Neural population activity exhibits complex, nonlinear dynamics, varying in time, over trials, and across experimental conditions. Here, we develop Conditionally Linear Dynamical System (CLDS) models as a general-purpose method to characterize these dynamics. These models use Gaussian Process (GP) priors to capture the nonlinear dependence of circuit dynamics on task and behavioral variables. Conditioned on these covariates, the data is modeled with linear dynamics. This allows for transparent interpretation and tractable Bayesian inference. We find that CLDS models can perform well even in severely data-limited regimes (e.g. one trial per condition) due to their Bayesian formulation and ability to share statistical power across nearby task conditions. In example applications, we apply CLDS to model thalamic neurons that nonlinearly encode heading direction and to model motor cortical neurons during a cued reaching task

Latent linear dynamical systems with Bernoulli observations provide a powerful modeling framework for identifying the temporal dynamics underlying binary time series data, which arise in a variety of contexts such as binary decision-making and discrete stochastic processes (e.g., binned neural spike trains). Here we develop a spectral learning method for fast, efficient fitting of probit-Bernoulli latent linear dynamical system (LDS) models. Our approach extends traditional subspace identification methods to the Bernoulli setting via a transformation of the first and second sample moments. This results in a robust, fixed-cost estimator that avoids the hazards of local optima and the long computation time of iterative fitting procedures like the expectation-maximization (EM) algorithm. In regimes where data is limited or assumptions about the statistical structure of the data are not met, we demonstrate that the spectral estimate provides a good initialization for Laplace-EM fitting. Finally, we show that the estimator provides substantial benefits to real world settings by analyzing data from mice performing a sensory decision-making task.

Active learning seeks to reduce the amount of data required to fit the parameters of a model, thus forming an important class of techniques in modern machine learning. However, past work on active learning has largely overlooked latent variable models, which play a vital role in neuroscience, psychology, and a variety of other engineering and scientific disciplines. Here we address this gap by proposing a novel framework for maximum-mutual-information input selection for discrete latent variable regression models. We first apply our method to a class of models known as "mixtures of linear regressions" (MLR). While it is well known that active learning confers no advantage for linear-Gaussian regression models, we use Fisher information to show analytically that active learning can nevertheless achieve large gains for mixtures of such models, and we validate this improvement using both simulations and real-world data. We then consider a powerful class of temporally structured latent variable models given by a Hidden Markov Model (HMM) with generalized linear model (GLM) observations, which has recently been used to identify discrete states from animal decision-making data. We show that our method substantially reduces the amount of data needed to fit GLM-HMM, and outperforms a variety of approximate methods based on variational and amortized inference. Infomax learning for latent variable models thus offers a powerful for characterizing temporally structured latent states, with a wide variety of applications in neuroscience and beyond.

Approximate Bayesian inference methods provide a powerful suite of tools for finding approximations to intractable posterior distributions. However, machine learning applications typically involve selecting actions, which -- in a Bayesian setting -- depend on the posterior distribution only via its contribution to expected utility. A growing body of work on loss-calibrated approximate inference methods has therefore sought to develop posterior approximations sensitive to the influence of the utility function. Here we introduce loss-calibrated expectation propagation (Loss-EP), a loss-calibrated variant of expectation propagation. This method resembles standard EP with an additional factor that "tilts" the posterior towards higher-utility decisions. We show applications to Gaussian process classification under binary utility functions with asymmetric penalties on False Negative and False Positive errors, and show how this asymmetry can have dramatic consequences on what information is "useful" to capture in an approximation.

A key challenge in understanding the sensory transformations of the visual system is to obtain a highly predictive model of responses from visual cortical neurons. Deep neural networks (DNNs) provide a promising candidate for such a model. However, DNNs require orders of magnitude more training data than neuroscientists can collect from real neurons because experimental recording time is severely limited. This motivates us to find images that train highly-predictive DNNs with as little training data as possible. We propose gaudy images---high-contrast binarized versions of natural images---to efficiently train DNNs. In extensive simulation experiments, we find that training DNNs with gaudy images substantially reduces the number of training images needed to accurately predict the simulated responses of visual cortical neurons. We also find that gaudy images, chosen before training, outperform images chosen during training by active learning algorithms. Thus, gaudy images overemphasize features of natural images, especially edges, that are the most important for efficiently training DNNs. We believe gaudy images will aid in the modeling of visual cortical neurons, potentially opening new scientific questions about visual processing, as well as aid general practitioners that seek ways to improve the training of DNNs.

The brain uses population codes to form distributed, noise-tolerant representations of sensory and motor variables. Recent work has examined the theoretical optimality of such codes in order to gain insight into the principles governing population codes found in the brain. However, the majority of the population coding literature considers either conditionally independent neurons or neurons with noise governed by a stimulus-independent covariance matrix. Here we analyze population coding under a simple alternative model in which latent input noise" corrupts the stimulus before it is encoded by the population. This provides a convenient and tractable description for irreducible uncertainty that cannot be overcome by adding neurons, and induces stimulus-dependent correlations that mimic certain aspects of the correlations observed in real populations. We examine prior-dependent, Bayesian optimal coding in such populations using exact analyses of cases in which the posterior is approximately Gaussian. These analyses extend previous results on independent Poisson population codes and yield an analytic expression for squared loss and a tight upper bound for mutual information. We show that, for homogeneous populations that tile the input domain, optimal tuning curve width depends on the prior, the loss function, the resource constraint, and the amount of input noise. This framework provides a practical testbed for examining issues of optimality, noise, correlation, and coding fidelity in realistic neural populations."

Probabilistic models for binary spike patterns provide a powerful tool for understanding the statistical dependencies in large-scale neural recordings. Maximum entropy (or maxent'') models, which seek to explain dependencies in terms of low-order interactions between neurons, have enjoyed remarkable success in modeling such patterns, particularly for small groups of neurons. However, these models are computationally intractable for large populations, and low-order maxent models have been shown to be inadequate for some datasets. To overcome these limitations, we propose a family of "universal'' models for binary spike patterns, where universality refers to the ability to model arbitrary distributions over all $2 m$ binary patterns. We construct universal models using a Dirichlet process centered on a well-behaved parametric base measure, which naturally combines the flexibility of a histogram and the parsimony of a parametric model. We derive computationally efficient inference methods using Bernoulli and cascade-logistic base measures, which scale tractably to large populations. We also establish a condition for equivalence between the cascade-logistic and the 2nd-order maxent or "Ising'' model, making cascade-logistic a reasonable choice for base measure in a universal model.

For spiking neurons, the entropy rate places an upper bound on the rate at which the spike train can convey stimulus information, and a large literature has focused on the problem of estimating entropy rate from spike train data. Our estimator leverages the fact that the entropy rate of an ergodic Markov Chain with known transition probabilities can be calculated analytically, and many stochastic processes that are non-Markovian can still be well approximated by Markov processes of sufficient depth. Choosing an appropriate depth of Markov model presents challenges due to possibly long time dependencies and short data sequences: a deeper model can better account for long time-dependencies, but is more difficult to infer from limited data. Our approach mitigates this difficulty by using a hierarchical prior to share statistical power across Markov chains of different depths. We present both a fully Bayesian and empirical Bayes entropy rate estimator based on this model, and demonstrate their performance on simulated and real neural spike train data.

Gaussian Process Factor Analysis (GPFA) has been broadly applied to the problem of identifying smooth, low-dimensional temporal structure underlying large-scale neural recordings. However, spike trains are non-Gaussian, which motivates combining GPFA with discrete observation models for binned spike count data. The drawback to this approach is that GPFA priors are not conjugate to count model likelihoods, which makes inference challenging. Here we address this obstacle by introducing a fast, approximate inference method for non-conjugate GPFA models. Our approach uses orthogonal second-order polynomials to approximate the nonlinear terms in the non-conjugate log-likelihood, resulting in a method we refer to as polynomial approximate log-likelihood (PAL) estimators. This approximation allows for accurate closed-form evaluation of marginal likelihood and fast numerical optimization for parameters and hyperparameters. We derive PAL estimators for GPFA models with binomial, Poisson, and negative binomial observations, and additionally show that the parameters obtained can be used to initialize black-box variational inference, which significantly speeds up and stabilizes the inference procedure for these factor analytic models. We apply these methods to data from mouse visual cortex and monkey higher-order visual and parietal cortices, and compare GPFA under three different spike count observation models to traditional GPFA. We demonstrate that PAL estimators achieve fast and accurate extraction of latent structure from multi-neuron spike train data.

A major difficulty in studying the neural mechanisms underlying olfactory perception is the lack of obvious structure in the relationship between odorants and the neural activity patterns they elicit. Here we use odor-evoked responses in piriform cortex to identify a latent manifold specifying latent distance relationships between olfactory stimuli. Our approach is based on the Gaussian process latent variable model, and seeks to map odorants to points in a low-dimensional embedding space, where distances between points in the embedding space relate to the similarity of population responses they elicit. The model is specified by an explicit continuous mapping from a latent embedding space to the space of high-dimensional neural population firing rates via nonlinear tuning curves, each parametrized by a Gaussian process. Population responses are then generated by the addition of correlated, odor-dependent Gaussian noise. We fit this model to large-scale calcium fluorescence imaging measurements of population activity in layers 2 and 3 of mouse piriform cortex following the presentation of a diverse set of odorants. The model identifies a low-dimensional embedding of each odor, and a smooth tuning curve over the latent embedding space that accurately captures each neuron's response to different odorants. The model captures both signal and noise correlations across more than 500 neurons. We validate the model using a cross-validation analysis known as co-smoothing to show that the model can accurately predict the responses of a population of held-out neurons to test odorants.