Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.

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 ▲]

Propofol anesthesia and sleep: a high-density EEG study.

in Sleep (2011), 34(3), 283-91

STUDY OBJECTIVES: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical ... [more ▼]

STUDY OBJECTIVES: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical processes underlying propofol anesthesia and compare them to sleep. DESIGN: 256-channel EEG recordings in humans during propofol anesthesia. SETTING: Hospital operating room. PATIENTS OR PARTICIPANTS: 8 healthy subjects (4 males) INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Initially, propofol induced increases in EEG power from 12-25 Hz. Loss of consciousness (LOC) was accompanied by the appearance of EEG slow waves that resembled the slow waves of NREM sleep. We compared slow waves in propofol to slow waves recorded during natural sleep and found that both populations of waves share similar cortical origins and preferentially propagate along the mesial components of the default network. However, propofol slow waves were spatially blurred compared to sleep slow waves and failed to effectively entrain spindle activity. Propofol also caused an increase in gamma (25-40 Hz) power that persisted throughout LOC. Source modeling analysis showed that this increase in gamma power originated from the anterior and posterior cingulate cortices. During LOC, we found increased gamma functional connectivity between these regions compared to the wakefulness. CONCLUSIONS: Propofol anesthesia is a sleep-like state and slow waves are associated with diminished consciousness even in the presence of high gamma activity. CITATION: Murphy M; Bruno MA; Riedner BA; Boveroux P; Noirhomme Q; Landsness EC; Brichant JF; Phillips C; Massimini M; Laureys S; Tononi G; Boly M. Propofol anesthesia and sleep: a high-density EEG study. SLEEP 2011;34(3):283-291. [less ▲]

Linking sleep and general anesthesia mechanisms: this is no walkover

in Acta Anaesthesiologica Belgica (2011), 62(3), 161-171

Surgical resection of a sphenoid wing meningioma in a patient with Glanzmann thrombasthenia.

in Acta anaesthesiologica Belgica (2011), 62(2), 83-6

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder characterized by a deficiency or functional defect of platelet glycoprotein (GP) IIb/IIIa. Physiologically, this platelet receptor ... [more ▼]

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder characterized by a deficiency or functional defect of platelet glycoprotein (GP) IIb/IIIa. Physiologically, this platelet receptor mediates aggregation of activated platelets by binding the adhesive proteins, fibrinogen, von Willebrand factor (VWF) and fibronectin. This facilitates attachment and aggregation of platelets at sites of vascular injury. We reported the management of a pterional meningioma resection in a patient with Glanzmann thrombasthenia, with recombinant factor VIIa (rFVIIa - NovoSeven) as haemostatic agent. A 48-year-old woman suffering from Glanzmann thrombasthenia was scheduled for spheno-orbital meningioma en plaque surgery. Because of repeated platelet transfusions, this patient developed isoantibodies against missing GPIIbIIIa and alloantibodies against Human Leukocyte Antigen (HLA) leading to refractoriness to platelet transfusions. We observed that Novoseven offered sufficient haemostasis conditions. Therefore, we noticed a deep vein thrombosis. This imposed us to use low weight molecular heparin despite recent surgery. [less ▲]

Brain connectivity in pathological and pharmacological coma

in Frontiers in Systems Neuroscience [=FNSYS] (2010), 4

Recent studies in patients with disorders of consciousness (DOC) tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the ... [more ▼]

Recent studies in patients with disorders of consciousness (DOC) tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the frontoparietal network. Functional neuroimaging studies have shown preserved albeit disconnected low-level cortical activation in response to external stimulation in patients in a “vegetative state” or unresponsive wakefulness syndrome. While activation of these “primary” sensory cortices does not necessarily reflect conscious awareness, activation in higher-order associative cortices in minimally conscious state patients seems to herald some residual perceptual awareness. PET studies have identified a metabolic dysfunction in a widespread frontoparietal “global neuronal workspace” in DOC patients including the midline default mode network (“intrinsic” system) and the lateral frontoparietal cortices or “extrinsic system.” Recent studies have investigated the relation of awareness to the functional connectivity within intrinsic and extrinsic networks, and with the thalami in both pathological and pharmacological coma. In brain damaged patients, connectivity in all default network areas was found to be non-linearly correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative, coma, and brain dead patients. Anesthesia-induced loss of consciousness was also shown to correlate with a global decrease in cortico-cortical and thalamo-cortical connectivity in both intrinsic and extrinsic networks, but not in auditory, or visual networks. In anesthesia, unconsciousness was also associated with a loss of cross-modal interactions between networks. These results suggest that conscious awareness critically depends on the functional integrity of thalamo-cortical and cortico-cortical frontoparietal connectivity within and between “intrinsic” and “extrinsic” brain networks. [less ▲]

Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients.

in Brain : A Journal of Neurology (2010), 133(Pt 1), 161-71

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than ... [more ▼]

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient's default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. [less ▲]

Functional Neuroimaging Approaches to the Changing Borders of Consciousness

in Journal of Psychophysiology (2010), 24(2), 68-75

The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could ... [more ▼]

The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could help disentangle complex cases and offer new prognostic criteria. These methods can be divided into to three categories: First, new anatomical MRI neuroimaging methods, like diffusion tensor imaging (DTI) or spectroscopy, and passive functional imaging methods (looking at the brain’s activation induced by external stimuli), could provide new diagnostic and prognostic markers. Second, neuroimaging methods based on active collaboration from the patient could help to detect clinically unnoticed signs of consciousness. Third, developments in brain-computer interfaces based on EEG, functional MRI, or EMG offer communication possibilities in brain-damaged patients who can neither verbally nor nonverbally express their thoughts or wishes. These new approaches raise important issues not only from a clinical and ethical perspective (i.e., patients’ diagnosis, prognosis and management) but also from a neuroscientific standpoint, as they enrich our current understanding of the emergence and function of the conscious human mind. [less ▲]

Mécanismes de l'anesthésie générale: apport de l'imagerie fonctionnelle

in Revue Médicale de Liège (2009), 64(Synthèse 2009), 36-41

Bispectral index correlates with regional cerebral blood flow during sleep in distinct cortical and subcortical structures in humans.

in Archives Italiennes de Biologie (2009), 147(1-2), 51-7

The relationship between the Bispectral Index (BIS), an EEG-based monitor of anesthesia, and brain activity is still unclear. This study aimed at investigating the relationship between changes in BIS ... [more ▼]

The relationship between the Bispectral Index (BIS), an EEG-based monitor of anesthesia, and brain activity is still unclear. This study aimed at investigating the relationship between changes in BIS values during natural sleep and regional cerebral blood flow (rCBF) variations, as measured by Positron Emission Tomography (PET). Data were obtained from six young, healthy, right-handed, male volunteers (20-30 years old) using the H2(15)O infusion method. PET scans were performed both during waking and various stages of sleep. BIS values were monitored continuously and recorded during each PET scan. Positive correlations were detected between BIS and rCBF values in dorsolateral prefontal, parietal, anterior and posterior cingulate, precuneal, mesiofrontal, mesiotemporal and insular cortices. These areas belong to a frontoparietal network known to be related to awareness of self conscious sensory perception, attention and memory. BIS values also positively correlated with activity in brainstem and thalami, both structures known to be involved in arousal and wakefulness. These results show that BIS changes associated with physiological sleep depth co-vary with the activity of specific cortical and subcortical areas. The latter are known to modulate arousal, which in turn allows sustained thalamo-cortical enhancement of activity in a specific frontoparietal network known to be related to the content of consciousness. Thus, although mainly derived from frontal EEG, BIS could represent a wider index of cerebral activity. [less ▲]

Comment prédire l'évolution du coma post-anoxique?

in Revue Médicale de Liège (2008), 63(5-6), 263-268