Development of EEG-based technologies for the characterization and treatment of neurological diseases affecting the motor function

This thesis presents a set of studies applying signal processing and data mining techniques in real-time working systems to register, characterize and condition the movement-related cortical activity of healthy subjects and of patients with neurological disorders affecting the motor function. Patients with two of the most widespread neurological affections impairing the motor function are considered here: patients with essential tremor and patients who have suffered a cerebro-vascular accident. The different chapters in the presented thesis show results regarding the normal cortical activity associated with the planning and execution of motor actions with the upper-limb, and the pathological activity related to the patients' motor dysfunction (measurable with muscle electrodes or movement sensors). The initial chapters of the book present i) a revision of the basic concepts regarding the role of the cerebral cortex in the motor control and the way in which the electroencephalographic activity allows its analysis and conditioning, ii) a study on the cortico-muscular interaction at the tremor frequency in patients with essential tremor under the effects of a drug reducing their tremor, and finally iii) a study based on evolutionary algorithms that aims to identify cortical patterns related to the planning of a number of motor tasks performed with a single arm. In the second half of the thesis book, two brain-computer interface systems to be used in rehabilitation scenarios with essential tremor patients and with patients with a stroke are proposed. In the first system, the electroencephalographic activity is used to anticipate voluntary movement actions, and this information is integrated in a multimodal platform estimating and suppressing the pathological tremors. In the second case, a conditioning paradigm for stroke patients based on the identification of the motor intention with temporal precision is presented and tested with a cohort of four patients along a month during which the patients undergo eight intervention sessions. The presented thesis has yielded advances from both the technological and the scientific points of view in all studies proposed. The main contributions from the technological point of view are: ¿ The design of an integrated upper-limb platform working in real-time. The platform was designed to acquire information from different types of noninvasive sensors (EEG, EMG and gyroscopic sensors) characterizing the planning and execution of voluntary movements. The platform was also capable of processing online the acquired data and generating an electrical feedback. ¿ The development of signal processing and classifying techniques adapted to the kind of signal recorded in the two kinds of patients considered in this thesis (patients with essential tremor and patients with a stroke) and to the requirements of online processing and real-time single-trial function desired for BCI applications. Especially in this regard, an original methodology to detect onsets of voluntary movements using slow cortical potentials and cortical rhythms has been presented. ¿ The design and validation in real-time of asynchronous BCI systems using motor planning EEG segments to anticipate or detect when patients begin a voluntary movement with the upper-limb. ¿ The proof of concept of the advantages of an EEG system integrated in a multimodal human-robot interface architecture that constitutes the first multimodal interface using the combined acquisition of EEG, EMG and gyroscopic data, which allows the concurrent characterization of different parts of the body associated with the execution of a movement. The main scientific contributions of this thesis are: ¿ The study of the EEG-based anticipation of voluntary movements presented in Chapter 5 of the thesis was the first demonstration (to the author's knowledge) of the capacity of the EEG signal to provide reliable movement predictions based on single-trial classification of online data of healthy subjects and ET patients. This study also provides, for the first time, the results of a BCI system tested in ET patients and it represents an original approach to BCI applications for this group of patients. ¿ It has been presented the first neurophysiological study using EEG and EMG data to analyze the effects of a drug on cortical activity and tremors of patients with ET. In addition, the obtained results have shown for the first time that a significant correlation exists between the dynamics of specific cortical oscillations and pathological tremor manifestation as a consequence of the drug effects. ¿ It has been proposed for the first time an experiment to inspect whether the EEG signal carries enough information to classify up to seven different tasks performed with a single limb. Both the methodology applied and the validation procedure are also innovative in this sort of studies. ¿ It has been demonstrated for the first time the relevance of combining different cortical sources of information (such as BP and ERD) to estimate the initiation of voluntary movements with the upper-limb. In this line, special relevance may be given to the positive results achieved with stroke patients, improving the results presented by similar previous EEG-based studies by other research groups. It has also been proposed for the first time an upper-limb intervention protocol for stroke patients using BP and ERD patterns to provide proprioceptive feedback tightly associated with the patients' expectations of movement. The effects of the proposed intervention have been studied with a small group of patients

A brain-computer interface for navigation in virtual reality

L'interface cerveau-ordinateur (ICO) décode les signaux électriques du cerveau requise par l’électroencéphalographie et transforme ces signaux en commande pour contrôler un appareil ou un logiciel. Un nombre limité de tâches mentales ont été détectés et classifier par différents groupes de recherche. D’autres types de contrôle, par exemple l’exécution d'un mouvement du pied, réel ou imaginaire, peut modifier les ondes cérébrales du cortex moteur. Nous avons utilisé un ICO pour déterminer si nous pouvions faire une classification entre la navigation de type marche avant et arrière, en temps réel et en temps différé, en utilisant différentes méthodes. Dix personnes en bonne santé ont participé à l’expérience sur les ICO dans un tunnel virtuel. L’expérience fut a était divisé en deux séances (48 min chaque). Chaque séance comprenait 320 essais. On a demandé au sujets d’imaginer un déplacement avant ou arrière dans le tunnel virtuel de façon aléatoire d’après une commande écrite sur l'écran. Les essais ont été menés avec feedback. Trois électrodes ont été montées sur le scalp, vis-à-vis du cortex moteur. Durant la 1re séance, la classification des deux taches (navigation avant et arrière) a été réalisée par les méthodes de puissance de bande, de représentation temporel-fréquence, des modèles autorégressifs et des rapports d’asymétrie du rythme β avec classificateurs d’analyse discriminante linéaire et SVM. Les seuils ont été calculés en temps différé pour former des signaux de contrôle qui ont été utilisés en temps réel durant la 2e séance afin d’initier, par les ondes cérébrales de l'utilisateur, le déplacement du tunnel virtuel dans le sens demandé. Après 96 min d'entrainement, la méthode « online biofeedback » de la puissance de bande a atteint une précision de classification moyenne de 76 %, et la classification en temps différé avec les rapports d’asymétrie et puissance de bande, a atteint une précision de classification d’environ 80 %.A Brain-Computer Interface (BCI) decodes the brain signals representing a desire to do something, and transforms those signals into a control command. However, only a limited number of mental tasks have been previously detected and classified. Performing a real or imaginary navigation movement can similarly change the brainwaves over the motor cortex. We used an ERS-BCI to see if we can classify between movements in forward and backward direction offline and then online using different methods. Ten healthy people participated in BCI experiments comprised two-sessions (48 min each) in a virtual environment tunnel. Each session consisted of 320 trials where subjects were asked to imagine themselves moving in the tunnel in a forward or backward motion after a randomly presented (forward versus backward) command on the screen. Three EEG electrodes were mounted bilaterally on the scalp over the motor cortex. Trials were conducted with feedback. In session 1, Band Power method, Time-frequency representation, Autoregressive models and asymmetry ratio were used in the β rhythm range with a Linear-Discriminant-analysis classifier and a Support Vector Machine classifier to discriminate between the two mental tasks. Thresholds for both tasks were computed offline and then used to form control signals that were used online in session 2 to trigger the virtual tunnel to move in the direction requested by the user's brain signals. After 96 min of training, the online band-power biofeedback training achieved an average classification precision of 76 %, whereas the offline classification with asymmetrical ratio and band-power achieved an average classification precision of 80%

Post-adaptation effects in a motor imagery brain-computer interface online coadaptive paradigm

Online coadaptive training has been successfully employed to enable people to control motor imagery (MI)-based brain-computer interfaces (BCIs), allowing to completely skip the lengthy and demotivating open-loop calibration stage traditionally applied before closed-loop control. However, practical reasons may often dictate to eventually switch off decoder adaptation and proceed with BCI control under a fixed BCI model, a situation that remains rather unexplored. This work studies the existence and magnitude of potential post-adaptation effects on system performance, subject learning and brain signal modulation stability in a state-of-the-art, coadaptive training regime inspired by a game-like design. The results extracted in a cohort of 20 able-bodied individuals reveal that ceasing classifier adaptation after three runs (approx. 30 min) of a single-session training protocol had no significant impact on any of the examined BCI control and learning aspects in the remaining two runs (about 20 min) with a fixed classifier. Fifteen individuals achieved accuracies that are better than chance level and allowed them to successfully execute the given task. These findings alleviate a major concern regarding the applicability of coadaptive MI BCI training, thus helping to further establish this training approach and allow full exploitation of its benefits

Enhancing brain/neural-machine interfaces for upper limb motor restoration in chronic stroke and cervical spinal cord injury

Operation of assistive exoskeletons based on voluntary control of sensorimotor rhythms (SMR, 8-12 Hz) enables intuitive control of finger or arm movements in severe paralysis after chronic stroke or cervical spinal cord injury (SCI). To improve reliability of such systems outside the laboratory, in particular when brain activity is recorded non-invasively with scalp electroencephalography (EEG), a hybrid EEG/electrooculography (EOG) brain/neural-machine interface (B/NMI) was recently introduced. Besides providing assistance, recent studies indicate that repeated use of such systems can trigger neural recovery. However, important prerequisites have to achieved before broader use in clinical settings or everyday life environments is feasible. Current B/NMI systems predominantly restore hand function, but do not allow simultaneous control of more proximal joints for whole-arm motor coordination as required for most stroke survivors suffering from paralysis in the entire upper limb. Besides paralysis, cognitive impairments including post-stroke fatigue due to the brain lesion reduce the capacity to maintain effortful B/NMI control over a longer period of time. This impedes the applicability in daily life assistance and might even limits the efficacy of neurorehabilitation training. In contrast to stroke survivors, tetraplegics due to cervical SCI lack motor function in both hands. Given that most activities of daily living (ADL) involve bimanual manipulation, e.g., to open the lid of a bottle, bilateral exoskeleton control is required but was not shown yet in tetraplegics. To further enhance B/NMI systems, we first investigated whether B/NMI whole-arm exoskeleton control in hemiplegia after chronic stroke is feasible and safe. In contrast to simple grasping, control of more complex tasks involving the entire upper limb was not feasible with established B/NMIs because high- dimensionality of such multiple joint systems exceeds the bandwidth of these interfaces. Thus, we blended B/NMI control with vision-guidance to receive a semiautonomous whole-arm exoskeleton control. Such setup allowed to divide ADL tasks into a sequence of EEG/EOG-triggered sub-tasks reducing complexity for the user. While, for instance, a drinking task was resolved into EOG-induced reaching, lifting and placing back the cup, grasping and releasing movements were based on intuitive SMR control. Feasibility of such shared vision-guided B/NMI control was assumed when executions were initialized within 3 s (fluent control) and a minimum of 75 % of subtasks were executed within that time (reliable control). We showed feasibility in healthy subjects as well as stroke survivors without report of any side effects documenting safe use. Similarly, feasibility and safety of bilateral B/NMI control after cervical SCI was evaluated. To enable bilateral B/NMI control, established EEG-based grasping and EOG-based releasing or stop commands were complemented with a novel EOG command allowing to switch laterality by performing prolonged horizontal eye movements (>1 s) to the left or to the right. Study results with healthy subjects and tetraplegics document fluent initialization of grasping motions below 3 s as well as safe use as unintended grasping could be stopped before a full motion was conducted. Superiority of novel bilateral control was documented by a higher accuracy of up to 22 % in tetraplegics compared to a bilateral control without prolonged EOG command. Lastly, as reliable B/NMI control is cognitively demanding, e.g., by imagining or attempting the desired movements, we investigated whether heart rate variability (HRV) can be used as biomarker to predict declining control performance, which is often reported in stroke survivors due to their cognitive impairments. Referring to the close brain-heart connection, we showed in healthy subjects that a decline in HRV is specific as well as predictive to a decline in B/NMI control performance within a single training session. The predictive link was revealed by a Granger-causality analysis. In conclusion, we could demonstrate important enhancements in B/NMI control paradigms including complex whole-arm exoskeleton control as well as individual performance monitoring within a training session based on HRV. Both achievements contribute to broaden the use as a standard therapy in stroke neurorehabilitation. Especially the predictive characteristic of HRV paves the way for adaptive B/NMI control paradigms to account for individual differences among impaired stroke survivors. Moreover, we also showed feasibility and safety of a novel implementation for bilateral B/NMI control, which is necessary for reliable operation of two hand-exoskeletons for bimanual ADLs after SCI

A Biosymtic (Biosymbiotic Robotic) Approach to Human Development and Evolution. The Echo of the Universe.

In the present work we demonstrate that the current Child-Computer Interaction paradigm is not potentiating human development to its fullest – it is associated with several physical and mental health problems and appears not to be maximizing children’s cognitive performance and cognitive development. In order to potentiate children’s physical and mental health (including cognitive performance and cognitive development) we have developed a new approach to human development and evolution. This approach proposes a particular synergy between the developing human body, computing machines and natural environments. It emphasizes that children should be encouraged to interact with challenging physical environments offering multiple possibilities for sensory stimulation and increasing physical and mental stress to the organism. We created and tested a new set of computing devices in order to operationalize our approach – Biosymtic (Biosymbiotic Robotic) devices: “Albert” and “Cratus”. In two initial studies we were able to observe that the main goal of our approach is being achieved. We observed that, interaction with the Biosymtic device “Albert”, in a natural environment, managed to trigger a different neurophysiological response (increases in sustained attention levels) and tended to optimize episodic memory performance in children, compared to interaction with a sedentary screen-based computing device, in an artificially controlled environment (indoors) - thus a promising solution to promote cognitive performance/development; and that interaction with the Biosymtic device “Cratus”, in a natural environment, instilled vigorous physical activity levels in children - thus a promising solution to promote physical and mental health

Rewiring the impulsive brain:Neurofeedback treatment in forensic psychiatric patients with substance use disorder

Mensen met een psychiatrische stoornis vertonen vaak inadequate copingsmechanismen als reactie op stressvolle situaties of gebeurtenissen. Hun gedrag is vaak onbezonnen en overhaast, waarbij er niet wordt nagedacht over de mogelijke (negatieve) consequenties. Soms kan dit gedrag leiden tot het plegen van een misdrijf. Patiënten binnen een Tbs-kliniek lijden doorgaans aan een combinatie van meerdere psychiatrische stoornissen, die gekenmerkt worden door een hoge mate van impulsiviteit. Impulsiviteit speelt ook een grote rol bij het ontstaan en in stand houden van middelenafhankelijkheid. Er is hierbij vaak sprake van een wisselwerking tussen een verhoogde mate van impulsiviteit die al aanwezig was voordat deze mensen afhankelijk zijn geworden van verslavende middelen, en de ontremmende werking van verslavende middelen. Op het moment dat deze patiënten behandeling zoeken voor hun middelenafhankelijkheid wordt ook de verdere de behandeling belemmerd door een hoge mate van impulsiviteit, omdat dit de kans op het voortijdig afbreken van de behandeling vergroot. Omdat verslaving de kans op terugval in delictgedrag verhoogd is het niet afronden van een verslavingsbehandeling vooral voor forensisch psychiatrische patiënten zeer risicovol. Daarom zijn behandelmethoden die de kans op een succesvolle vermindering van impulsiviteit en middelenafhankelijkheid vergroten van groot belang. Verslavende middelen kunnen leiden tot structurele neurofysiologische en neurocognitieve veranderingen, die de impulscontrole nog verder negatief beïnvloeden. Neurofeedback-training is gericht op het corrigeren van afwijkende hersenfrequenties, waarbij er verondersteld wordt dat deze afwijkende hersenfrequenties psychische stoornissen weerspiegelen. Door het verhogen of verlagen van bepaalde hersenfrequenties kunnen symptomen van psychische stoornissen verminderen. Tot op heden wordt neurofeedback-training echter nog niet vaak ingezet in de behandeling van forensisch psychiatrische patiënten, zowel in Nederland als ook internationaal. Dit proefschrift onderzocht of een theta/sensorimotor rhythm (SMR) neurofeedback training een geschikte behandelmethode is om een hoge mate van impulsiviteit en daarmee de bijkomende verslavingsproblematiek te verminderen. De studies in dit proefschrift laten zien dat forensische patiënten moeite hebben om de principes van neurofeedback training te kunnen leren, en hun hersenfrequenties door middel van de behandeling succesvol te trainen. Interpersoonlijke verschillen tussen patiënten lijken hierbij te bepalen in hoeverre patiënten van deze interventie kunnen profiteren. Slechts een gering aantal patiënten in deze studie is het gelukt om door middel van de neurofeedback training hun hersenfrequenties te reguleren. Daarnaast was neurofeedback training niet beter dan de reguliere behandeling om klinische symptomen, zoals hoge mate van impulsiviteit en zucht naar middelen te verminderen. Dit is een van de eerste studies die een neurofeedback-interventie heeft toegepast in een forensisch psychiatrische doelgroep met diverse stoornissen en comorbide middelenafhankelijkheid. Dit proefschrift geeft een eerste aanzet voor het toepassen van de training in deze populatie, en we hopen dan ook dat toekomstig onderzoek kan voortbouwen op de uitkomsten in dit proefschrift. Toekomstig onderzoek zou zich daarom moeten focussen op het identificeren van factoren die bepalen welke patiënten in staat zullen zijn om van de interventie te profiteren. Dit proefschrift geeft een eerste aanzet voor het toepassen van de training in dit populatie, waarbij toekomstig onderzoek kan voortbouwen op de uitkomsten in dit proefschrift

Hybridizing 3-dimensional multiple object tracking with neurofeedback to enhance preparation, performance, and learning

Le vaste domaine de l’amélioration cognitive traverse les applications comportementales, biochimiques et physiques. Aussi nombreuses sont les techniques que les limites de ces premières : des études de pauvre méthodologie, des pratiques éthiquement ambiguës, de faibles effets positifs, des effets secondaires significatifs, des couts financiers importants, un investissement de temps significatif, une accessibilité inégale, et encore un manque de transfert. L’objectif de cette thèse est de proposer une méthode novatrice d’intégration de l’une de ces techniques, le neurofeedback, directement dans un paradigme d’apprentissage afin d’améliorer la performance cognitive et l’apprentissage. Cette thèse propose les modalités, les fondements empiriques et des données à l’appui de ce paradigme efficace d’apprentissage ‘bouclé’. En manipulant la difficulté dans une tâche en fonction de l’activité cérébrale en temps réel, il est démontré que dans un paradigme d’apprentissage traditionnel (3-dimentional multiple object tracking), la vitesse et le degré d’apprentissage peuvent être améliorés de manière significative lorsque comparés au paradigme traditionnel ou encore à un groupe de contrôle actif. La performance améliorée demeure observée même avec un retrait du signal de rétroaction, ce qui suggère que les effets de l’entrainement amélioré sont consolidés et ne dépendent pas d’une rétroaction continue. Ensuite, cette thèse révèle comment de tels effets se produisent, en examinant les corrélés neuronaux des états de préparation et de performance à travers les conditions d’état de base et pendant la tâche, de plus qu’en fonction du résultat (réussite/échec) et de la difficulté (basse/moyenne/haute vitesse). La préparation, la performance et la charge cognitive sont mesurées via des liens robustement établis dans un contexte d’activité cérébrale fonctionnelle mesurée par l’électroencéphalographie quantitative. Il est démontré que l’ajout d’une assistance- à-la-tâche apportée par la fréquence alpha dominante est non seulement appropriée aux conditions de ce paradigme, mais influence la charge cognitive afin de favoriser un maintien du sujet dans sa zone de développement proximale, ce qui facilite l’apprentissage et améliore la performance. Ce type de paradigme d’apprentissage peut contribuer à surmonter, au minimum, un des limites fondamentales du neurofeedback et des autres techniques d’amélioration cognitive : le manque de transfert, en utilisant une méthode pouvant être intégrée directement dans le contexte dans lequel l’amélioration de la performance est souhaitée.The domain of cognitive enhancement is vast, spanning behavioral, biochemical and physical applications. The techniques are as numerous as are the limitations: poorly conducted studies, ethically ambiguous practices, limited positive effects, significant side-effects, high financial costs, significant time investment, unequal accessibility, and lack of transfer. The purpose of this thesis is to propose a novel way of integrating one of these techniques, neurofeedback, directly into a learning context in order to enhance cognitive performance and learning. This thesis provides the framework, empirical foundations, and supporting evidence for a highly efficient ‘closed-loop’ learning paradigm. By manipulating task difficulty based on a measure of cognitive load within a classic learning scenario (3-dimentional multiple object tracking) using real-time brain activity, results demonstrate that over 10 sessions, speed and degree of learning can be substantially improved compared with a classic learning system or an active sham-control group. Superior performance persists even once the feedback signal is removed, which suggests that the effects of enhanced training are consolidated and do not rely on continued feedback. Next, this thesis examines how these effects occur, exploring the neural correlates of the states of preparedness and performance across baseline and task conditions, further examining correlates related to trial results (correct/incorrect) and task difficulty (slow/medium/fast speeds). Cognitive preparedness, performance and load are measured using well-established relationships between real-time quantified brain activity as measured by quantitative electroencephalography. It is shown that the addition of neurofeedback-based task assistance based on peak alpha frequency is appropriate to task conditions and manages to influence cognitive load, keeping the subject in the zone of proximal development more often, facilitating learning and improving performance. This type of learning paradigm could contribute to overcoming at least one of the fundamental limitations of neurofeedback and other cognitive enhancement techniques : a lack of observable transfer effects, by utilizing a method that can be directly integrated into the context in which improved performance is sought

Brain Computer Interfaces and Emotional Involvement: Theory, Research, and Applications

This reprint is dedicated to the study of brain activity related to emotional and attentional involvement as measured by Brain–computer interface (BCI) systems designed for different purposes. A BCI system can translate brain signals (e.g., electric or hemodynamic brain activity indicators) into a command to execute an action in the BCI application (e.g., a wheelchair, the cursor on the screen, a spelling device or a game). These tools have the advantage of having real-time access to the ongoing brain activity of the individual, which can provide insight into the user’s emotional and attentional states by training a classification algorithm to recognize mental states. The success of BCI systems in contemporary neuroscientific research relies on the fact that they allow one to “think outside the lab”. The integration of technological solutions, artificial intelligence and cognitive science allowed and will allow researchers to envision more and more applications for the future. The clinical and everyday uses are described with the aim to invite readers to open their minds to imagine potential further developments