Integrating Statistical and Machine Learning Approaches to Identify Receptive Field Structure in Neural Populations

Neurons can code for multiple variables simultaneously and neuroscientists are often interested in classifying neurons based on their receptive field properties. Statistical models provide powerful tools for determining the factors influencing neural spiking activity and classifying individual neurons. However, as neural recording technologies have advanced to produce simultaneous spiking data from massive populations, classical statistical methods often lack the computational efficiency required to handle such data. Machine learning (ML) approaches are known for enabling efficient large scale data analyses; however, they typically require massive training sets with balanced data, along with accurate labels to fit well. Additionally, model assessment and interpretation are often more challenging for ML than for classical statistical methods. To address these challenges, we develop an integrated framework, combining statistical modeling and machine learning approaches to identify the coding properties of neurons from large populations. In order to demonstrate this framework, we apply these methods to data from a population of neurons recorded from rat hippocampus to characterize the distribution of spatial receptive fields in this region

Scaling Multidimensional Inference for Big Structured Data

In information technology, big data is a collection of data sets so large and complex that it becomes difficult to process using traditional data processing applications [151]. In a world of increasing sensor modalities, cheaper storage, and more data oriented questions, we are quickly passing the limits of tractable computations using traditional statistical analysis methods. Methods which often show great results on simple data have difficulties processing complicated multidimensional data. Accuracy alone can no longer justify unwarranted memory use and computational complexity. Improving the scaling properties of these methods for multidimensional data is the only way to make these methods relevant. In this work we explore methods for improving the scaling properties of parametric and nonparametric models. Namely, we focus on the structure of the data to lower the complexity of a specific family of problems. The two types of structures considered in this work are distributive optimization with separable constraints (Chapters 2-3), and scaling Gaussian processes for multidimensional lattice input (Chapters 4-5). By improving the scaling of these methods, we can expand their use to a wide range of applications which were previously intractable open the door to new research questions

Integrating statistical and machine learning approaches to identify receptive field structure in neural populations

Neural coding is essential for understanding how the activity of individual neurons or ensembles of neurons relates to cognitive processing of the world. Neurons can code for multiple variables simultaneously and neuroscientists are interested in classifying neurons based on the variables they represent. Building a model identification paradigm to identify neurons in terms of their coding properties is essential to understanding how the brain processes information. Statistical paradigms are capable of methodologically determining the factors influencing neural observations and assessing the quality of the resulting models to characterize and classify individual neurons. However, as neural recording technologies develop to produce data from massive populations, classical statistical methods often lack the computational efficiency required to handle such data. Machine learning (ML) approaches are known for enabling efficient large scale data analysis; however, they require huge training data sets, and model assessment and interpretation are more challenging than for classical statistical methods. To address these challenges, we develop an integrated framework, combining statistical modeling and machine learning approaches to identify the coding properties of neurons from large populations. In order to evaluate our approaches, we apply them to data from a population of neurons in rat hippocampus and prefrontal cortex (PFC), to characterize how spatial learning and memory processes are represented in these areas. The data consist of local field potentials (LFP) and spiking data simultaneously recorded from the CA1 region of hippocampus and the PFC of a male Long Evans rat performing a spatial alternation task on a W-shaped track. We have examined this data in three separate but related projects. In one project, we build an improved class of statistical models for neural activity by expanding a common set of basis functions to increase the statistical power of the resulting models. In the second project, we identify the individual neurons in hippocampus and PFC and classify them based on their coding properties by using statistical model identification methods. We found that a substantial proportion of hippocampus and PFC cells are spatially selective, with position and velocity coding, and rhythmic firing properties. These methods identified clear differences between hippocampal and prefrontal populations, and allowed us to classify the coding properties of the full population of neurons in these two regions. For the third project, we develop a supervised machine learning classifier based on convolutional neural networks (CNNs), which use classification results from statistical models and additional simulated data as ground truth signals for training. This integration of statistical and ML approaches allows for statistically principled and computationally efficient classification of the coding properties of general neural populations

Bayesian Methods for Discovering Structure in Neural Spike Trains

Neuroscience is entering an exciting new age. Modern recording technologies enable simultaneous measurements of thousands of neurons in organisms performing complex behaviors. Such recordings offer an unprecedented opportunity to glean insight into the mechanistic underpinnings of intelligence, but they also present an extraordinary statistical and computational challenge: how do we make sense of these large scale recordings? This thesis develops a suite of tools that instantiate hypotheses about neural computation in the form of probabilistic models and a corresponding set of Bayesian inference algorithms that efficiently fit these models to neural spike trains. From the posterior distribution of model parameters and variables, we seek to advance our understanding of how the brain works. Concretely, the challenge is to hypothesize latent structure in neural populations, encode that structure in a probabilistic model, and efficiently fit the model to neural spike trains. To surmount this challenge, we introduce a collection of structural motifs, the design patterns from which we construct interpretable models. In particular, we focus on random network models, which provide an intuitive bridge between latent types and features of neurons and the temporal dynamics of neural populations. In order to reconcile these models with the discrete nature of spike trains, we build on the Hawkes process — a multivariate generalization of the Poisson process — and its discrete time analogue, the linear autoregressive Poisson model. By leveraging the linear nature of these models and the Poisson superposition principle, we derive elegant auxiliary variable formulations and efficient inference algorithms. We then generalize these to nonlinear and nonstationary models of neural spike trains and take advantage of the Pólya-gamma augmentation to develop novel Markov chain Monte Carlo (MCMC) inference algorithms. In a variety of real neural recordings, we show how our methods reveal interpretable structure underlying neural spike trains. In the latter chapters, we shift our focus from autoregressive models to latent state space models of neural activity. We perform an empirical study of Bayesian nonparametric methods for hidden Markov models of neural spike trains. Then, we develop an MCMC algorithm for switching linear dynamical systems with discrete observations and a novel algorithm for sampling Pólya-gamma random variables that enables efficient annealed importance sampling for model comparison. Finally, we consider the “Bayesian brain” hypothesis — the hypothesis that neural circuits are themselves performing Bayesian inference. We show how one particular implementation of this hypothesis implies autoregressive dynamics of the form studied in earlier chapters, thereby providing a theoretical interpretation of our probabilistic models. This closes the loop, connecting top-down theory with bottom-up inferences, and suggests a path toward translating large scale recording capabilities into new insights about neural computation.Engineering and Applied Sciences - Computer Scienc

Simulation and Theory of Large-Scale Cortical Networks

Cerebral cortex is composed of intricate networks of neurons. These neuronal networks are strongly interconnected: every neuron receives, on average, input from thousands or more presynaptic neurons. In fact, to support such a number of connections, a majority of the volume in the cortical gray matter is filled by axons and dendrites. Besides the networks, neurons themselves are also highly complex. They possess an elaborate spatial structure and support various types of active processes and nonlinearities. In the face of such complexity, it seems necessary to abstract away some of the details and to investigate simplified models. In this thesis, such simplified models of neuronal networks are examined on varying levels of abstraction. Neurons are modeled as point neurons, both rate-based and spike-based, and networks are modeled as block-structured random networks. Crucially, on this level of abstraction, the models are still amenable to analytical treatment using the framework of dynamical mean-field theory. The main focus of this thesis is to leverage the analytical tractability of random networks of point neurons in order to relate the network structure, and the neuron parameters, to the dynamics of the neurons—in physics parlance, to bridge across the scales from neurons to networks. More concretely, four different models are investigated: 1) fully connected feedforward networks and vanilla recurrent networks of rate neurons; 2) block-structured networks of rate neurons in continuous time; 3) block-structured networks of spiking neurons; and 4) a multi-scale, data-based network of spiking neurons. We consider the first class of models in the light of Bayesian supervised learning and compute their kernel in the infinite-size limit. In the second class of models, we connect dynamical mean-field theory with large-deviation theory, calculate beyond mean-field fluctuations, and perform parameter inference. For the third class of models, we develop a theory for the autocorrelation time of the neurons. Lastly, we consolidate data across multiple modalities into a layer- and population-resolved model of human cortex and compare its activity with cortical recordings. In two detours from the investigation of these four network models, we examine the distribution of neuron densities in cerebral cortex and present a software toolbox for mean-field analyses of spiking networks