Recent advancements in miniaturized fluorescence microscopy have made it possible to investigate neuronal responses to external stimuli in awake behaving animals through the analysis of intra-cellular calcium signals. An on-going challenge is deconvolving the temporal signals to extract the spike trains from the noisy calcium signals' time-series. In this manuscript, we propose a nested Bayesian finite mixture specification that allows the estimation of spiking activity and, simultaneously, reconstructing the distributions of the calcium transient spikes' amplitudes under different experimental conditions. The proposed model leverages two nested layers of random discrete mixture priors to borrow information between experiments and discover similarities in the distributional patterns of neuronal responses to different stimuli. Furthermore, the spikes' intensity values are also clustered within and between experimental conditions to determine the existence of common (recurring) response amplitudes. Simulation studies and the analysis of a data set from the Allen Brain Observatory show the effectiveness of the method in clustering and detecting neuronal activities.
We present efficient Bayesian methods for extracting neuronal spiking information from calcium imaging data. The goal of our methods is to sample from the posterior distribution of spike trains and model parameters (baseline concentration, spike amplitude etc) given noisy calcium imaging data. We present discrete time algorithms where we sample the existence of a spike at each time bin using Gibbs methods, as well as continuous time algorithms where we sample over the number of spikes and their locations at an arbitrary resolution using Metropolis-Hastings methods for point processes. We provi…
Janelia Research Campus（珍妮亚研究园区）；HHMI（霍华德·休斯医学研究所）
The Importance Weighted Auto Encoder (IWAE) objective has been shown to improve the training of generative models over the standard Variational Auto Encoder (VAE) objective. Here, we derive importance weighted extensions to AVB and AAE. These latent variable models use implicitly defined inference networks whose approximate posterior density q_ϕ(z|x) cannot be directly evaluated, an essential ingredient for importance weighting. We show improved training and inference in latent variable models with our adversarially trained importance weighting method, and derive new theoretical connections be…
Discrete Bayesian nonparametric models whose expectation is a convex linear combination of a point mass at some point of the support and a diffuse probability distribution allow to incorporate strong prior information, while still being extremely flexible. Recent contributions in the statistical literature have successfully implemented such a modelling strategy in a variety of applications, including density estimation, nonparametric regression and model-based clustering. We provide a thorough study of a large class of nonparametric models we call inner spike and slab hNRMI models, which are o…
Centre for Cognitive Science, Technical University Darmstadt（达姆施塔特工业大学认知科学中心）；DeepMind；research center caesar, an associate of the Max Planck Society（凯撒研究中心，马克斯·普朗克学会合作机构）；IMPRS Brain and Behavior Bonn/Florida（波恩/佛罗里达国际马克斯·普朗克脑与行为研究学院）；HHMI Janelia Research Campus（霍华德·休斯医学研究所珍妮莉亚研究园区）；Columbia University（哥伦比亚大学）
Calcium imaging permits optical measurement of neural activity. Since intracellular calcium concentration is an indirect measurement of neural activity, computational tools are necessary to infer the true underlying spiking activity from fluorescence measurements. Bayesian model inversion can be used to solve this problem, but typically requires either computationally expensive MCMC sampling, or faster but approximate maximum-a-posteriori optimization. Here, we introduce a flexible algorithmic framework for fast, efficient and accurate extraction of neural spikes from imaging data. Using the f…
With the increasing popularity of calcium imaging data in neuroscience research, methods for analyzing calcium trace data are critical to address various questions. The observed calcium traces are either analyzed directly or deconvolved to spike trains to infer neuronal activities. When both approaches are applicable, it is unclear whether deconvolving calcium traces is a necessary step. In this article, we compare the performance of using calcium traces or their deconvolved spike trains for three common analyses: clustering, principal component analysis (PCA), and population decoding. Our sim…
Optical imaging of genetically encoded calcium indicators is a powerful tool to record the activity of a large number of neurons simultaneously over a long period of time from freely behaving animals. However, determining the exact time at which a neuron spikes and estimating the underlying firing rate from calcium fluorescence data remains challenging, especially for calcium imaging data obtained from a longitudinal study. We propose a multi-trial time-varying $\ell_0$ penalized method to jointly detect spikes and estimate firing rates by robustly integrating evolving neural dynamics across t…
A fundamental challenge in calcium imaging has been to infer the timing of action potentials from the measured noisy calcium fluorescence traces. We systematically evaluate a range of spike inference algorithms on a large benchmark dataset recorded from varying neural tissue (V1 and retina) using different calcium indicators (OGB-1 and GCamp6). We show that a new algorithm based on supervised learning in flexible probabilistic models outperforms all previously published techniques, setting a new standard for spike inference from calcium signals. Importantly, it performs better than other algor…
Supremum norm loss is intuitively more meaningful to quantify function estimation error in statistics. In the context of multivariate nonparametric regression with unknown error, we propose a Bayesian procedure based on spike-and-slab prior and wavelet projections to estimate the regression function and all its mixed partial derivatives. We show that their posterior distributions contract to the truth optimally and adaptively under supremum-norm loss. The master theorem through tests with exponential errors used in Bayesian nonparametrics was not adequate to deal with this problem, and we deve…
This article provides a brief introduction to seven papers that are included in this special section on Statistics in Neuroscience: (1) Xiaoyan Shi, Joseph G. Ibrahim, Jeffrey Lieberman, Martin Styner, Yimei Li and Hongtu Zhu: Two-state empirical likelihood for longitudinal neuroimaging data (2) Vincent Q. Vu, Pradeep Ravikumar, Thomas Naselaris, Kendrick N. Kay, Jack L. Gallant and Bin Yu: Encoding and decoding V1 fMRI responses to natural images with sparse nonparametric models (3) Sourabh Bhattacharya and Ranjan Maitra: A nonstationary nonparametric Bayesian approach to dynamically modeling…
Over the last decade, big data have poured into econometrics, demanding new statistical methods for analysing high-dimensional data and complex non-linear relationships. A common approach for addressing dimensionality issues relies on the use of static graphical structures for extracting the most significant dependence interrelationships between the variables of interest. Recently, Bayesian nonparametric techniques have become popular for modelling complex phenomena in a flexible and efficient manner, but only few attempts have been made in econometrics. In this paper, we provide an innovative…
We discuss Bayesian nonparametric procedures for the regression analysis of compositional responses, that is, data supported on a multivariate simplex. The procedures are based on a modified class of multivariate Bernstein polynomials and on the use of dependent stick-breaking processes. A general model and two simplified versions of the general model are discussed. Appealing theoretical properties such as continuity, association structure, support, and consistency of the posterior distribution are established. Additionally, we exploit the use of spike-and-slab priors for choosing the version …
Spike-and-slab and horseshoe regression are arguably the most popular Bayesian variable selection approaches for linear regression models. However, their performance can deteriorate if outliers and heteroskedasticity are present in the data, which are common features in many real-world statistics and machine learning applications. In this work, we propose a Bayesian nonparametric approach to linear regression that performs variable selection while accounting for outliers and heteroskedasticity. Our proposed model is an instance of a Dirichlet process scale mixture model with the advantage that…
Calcium imaging data promises to transform the field of neuroscience by making it possible to record from large populations of neurons simultaneously. However, determining the exact moment in time at which a neuron spikes, from a calcium imaging data set, amounts to a non-trivial deconvolution problem which is of critical importance for downstream analyses. While a number of formulations have been proposed for this task in the recent literature, in this paper we focus on a formulation recently proposed in Jewell and Witten (2017) which has shown initial promising results. However, this proposa…
In the density estimation model, the question of adaptive inference using Pólya tree-type prior distributions is considered. A class of prior densities having a tree structure, called spike-and-slab Pólya trees, is introduced. For this class, two types of results are obtained: first, the Bayesian posterior distribution is shown to converge at the minimax rate for the supremum norm in an adaptive way, for any Hölder regularity of the true density between $0$ and $1$, thereby providing adaptive counterparts to the results for classical Pólya trees in Castillo (2017). Second, the question of unce…
Spatiotemporal Clustering with Neyman-Scott Processes via Connections to Bayesian Nonparametric Mixture Models
University of Michigan（密歇根大学）；Stanford University（斯坦福大学）；New York University（纽约大学）；Flatiron Institute（弗拉蒂伦研究所）；Wu Tsai Neurosciences Institute（吴蔡神经科学研究所）
Although multivariate count data are routinely collected in many application areas, there is surprisingly little work developing flexible models for characterizing their dependence structure. This is particularly true when interest focuses on inferring the conditional independence graph. In this article, we propose a new class of pairwise Markov random field-type models for the joint distribution of a multivariate count vector. By employing a novel type of transformation, we avoid restricting to non-negative dependence structures or inducing other restrictions through truncations. Taking a Bay…
Functional data are frequently accompanied by a parametric template that describes the typical shapes of the functions. However, these parametric templates can incur significant bias, which undermines both utility and interpretability. To correct for model misspecification, we augment the parametric template with an infinite-dimensional nonparametric functional basis. The nonparametric basis functions are learned from the data and constrained to be orthogonal to the parametric template, which preserves distinctness between the parametric and nonparametric terms. This distinctness is essential …
We propose a scalable semiparametric Bayesian model to capture dependencies among multiple neurons by detecting their co-firing (possibly with some lag time) patterns over time. After discretizing time so there is at most one spike at each interval, the resulting sequence of 1's (spike) and 0's (silence) for each neuron is modeled using the logistic function of a continuous latent variable with a Gaussian process prior. For multiple neurons, the corresponding marginal distributions are coupled to their joint probability distribution using a parametric copula model. The advantages of our approa…
Bayesian nonparametric hierarchical priors are highly effective in providing flexible models for latent data structures exhibiting sharing of information between and across groups. Most prominent is the Hierarchical Dirichlet Process (HDP), and its subsequent variants, which model latent clustering between and across groups. The HDP, may be viewed as a more flexible extension of Latent Dirichlet Allocation models (LDA), and has been applied to, for example, topic modelling, natural language processing, and datasets arising in health-care. We focus on analogous latent feature allocation models,…
With the rapid growth of neuroimaging technologies, a great effort has been dedicated recently to investigate the dynamic changes in brain activity. Examples include time course calcium imaging and dynamic brain functional connectivity. In this paper, we propose a novel nonparametric matrix response regression model to characterize the nonlinear association between 2D image outcomes and predictors such as time and patient information. Our estimation procedure can be formulated as a nuclear norm regularization problem, which can capture the underlying low-rank structure of the dynamic 2D images…
In Bayesian nonparametrics there exists a rich variety of discrete priors, including the Dirichlet process and its generalizations, which are nowadays well-established tools. Despite the remarkable advances, few proposals are tailored for modeling observations lying on product spaces, such as $\mathbb{R}^p$. Indeed, for multivariate random measures, most available priors lack flexibility and do not allow for separate partition structures among the spaces. We introduce a discrete nonparametric prior, termed enriched Pitman-Yor process (EPY), aimed at addressing these issues. Theoretical propert…
I propose a frequency domain adaptation of the Expectation Maximization (EM) algorithm to group a family of time series in classes of similar dynamic structure. It does this by viewing the magnitude of the discrete Fourier transform (DFT) of each signal (or power spectrum) as a probability density/mass function (pdf/pmf) on the unit circle: signals with similar dynamics have similar pdfs; distinct patterns have distinct pdfs. An advantage of this approach is that it does not rely on any parametric form of the dynamic structure, but can be used for non-parametric, robust and model-free classifi…
We investigate the problem of deriving adaptive posterior rates of contraction on $\mathbb{L}^{\infty}$ balls in density estimation. Although it is known that log-density priors can achieve optimal rates when the true density is sufficiently smooth, adaptive rates were still to be proven. Here we establish that the so-called spike-and-slab prior can achieve adaptive and optimal posterior contraction rates. Along the way, we prove a generic $\mathbb{L}^{\infty}$ contraction result for log-density priors with independent wavelet coefficients. Interestingly, our approach is different from previou…
We develop a scoring and classification procedure based on the PAC-Bayesian approach and the AUC (Area Under Curve) criterion. We focus initially on the class of linear score functions. We derive PAC-Bayesian non-asymptotic bounds for two types of prior for the score parameters: a Gaussian prior, and a spike-and-slab prior; the latter makes it possible to perform feature selection. One important advantage of our approach is that it is amenable to powerful Bayesian computational tools. We derive in particular a Sequential Monte Carlo algorithm, as an efficient method which may be used as a gold…
Fluorescent calcium indicators are a popular means for observing the spiking activity of large neuronal populations, but extracting the activity of each neuron from raw fluorescence calcium imaging data is a nontrivial problem. We present a fast online active set method to solve this sparse non-negative deconvolution problem. Importantly, the algorithm progresses through each time series sequentially from beginning to end, thus enabling real-time online estimation of neural activity during the imaging session. Our algorithm is a generalization of the pool adjacent violators algorithm (PAVA) fo…
A common way of studying the relationship between neural activity and behavior is through the analysis of neuronal spike trains that are recorded using one or more electrodes implanted in the brain. Each spike train typically contains spikes generated by multiple neurons. A natural question that arises is "what is the number of neurons $ν$ generating the spike train?"; This article proposes a method-of-moments technique for estimating $ν$. This technique estimates the noise nonparametrically using data from the silent region of the spike train and it applies to isolated spikes with a possibly …
Multivariate point processes are widely applied to model event-type data such as natural disasters, online message exchanges, financial transactions or neuronal spike trains. One very popular point process model in which the probability of occurrences of new events depend on the past of the process is the Hawkes process. In this work we consider the nonlinear Hawkes process, which notably models excitation and inhibition phenomena between dimensions of the process. In a nonparametric Bayesian estimation framework, we obtain concentration rates of the posterior distribution on the parameters, u…
Probabilistic clustering models (or equivalently, mixture models) are basic building blocks in countless statistical models and involve latent random variables over discrete spaces. For these models, posterior inference methods can be inaccurate and/or very slow. In this work we introduce deep network architectures trained with labeled samples from any generative model of clustered datasets. At test time, the networks generate approximate posterior samples of cluster labels for any new dataset of arbitrary size. We develop two complementary approaches to this task, requiring either O(N) or O(K…
Spatial point pattern data are routinely encountered. A flexible regression model for the underlying intensity is essential to characterizing the spatial point pattern and understanding the impacts of potential risk factors on such pattern. We propose a Bayesian semiparametric regression model where the observed spatial points follow a spatial Poisson process with an intensity function which adjusts a nonparametric baseline intensity with multiplicative covariate effects. The baseline intensity is piecewise constant, approached with a powered Chinese restaurant process prior which prevents an …
Deducing the structure of neural circuits is one of the central problems of modern neuroscience. Recently-introduced calcium fluorescent imaging methods permit experimentalists to observe network activity in large populations of neurons, but these techniques provide only indirect observations of neural spike trains, with limited time resolution and signal quality. In this work we present a Bayesian approach for inferring neural circuitry given this type of imaging data. We model the network activity in terms of a collection of coupled hidden Markov chains, with each chain corresponding to a si…
Modern disease mapping draws upon a wealth of high resolution spatial data products reflecting environmental and/or socioeconomic factors as covariates, or `features', within a geostatistical framework to improve predictions of disease risk. Feature selection is an important step in building these models, helping to reduce overfitting and computational complexity, and to improve model interpretability. Selecting only features that have a causal relationship with the response variable could potentially improve predictions and generalisability, but identifying these causal features from non-inte…
The problem of denoising a one-dimensional signal possessing varying degrees of smoothness is ubiquitous in time-domain astronomy and astronomical spectroscopy. For example, in the time domain, an astronomical object may exhibit a smoothly varying intensity that is occasionally interrupted by abrupt dips or spikes. Likewise, in the spectroscopic setting, a noiseless spectrum typically contains intervals of relative smoothness mixed with localized higher frequency components such as emission peaks and absorption lines. In this work, we present trend filtering, a modern nonparametric statistical…
We use statistical estimates of the entropy rate of spike train data in order to make inferences about the underlying structure of the spike train itself. We first examine a number of different parametric and nonparametric estimators (some known and some new), including the ``plug-in'' method, several versions of Lempel-Ziv-based compression algorithms, a maximum likelihood estimator tailored to renewal processes, and the natural estimator derived from the Context-Tree Weighting method (CTW). The theoretical properties of these estimators are examined, several new theoretical results are devel…
