Scalable Inference for Neuronal Connectivity from Calcium Imaging

Neural Information Processing Systems

Fluorescent calcium imaging provides a potentially powerful tool for inferring connectivity in neural circuits with up to thousands of neurons. However, a key challenge in using calcium imaging for connectivity detection is that current systems often have a temporal response and frame rate that can be orders of magnitude slower than the underlying neural spiking process. Bayesian inference based on expectation-maximization (EM) have been proposed to overcome these limitations, but they are often computationally demanding since the E-step in the EM procedure typically involves state estimation in a high-dimensional nonlinear dynamical system. In this work, we propose a computationally fast method for the state estimation based on a hybrid of loopy belief propagation and approximate message passing (AMP). The key insight is that a neural system as viewed through calcium imaging can be factorized into simple scalar dynamical systems for each neuron with linear interconnections between the neurons. Using the structure, the updates in the proposed hybrid AMP methodology can be computed by a set of one-dimensional state estimation procedures and linear transforms with the connectivity matrix. This yields a computationally scalable method for inferring connectivity of large neural circuits. Simulations of the method on realistic neural networks demonstrate good accuracy with computation times that are potentially significantly faster than current approaches based on Markov Chain Monte Carlo methods.

Inferring neural population dynamics from multiple partial recordings of the same neural circuit

Neural Information Processing Systems

Simultaneous recordings of the activity of large neural populations are extremely valuable as they can be used to infer the dynamics and interactions of neurons in a local circuit, shedding light on the computations performed. It is now possible to measure the activity of hundreds of neurons using 2-photon calcium imaging. However, many computations are thought to involve circuits consisting of thousands of neurons, such as cortical barrels in rodent somatosensory cortex. Here we contribute a statistical method for stitching" together sequentially imaged sets of neurons into one model by phrasing the problem as fitting a latent dynamical system with missing observations. This method allows us to substantially expand the population-sizes for which population dynamics can be characterized---beyond the number of simultaneously imaged neurons. In particular, we demonstrate using recordings in mouse somatosensory cortex that this method makes it possible to predict noise correlations between non-simultaneously recorded neuron pairs."

Model-based Bayesian inference of neural activity and connectivity from all-optical interrogation of a neural circuit

Neural Information Processing Systems

Population activity measurement by calcium imaging can be combined with cellular resolution optogenetic activity perturbations to enable the mapping of neural connectivity in vivo. This requires accurate inference of perturbed and unperturbed neural activity from calcium imaging measurements, which are noisy and indirect, and can also be contaminated by photostimulation artifacts. We have developed a new fully Bayesian approach to jointly inferring spiking activity and neural connectivity from in vivo all-optical perturbation experiments. In contrast to standard approaches that perform spike inference and analysis in two separate maximum-likelihood phases, our joint model is able to propagate uncertainty in spike inference to the inference of connectivity and vice versa. We use the framework of variational autoencoders to model spiking activity using discrete latent variables, low-dimensional latent common input, and sparse spike-and-slab generalized linear coupling between neurons.

Learning convolution filters for inverse covariance estimation of neural network connectivity

Neural Information Processing Systems

We consider the problem of inferring direct neural network connections from Calcium imaging time series. Inverse covariance estimation has proven to be a fast and accurate method for learning macro- and micro-scale network connectivity in the brain and in a recent Kaggle Connectomics competition inverse covariance was the main component of several top ten solutions, including our own and the winning team's algorithm. However, the accuracy of inverse covariance estimation is highly sensitive to signal preprocessing of the Calcium fluorescence time series. Furthermore, brute force optimization methods such as grid search and coordinate ascent over signal processing parameters is a time intensive process, where learning may take several days and parameters that optimize one network may not generalize to networks with different size and parameters. In this paper we show how inverse covariance estimation can be dramatically improved using a simple convolution filter prior to applying sample covariance.

Learning Nonlinear Brain Dynamics: van der Pol Meets LSTM Machine Learning

Many real-world data sets, especially in biology, are produced by complex nonlinear dynamical systems. In this paper, we focus on brain calcium imaging (CaI) of different organisms (zebrafish and rat), aiming to build a model of joint activation dynamics in large neuronal populations, including the whole brain of zebrafish. We propose a new approach for capturing dynamics of temporal SVD components that uses the coupled (multivariate) van der Pol (VDP) oscillator, a nonlinear ordinary differential equation (ODE) model describing neural activity, with a new parameter estimation technique that combines variable projection optimization and stochastic search. We show that the approach successfully handles nonlinearities and hidden state variables in the coupled VDP. The approach is accurate, achieving 0.82 to 0.94 correlation between the actual and model-generated components, and interpretable, as VDP's coupling matrix reveals anatomically meaningful positive (excitatory) and negative (inhibitory) interactions across different brain subsystems corresponding to spatial SVD components. Moreover, VDP is comparable to (or sometimes better than) recurrent neural networks (LSTM) for (short-term) prediction of future brain activity; VDP needs less parameters to train, which was a plus on our small training data. Finally, the overall best predictive method, greatly outperforming both VDP and LSTM in short- and long-term predictive settings on both datasets, was the new hybrid VDP-LSTM approach that used VDP to simulate large domain-specific dataset for LSTM pretraining; note that simple LSTM data-augmentation via noisy versions of training data was much less effective.