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See detailQuantifying cortical EEG responses to TMS in (un)consciousness
Sarasso, S; Rosanova, M; Casali, A.G 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 ▲]

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See detailDIRECTED INFORMATION TRANSFER IN SCALP ELECTROENCEPHALOGRAPHIC RECORDINGS: INSIGHTS ON DISORDERS OF CONSCIOUSNESS
Marinazzo, Daniele; Gosseries, Olivia ULg; Boly, Mélanie ULg 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 ▲]

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See detailAmantadine, Apomorphine and Zolpidem in the Treatment of Disorders of Consciousness
Gosseries, Olivia ULg; Charland-Verville, Vanessa ULg; Thonnard, Marie ULg et al

in Current Pharmaceutical Design (2014), 20

Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to ... [more ▼]

Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to improve arousal levels and recovery of consciousness. We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements. These findings are discussed in the context of current hypotheses of these agents' therapeutic mechanisms on cerebral function. In order to enhance our understanding of the underlying pathophysiological mechanisms of these drugs, we suggest combining sensitive and specific behavioral tools with neuroimaging and electrophysiological measures in large randomized, double-blind, placebo-controlled experimental designs. We conclude that the pharmacokinetics and pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration to determine which treatment would provide a better neurological outcome regarding the patient's etiology, diagnosis, time since injury and overall condition. [less ▲]

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See detailDetection of visual pursuit in patients in minimally conscious state: a matter of stimuli and visual plane?
Thonnard, Marie; Wannez, Sarah ULg; Keen, Shannan et al

in Brain injury (2014), 28(9), 1164-70

OBJECTIVES: The aim of this study was to determine whether the assessment of pursuit eye movements in patients in minimally conscious state (MCS) is influenced by the choice of the visual stimulus (study ... [more ▼]

OBJECTIVES: The aim of this study was to determine whether the assessment of pursuit eye movements in patients in minimally conscious state (MCS) is influenced by the choice of the visual stimulus (study 1) and by the moving plane (study 2). METHODS: Patients with MCS (MCS- and MCS+) in the acute (<1 month post-injury) or chronic (>1 month) setting were assessed. The Coma Recovery Scale-Revised (CRS-R) procedure was used to test visual pursuit of a moving mirror, object and person (study 1, n = 88) and to test vertical and horizontal visual tracking (study 2, n = 94). RESULTS: Study 1: Patients with visual pursuit tracked preferentially the moving mirror over the moving person or object. Study 2: Patients displaying visual pursuit, especially in MCS- and in chronic setting, preferentially tracked on the horizontal rather than the vertical plane. CONCLUSION: The findings confirm the importance of using a mirror to assess visual pursuit in patients in MCS and of initiating testing using the horizontal plane, specifically in patients in MCS- and those in chronic setting. Assessment should then be done on the vertical plane if visual pursuit is not detected on the horizontal plane. [less ▲]

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See detailFunctional neuroanatomy of disorders of consciousness
Di Perri, Carol; Stender, Johan; Laureys, Steven ULg et al

in CAVANNA, Andrea (Ed.) Epilepsy and behavior Alteration of Counsciousness in Epilepsy (2014)

Our understanding of the mechanisms of loss and recovery of consciousness, following severe brain injury or during anesthesia, is changing rapidly. Recent neuroimaging studies have shown that patients ... [more ▼]

Our understanding of the mechanisms of loss and recovery of consciousness, following severe brain injury or during anesthesia, is changing rapidly. Recent neuroimaging studies have shown that patients with chronic disorders of consciousness and subjects undergoing general anesthesia present a complex dysfunctionality in the architecture of brain connectivity. At present, the global hallmark of impaired consciousness appears to be amultifaceted dysfunctional connectivity pattern with both within-network loss of connectivity in awidespread frontoparietal network and between-network hyperconnectivity involving other regions such as the insula and ventral tegmental area. Despite ongoing efforts, the mechanisms underlying the emergence of consciousness after severe brain injury are not thoroughly understood. Important questions remain unanswered:What triggers the connectivity impairment leading to disorders of consciousness? Why do some patients recover from coma, while others with apparently similar brain injuries do not? Understanding these mechanisms could lead to a better comprehension of brain function and, hopefully, lead to new therapeutic strategies in this challenging patient population. [less ▲]

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See detailNeuroimaging in Disorders of Consciousness
Bodart, Olivier ULg; Charland-Verville, Vanessa ULg; Laureys, Steven ULg et al

in Filippi, M. (Ed.) Oxford Textbook of Clinical Neurology (2014)

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See detailCommon resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury
Williams, Shawniqua; Conte, Mary; Goldfine, Andrew et al

in eLife (2013)

Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known ... [more ▼]

Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model. In the absence of zolpidem, all subjects show a strong low frequency oscillatory peak ∼6–10 Hz in the EEG power spectrum most prominent over frontocentral regions and with high coherence (∼0.7–0.8) within and between hemispheres. Zolpidem administration sharply reduces EEG power and coherence at these low frequencies. The ∼6–10 Hz activity is proposed to arise from intrinsic membrane properties of pyramidal neurons that are passively entrained across the cortex by locally-generated spontaneous activity. Activation by zolpidem is proposed to arise from a combination of initial direct drug effects on cortical, striatal, and thalamic populations and further activation of underactive brain regions induced by restoration of cognitively-mediated behaviors. [less ▲]

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See detailDynamic change of global and local information processing in Propofol-induced loss and recovery of consciousness
Monti, Martin; Lutkenoff, Evan; Rubinov, Mikail et al

in PLoS Computational Biology (2013), 9

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See detailChanges in Effective Connectivity by Propofol Sedation
Gomez Jaramillo, Francisco Albeiro ULg; Phillips, Christophe ULg; Soddu, Andrea ULg 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 ▲]

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See detailA theoretically based index of consciousness independent of sensory processing and behavior
Casali, AG; Gosseries, Olivia ULg; Rosanova, M et al

in Science Translational Medicine (2013), 5

One challenging aspect of the clinical assessment of brain-injured, unresponsive patients is the lack of an objective measure of consciousness that is independent of the subject's ability to interact with ... [more ▼]

One challenging aspect of the clinical assessment of brain-injured, unresponsive patients is the lack of an objective measure of consciousness that is independent of the subject's ability to interact with the external environment. Theoretical considerations suggest that consciousness depends on the brain's ability to support complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). We introduce and test a theory-driven index of the level of consciousness called the perturbational complexity index (PCI). PCI is calculated by (i) perturbing the cortex with transcranial magnetic stimulation (TMS) to engage distributed interactions in the brain (integration) and (ii) compressing the spatiotemporal pattern of these electrocortical responses to measure their algorithmic complexity (information). We test PCI on a large data set of TMS-evoked potentials recorded in healthy subjects during wakefulness, dreaming, nonrapid eye movement sleep, and different levels of sedation induced by anesthetic agents (midazolam, xenon, and propofol), as well as in patients who had emerged from coma (vegetative state, minimally conscious state, and locked-in syndrome). PCI reliably discriminated the level of consciousness in single individuals during wakefulness, sleep, and anesthesia, as well as in patients who had emerged from coma and recovered a minimal level of consciousness. PCI can potentially be used for objective determination of the level of consciousness at the bedside [less ▲]

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See detailAbnormal corticospinal excitability in patients with disorders of consciousness
Lapitskaya, Natallia; Gosseries, Olivia ULg; DE PASQUA, Victor ULg et al

in Brain Stimulation (2013), Volume 6

Background: Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in ... [more ▼]

Background: Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in patients in vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) and minimally conscious (MCS) states due to severe brain damage remains largely unknown. Objective/hypothesis: It was hypothesized that cortical motor excitability would be decreased and would correlate to the level of consciousness in patients with disorders of consciousness. Methods: Corticospinal excitability was assessed in 47 patients (24 VS/UWS and 23 MCS) and 14 healthy controls. The test parameters included maximal peak-to-peak M-wave (Mmax), F-wave persistence, peripheral and central motor conduction times, sensory (SEP) and motor evoked (MEP) potential latencies and amplitudes, resting motor threshold (RMT), stimulus/response curves, and short latency afferent inhibition (SAI). TMS measurements were correlated to the level of consciousness (assessed using the Coma Recovery Scale-Revised). Results: On average, the patient group had lower Mmax, lower MEP and SEP amplitudes, higher RMTs, narrower stimulus/response curves, and reduced SAI compared to the healthy controls (P < 0.05). The SAI alterations were correlated to the level of consciousness (P < 0.05). Conclusions: The findings demonstrated the impairment of the cortical inhibitory circuits in patients with disorders of consciousness. Moreover, the significant relationship was found between cortical inhibition and clinical consciousness dysfunction. [less ▲]

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See detailAssessment of localisation to auditory stimulation in post-comatose states: Use the patient's own name
Cheng, L; Gosseries, Olivia ULg; Ying, L et al

in BMC Neurology (2013), Vol 13

Background: At present, there is no consensus on how to clinically assess localisation to sound in patients recovering from coma. We here studied auditory localisation using the patient's own name as ... [more ▼]

Background: At present, there is no consensus on how to clinically assess localisation to sound in patients recovering from coma. We here studied auditory localisation using the patient's own name as compared to a meaningless sound (i.e., ringing bell).Methods: Eighty-six post-comatose patients diagnosed with a vegetative state/unresponsive wakefulness syndrome or a minimally conscious state were prospectively included. Localisation of auditory stimulation (i.e., head or eyes orientation toward the sound) was assessed using the patient's own name as compared to a ringing bell. Statistical analyses used binomial testing with bonferroni correction for multiple comparisons.Results: 37 (43%) out of the 86 studied patients showed localisation to auditory stimulation. More patients (n=34, 40%) oriented the head or eyes to their own name as compared to sound (n=20, 23%; p<0.001).Conclusions: When assessing auditory function in disorders of consciousness, using the patient's own name is here shown to be more suitable to elicit a response as compared to neutral sound [less ▲]

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See detailActigraphy assessments of circadian sleep-wake cycles in the Vegetative and Minimally Conscious States
Cruse, Damian; Thibaut, Aurore ULg; Demertzi, Athina ULg et al

in BMC Neuroscience (2013), 11(18),

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See detailSpasticity after stroke: Physiology, assessment and treatment
Thibaut, Aurore ULg; Chatelle, Camille ULg; Ziegler, Erik ULg et al

in Brain Injury (2013), 27(10), 1093-1105

Spasticity following a stroke occurs in about 30% of patients. The mechanisms underlying this disorder, however, are not well understood. This review aims to define spasticity, describe hypotheses ... [more ▼]

Spasticity following a stroke occurs in about 30% of patients. The mechanisms underlying this disorder, however, are not well understood. This review aims to define spasticity, describe hypotheses explaining its development after a stroke, give an overview of related neuroimaging studies as well as a description of the most common scales used to quantify the degree of spasticity and finally explore which treatments are currently being used to treat this disorder. The lack of consensus is highlighted on the basis of spasticity and the associated absence of guidelines for treatment, use of drugs and rehabilitation programmes. Future studies require controlled protocols to determine the efficiency of pharmacological and non-pharmacological treatments for spasticity. Neuroimaging may help predict the occurrence of spasticity and could provide insight into its neurological basis. [less ▲]

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See detailComa and disorders of consciousness: scientific advances and practical considerations for clinicians
Bodart, Olivier ULg; Laureys, Steven ULg; Gosseries, Olivia ULg

in Seminars in Neurology (2013), 33

Recently, neuroscientists and clinicians have seen the rapid evolution of diagnoses in disorders of consciousness. The unresponsive wakefulness syndrome–vegetative state, the minimally conscious state ... [more ▼]

Recently, neuroscientists and clinicians have seen the rapid evolution of diagnoses in disorders of consciousness. The unresponsive wakefulness syndrome–vegetative state, the minimally conscious state plus and minus, and the functional locked-in syndrome have been defined using new neuroimaging techniques. Diffusion tensor imaging, positron emission tomography, functional magnetic resonance imaging, electroen- cephalography, and transcranial magnetic stimulation techniques have all promoted important discoveries in the field of disorders of consciousness. This has led to a better understanding of these patients’ condition and to the development of new prognosis, therapeutic, and communication tools. However, low sensitivity and artifacts problems need to be solved to bring these new technologies to the single-patient level; they also need to be studied in larger scale and randomized control trials. In addition, new ethics questions have arisen and need to be investigated. [less ▲]

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See detailA multiscale method for a robust detection of the default mode network.
Baquero, Katherine; Gómez, Francisco; Cifuentes, Christian et al

Poster (2013)

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See detailLa stimulation transcranienne a courant continu : un nouvel outil de neurostimulation.
Thibaut, Aurore ULg; Chatelle, Camille ULg; Gosseries, Olivia ULg et al

in Revue Neurologique (2013), 169

Transcranial direct current stimulation (tDCS) is a safe method to modulate cortical excitability. Anodal stimulation can improve the stimulated area's functions whereas cathodal stimulation reduces them ... [more ▼]

Transcranial direct current stimulation (tDCS) is a safe method to modulate cortical excitability. Anodal stimulation can improve the stimulated area's functions whereas cathodal stimulation reduces them. Currently, a lot of clinical trials have been conducted to study the effect of tDCS on post-stroke motor and language deficits, in depression, chronic pain, memory impairment and tinnitus in order to decrease symptoms. Results showed that, if an effect is observed with tDCS, it does not persist over time. Current studies suggest that direct current stimulation is a promising technique that helps to improve rehabilitation after stroke, to enhance cognitive deficiencies, to reduce depression and to relieve chronic pain. Moreover, it is a safe, simple and cheap device that could be easily integrated in a rehabilitation program. [less ▲]

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See detailCorticospinal excitability in patients with anoxic, traumatic, and non-traumatic diffuse brain injury.
Lapitskaya, Natallia; Moerk, Sofie Kirial; Gosseries, Olivia ULg et al

in Brain Stimulation (2013), 6(2),

BACKGROUND: Transcranial magnetic stimulation (TMS) have been frequently used to explore changes in motor cortex excitability in stroke and traumatic brain injury, while the extent of motor cortex ... [more ▼]

BACKGROUND: Transcranial magnetic stimulation (TMS) have been frequently used to explore changes in motor cortex excitability in stroke and traumatic brain injury, while the extent of motor cortex reorganization in patients with diffuse non-traumatic brain injury remains largely unknown. OBJECTIVE/HYPOTHESIS: It was hypothesized that the motor cortex excitability would be decreased and would correlate to the severity of brain injury and level of functioning in patients with anoxic, traumatic, and non-traumatic diffuse brain injury. METHODS: TMS was applied to primary motor cortices of 19 patients with brain injury (5 traumatic and 14 non-traumatic causes; on average four months after insult), and 9 healthy controls. The test parameters included resting motor threshold (RMT), short intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI). Excitability parameters were correlated to the severity of brain injury measured with Glasgow Coma Scale and the level of functioning assessed using the Ranchos Los Amigos Levels of Cognitive Functioning Assessment Scale and Functional Independence Measure. RESULTS: The patient group revealed a significantly decreased SICI and SAI compared to healthy controls with the amount of SICI correlated significantly to the severity of brain injury. Other electrophysiological parameters did not differ between the groups and did not exhibit any significant relationship with clinical functional scores. CONCLUSIONS: The present study demonstrated the impairment of the cortical inhibitory circuits in patients with brain injury of traumatic and non-traumatic aetiology. Moreover, the significant correlation was found between the amount of SICI and the severity of brain injury. [less ▲]

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See detailThalamus, Brainstem and Salience Network Connectivity Changes During Propofol-Induced Sedation and Unconsciousness
Guldenmund, Justus Pieter ULg; Demertzi, Athina ULg; BOVEROUX, Pierre ULg 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 ▲]

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