altered in a dose-dependent manner. Higher order networks, thought to be involved in mental content generation, as well as sub-cortical networks involved in thalamic activity regulation seems to be affected first by increasing concentrations of hypnotic agents that enhance inhibitory neurotransmission. Lower order sensory networks are preserved, including thalamo-cortical connectivity into those networks, even at concentrations that suppress responsiveness, but cross-modal sensory interactions are inhibited. Thalamo-cortical connectivity into the consciousness networks decreases with increasing concentrations of those agents, and is transformed into an anti-correlated activity between the thalamus and the cortex for the deepest levels of sedation, when the subject is non responsive. Future will tell us whether these brain function alterations are also observed with hypnotic agents that mainly inhibit excitatory neurotransmission. The link between the observations made using fMRI and the identified biochemical targets of hypnotic anesthetic agents still remains to be identified. [less ▲]Detailed reference viewed: 18 (2 ULg)
Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness.
Boly, Mélanie ; ; et al
in The Journal of neuroscience : the official journal of the Society for Neuroscience (2012), 32(20), 7082-90
The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast ... [more ▼]
The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics. [less ▲]Detailed reference viewed: 29 (4 ULg)
Neural Correlates of Performance Variabilty during Motor Sequence Acquisition
Albouy, Geneviève ; ; Vandewalle, Gilles et al
in NeuroImage (2012), 60(1), 324-331Detailed reference viewed: 63 (15 ULg)
Granger causality analysis of steady-state electroencephalographic signals during propofol-induced anaesthesia.
; ; Bruno, Marie-Aurélie et al
in PLoS ONE (2012), 7(1), 29072
Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed ... [more ▼]
Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as 'integrated information' and 'causal density'. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness. [less ▲]Detailed reference viewed: 127 (5 ULg)
A default mode of brain function in altered states of consciousness.
; Vanhaudenhuyse, Audrey ; Boly, Mélanie et al
in Archives Italiennes de Biologie (2012), 150(2-3), 107-21
Using modern brain imaging techniques, new discoveries are being made concerning the spontaneous activity of the brain when it is devoid of attention-demanding tasks. Spatially separated patches of ... [more ▼]
Using modern brain imaging techniques, new discoveries are being made concerning the spontaneous activity of the brain when it is devoid of attention-demanding tasks. Spatially separated patches of neuronal assemblies have been found to show synchronized oscillatory activity behavior and are said to be functionally connected. One of the most robust of these is the default mode network, which is associated with intrinsic processes like mind wandering and self-projection. Furthermore, activity in this network is anticorrelated with activity in a network that is linked to attention to external stimuli. The integrity of both networks is disturbed in altered states of consciousness, like sleep, general anesthesia and hypnosis. In coma and related disorders of consciousness, encompassing the vegetative state (unresponsive wakefulness syndrome) and minimally conscious state, default mode network integrity correlates with the level of remaining consciousness, offering the possibility of using this information for diagnostic and prognostic purposes. Functional brain imaging is currently being validated as a valuable addition to the standardized behavioral assessments that are already in use. [less ▲]Detailed reference viewed: 182 (4 ULg)
The fate of incoming stimuli during NREM sleep is determined by spindles and the phase of the slow oscillation
; Dang Vu, Thien Thanh ; et al
in Frontiers in Neurology (2012), 3(40), 1-11Detailed reference viewed: 20 (2 ULg)
Metabolic activity in external and internal awareness networks in severely brain-damaged patients.
Thibaut, Aurore ; Bruno, Marie-Aurélie ; Chatelle, Camille et al
in Journal of Rehabilitation Medicine (2012), 44(6), 487-94
OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been ... [more ▼]
OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been identified recently. This study measured brain metabolism in both networks in patients with severe brain damage. DESIGN: Prospective [18F]-fluorodeoxyglucose-positron emission tomography and Coma Recovery Scale-Revised assessments in a university hospital setting. SUBJECTS: Healthy volunteers and patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from MCS (EMCS), and locked-in syndrome (LIS). RESULTS: A total of 70 patients were included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS showed impairment in posterior cingulate/retrosplenial cortices. LIS showed dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total scores correlated with metabolic activity in both extrinsic and part of the intrinsic network and thalami. CONCLUSION: Progressive recovery of extrinsic and intrinsic awareness network activity was observed in severely brain-damaged patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic network impairment in MCS could reflect altered internal/self-awareness in these patients, which is difficult to quantify at the bedside. [less ▲]Detailed reference viewed: 246 (55 ULg)
Reduction in inter-hemispheric connectivity in disorders of consciousness.
; ; Soddu, Andrea et al
in PLoS ONE (2012), 7(5), 37238
Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC ... [more ▼]
Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC diagnosis may be offered by the analysis of ultra-slow (<0.1 Hz) spontaneous brain activity fluctuations measured with functional magnetic resonance imaging (fMRI) during the resting-state. Previous work has shown reduced functional connectivity within the "default network", a subset of regions known to be deactivated during engaging tasks, which correlated with the degree of consciousness impairment. However, it remains unclear whether the breakdown of connectivity is restricted to the "default network", and to what degree changes in functional connectivity can be observed at the single subject level. Here, we analyzed resting-state inter-hemispheric connectivity in three homotopic regions of interest, which could reliably be identified based on distinct anatomical landmarks, and were part of the "Extrinsic" (externally oriented, task positive) network (pre- and postcentral gyrus, and intraparietal sulcus). Resting-state fMRI data were acquired for a group of 11 healthy subjects and 8 DOC patients. At the group level, our results indicate decreased inter-hemispheric functional connectivity in subjects with impaired awareness as compared to subjects with intact awareness. Individual connectivity scores significantly correlated with the degree of consciousness. Furthermore, a single-case statistic indicated a significant deviation from the healthy sample in 5/8 patients. Importantly, of the three patients whose connectivity indices were comparable to the healthy sample, one was diagnosed as locked-in. Taken together, our results further highlight the clinical potential of resting-state connectivity analysis and might guide the way towards a connectivity measure complementing existing DOC diagnosis. [less ▲]Detailed reference viewed: 30 (2 ULg)
Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients.
Bruno, Marie-Aurélie ; Majerus, Steve ; Boly, Mélanie et al
in Journal of Neurology (2012), 259(6), 1087-98
Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this ... [more ▼]
Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [(18)F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 +/- 18 years) and 27 MCS patients of whom 13 were MCS- (aged 49 +/- 19 years; 4 traumatic; 21 +/- 23 months post injury) and 14 MCS+ (aged 43 +/- 19 years; 5 traumatic; 19 +/- 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS- as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS- is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression. [less ▲]Detailed reference viewed: 233 (10 ULg)
Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.
; Gosseries, Olivia ; et al
in Brain : A Journal of Neurology (2012), 135(Pt 4), 1308-20
Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing ... [more ▼]
Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment. [less ▲]Detailed reference viewed: 85 (2 ULg)
Brain connectivity in disorders of consciousness.
Boly, Mélanie ; ; et al
in Brain connectivity (2012), 2(1), 1-10
The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest ... [more ▼]
The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest developed for the use of functional neuroimaging as a new diagnostic tool in these patients. In this context, particular attention has been devoted to connectivity studies-as these, more than measures of brain metabolism, may be more appropriate to capture the dynamics of large populations of neurons. Here, we will review the pros and cons of various connectivity methods as potential diagnostic tools in brain-damaged patients with DOC. We will also discuss the relevance of the study of the level versus the contents of consciousness in this context. [less ▲]Detailed reference viewed: 45 (1 ULg)
Hierarchical clustering of brain activity during human nonrapid eye movement sleep.
Boly, Mélanie ; ; et al
in Proceedings of the National Academy of Sciences of the United States of America (2012)
Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM ... [more ▼]
Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM sleep is associated with an increased modularity of brain activity. Cerebral connectivity was quantified in resting-state functional magnetic resonance imaging times series acquired in 13 healthy volunteers during wakefulness and NREM sleep. The analysis revealed a modification of the hierarchical organization of large-scale networks into smaller independent modules during NREM sleep, independently from EEG markers of the slow oscillation. Such modifications in brain connectivity, possibly driven by sleep ultraslow oscillations, could hinder the brain's ability to integrate information and account for decreased consciousness during NREM sleep. [less ▲]Detailed reference viewed: 61 (4 ULg)