A Nonparametric Bayesian Approach to Uncovering Rat Hippocampal Population Codes During Spatial Navigation

Rodent hippocampal population codes represent important spatial information about the environment during navigation. Several computational methods have been developed to uncover the neural representation of spatial topology embedded in rodent hippocampal ensemble spike activity. Here we extend our previous work and propose a nonparametric Bayesian approach to infer rat hippocampal population codes during spatial navigation. To tackle the model selection problem, we leverage a nonparametric Bayesian model. Specifically, to analyze rat hippocampal ensemble spiking activity, we apply a hierarchical Dirichlet process-hidden Markov model (HDP-HMM) using two Bayesian inference methods, one based on Markov chain Monte Carlo (MCMC) and the other based on variational Bayes (VB). We demonstrate the effectiveness of our Bayesian approaches on recordings from a freely-behaving rat navigating in an open field environment. We find that MCMC-based inference with Hamiltonian Monte Carlo (HMC) hyperparameter sampling is flexible and efficient, and outperforms VB and MCMC approaches with hyperparameters set by empirical Bayes

Contributions to statistical analysis methods for neural spiking activity

With the technical advances in neuroscience experiments in the past few decades, we have seen a massive expansion in our ability to record neural activity. These advances enable neuroscientists to analyze more complex neural coding and communication properties, and at the same time, raise new challenges for analyzing neural spiking data, which keeps growing in scale, dimension, and complexity. This thesis proposes several new statistical methods that advance statistical analysis approaches for neural spiking data, including sequential Monte Carlo (SMC) methods for efficient estimation of neural dynamics from membrane potential threshold crossings, state-space models using multimodal observation processes, and goodness-of-fit analysis methods for neural marked point process models. In a first project, we derive a set of iterative formulas that enable us to simulate trajectories from stochastic, dynamic neural spiking models that are consistent with a set of spike time observations. We develop a SMC method to simultaneously estimate the parameters of the model and the unobserved dynamic variables from spike train data. We investigate the performance of this approach on a leaky integrate-and-fire model. In another project, we define a semi-latent state-space model to estimate information related to the phenomenon of hippocampal replay. Replay is a recently discovered phenomenon where patterns of hippocampal spiking activity that typically occur during exploration of an environment are reactivated when an animal is at rest. This reactivation is accompanied by high frequency oscillations in hippocampal local field potentials. However, methods to define replay mathematically remain undeveloped. In this project, we construct a novel state-space model that enables us to identify whether replay is occurring, and if so to estimate the movement trajectories consistent with the observed neural activity, and to categorize the content of each event. The state-space model integrates information from the spiking activity from the hippocampal population, the rhythms in the local field potential, and the rat's movement behavior. Finally, we develop a new, general time-rescaling theorem for marked point processes, and use this to develop a general goodness-of-fit framework for neural population spiking models. We investigate this approach through simulation and a real data application

Particle-filtering approaches for nonlinear Bayesian decoding of neuronal spike trains

The number of neurons that can be simultaneously recorded doubles every seven years. This ever increasing number of recorded neurons opens up the possibility to address new questions and extract higher dimensional stimuli from the recordings. Modeling neural spike trains as point processes, this task of extracting dynamical signals from spike trains is commonly set in the context of nonlinear filtering theory. Particle filter methods relying on importance weights are generic algorithms that solve the filtering task numerically, but exhibit a serious drawback when the problem dimensionality is high: they are known to suffer from the 'curse of dimensionality' (COD), i.e. the number of particles required for a certain performance scales exponentially with the observable dimensions. Here, we first briefly review the theory on filtering with point process observations in continuous time. Based on this theory, we investigate both analytically and numerically the reason for the COD of weighted particle filtering approaches: Similarly to particle filtering with continuous-time observations, the COD with point-process observations is due to the decay of effective number of particles, an effect that is stronger when the number of observable dimensions increases. Given the success of unweighted particle filtering approaches in overcoming the COD for continuous- time observations, we introduce an unweighted particle filter for point-process observations, the spike-based Neural Particle Filter (sNPF), and show that it exhibits a similar favorable scaling as the number of dimensions grows. Further, we derive rules for the parameters of the sNPF from a maximum likelihood approach learning. We finally employ a simple decoding task to illustrate the capabilities of the sNPF and to highlight one possible future application of our inference and learning algorithm

Point process modeling and estimation: advances in the analysis of dynamic neural spiking data

A common interest of scientists in many fields is to understand the relationship between the dynamics of a physical system and the occurrences of discrete events within such physical system. Seismologists study the connection between mechanical vibrations of the Earth and the occurrences of earthquakes so that future earthquakes can be better predicted. Astrophysicists study the association between the oscillating energy of celestial regions and the emission of photons to learn the Universe's various objects and their interactions. Neuroscientists study the link between behavior and the millisecond-timescale spike patterns of neurons to understand higher brain functions. Such relationships can often be formulated within the framework of state-space models with point process observations. The basic idea is that the dynamics of the physical systems are driven by the dynamics of some stochastic state variables and the discrete events we observe in an interval are noisy observations with distributions determined by the state variables. This thesis proposes several new methodological developments that advance the framework of state-space models with point process observations at the intersection of statistics and neuroscience. In particular, we develop new methods 1) to characterize the rhythmic spiking activity using history-dependent structure, 2) to model population spike activity using marked point process models, 3) to allow for real-time decision making, and 4) to take into account the need for dimensionality reduction for high-dimensional state and observation processes. We applied these methods to a novel problem of tracking rhythmic dynamics in the spiking of neurons in the subthalamic nucleus of Parkinson's patients with the goal of optimizing placement of deep brain stimulation electrodes. We developed a decoding algorithm that can make decision in real-time (for example, to stimulate the neurons or not) based on various sources of information present in population spiking data. Lastly, we proposed a general three-step paradigm that allows us to relate behavioral outcomes of various tasks to simultaneously recorded neural activity across multiple brain areas, which is a step towards closed-loop therapies for psychological diseases using real-time neural stimulation. These methods are suitable for real-time implementation for content-based feedback experiments

Hidden Markov Models

Hidden Markov Models (HMMs), although known for decades, have made a big career nowadays and are still in state of development. This book presents theoretical issues and a variety of HMMs applications in speech recognition and synthesis, medicine, neurosciences, computational biology, bioinformatics, seismology, environment protection and engineering. I hope that the reader will find this book useful and helpful for their own research