BCI performance and brain metabolism profile in severely brain-injured patients without response to command at bedside

peer reviewedDetection and interpretation of signs of "covert command following" in patients with disorders of consciousness (DOC) remains a challenge for clinicians. In this study, we used a tactile P3-based BCI in 12 patients without behavioral command following, attempting to establish "covert command following." These results were then confronted to cerebral metabolism preservation as measured with glucose PET (FDG-PET). One patient showed "covert command following" (i.e., above-threshold BCI performance) during the active tactile paradigm. This patient also showed a higher cerebral glucose metabolism within the language network (presumably required for command following) when compared with the other patients without "covert command-following" but having a cerebral glucose metabolism indicative of minimally conscious state. Our results suggest that the P3-based BCI might probe "covert command following" in patients without behavioral response to command and therefore could be a valuable addition in the clinical assessment of patients with DOC

Treating Disorders of Consciousness With Apomorphine: Protocol for a Double-Blind Randomized Controlled Trial Using Multimodal Assessments

Background: There are few available therapeutic options to promote recovery among patients with chronic disorders of consciousness (DOC). Among pharmacological treatments, apomorphine, a dopamine agonist, has exhibited promising behavioral effects and safety of use in small-sample pilot studies. The true efficacy of the drug and its neural mechanism are still unclear. Apomorphine may act through a modulation of the anterior forebrain mesocircuit, but neuroimaging and neurophysiological investigations to test this hypothesis are scarce. This clinical trial aims to (1) assess the treatment effect of subcutaneous apomorphine infusions in patients with DOC, (2) better identify the phenotype of responders to treatment, (3) evaluate tolerance and side effects in this population, and (4) examine the neural networks underlying its modulating action on consciousness.Methods/Design: This study is a prospective double-blind randomized parallel placebo-controlled trial. Forty-eight patients diagnosed with DOC will be randomized to receive a 30-day regimen of either apomorphine hydrochloride or placebo subcutaneous infusions. Patients will be monitored at baseline 30 days before initiation of therapy, during treatment and for 30 days after treatment washout, using standardized behavioral scales (Coma Recovery Scale-Revised, Nociception Coma Scale-Revised), neurophysiological measures (electroencephalography, body temperature, actigraphy) and brain imaging (magnetic resonance imaging, positron emission tomography). Behavioral follow-up will be performed up to 2 years using structured phone interviews. Analyses will look for changes in behavioral status, circadian rhythmicity, brain metabolism, and functional connectivity at the individual level (comparing before and after treatment) and at the group level (comparing apomorphine and placebo arms, and comparing responder and non-responder groups).Discussion: This study investigates the use of apomorphine for the recovery of consciousness in the first randomized placebo-controlled double-blind trial using multimodal assessments. The results will contribute to define the role of dopamine agonists for the treatment of these challenging conditions and identify the neural correlates to their action. Results will bring objective evidence to further assess the modulation of the anterior forebrain mesocircuit by pharmacological agents, which may open new therapeutic perspectives.Clinical Trial Registration: EudraCT n°2018-003144-23; Clinicaltrials.gov n°NCT03623828 (https://clinicaltrials.gov/ct2/show/NCT03623828)

SUpporting well-being through PEeR-Befriending (SUPERB) trial: an exploration of fidelity in peer-befriending for people with aphasia

Assessing the evolution of severely brain-injured patients with disorders of consciousness (DOC) with current tools like the Glasgow Outcome Scale-Extended (GOS-E) remains a challenge. At the bedside, the most reliable diagnostic tool is currently the Coma Recovery Scale-Revised. The CRS-R distinguishes patients with unresponsive wakefulness syndrome (UWS) from patients in minimally conscious state (MCS) and patients who have emerged from MCS (EMCS). This international multi-centric study aims to validate a phone outcome questionnaire (POQ) based on the CRS-R and compare it to the CRS-R performed at the bedside and to the GOS-E which evaluates the level of disability and assigns patient’s in outcomes categories. The POQ will allow clinicians to probe the evolution of patient’s state of consciousness based on caregivers feedback. This research project is part of the International Brain Injury Association, Disorders of Consciousness-Special Interest Group (DOCSIG) and DOCMA consortium

L'exploration du phénomène d'extinction à la double stimulation nociceptive chez les sujets sains

Imaginons que vous êtes confortablement installé sur un banc en train de siroter un soda dans le Parc de la Source, à Louvain-la-Neuve. Soudain, une guêpe arrive pour vous importuner. Le premier réflexe est d’essayer de chasser cette guêpe avec – en général – votre main. Cette guêpe est ce que nous allons appeler une menace. Pour agir efficacement contre cette menace, il est nécessaire de coordonner la localisation de cette guêpe dans l’espace externe avec la zone du corps où cette guêpe peut vous piquer. Cet espace nous protégeant des stimuli nociceptifs potentiellement dangereux pour notre intégrité physique, est l’espace péripersonnel. Ainsi, la douleur provoquée par cette piqûre constitue une sensation désagréable qui agit comme un signal d’alarme nous permettant de détecter, localiser et agir contre des stimuli potentiellement dangereux (Legrain et al., 2012). Afin d’étudier la façon dont notre cerveau va intègrer l’information concernant l’espace corporel ainsi que l’espace entourant le corps, il est possible d’utiliser le phénomène d’extinction comme outil fiable. Ce phénomène d’extinction est régulièrement constaté après une lésion cérébrale du côté droit. Lorsque le patient est soumis à des doubles stimulations simultanées, il « néglige » une des deux stimulations. Par contre, lorsque chaque côté est stimulé indépendamment, chacun des stimuli est correctement rapporté. Le phénomène d’extinction crossmodale implique une compétition entre différentes modalités sensorielles par des stimuli somatiques et non-somatiques. Nous avons voulu répliquer les résultats préalablement obtenus dans la recherche, en investissant la nociception au moyen du modèle d’extinction ainsi que de l’extinction crossmodale, chez les sujets sains. Pour la première expérience, nous avons utilisé une tâche comportementale impliquant la détection de doubles stimulations nociceptives simultanées. Pour la deuxième expérience, en plus des stimulations nociceptives, nous avons ajouté des stimulations visuelles à détecter, dans le but de créer une compétition entre les différentes modalités sensorielles. Nos résultats suggèrent qu’il est possible de recréer un phénomène ressemblant à de l’extinction des stimulations nociceptives chez les participants sains.Master [120] en sciences psychologiques, Université catholique de Louvain, 201

Shaping visual space perception through bodily sensations: testing the impact of nociceptive stimuli on visual perception in the peripersonal space with temporal order judgments

Coordinating spatial perception between body space and its external surrounding space is essential to adapt behaviors to objects, especially when they are noxious. Such coherent multisensory representation of the body extended into external space is conceptualized by the notion of peripersonal reference frame, mapping the portion of space in which somatic and extra-somatic inputs interact closely. Studies on crossmodal interactions between nociception and vision have been scarce. Here we investigated how the perception of visual stimuli, especially those surrounding the body, can be impacted by a nociceptive and potentially harmful stimulus inflicted on a particular body part. In two temporal order judgment tasks, participants judged which of two lateralized visual stimuli, presented either near or far from the body, had been presented first. Visual stimuli were preceded by nociceptive stimuli, either applied unilaterally (on one single hand) or bilaterally (on both hands simultaneously). In Experiment 1 participants' hands were always placed next to the visual stimuli presented near the trunk, while in Experiment 2 they could also be placed next to the visual stimuli presented far from the trunk. In Experiment 1, the presence of unilateral nociceptive stimuli prioritized the perception of visual stimuli presented in the same side of space as the stimulated hand, with a significantly larger effect when visual stimuli were presented near the body than when presented farther away. Experiment 2 showed that these visuospatial biases were related to the spatial congruency between the hand on which nociceptive stimuli were applied and the visual stimuli, independently of the relative distance of both the stimulated hand and the visual stimuli from the trunk. Indeed, nociceptive stimuli mostly impacted the perception of the closest visual stimuli. It is hypothesized that these crossmodal interactions may rely on representations of the space directly surrounding specific body parts

Evaluation de la douleur chez le patient cérébrolésé en état de conscience altérée

peer reviewedLa douleur se définit comme une “expérience sensorielle et émotionnelle désagréable associée à un dommage tissulaire potentiel ou réel” [1]. La douleur est donc une expérience subjective négative consciente. La nociception, quant à elle, correspond au “processus neuronal de codage des stimuli nociceptifs ( traduit et codé par les nocicepteurs)” et n’engendre pas nécessairement de la douleur. Certaines conditions, comme l’état de conscience altérée (ECA), peuvent entraver une évaluation optimale de la douleur. Néanmoins, l’évaluation de cette douleur est un élément important de la prise en charge clinique ainsi que du diagnostic, puisque le simple fait de ne pas pouvoir communiquer verbalement ne peut écarter la possibilité qu’un individu présente des douleurs [2]. De plus, de nombreuses situations en phase aigüe (mise en place d’un cathéter, polytraumatisme, etc.) ou chronique (présence de spasticité, d’escarres, etc.) peuvent être des sources potentielles de douleur pour les patients en ECA, celles-ci pouvant alors entraver la rééducation et diminuer leur qualité de vie [3]. Bien que nous ne puissions pas utiliser le compte rendu subjectif du patient non communicant, les outils dont nous disposons actuellement nous permettent malgré tout d’étudier ce qui se passe au niveau cérébral en réponse à des stimulations potentiellement douloureuses, ce qui nous permet de mieux comprendre et de tenter d’inférer la présence de douleur potentielle chez ces patients. Par ailleurs, nous pouvons également observer les réponses du patient à son chevet, comme pratiqué avec d’autres populations non communicantes telles que les patients déments et les nouveau-nés. Ce chapitre tentera d’apporter des clés permettant de mieux appréhender et gérer les signes de douleurs potentielles chez ces patients, sur la base des études de neuro-imagerie et des instruments cliniques disponibles

Nociceptive extinction in response to double stimulation

Assessing the efficiency of an analgesic treatment requires to measure pain and the integrity of the neural system mediating pain perception, i.e., the nociceptive system. However, the interpretation of these measurements often relies on the idea that the response of a patient to a nociceptive stimulus is only determined by the properties of this stimulus. Here, we would like to challenge this interpretation in terms of labelled lines by showing that the ability to respond to a nociceptive stimulus is determined by surrounding stimuli and their integration by the processing system. We did so by means of the phenomenon of extinction. This phenomenon, usually observed after a brain lesion, is characterized by the patient's inability to report a stimulus presented on the side contralateral to the damaged cortical hemisphere, but only when it is presented simultaneously with a stimulus on the ipsilateral side.As compared to the single stimulation condition, participants' performance was significantly lower in the double stimulation condition. Indeed, they failed to report the presence of a nociceptive stimulus applied to one of the hands more often when another stimulus was simultaneously applied to the other hand, as compared to when it was applied alone. Our data show that the ability to perceive a nociceptive stimulus depends on the integration of sensory inputs from different sources. The present paradigm of double stimulation could be used as a valid tool to investigate the contextual and cognitive conditions in which the perception of a nociceptive stimuli emerges

Behavioral evaluations in patients with disorders of consciousness

peer reviewedA l’heure actuelle, l’évaluation de la conscience chez les patients sortant du coma reste un challenge car elle ne peut directement s’observer et être quantifiée, comme peuvent l’être par exemple le poids ou la taille. Le diagnostic des états de conscience altérés doit donc se baser une évaluation indirecte, et seulement sur ce qui est observable. Les évaluations comportementales restent encore à l’heure actuelle le gold standard pour les cliniciens et des études récentes ont mis en avant la nécessité d’utiliser des outils d’évaluation standardisés. Dans ce chapitre, nous aborderons brièvement quatre échelles utilisées régulièrement dans la pratique clinique en développant plus en profondeur la Coma Recovery Scale – Revised. Le but ici est de donner une vue globale des différentes échelles ainsi que d’apporter quelques recommandations pratiques quant à la réalisation des évaluations comportementales

Unimodal and crossmodal extinction of nociceptive stimuli in healthy volunteers

Nociception, the physiological mechanisms specifically processing information about noxious and potentially painful stimuli, has the double function to warn about potential body damages (interoception) and about the cause of such potential damages (exteroception). The exteroceptive function is thought to rely on multisensory integration between somatic and extra-somatic stimuli, provided that extra-somatic stimuli occur near the stimulated body area. To corroborate this hypothesis, we succeeded to show in healthy volunteers that the perception of nociceptive stimuli applied on one hand can be extinguished, as compared to single presentation, by the simultaneous application of nociceptive stimuli on the opposite hand, as well as by the presentation of visual stimuli near the opposite hand. On the contrary, visual stimuli presented near the same stimulated hand facilitated the perception of nociceptive stimuli. This nociceptive extinction phenomenon indicates that the perception of noxious events does not merely rely on the specific activation of the nociceptive system, but also depends on other sensory experiences about the body and the space around it

Individual PSS values for Experiment 1.

<p>The left graphic illustrates the PSS values for the <i>unilateral cue</i> conditions (1), and the right graphic the PSS values for the <i>bilateral cue</i> conditions (2). Within each graphic, the left side illustrate the PSS values of the tasks performed with the near visual stimuli, the right side those with the far visual stimuli. Each color line represents one of the 17 participants who participated in the task. For the unilateral cue conditions (1) there is almost systematically a shift of the PSS to the uncued side, and these shifts are also almost systematically larger for near than for far visual stimuli. For the bilateral (2) cue conditions, shifts in PSS seem rather random, either to the left or to the right side, and there is also no systematic difference between near and far visual stimuli.</p