6 research outputs found
Neural Connectivity with Hidden Gaussian Graphical State-Model
The noninvasive procedures for neural connectivity are under questioning.
Theoretical models sustain that the electromagnetic field registered at
external sensors is elicited by currents at neural space. Nevertheless, what we
observe at the sensor space is a superposition of projected fields, from the
whole gray-matter. This is the reason for a major pitfall of noninvasive
Electrophysiology methods: distorted reconstruction of neural activity and its
connectivity or leakage. It has been proven that current methods produce
incorrect connectomes. Somewhat related to the incorrect connectivity
modelling, they disregard either Systems Theory and Bayesian Information
Theory. We introduce a new formalism that attains for it, Hidden Gaussian
Graphical State-Model (HIGGS). A neural Gaussian Graphical Model (GGM) hidden
by the observation equation of Magneto-encephalographic (MEEG) signals. HIGGS
is equivalent to a frequency domain Linear State Space Model (LSSM) but with
sparse connectivity prior. The mathematical contribution here is the theory for
high-dimensional and frequency-domain HIGGS solvers. We demonstrate that HIGGS
can attenuate the leakage effect in the most critical case: the distortion EEG
signal due to head volume conduction heterogeneities. Its application in EEG is
illustrated with retrieved connectivity patterns from human Steady State Visual
Evoked Potentials (SSVEP). We provide for the first time confirmatory evidence
for noninvasive procedures of neural connectivity: concurrent EEG and
Electrocorticography (ECoG) recordings on monkey. Open source packages are
freely available online, to reproduce the results presented in this paper and
to analyze external MEEG databases
Maximum likelihood estimation of state space models from frequency domain data
This paper addresses the problem of estimating linear time invariant models from observed frequency domain data. Here an emphasis is placed on deriving numerically robust and efficient methods that can reliably deal with high order models over wide bandwidths. This involves a novel application of the expectation-maximization algorithm in order to find maximum likelihood estimates of state space structures. An empirical study using both simulated and real measurement data is presented to illustrate the efficacy of the solutions derived here
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Novel methods for biological network inference: an application to circadian Ca2+ signaling network
Biological processes involve complex biochemical interactions among a large number of species like cells, RNA, proteins and metabolites. Learning these interactions is essential to interfering artificially with biological processes in order to, for example, improve crop yield, develop new therapies, and predict new cell or organism behaviors to genetic or environmental perturbations. For a biological process, two pieces of information are of most interest. For a particular species, the first step is to learn which other species are regulating it. This reveals topology and causality. The second step involves learning the precise mechanisms of how this regulation occurs. This step reveals the dynamics of the system. Applying this process to all species leads to the complete dynamical network. Systems biology is making considerable efforts to learn biological networks at low experimental costs. The main goal of this thesis is to develop advanced methods to build models for biological networks, taking the circadian system of Arabidopsis thaliana as a case study. A variety of network inference approaches have been proposed in the literature to study dynamic biological networks. However, many successful methods either require prior knowledge of the system or focus more on topology. This thesis presents novel methods that identify both network topology and dynamics, and do not depend on prior knowledge. Hence, the proposed methods are applicable to general biological networks. These methods are initially developed for linear systems, and, at the cost of higher computational complexity, can also be applied to nonlinear systems. Overall, we propose four methods with increasing computational complexity: one-to-one, combined group and element sparse Bayesian learning (GESBL), the kernel method and reversible jump Markov chain Monte Carlo method (RJMCMC). All methods are tested with challenging dynamical network simulations (including feedback, random networks, different levels of noise and number of samples), and realistic models of circadian system of Arabidopsis thaliana. These simulations show that, while the one-to-one method scales to the whole genome, the kernel method and RJMCMC method are superior for smaller networks. They are robust to tuning variables and able to provide stable performance. The simulations also imply the advantage of GESBL and RJMCMC over the state-of-the-art method. We envision that the estimated models can benefit a wide range of research. For example, they can locate biological compounds responsible for human disease through mathematical analysis and help predict the effectiveness of new treatments