arXiv subjects

Liam Paninski

Publications and source records attributed to Liam Paninski.

At least 37 records · Page 2Linked to original sources

arXiv2020

A zero-inflated gamma model for deconvolved calcium imaging traces

Calcium imaging is a critical tool for measuring the activity of large neural populations. Much effort has been devoted to developing "pre-processing" tools for calcium video data, addressing the important issues of e.g., motion correction, denoising, compression, demixing, and deconvolution. However, statistical modeling of deconvolved calcium signals (i.e., the estimated activity extracted by a pre-processing pipeline) is just as critical for interpreting calcium measurements, and for incorporating these observations into downstream probabilistic encoding and decoding models. Surprisingly, these issues have to date received significantly less attention. In this work we examine the statistical properties of the deconvolved activity estimates, and compare probabilistic models for these random signals. In particular, we propose a zero-inflated gamma (ZIG) model, which characterizes the calcium responses as a mixture of a gamma distribution and a point mass that serves to model zero responses. We apply the resulting models to neural encoding and decoding problems. We find that the ZIG model outperforms simpler models (e.g., Poisson or Bernoulli models) in the context of both simulated and real neural data, and can therefore play a useful role in bridging calcium imaging analysis methods with tools for analyzing activity in large neural populations.

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arXiv2018

Amortized Bayesian inference for clustering models

We develop methods for efficient amortized approximate Bayesian inference over posterior distributions of probabilistic clustering models, such as Dirichlet process mixture models. The approach is based on mapping distributed, symmetry-invariant representations of cluster arrangements into conditional probabilities. The method parallelizes easily, yields iid samples from the approximate posterior of cluster assignments with the same computational cost of a single Gibbs sampler sweep, and can easily be applied to both conjugate and non-conjugate models, as training only requires samples from the generative model.

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arXiv2018

Penalized matrix decomposition for denoising, compression, and improved demixing of functional imaging data

Calcium imaging has revolutionized systems neuroscience, providing the ability to image large neural populations with single-cell resolution. The resulting datasets are quite large, which has presented a barrier to routine open sharing of this data, slowing progress in reproducible research. State of the art methods for analyzing this data are based on non-negative matrix factorization (NMF); these approaches solve a non-convex optimization problem, and are effective when good initializations are available, but can break down in low-SNR settings where common initialization approaches fail. Here we introduce an approach to compressing and denoising functional imaging data. The method is based on a spatially-localized penalized matrix decomposition (PMD) of the data to separate (low-dimensional) signal from (temporally-uncorrelated) noise. This approach can be applied in parallel on local spatial patches and is therefore highly scalable, does not impose non-negativity constraints or require stringent identifiability assumptions (leading to significantly more robust results compared to NMF), and estimates all parameters directly from the data, so no hand-tuning is required. We have applied the method to a wide range of functional imaging data (including one-photon, two-photon, three-photon, widefield, somatic, axonal, dendritic, calcium, and voltage imaging datasets): in all cases, we observe ~2-4x increases in SNR and compression rates of 20-300x with minimal visible loss of signal, with no adjustment of hyperparameters; this in turn facilitates the process of demixing the observed activity into contributions from individual neurons. We focus on two challenging applications: dendritic calcium imaging data and voltage imaging data in the context of optogenetic stimulation. In both cases, we show that our new approach leads to faster and much more robust extraction of activity from the data.

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arXiv2017

Reparameterizing the Birkhoff Polytope for Variational Permutation Inference

Many matching, tracking, sorting, and ranking problems require probabilistic reasoning about possible permutations, a set that grows factorially with dimension. Combinatorial optimization algorithms may enable efficient point estimation, but fully Bayesian inference poses a severe challenge in this high-dimensional, discrete space. To surmount this challenge, we start with the usual step of relaxing a discrete set (here, of permutation matrices) to its convex hull, which here is the Birkhoff polytope: the set of all doubly-stochastic matrices. We then introduce two novel transformations: first, an invertible and differentiable stick-breaking procedure that maps unconstrained space to the Birkhoff polytope; second, a map that rounds points toward the vertices of the polytope. Both transformations include a temperature parameter that, in the limit, concentrates the densities on permutation matrices. We then exploit these transformations and reparameterization gradients to introduce variational inference over permutation matrices, and we demonstrate its utility in a series of experiments.

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arXiv2017

Stochastic Bouncy Particle Sampler

We introduce a novel stochastic version of the non-reversible, rejection-free Bouncy Particle Sampler (BPS), a Markov process whose sample trajectories are piecewise linear. The algorithm is based on simulating first arrival times in a doubly stochastic Poisson process using the thinning method, and allows efficient sampling of Bayesian posteriors in big datasets. We prove that in the BPS no bias is introduced by noisy evaluations of the log-likelihood gradient. On the other hand, we argue that efficiency considerations favor a small, controllable bias in the construction of the thinning proposals, in exchange for faster mixing. We introduce a simple regression-based proposal intensity for the thinning method that controls this trade-off. We illustrate the algorithm in several examples in which it outperforms both unbiased, but slowly mixing stochastic versions of BPS, as well as biased stochastic gradient-based samplers.

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arXiv2017

Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data

In vivo calcium imaging through microscopes has enabled deep brain imaging of previously inaccessible neuronal populations within the brains of freely moving subjects. However, microendoscopic data suffer from high levels of background fluorescence as well as an increased potential for overlapping neuronal signals. Previous methods fail in identifying neurons and demixing their temporal activity because the cellular signals are often submerged in the large fluctuating background. Here we develop an efficient method to extract cellular signals with minimal influence from the background. We model the background with two realistic components: (1) one models the constant baseline and slow trends of each pixel, and (2) the other models the fast fluctuations from out-of-focus signals and is therefore constrained to have low spatial-frequency structure. This decomposition avoids cellular signals being absorbed into the background term. After subtracting the background approximated with this model, we use Constrained Nonnegative Matrix Factorization (CNMF, Pnevmatikakis et al. (2016)) to better demix neural signals and get their denoised and deconvolved temporal activity. We validate our method on simulated and experimental data, where it shows fast, reliable, and high quality signal extraction under a wide variety of imaging parameters.

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arXiv2017

Fast Online Deconvolution of Calcium Imaging Data

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) for isotonic regression and inherits its linear-time computational complexity. We gain remarkable increases in processing speed: more than one order of magnitude compared to currently employed state of the art convex solvers relying on interior point methods. Unlike these approaches, our method can exploit warm starts; therefore optimizing model hyperparameters only requires a handful of passes through the data. A minor modification can further improve the quality of activity inference by imposing a constraint on the minimum spike size. The algorithm enables real-time simultaneous deconvolution of $O(10^5)$ traces of whole-brain larval zebrafish imaging data on a laptop.

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arXiv2017

Automated scalable segmentation of neurons from multispectral images

Reconstruction of neuroanatomy is a fundamental problem in neuroscience. Stochastic expression of colors in individual cells is a promising tool, although its use in the nervous system has been limited due to various sources of variability in expression. Moreover, the intermingled anatomy of neuronal trees is challenging for existing segmentation algorithms. Here, we propose a method to automate the segmentation of neurons in such (potentially pseudo-colored) images. The method uses spatio-color relations between the voxels, generates supervoxels to reduce the problem size by four orders of magnitude before the final segmentation, and is parallelizable over the supervoxels. To quantify performance and gain insight, we generate simulated images, where the noise level and characteristics, the density of expression, and the number of fluorophore types are variable. We also present segmentations of real Brainbow images of the mouse hippocampus, which reveal many of the dendritic segments.

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arXiv2016

Recurrent switching linear dynamical systems

Many natural systems, such as neurons firing in the brain or basketball teams traversing a court, give rise to time series data with complex, nonlinear dynamics. We can gain insight into these systems by decomposing the data into segments that are each explained by simpler dynamic units. Building on switching linear dynamical systems (SLDS), we present a new model class that not only discovers these dynamical units, but also explains how their switching behavior depends on observations or continuous latent states. These "recurrent" switching linear dynamical systems provide further insight by discovering the conditions under which each unit is deployed, something that traditional SLDS models fail to do. We leverage recent algorithmic advances in approximate inference to make Bayesian inference in these models easy, fast, and scalable.

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arXiv2016

Linear dynamical neural population models through nonlinear embeddings

A body of recent work in modeling neural activity focuses on recovering low-dimensional latent features that capture the statistical structure of large-scale neural populations. Most such approaches have focused on linear generative models, where inference is computationally tractable. Here, we propose fLDS, a general class of nonlinear generative models that permits the firing rate of each neuron to vary as an arbitrary smooth function of a latent, linear dynamical state. This extra flexibility allows the model to capture a richer set of neural variability than a purely linear model, but retains an easily visualizable low-dimensional latent space. To fit this class of non-conjugate models we propose a variational inference scheme, along with a novel approximate posterior capable of capturing rich temporal correlations across time. We show that our techniques permit inference in a wide class of generative models.We also show in application to two neural datasets that, compared to state-of-the-art neural population models, fLDS captures a much larger proportion of neural variability with a small number of latent dimensions, providing superior predictive performance and interpretability.

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arXiv2016

Robust and scalable Bayesian analysis of spatial neural tuning function data

A common analytical problem in neuroscience is the interpretation of neural activity with respect to sensory input or behavioral output. This is typically achieved by regressing measured neural activity against known stimuli or behavioral variables to produce a "tuning function" for each neuron. Unfortunately, because this approach handles neurons individually, it cannot take advantage of simultaneous measurements from spatially adjacent neurons that often have similar tuning properties. On the other hand, sharing information between adjacent neurons can errantly degrade estimates of tuning functions across space if there are sharp discontinuities in tuning between nearby neurons. In this paper, we develop a computationally efficient block Gibbs sampler that effectively pools information between neurons to de-noise tuning function estimates while simultaneously preserving sharp discontinuities that might exist in the organization of tuning across space. This method is fully Bayesian and its computational cost per iteration scales sub-quadratically with total parameter dimensionality. We demonstrate the robustness and scalability of this approach by applying it to both real and synthetic datasets. In particular, an application to data from the spinal cord illustrates that the proposed methods can dramatically decrease the experimental time required to accurately estimate tuning functions.

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arXiv2016

Partition Functions from Rao-Blackwellized Tempered Sampling

Partition functions of probability distributions are important quantities for model evaluation and comparisons. We present a new method to compute partition functions of complex and multimodal distributions. Such distributions are often sampled using simulated tempering, which augments the target space with an auxiliary inverse temperature variable. Our method exploits the multinomial probability law of the inverse temperatures, and provides estimates of the partition function in terms of a simple quotient of Rao-Blackwellized marginal inverse temperature probability estimates, which are updated while sampling. We show that the method has interesting connections with several alternative popular methods, and offers some significant advantages. In particular, we empirically find that the new method provides more accurate estimates than Annealed Importance Sampling when calculating partition functions of large Restricted Boltzmann Machines (RBM); moreover, the method is sufficiently accurate to track training and validation log-likelihoods during learning of RBMs, at minimal computational cost.

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arXiv2016

Bayesian methods for event analysis of intracellular currents

Investigation of neural circuit functioning often requires statistical interpretation of events in subthreshold electrophysiological recordings. This problem is non-trivial because recordings may have moderate levels of structured noise and events may have distinct kinetics. In addition, novel experimental designs that combine optical and electrophysiological methods will depend upon statistical tools that combine multimodal data. We present a Bayesian approach for inferring the timing, strength, and kinetics of postsynaptic currents (PSCs) from voltage-clamp recordings on a per event basis. The simple generative model for a single voltage-clamp recording flexibly extends to include network-level structure to enable experiments designed to probe synaptic connectivity. We validate the approach on simulated and real data. We also demonstrate that extensions of the basic PSC detection algorithm can handle recordings contaminated with optically evoked currents, and we simulate a scenario in which calcium imaging observations, available for a subset of neurons, can be fused with electrophysiological data to achieve higher temporal resolution. We apply this approach to simulated and real ground truth data to demonstrate its higher sensitivity in detecting small signal-to-noise events and its increased robustness to noise compared to standard methods for detecting PSCs. The new Bayesian event analysis approach for electrophysiological recordings should allow for better estimation of physiological parameters under more variable conditions and help support new experimental designs for circuit mapping.

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arXiv2016

Neuroprosthetic decoder training as imitation learning

Neuroprosthetic brain-computer interfaces function via an algorithm which decodes neural activity of the user into movements of an end effector, such as a cursor or robotic arm. In practice, the decoder is often learned by updating its parameters while the user performs a task. When the user's intention is not directly observable, recent methods have demonstrated value in training the decoder against a surrogate for the user's intended movement. We describe how training a decoder in this way is a novel variant of an imitation learning problem, where an oracle or expert is employed for supervised training in lieu of direct observations, which are not available. Specifically, we describe how a generic imitation learning meta-algorithm, dataset aggregation (DAgger, [1]), can be adapted to train a generic brain-computer interface. By deriving existing learning algorithms for brain-computer interfaces in this framework, we provide a novel analysis of regret (an important metric of learning efficacy) for brain-computer interfaces. This analysis allows us to characterize the space of algorithmic variants and bounds on their regret rates. Existing approaches for decoder learning have been performed in the cursor control setting, but the available design principles for these decoders are such that it has been impossible to scale them to naturalistic settings. Leveraging our findings, we then offer an algorithm that combines imitation learning with optimal control, which should allow for training of arbitrary effectors for which optimal control can generate goal-oriented control. We demonstrate this novel and general BCI algorithm with simulated neuroprosthetic control of a 26 degree-of-freedom model of an arm, a sophisticated and realistic end effector.

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arXiv2015

Black box variational inference for state space models

Latent variable time-series models are among the most heavily used tools from machine learning and applied statistics. These models have the advantage of learning latent structure both from noisy observations and from the temporal ordering in the data, where it is assumed that meaningful correlation structure exists across time. A few highly-structured models, such as the linear dynamical system with linear-Gaussian observations, have closed-form inference procedures (e.g. the Kalman Filter), but this case is an exception to the general rule that exact posterior inference in more complex generative models is intractable. Consequently, much work in time-series modeling focuses on approximate inference procedures for one particular class of models. Here, we extend recent developments in stochastic variational inference to develop a `black-box' approximate inference technique for latent variable models with latent dynamical structure. We propose a structured Gaussian variational approximate posterior that carries the same intuition as the standard Kalman filter-smoother but, importantly, permits us to use the same inference approach to approximate the posterior of much more general, nonlinear latent variable generative models. We show that our approach recovers accurate estimates in the case of basic models with closed-form posteriors, and more interestingly performs well in comparison to variational approaches that were designed in a bespoke fashion for specific non-conjugate models.

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arXiv2015

Auxiliary-variable Exact Hamiltonian Monte Carlo Samplers for Binary Distributions

We present a new approach to sample from generic binary distributions, based on an exact Hamiltonian Monte Carlo algorithm applied to a piecewise continuous augmentation of the binary distribution of interest. An extension of this idea to distributions over mixtures of binary and possibly-truncated Gaussian or exponential variables allows us to sample from posteriors of linear and probit regression models with spike-and-slab priors and truncated parameters. We illustrate the advantages of these algorithms in several examples in which they outperform the Metropolis or Gibbs samplers.

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arXiv2014

A shotgun sampling solution for the common input problem in neural connectivity inference

Inferring connectivity in neuronal networks remains a key challenge in statistical neuroscience. The `common input' problem presents the major roadblock: it is difficult to reliably distinguish causal connections between pairs of observed neurons from correlations induced by common input from unobserved neurons. Since available recording techniques allow us to sample from only a small fraction of large networks simultaneously with sufficient temporal resolution, naive connectivity estimators that neglect these common input effects are highly biased. This work proposes a `shotgun' experimental design, in which we observe multiple sub-networks briefly, in a serial manner. Thus, while the full network cannot be observed simultaneously at any given time, we may be able to observe most of it during the entire experiment. Using a generalized linear model for a spiking recurrent neural network, we develop scalable approximate Bayesian methods to perform network inference given this type of data, in which only a small fraction of the network is observed in each time bin. We demonstrate in simulation that, using this method: (1) The shotgun experimental design can eliminate the biases induced by common input effects. (2) Networks with thousands of neurons, in which only a small fraction of the neurons is observed in each time bin, could be quickly and accurately estimated. (3) Performance can be improved if we exploit prior information about the probability of having a connection between two neurons, its dependence on neuronal cell types (e.g., Dale's law), or its dependence on the distance between neurons.

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arXiv2014

A structured matrix factorization framework for large scale calcium imaging data analysis

We present a structured matrix factorization approach to analyzing calcium imaging recordings of large neuronal ensembles. Our goal is to simultaneously identify the locations of the neurons, demix spatially overlapping components, and denoise and deconvolve the spiking activity of each neuron from the slow dynamics of the calcium indicator. The matrix factorization approach relies on the observation that the spatiotemporal fluorescence activity can be expressed as a product of two matrices: a spatial matrix that encodes the location of each neuron in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time. We present a simple approach for estimating the dynamics of the calcium indicator as well as the observation noise statistics from the observed data. These parameters are then used to set up the matrix factorization problem in a constrained form that requires no further parameter tuning. We discuss initialization and post-processing techniques that enhance the performance of our method, along with efficient and largely parallelizable algorithms. We apply our method to {\it in vivo} large scale multi-neuronal imaging data and also demonstrate how similar methods can be used for the analysis of {\it in vivo} dendritic imaging data.

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