Dysfunction of neurovascular/metabolic coupling in chronic focal epilepsy

In this study, we aim to evaluate the mechanisms underlying the neuro-vascular/metabolic coupling in the epileptogenic cortices of rats with chronic focal epilepsy. To that end, we first analyzed intracranial recordings (electrophysiology, laser Doppler flowmetry and optical imaging) obtained from the seizure onset zones during ictal periods and then used these data to fit a metabolically-coupled balloon model. This biophysical model is an extension of the standard balloon model with modulatory effects of changes in tissue oxygenation, capillary dynamics and variable O2 extraction fraction. As previously reported using acute seizure models, we found that there is a significant higher contribution from high local field potential frequency bands to the cerebral blood flow (CBF) responses in the epileptogenic cortices during ictal neuronal activities. The hemodynamic responses associated with ictal activities were distance-dependent with regard to the seizure focus, though varied in profiles from those obtained from acute seizure models. Parameters linking the CBF and relative concentration of deoxy-hemoglobin to neuronal activity in the biophysical model were significantly different between epileptic and normal rats. In particular, we found that the coefficient associated with the strength of the functional hyperemic response was significantly larger in the epileptogenic cortices, although changes in hemoglobin concentration associated with ictal activity reflected the existence of a significantly higher baseline for oxygen metabolism in the epileptogenic cortices

Advanced Invasive Neurophysiological Methods to Aid Decision Making in Paediatric Epilepsy Surgery

For patients with drug-resistant focal epilepsy, surgery is the most effective treatment to attain seizure freedom. Intracranial electroencephalogram investigations succeed in defining the seizure onset zone (SOZ) where non-invasive methods fail to identify a single seizure generator. However, resection of the SOZ does not always lead to a surgical benefit and, in addition, eloquent functions like language might be compromised. The aim of this thesis was to use advanced invasive neurophysiological methods to improve pre-surgical planning in two ways. The first aim was to improve delineation of the pathological tissue, the SOZ using novel quantitative neurophysiological biomarkers: high gamma activity (80–150Hz) phase-locked to low frequency iEEG discharges (phase-locked high gamma, PLHG) and high frequency oscillations called fast ripples (FR, 250–500Hz). Resection of contacts containing these markers were recently reported to lead to an improved seizure outcome. The current work shows the first replication of the PLHG metric in a small adult pilot study and a larger paediatric cohort. Furthermore, I tested whether surgical removal of PLHG- and/or FR-generating brain areas resulted in better outcome compared to the current clinical SOZ delineation. The second aim of this work was to aid delineation of eloquent language cortex. Invasive event-related potentials (iERP) and spectral changes in the beta and gamma frequency bands were used to determine cortical dynamics during speech perception and production across widespread brain regions. Furthermore, the relationship between these cortical dynamics and the relationship to electrical stimulation responses was explored. For delineation of pathological tissue, the combination of FRs and SOZ proved to be a promising biomarker. Localising language cortex showed the highest level of activity around the perisylvian brain regions with a significantly higher occurrence rate of iERPs compared to spectral changes. Concerning electrical stimulation mapping beta and high gamma frequency bands represented the most promising markers

Spatial Detection of Multiple Movement Intentions from SAM-Filtered Single-Trial MEG for a high performance BCI

The objective of this study is to test whether human intentions to sustain or cease movements in right and left hands can be decoded reliably from spatially filtered single trial magneto-encephalographic (MEG) signals. This study was performed using motor execution and motor imagery movements to achieve a potential high performance Brain-Computer interface (BCI). Seven healthy volunteers, naïve to BCI technology, participated in this study. Signals were recorded from 275-channel MEG and synthetic aperture magnetometry (SAM) was employed as the spatial filter. The four-class classification for natural movement intentions was performed offline; Genetic Algorithm based Mahalanobis Linear Distance (GA-MLD) and direct-decision tree classifier (DTC) techniques were adopted for the classification through 10-fold cross-validation. Through SAM imaging, strong and distinct event related desynchronisation (ERD) associated with sustaining, and event related synchronisation (ERS) patterns associated with ceasing of hand movements were observed in the beta band (15 - 30 Hz). The right and left hand ERD/ERS patterns were observed on the contralateral hemispheres for motor execution and motor imagery sessions. Virtual channels were selected from these cortical areas of high activity to correspond with the motor tasks as per the paradigm of the study. Through a statistical comparison between SAM-filtered virtual channels from single trial MEG signals and basic MEG sensors, it was found that SAM-filtered virtual channels significantly increased the classification accuracy for motor execution (GA-MLD: 96.51 ± 2.43 %) as well as motor imagery sessions (GA-MLD: 89.69 ± 3.34%). Thus, multiple movement intentions can be reliably detected from SAM-based spatially-filtered single trial MEG signals. MEG signals associated with natural motor behavior may be utilized for a reliable high-performance brain-computer interface (BCI) and may reduce long-term training compared with conventional BCI methods using rhythm control. This may prove tremendously helpful for patients suffering from various movement disorders to improve their quality of life

Biomimetic Sonar for Electrical Activation of the Auditory Pathway

Relying on the mechanism of bat’s echolocation system, a bioinspired electronic device has been developed to investigate the cortical activity of mammals in response to auditory sensorial stimuli. By means of implanted electrodes, acoustical information about the external environment generated by a biomimetic system and converted in electrical signals was delivered to anatomically selected structures of the auditory pathway. Electrocorticographic recordings showed that cerebral activity response is highly dependent on the information carried out by ultrasounds and is frequency-locked with the signal repetition rate. Frequency analysis reveals that delta and beta rhythm content increases, suggesting that sensorial information is successfully transferred and integrated. In addition, principal component analysis highlights how all the stimuli generate patterns of neural activity which can be clearly classified. The results show that brain response is modulated by echo signal features suggesting that spatial information sent by biomimetic sonar is efficiently interpreted and encoded by the auditory system. Consequently, these results give new perspective in artificial environmental perception, which could be used for developing new techniques useful in treating pathological conditions or influencing our perception of the surroundings

Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness.

International audienceImproving our ability to detect conscious processing in non communicating patients remains a major goal of clinical cognitive neurosciences. In this perspective, several functional brain imaging tools are currently under development. Bedside cognitive event-related potentials (ERPs) derived from the EEG signal are a good candidate to explore consciousness in these patients because: (1) they have an optimal time resolution within the millisecond range able to monitor the stream of consciousness, (2) they are fully non-invasive and relatively cheap, (3) they can be recorded continuously on dedicated individual systems to monitor consciousness and to communicate with patients, (4) and they can be used to enrich patients' autonomy through brain-computer interfaces. We recently designed an original auditory rule extraction ERP test that evaluates cerebral responses to violations of temporal regularities that are either local in time or global across several seconds. Local violations led to an early response in auditory cortex, independent of attention or the presence of a concurrent visual task, while global violations led to a late and spatially distributed response that was only present when subjects were attentive and aware of the violations. In the present work, we report the results of this test in 65 successive recordings obtained at bedside from 49 non-communicating patients affected with various acute or chronic neurological disorders. At the individual level, we confirm the high specificity of the 'global effect': only conscious patients presented this proposed neural signature of conscious processing. Here, we also describe in details the respective neural responses elicited by violations of local and global auditory regularities, and we report two additional ERP effects related to stimuli expectancy and to task learning, and we discuss their relations to consciousness

Brain-machine interface using electrocorticography in humans

Paralysis has a severe impact on a patient’s quality of life and entails a high emotional burden and life-long social and financial costs. More than 5 million people in the USA suffer from some form of paralysis and about 50% of the people older than 65 experience difficulties or inabilities with movement. Restoring movement and communication for patients with neurological and motor disorders, stroke and spinal cord injuries remains a challenging clinical problem without an adequate solution. A brain-machine interface (BMI) allows subjects to control a device, such as a computer cursor or an artificial hand, exclusively by their brain activity. BMIs can be used to control communication and prosthetic devices, thereby restoring the communication and movement capabilities of the paralyzed patients. So far, most powerful BMIs have been realized by extracting movement parameters from the activity of single neurons. To record such activity, electrodes have to penetrate the brain tissue, thereby generating risk of brain injury. In addition, recording instability, due to small movements of the electrodes within the brain and the neuronal tissue response to the electrode implant, is also an issue. In this thesis, I investigate whether electrocorticography (ECoG), an alternative recording technique, can be used to achieve BMIs with similar accuracy. First, I demonstrate a BMI based on the approach of extracting movement parameters from ECoG signals. Such ECoG based BMI can further be improved using supervised adaptive algorithms. To implement such algorithms, it is necessary to continuously receive feedback from the subject whether the BMI-decoded trajectory was correct or incorrect. I show that, by using the same ECoG recordings, neuronal responses to trajectory errors can be recorded, detected and differentiated from other types of errors. Finally, I devise a method that could be used to improve the detection of error related neuronal responses

The mechanisms of tinnitus: perspectives from human functional neuroimaging

In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural substrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power

From locomotion to dance and back : exploring rhythmic sensorimotor synchronization

Le rythme est un aspect important du mouvement et de la perception de l’environnement. Lorsque l’on danse, la pulsation musicale induit une activité neurale oscillatoire qui permet au système nerveux d’anticiper les évènements musicaux à venir. Le système moteur peut alors s’y synchroniser. Cette thèse développe de nouvelles techniques d’investigation des rythmes neuraux non strictement périodiques, tels que ceux qui régulent le tempo naturellement variable de la marche ou la perception rythmes musicaux. Elle étudie des réponses neurales reflétant la discordance entre ce que le système nerveux anticipe et ce qu’il perçoit, et qui sont nécessaire pour adapter la synchronisation de mouvements à un environnement variable. Elle montre aussi comment l’activité neurale évoquée par un rythme musical complexe est renforcée par les mouvements qui y sont synchronisés. Enfin, elle s’intéresse à ces rythmes neuraux chez des patients ayant des troubles de la marche ou de la conscience.Rhythms are central in human behaviours spanning from locomotion to music performance. In dance, self-sustaining and dynamically adapting neural oscillations entrain to the regular auditory inputs that is the musical beat. This entrainment leads to anticipation of forthcoming sensory events, which in turn allows synchronization of movements to the perceived environment. This dissertation develops novel technical approaches to investigate neural rhythms that are not strictly periodic, such as naturally tempo-varying locomotion movements and rhythms of music. It studies neural responses reflecting the discordance between what the nervous system anticipates and the actual timing of events, and that are critical for synchronizing movements to a changing environment. It also shows how the neural activity elicited by a musical rhythm is shaped by how we move. Finally, it investigates such neural rhythms in patient with gait or consciousness disorders