<p>Brain-machine interfaces (BMI) are systems which connect brains directly to machines or computers for communication. BMI-controlled prosthetic devices use algorithms to decode neuronal recordings into movement commands. These algorithms operate using models of how recorded neuronal signals relate to desired movements, called models of tuning. Models of tuning have typically been linear in prior work, due to the simplicity and speed of the algorithms used with them. Neuronal tuning has been shown to slowly change over time, but most prior work do not adapt tuning models to these changes. Furthermore, extracellular electrical recordings of neurons' action potentials slowly change over time, impairing the preprocessing step of spike-sorting, during which the neurons responsible for recorded action potentials are identified.</p> <p></p> <p>This dissertation presents a non-linear adaptive Bayesian filter and an adaptive spike-sorting method for BMI decoding. The adaptive filter consists of the n-th order unscented Kalman filter and Bayesian regression self-training updates. The unscented Kalman filter estimates desired prosthetic movements using a non-linear model of tuning as its observation model. The model is quadratic with terms for position, velocity, distance from center of workspace, and velocity magnitude. The tuning model relates neuronal activity to movements at multiple time offsets simultaneously, and the movement model of the filter is an order n autoregressive model.</p> <p>To adapt the tuning model parameters to changes in the brain, Bayesian regression self-training updates are performed periodically. Tuning model parameters are stored as probability distributions instead of point estimates. Bayesian regression uses the previous model parameters as priors and calculates the posteriors of the regression between filter outputs, which are assumed to be the desired movements, and neuronal recordings. Before each update, filter outputs are smoothed using a Kalman smoother, and tuning model parameters are passed through a transition model describing how parameters change over time. Two variants of Bayesian regression are presented: one uses a joint distribution for the model parameters which allows analytical inference, and the other uses a more flexible factorized distribution that requires approximate inference using variational Bayes.</p> <p>To adapt spike-sorting parameters to changes in spike waveforms, variational Bayesian Gaussian mixture clustering updates are used to update the waveform clustering used to calculate these parameters. This Bayesian extension of expectation-maximization clustering uses the previous clustering parameters as priors and computes the new parameters as posteriors. The use of priors allows tracking of clustering parameters over time and facilitates fast convergence.</p> <p>To evaluate the proposed methods, experiments were performed with 3 Rhesus monkeys implanted with micro-wire electrode arrays in arm-related areas of the cortex. Off-line reconstructions and on-line, closed-loop experiments with brain-control show that the n-th order unscented Kalman filter is more accurate than previous linear methods. Closed-loop experiments over 29 days show that Bayesian regression self-training helps maintain control accuracy. Experiments on synthetic data show that Bayesian regression self-training can be applied to other tracking problems with changing observation models. Bayesian clustering updates on synthetic and neuronal data demonstrate tracking of cluster and waveform changes. These results indicate the proposed methods improve the accuracy and robustness of BMIs for prosthetic devices, bringing BMI-controlled prosthetics closer to clinical use.</p> / Dissertation

Background Spinal pain is one of humanity’s most frequent complaints with high costs for the individual and society, and is commonly related to spinal disorders. There are many origins behind these disorders e.g., trauma, disc hernia or of other organic origins. However, for many of the disorders, the origin is not known. Thus, more knowledge is needed about how pain affects the neck and neural function in pain affected regions. The purpose of this dissertation was to improve the medical examination of patients suffering from chronic whiplash-associated disorders or other pain related neck-disorders. Methods A new assessment tool for objective movement analysis was developed. In addition, basic aspects of proprioceptive information transmission, which can be of relevance for muscular tension and pain, are investigated by studying the coding of populations of different types of sensory afferents by using a new spike sorting method. Both experiments in animal models and humans were studied to accomplish the goals of this dissertation. Four cats where were studied in acute animal experiments. Mixed ensembles of afferents were recorded from L7-S1 dorsal root filaments when mechanical stimulating the innervated muscle. A real-time spike sorting method was developed to sort units in a multi-unit recording. The quantification of population coding was performed using a method based on principal component analysis. In the human studies, 3D neck movement data were collected from 59 subjects with whiplash-associated disorders (WAD) and 56 control subjects. Neck movement patterns were identified by processing movement data into parameters describing the rotation of the head for each subject. Classification of neck movement patterns was performed using a neural network using processed collected data as input. Finally, the effect of marker position error on the estimated rotation of the head was evaluated by computer simulations. Results Animal experiments showed that mixed ensembles of different types of afferents discriminated better between different muscle stimuli than ensembles of single types of these afferents. All kinds of ensembles showed an increase in discriminative ability with increased ensemble size. It is hypothesized that the main reason for the greater discriminative ability might be the variation in sensitivity tuning among the individual afferents of the mixed ensemble will be larger than that for ensembles of only one type of afferent. In the human studies, the neural networks had a predictivity of 0.89, a sensitivity of 0.90 and a specificity of 0.88 when discriminating between control and WAD subjects. Also, a systematic error along the radial axis of the rigid body added to a single marker had no affect on the estimated rotation of the head. Conclusion The developed spike sorting method, using neural networks, was suitable for sorting a multiunit recording into single units when performing neurophysiological experiments. Also, it was shown that neck movement analysis combined with a neural network could build the basis of a decision support system for classifying suspected WAD or other pain related neck-disorders.

This research consists of probabilistic modeling of speech audio signals and deep-brain neurological signals in brain-computer interfaces. A significant portion of this research consists of a collaborative effort with Neural Signals Inc., Duluth, GA, and Boston University to develop an intracortical neural prosthetic system for speech restoration in a human subject living with Locked-In Syndrome, i.e., he is paralyzed and unable to speak. The work is carried out in three major phases. We first use kernel-based classifiers to detect evidence of articulation gestures and phonological attributes speech audio signals. We demonstrate that articulatory information can be used to decode speech content in speech audio signals. In the second phase of the research, we use neurological signals collected from a human subject with Locked-In Syndrome to predict intended speech content. The neural data were collected with a microwire electrode surgically implanted in speech motor cortex of the subject's brain, with the implant location chosen to capture extracellular electric potentials related to speech motor activity. The data include extracellular traces, and firing occurrence times for neural clusters in the vicinity of the electrode identified by an expert. We compute continuous firing rate estimates for the ensemble of neural clusters using several rate estimation methods and apply statistical classifiers to the rate estimates to predict intended speech content. We use Gaussian mixture models to classify short frames of data into 5 vowel classes and to discriminate intended speech activity in the data from non-speech. We then perform a series of data collection experiments with the subject designed to test explicitly for several speech articulation gestures, and decode the data offline. Finally, in the third phase of the research we develop an original probabilistic method for the task of spike-sorting in intracortical brain-computer interfaces, i.e., identifying and distinguishing action potential waveforms in extracellular traces. Our method uses both action potential waveforms and their occurrence times to cluster the data. We apply the method to semi-artificial data and partially labeled real data. We then classify neural spike waveforms, modeled with single multivariate Gaussians, using the method of minimum classification error for parameter estimation. Finally, we apply our joint waveforms and occurrence times spike-sorting method to neurological data in the context of a neural prosthesis for speech.

<p>Signal processing within the neurophysiological field is challenging and requires short processing time and reliable results. In this thesis, three main problems are considered.</p><p>First, a modified line source model for simulation of muscle action potentials (APs) is presented. It is formulated in continuous-time as a convolution of a muscle-fiber dependent transmembrane current and an electrode dependent weighting (impedance) function. In the discretization of the model, the Nyquist criterion is addressed. By applying anti-aliasing filtering, it is possible to decrease the discretization frequency while retaining the accuracy. Finite length muscle fibers are incorporated in the model through a simple transformation of the weighting function. The presented model is suitable for modeling large motor units.</p><p>Second, the possibility of discerning the individual AP components of the concentric needle electromyogram (EMG) is explored. Simulated motor unit APs (MUAPs) are prefiltered using Wiener filtering. The mean fiber concentration (MFC) and jitter are estimated from the prefiltered MUAPs. The results indicate that the assessment of the MFC may well benefit from the presented approach and that the jitter may be estimated from the concentric needle EMG with an accuracy comparable with traditional single fiber EMG.</p><p>Third, automatic, rather than manual, detection and discrimination of recorded C-fiber APs is addressed. The algorithm, detects the Aps reliably using a matched filter. Then, the detected APs are discriminated using multiple hypothesis tracking combined with Kalman filtering which identifies the APs originating from the same C-fiber. To improve the performance, an amplitude estimate is incorporated into the tracking algorithm. Several years of use show that the performance of the algorithm is excellent with minimal need for audit.</p>

Signal processing within the neurophysiological field is challenging and requires short processing time and reliable results. In this thesis, three main problems are considered. First, a modified line source model for simulation of muscle action potentials (APs) is presented. It is formulated in continuous-time as a convolution of a muscle-fiber dependent transmembrane current and an electrode dependent weighting (impedance) function. In the discretization of the model, the Nyquist criterion is addressed. By applying anti-aliasing filtering, it is possible to decrease the discretization frequency while retaining the accuracy. Finite length muscle fibers are incorporated in the model through a simple transformation of the weighting function. The presented model is suitable for modeling large motor units. Second, the possibility of discerning the individual AP components of the concentric needle electromyogram (EMG) is explored. Simulated motor unit APs (MUAPs) are prefiltered using Wiener filtering. The mean fiber concentration (MFC) and jitter are estimated from the prefiltered MUAPs. The results indicate that the assessment of the MFC may well benefit from the presented approach and that the jitter may be estimated from the concentric needle EMG with an accuracy comparable with traditional single fiber EMG. Third, automatic, rather than manual, detection and discrimination of recorded C-fiber APs is addressed. The algorithm, detects the Aps reliably using a matched filter. Then, the detected APs are discriminated using multiple hypothesis tracking combined with Kalman filtering which identifies the APs originating from the same C-fiber. To improve the performance, an amplitude estimate is incorporated into the tracking algorithm. Several years of use show that the performance of the algorithm is excellent with minimal need for audit.

Cette thèse a pour objectif de contribuer à la modélisation, à la simulation et à l’analyse des signaux contenant des potentiels d’action extracellulaires (EAPs), tels que mesurés in-vivo par des microélectrodes implantées dans le cerveau. Les modèles actuels pour la simulation des EAPs consistent soit en des modèles compartimentaux très détaillés et lourds en calcul, soit en des modèles dipolaires jugés trop simplistes. Dans un premier temps, une approche de simulation des EAPs se situant entre ces deux extrêmes est proposée, où la somme des contributions des compartiments du neurone est traitée comme une convolution, appliquée aux courants membranaires d’un seul compartiment actif. L'analyse des EAPs passe par une étape de classification des potentiels d'action détectés dans le signal enregistré, qui consiste à discriminer les formes de potentiels d’action et ainsi à identifier l'activité de neurones uniques. Dans cette thèse, une nouvelle approche basée sur l’inférence bayésienne est développée permettant l'extraction et la classification simultanées des EAPs. La méthode est appliquée à des signaux générés à l'aide de l'approche de simulation proposée plus haut, confirmant la qualité de la méthode de classification introduite et illustrant la capacité de la méthode de simulation à générer des EAPs réalistes de formes diverses et discriminables. Nous avons enrichi une modélisation de l’activité hippocampique réalisée dans l’équipe permettant de reproduire des oscillations dans ces bandes fréquentielles spécifiques en introduisant les EAPs, ceci afin d’évaluer les contributions de l'activité synaptique et celle des potentiels d’action à certaines bandes de fréquence des signaux enregistrés. Finalement, une étude sur signaux réels enregistrés dans le cadre de l'étude de la perception des visages chez l'homme a été menée, illustrant les performances de la méthode de spike sorting proposée dans un cadre réel et ouvrant la discussion sur les perspectives qu'offrent ces travaux de thèse pour l'étude de questions neuroscientifiques basées sur l'analyse de signaux multi-échelle. / The objective of this thesis is to contribute to the modelling, simulation and analysis of signals containing extracellular action potentials (EAPs), as measured in vivo by microelectrodes implanted in the brain. Current models for the EAPs simulation consist either of very detailed and computationally heavy compartmental models or dipole models considered too simplistic. An EAP simulation approach between these two extremes is proposed, where the sum of the contributions of the neuron compartments is treated as a convolution, applied to the membrane currents of a single active compartment. The analysis of EAPs involves a step of classifying the action potentials detected in the recorded signal, which consists in discriminating the forms of action potentials and thus identifying the activity of single neurons In this thesis, a new approach based on Bayesian inference is developed allowing the simultaneous extraction and classification of EAPs. The method is applied to signals generated using the simulation approach proposed above, confirming the quality of the sorting method introduced and illustrating the ability of the simulation method to generate realistic EAPs of various and discriminatory forms. We modified a model of hippocampal activity previously proposed in our team, able to reproduce oscillations in specific frequency bands, by including the EAPs model, which allowed to evaluate the contributions of synaptic activity and that of action potentials the recorded signals. Finally, a study on real signals recorded as part of the study of face perception in humans is conducted, illustrating the performance of the proposed spike sorting method in a real setting and opening the discussion on the perspectives offered by this thesis work for the study of neuroscientific questions based on multiscale signal analysis.

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