Sequential estimation of intrinsic activity and synaptic input in single neurons by particle filtering with optimal importance density

This paper deals with the problem of inferring the signals and parameters that cause neural activity to occur. The ultimate challenge being to unveil brain’s connectivity, here we focus on a microscopic vision of the problem, where single neurons (potentially connected to a network of peers) are at the core of our study. The sole observation available are noisy, sampled voltage traces obtained from intracellular recordings. We design algorithms and inference methods using the tools provided by stochastic filtering that allow a probabilistic interpretation and treatment of the problem. Using particle filtering, we are able to reconstruct traces of voltages and estimate the time course of auxiliary variables. By extending the algorithm, through PMCMC methodology, we are able to estimate hidden physiological parameters as well, like intrinsic conductances or reversal potentials. Last, but not least, the method is applied to estimate synaptic conductances arriving at a target cell, thus reconstructing the synaptic excitatory/inhibitory input traces. Notably, the performance of these estimations achieve the theoretical lower bounds even in spiking regimes.Postprint (published version

Estimation in the partially observed stochastic Morris-Lecar neuronal model with particle filter and stochastic approximation methods

Parameter estimation in multidimensional diffusion models with only one coordinate observed is highly relevant in many biological applications, but a statistically difficult problem. In neuroscience, the membrane potential evolution in single neurons can be measured at high frequency, but biophysical realistic models have to include the unobserved dynamics of ion channels. One such model is the stochastic Morris-Lecar model, defined by a nonlinear two-dimensional stochastic differential equation. The coordinates are coupled, that is, the unobserved coordinate is nonautonomous, the model exhibits oscillations to mimic the spiking behavior, which means it is not of gradient-type, and the measurement noise from intracellular recordings is typically negligible. Therefore, the hidden Markov model framework is degenerate, and available methods break down. The main contributions of this paper are an approach to estimate in this ill-posed situation and nonasymptotic convergence results for the method. Specifically, we propose a sequential Monte Carlo particle filter algorithm to impute the unobserved coordinate, and then estimate parameters maximizing a pseudo-likelihood through a stochastic version of the Expectation-Maximization algorithm. It turns out that even the rate scaling parameter governing the opening and closing of ion channels of the unobserved coordinate can be reasonably estimated. An experimental data set of intracellular recordings of the membrane potential of a spinal motoneuron of a red-eared turtle is analyzed, and the performance is further evaluated in a simulation study.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS729 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Sequential estimation of neural models by Bayesian filtering

Un dels reptes més difícils de la neurociència és el d'entendre la connectivitat del cervell. Aquest problema es pot tractar des de diverses perspectives, aquí ens centrem en els fenòmens locals que ocorren en una sola neurona. L'objectiu final és, doncs, entendre la dinàmica de les neurones i com la interconnexió amb altres neurones afecta al seu estat. Les observacions de traces del potencial de membrana constitueixen la principal font d'informació per a derivar models matemàtics d'una neurona, amb cert sentit biofísic. En particular, la dinàmica de les variables auxiliars i els paràmetres del model són estimats a partir d'aquestes traces de voltatge. El procés és en general costós i típicament implica una gran varietat de blocatges químics de canals iònics, així com una certa incertesa en els valors dels paràmetres a causa del soroll de mesura. D'altra banda, les traces de potencial de membrana també són útils per obtenir informació valuosa sobre l'entrada sinàptica, un problema invers sense solució satisfactòria a hores d'ara. En aquesta Tesi, estem interessats en mètodes d'estimació seqüencial, que permetin evitar la necessitat de repeticions que podrien ser contaminades per la variabilitat neuronal. En particular, ens concentrem en mètodes per extreure l'activitat intrínseca dels canals iònics, és a dir, les probabilitats d'obertura i tancament de canals iònics, i la contribució de les conductàncies sinàptiques. Hem dissenyat un mètode basat en la teoria Bayesiana de filtrat per inferir seqüencialment aquestes quantitats a partir d'una única traça de voltatge, potencialment sorollosa. El mètode d'estimació proposat està basat en la suposició d'un model de neurona conegut. Això és cert fins a cert punt, però la majoria dels paràmetres en el model han de ser estimats per endavant (això és valid per a qualsevol model). Per tant, el mètode s'ha millorat pel cas de models amb paràmetres desconeguts, incloent-hi un procediment per estimar conjuntament els paràmetres i les variables dinàmiques. Hem validat els mètodes d'inferència proposats mitjançant simulacions realistes. Les prestacions en termes d'error d'estimació s'han comparat amb el límit teòric, que s'ha derivat també en el marc d'aquesta Tesi

A State Space Approach for Piecewise-Linear Recurrent Neural Networks for Reconstructing Nonlinear Dynamics from Neural Measurements

The computational properties of neural systems are often thought to be implemented in terms of their network dynamics. Hence, recovering the system dynamics from experimentally observed neuronal time series, like multiple single-unit (MSU) recordings or neuroimaging data, is an important step toward understanding its computations. Ideally, one would not only seek a state space representation of the dynamics, but would wish to have access to its governing equations for in-depth analysis. Recurrent neural networks (RNNs) are a computationally powerful and dynamically universal formal framework which has been extensively studied from both the computational and the dynamical systems perspective. Here we develop a semi-analytical maximum-likelihood estimation scheme for piecewise-linear RNNs (PLRNNs) within the statistical framework of state space models, which accounts for noise in both the underlying latent dynamics and the observation process. The Expectation-Maximization algorithm is used to infer the latent state distribution, through a global Laplace approximation, and the PLRNN parameters iteratively. After validating the procedure on toy examples, the approach is applied to MSU recordings from the rodent anterior cingulate cortex obtained during performance of a classical working memory task, delayed alternation. A model with 5 states turned out to be sufficient to capture the essential computational dynamics underlying task performance, including stimulus-selective delay activity. The estimated models were rarely multi-stable, but rather were tuned to exhibit slow dynamics in the vicinity of a bifurcation point. In summary, the present work advances a semi-analytical (thus reasonably fast) maximum-likelihood estimation framework for PLRNNs that may enable to recover the relevant dynamics underlying observed neuronal time series, and directly link them to computational properties

Contributions to statistical analysis methods for neural spiking activity

With the technical advances in neuroscience experiments in the past few decades, we have seen a massive expansion in our ability to record neural activity. These advances enable neuroscientists to analyze more complex neural coding and communication properties, and at the same time, raise new challenges for analyzing neural spiking data, which keeps growing in scale, dimension, and complexity. This thesis proposes several new statistical methods that advance statistical analysis approaches for neural spiking data, including sequential Monte Carlo (SMC) methods for efficient estimation of neural dynamics from membrane potential threshold crossings, state-space models using multimodal observation processes, and goodness-of-fit analysis methods for neural marked point process models. In a first project, we derive a set of iterative formulas that enable us to simulate trajectories from stochastic, dynamic neural spiking models that are consistent with a set of spike time observations. We develop a SMC method to simultaneously estimate the parameters of the model and the unobserved dynamic variables from spike train data. We investigate the performance of this approach on a leaky integrate-and-fire model. In another project, we define a semi-latent state-space model to estimate information related to the phenomenon of hippocampal replay. Replay is a recently discovered phenomenon where patterns of hippocampal spiking activity that typically occur during exploration of an environment are reactivated when an animal is at rest. This reactivation is accompanied by high frequency oscillations in hippocampal local field potentials. However, methods to define replay mathematically remain undeveloped. In this project, we construct a novel state-space model that enables us to identify whether replay is occurring, and if so to estimate the movement trajectories consistent with the observed neural activity, and to categorize the content of each event. The state-space model integrates information from the spiking activity from the hippocampal population, the rhythms in the local field potential, and the rat's movement behavior. Finally, we develop a new, general time-rescaling theorem for marked point processes, and use this to develop a general goodness-of-fit framework for neural population spiking models. We investigate this approach through simulation and a real data application