The primate hand, a biomechanical structure with over twenty kinematic degrees of freedom, has an elaborate anatomical architecture. Although the hand requires complex, coordinated neural control, it endows its owner with an astonishing range of dexterous finger movements. Despite a century of research, however, the neural mechanisms that enable finger and grasping movements in primates are largely unknown. In this thesis, we investigate statistical models of finger movement that can provide insights into the mechanics of the hand, and that can have applications in neural-motor prostheses, enabling people with limb loss to regain natural function of the hands. There are many challenges associated with (1) the understanding and modeling of the kinematics of fingers, and (2) the mapping of intracortical neural recordings into motor commands that can be used to control a Brain-Machine Interface. These challenges include: potential nonlinearities; confounded sources of variation in experimental datasets; and dealing with high degrees of kinematic freedom. In this work we analyze kinematic and neural datasets from repeated-trial experiments of hand motion, with the following contributions: We identified static, nonlinear, low-dimensional representations of grasping finger motion, with accompanying evidence that these nonlinear representations are better than linear representations at predicting the type of object being grasped over the course of a reach-to-grasp movement. In addition, we show evidence of better encoding of these nonlinear (versus linear) representations in the firing of some neurons collected from the primary motor cortex of rhesus monkeys. A functional alignment of grasping trajectories, based on total kinetic energy, as a strategy to account for temporal variation and to exploit a repeated-trial experiment structure. An interpretable model for extracting dynamic synergies of finger motion, based on Gaussian Processes, that decomposes and reduces the dimensionality of variance in the dataset. We derive efficient algorithms for parameter estimation, show accurate reconstruction of grasping trajectories, and illustrate the interpretation of the model parameters. Sound evidence of single-neuron decoding of interpretable grasping events, plus insights about the amount of grasping information extractable from just a single neuron. The Laplace Gaussian Filter (LGF), a deterministic approximation to the posterior mean that is more accurate than Monte Carlo approximations for the same computational cost, and that in an off-line decoding task is more accurate than the standard Population Vector Algorithm.

In the framework of Bayesian model-based clustering based on a finite mixture of Gaussian distributions, we present a joint approach to estimate the number of mixture components and identify cluster-relevant variables simultaneously as well as to obtain an identified model. Our approach consists in specifying sparse hierarchical priors on the mixture weights and component means. In a deliberately overfitting mixture model the sparse prior on the weights empties superfluous components during MCMC. A straightforward estimator for the true number of components is given by the most frequent number of non-empty components visited during MCMC sampling. Specifying a shrinkage prior, namely the normal gamma prior, on the component means leads to improved parameter estimates as well as identification of cluster-relevant variables. After estimating the mixture model using MCMC methods based on data augmentation and Gibbs sampling, an identified model is obtained by relabeling the MCMC output in the point process representation of the draws. This is performed using K-centroids cluster analysis based on the Mahalanobis distance. We evaluate our proposed strategy in a simulation setup with artificial data and by applying it to benchmark data sets. (authors' abstract)

Yes / Human activity recognition from sensor readings have proved to be an effective approach in pervasive computing for smart healthcare. Recent approaches to ambient assisted living (AAL) within a home or community setting offers people the prospect of more individually-focused care and improved quality of living. However, most of the available AAL systems are often limited by computational cost. In this paper, a simple, novel non-wearable human activity classification framework using the multivariate Gaussian is proposed. The classification framework augments prior information from the passive RFID tags to obtain more detailed activity profiling. The proposed algorithm based on multivariate Gaussian via maximum likelihood estimation is used to learn the features of the human activity model. Twelve sequential and concurrent experimental evaluations are conducted in a mock apartment environment. The sampled activities are predicted using a new dataset of the same activity and high prediction accuracy is established. The proposed framework suits well for the single and multi-dwelling environment and offers pervasive sensing environment for both patients and carers. / Tertiary Education Trust Fund of Federal Government of Nigeria and by the European Union’s Horizon 2020 research and innovation programme under Grant Agreement H2020-MSCA-ITN-2016 SECRET-722424

In this thesis, newer Markov Chain Monte Carlo (MCMC) algorithms are implemented and compared in terms of their efficiency in the context of sampling from Gaussian processes under linear inequality constraints. Extending the framework of Gaussian process that uses Gibbs sampler, two MCMC algorithms, Exact Hamiltonian Monte Carlo (HMC) and Analytic Elliptical Slice Sampling (ESS), are used to sample values of truncated multivariate Gaussian distributions that are used for Gaussian process regression models with linear inequality constraints. In terms of generating samples from Gaussian processes under linear inequality constraints, the proposed methods generally produce samples that are less correlated than samples from the Gibbs sampler. Time-wise, Analytic ESS is proven to be a faster choice while Exact HMC produces the least correlated samples.

Modern medical practice and science involve complex phenotypic definitions. Understanding patterns of association across this range of phenotypes requires co-analysis of high-dimensional association studies in order to characterise shared and distinct elements. In this thesis I address several problems in this area, with a general linking aim of making more efficient use of available data. The main application of these methods is in the analysis of genome-wide association studies (GWAS) and similar studies. Firstly, I developed methodology for a Bayesian conditional false discovery rate (cFDR) for levering GWAS results using summary statistics from a related disease. I extended an existing method to enable a shared control design, increasing power and applicability, and developed an approximate bound on false-discovery rate (FDR) for the procedure. Using the new method I identified several new variant-disease associations. I then developed a second application of shared control design in the context of study replication, enabling improvement in power at the cost of changing the spectrum of sensitivity to systematic errors in study cohorts. This has application in studies on rare diseases or in between-case analyses. I then developed a method for partially characterising heterogeneity within a disease by modelling the bivariate distribution of case-control and within-case effect sizes. Using an adaptation of a likelihood-ratio test, this allows an assessment to be made of whether disease heterogeneity corresponds to differences in disease pathology. I applied this method to a range of simulated and real datasets, enabling insight into the cause of heterogeneity in autoantibody positivity in type 1 diabetes (T1D). Finally, I investigated the relation of subtypes of juvenile idiopathic arthritis (JIA) to adult diseases, using modified genetic risk scores and linear discriminants in a penalised regression framework. The contribution of this thesis is in a range of methodological developments in the analysis of high-dimensional association study comparison. Methods such as these will have wide application in the analysis of GWAS and similar areas, particularly in the development of stratified medicine.