Prediction of awakening from hypothermic post anoxic coma based on auditory discrimination.

OBJECTIVE: Most of the available clinical tests for prognosis of post-anoxic coma are informative of poor outcome. Previous work has shown that an improvement in auditory discrimination over the first days of coma is predictive of awakening. Here, we aimed at evaluating this test on a large cohort of patients undergoing therapeutic hypothermia and at investigating its added value on existing clinical measures. METHODS: We recorded electroencephalography responses to auditory stimuli in 94 comatose patients, under hypothermia and after re-warming to normal temperature. Auditory discrimination was semi-automatically quantified by decoding electroencephalography responses to frequently repeated vs. rare sounds. Outcome prediction was based on the change of decoding performance from hypothermia to normothermia. RESULTS: An increase in auditory discrimination from hypothermia to normothermia was observed for 33 out of 94 patients. Among them, 27 awoke from coma, resulting in a positive predictive value of awakening of 82% (95% confidence interval: 0.65-0.93). Most non-survivors showing an improvement in auditory discrimination had incident status epilepticus. By excluding them, 27 out of 29 patients with improvement in auditory discrimination survived, resulting in a considerable improvement of the predictive value for awakening (93%, with 95% confidence interval: 0.77-0.99). Importantly, this test predicted the awakening of 13 out of 51 patients for which the outcome was uncertain based on current tests. INTERPRETATION: The progression of auditory discrimination from hypothermia to normothermia has a high predictive value for awakening. This quantitative measure provides an added value to existing clinical tests and encourages the maintenance of life support. This article is protected by copyright. All rights reserved

Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds.

Trace conditioning refers to a learning process occurring after repeated presentation of a neutral conditioned stimulus (CS+) and a salient unconditioned stimulus (UCS) separated by a temporal gap. Recent studies have reported that trace conditioning can occur in humans in reduced levels of consciousness by showing a transfer of the unconditioned autonomic response to the CS+ in healthy sleeping individuals and in vegetative state patients. However, no previous studies have investigated the neural underpinning of trace conditioning in the absence of consciousness in humans. In the present study, we recorded the EEG activity of 29 post-anoxic comatose patients while presenting a trace conditioning paradigm using neutral tones as CS+ and alerting sounds as UCS. Most patients received therapeutic hypothermia and all were deeply unconscious according to standardized clinical scales. After repeated presentation of the CS+ and UCS couple, learning was assessed by measuring the EEG activity during the period where the UCS is omitted after CS+ presentation. Specifically we assessed the 'reactivation' of the neural response to UCS omission by applying a decoding algorithm derived from the statistical model of the EEG activity in response to the UCS presentation. The same procedure was used in a group of 12 awake healthy controls. We found a reactivation of the UCS response in absence of stimulation in eight patients (five under therapeutic hypothermia) and four healthy controls. Additionally, the reactivation effect was temporally specific within trials since it manifested primarily at the specific latency of UCS presentation and significantly less before or after this period. Our results show for the first time that trace conditioning may manifest as a reactivation of the EEG activity related to the UCS and even in the absence of consciousness

How Do You Feel? Subjective Perception of Recovery as a Reliable Surrogate of Cognitive and Functional Outcome in Cardiac Arrest Survivors.

To show that subjective estimate of patient's condition is related to objective cognitive and functional outcome in cardiac arrest survivors. Longitudinal cohort study. ICU and Neuropsychology Service in two hospitals in Switzerland. Fifty survivors included from a prospective cohort of 138 patients admitted at the ICU for cardiopulmonary arrest. Comprehensive cognitive and functional evaluation at 6 months follow-up. Subjectively, 70% of survivors reported satisfactory recovery and 29% reported no complaints. Objectively, 76% were classified as good neurologic outcome (Cerebral Performance Category 1), 26% as having no symptoms (modified Rankin Scale 0), and 38% as upper good recovery (Glasgow Outcome Scale Extended 1). Cognitive assessment detected substantial cognitive impairment in 26%, primarily concerning processing speed, language, long-term memory, and executive functions. Subjective complaints severity correlated significantly with objective cognitive impairment (rS = 0.64; p < 0.001). Finally, patients reporting unsatisfactory recovery displayed lower functional scores than those reporting satisfactory recovery (e.g., quality of life satisfaction: 64% vs 81%; Z = 2.18; p = 0.03) and more cognitive impairment (three vs one cognitive domains impaired; Z = -3.21; p < 0.001), concerning in particular learning and long-term verbal and visual memory. Long-term subjective and objective outcome appears good in the majority of cardiac arrest survivors. Specific functional and cognitive impairments were found in patients reporting unsatisfactory recovery. Subjective recovery was strongly correlated with objective assessment

Brain-actuated functional electrical stimulation elicits lasting arm motor recovery after stroke

Brain-computer interfaces (BCI) are used in stroke rehabilitation to translate brain signals into intended movements of the paralyzed limb. However, the efficacy and mechanisms of BCI-based therapies remain unclear. Here we show that BCI coupled to functional electrical stimulation (FES) elicits significant, clinically relevant, and lasting motor recovery in chronic stroke survivors more effectively than sham FES. Such recovery is associated to quantitative signatures of functional neuroplasticity. BCI patients exhibit a significant functional recovery after the intervention, which remains 6–12 months after the end of therapy. Electroencephalography analysis pinpoints significant differences in favor of the BCI group, mainly consisting in an increase in functional connectivity between motor areas in the affected hemisphere. This increase is significantly correlated with functional improvement. Results illustrate how a BCI–FES therapy can drive significant functional recovery and purposeful plasticity thanks to contingent activation of body natural efferent and afferent pathways

Somatosensory and auditory deviance detection for outcome prediction during postanoxic coma.

Prominent research in patients with disorders of consciousness investigated the electrophysiological correlates of auditory deviance detection as a marker of consciousness recovery. Here, we extend previous studies by investigating whether somatosensory deviance detection provides an added value for outcome prediction in postanoxic comatose patients. Electroencephalography responses to frequent and rare stimuli were obtained from 66 patients on the first and second day after coma onset. Multivariate decoding analysis revealed an above chance-level auditory discrimination in 25 patients on the first day and in 31 patients on the second day. Tactile discrimination was significant in 16 patients on the first day and in 23 patients on the second day. Single-day sensory discrimination was unrelated to patients' outcome in both modalities. However, improvement of auditory discrimination from first to the second day was predictive of good outcome with a positive predictive power (PPV) of 0.73 (CI = 0.52-0.88). Analyses considering the improvement of tactile, auditory and tactile, or either auditory or tactile discrimination showed no significant prediction of good outcome (PPVs = 0.58-0.68). Our results show that in the acute phase of coma deviance detection is largely preserved for both auditory and tactile modalities. However, we found no evidence for an added value of somatosensory to auditory deviance detection function for coma-outcome prediction

Brain surface non-rigid registration in auditory processing

Résumé: Le développement rapide de nouvelles technologies comme l'imagerie médicale a permis l'expansion des études sur les fonctions cérébrales. Le rôle principal des études fonctionnelles cérébrales est de comparer l'activation neuronale entre différents individus. Dans ce contexte, la variabilité anatomique de la taille et de la forme du cerveau pose un problème majeur. Les méthodes actuelles permettent les comparaisons interindividuelles par la normalisation des cerveaux en utilisant un cerveau standard. Les cerveaux standards les plus utilisés actuellement sont le cerveau de Talairach et le cerveau de l'Institut Neurologique de Montréal (MNI) (SPM99). Les méthodes de recalage qui utilisent le cerveau de Talairach, ou celui de MNI, ne sont pas suffisamment précises pour superposer les parties plus variables d'un cortex cérébral (p.ex., le néocortex ou la zone perisylvienne), ainsi que les régions qui ont une asymétrie très importante entre les deux hémisphères. Le but de ce projet est d'évaluer une nouvelle technique de traitement d'images basée sur le recalage non-rigide et utilisant les repères anatomiques. Tout d'abord, nous devons identifier et extraire les structures anatomiques (les repères anatomiques) dans le cerveau à déformer et celui de référence. La correspondance entre ces deux jeux de repères nous permet de déterminer en 3D la déformation appropriée. Pour les repères anatomiques, nous utilisons six points de contrôle qui sont situés : un sur le gyrus de Heschl, un sur la zone motrice de la main et le dernier sur la fissure sylvienne, bilatéralement. Evaluation de notre programme de recalage est accomplie sur les images d'IRM et d'IRMf de neuf sujets parmi dix-huit qui ont participés dans une étude précédente de Maeder et al. Le résultat sur les images anatomiques, IRM, montre le déplacement des repères anatomiques du cerveau à déformer à la position des repères anatomiques de cerveau de référence. La distance du cerveau à déformer par rapport au cerveau de référence diminue après le recalage. Le recalage des images fonctionnelles, IRMf, ne montre pas de variation significative. Le petit nombre de repères, six points de contrôle, n'est pas suffisant pour produire les modifications des cartes statistiques. Cette thèse ouvre la voie à une nouvelle technique de recalage du cortex cérébral dont la direction principale est le recalage de plusieurs points représentant un sillon cérébral. Abstract : The fast development of new technologies such as digital medical imaging brought to the expansion of brain functional studies. One of the methodolgical key issue in brain functional studies is to compare neuronal activation between individuals. In this context, the great variability of brain size and shape is a major problem. Current methods allow inter-individual comparisions by means of normalisation of subjects' brains in relation to a standard brain. A largerly used standard brains are the proportional grid of Talairach and Tournoux and the Montreal Neurological Insititute standard brain (SPM99). However, there is a lack of more precise methods for the superposition of more variable portions of the cerebral cortex (e.g, neocrotex and perisyvlian zone) and in brain regions highly asymmetric between the two cerebral hemipsheres (e.g. planum termporale). The aim of this thesis is to evaluate a new image processing technique based on non-linear model-based registration. Contrary to the intensity-based, model-based registration uses spatial and not intensitiy information to fit one image to another. We extract identifiable anatomical features (point landmarks) in both deforming and target images and by their correspondence we determine the appropriate deformation in 3D. As landmarks, we use six control points that are situated: one on the Heschl'y Gyrus, one on the motor hand area, and one on the sylvian fissure, bilaterally. The evaluation of this model-based approach is performed on MRI and fMRI images of nine of eighteen subjects participating in the Maeder et al. study. Results on anatomical, i.e. MRI, images, show the mouvement of the deforming brain control points to the location of the reference brain control points. The distance of the deforming brain to the reference brain is smallest after the registration compared to the distance before the registration. Registration of functional images, i.e fMRI, doesn't show a significant variation. The small number of registration landmarks, i.e. six, is obvious not sufficient to produce significant modification on the fMRI statistical maps. This thesis opens the way to a new computation technique for cortex registration in which the main directions will be improvement of the registation algorithm, using not only one point as landmark, but many points, representing one particular sulcus

Human auditory belt areas specialized in sound recognition: a functional magnetic resonance imaging study.

The human primary auditory cortex is surrounded by at least six other, anatomically distinct areas that process auditory information. We have investigated their specialization with respect to sound recognition or sound localization with triple epoch functional magnetic resonance imaging paradigm (recognition-localization-rest) in 18 normal individuals. In each study participant, the pattern of selective activation by the recognition or by the localization tasks was superimposed on the map of the nonprimary auditory areas, as identified in previous anatomical studies. Two areas, anterior lateral and anterior areas, were activated bilaterally in significantly more individuals by the recognition than by the localization task. They are proposed to be human homologues of macaque anterolateral auditory belt area

Local landmark-based registration for fMRI group studies of nonprimary auditory cortex.

Interindividual functional and structural brain variability is a major problem in group studies, in which very focal activations are expected. Architectonic studies have shown that the human primary auditory area, which is located with a great constancy on Heschl's gyrus, is surrounded by several nonprimary auditory areas with surface areas of 40-310 mm(2). The small size of the latter makes them only partially accessible to fMRI group studies, because of imprecision in realignment when using currently available registration procedures. We describe here a new method for sulcal realignment using a non-rigid local landmark-based registration and show its application to the registration of fMRI acquisitions on the supratemporal plane. After an affine global voxel-based registration, which transforms all brains into the same standard space, we propose a non-rigid local landmark-based registration method based on thin-plate splines for matching the two sulci delimiting Heschl's gyrus of a given brain to the corresponding sulci of a reference brain. We show here that, in comparison with global affine and non-rigid approaches, our method leads in group studies to i) a much more precise alignment of Heschl's gyrus; and ii) a putatively optimal superposition of functionally corresponding areas on and around Heschl's gyrus