Multivariate Autoregressive Modeling and Granger Causality Analysis of Multiple Spike Trains

Recent years have seen the emergence of microelectrode arrays and optical methods allowing simultaneous recording of spiking activity from populations of neurons in various parts of the nervous system. The analysis of multiple neural spike train data could benefit significantly from existing methods for multivariate time-series analysis which have proven to be very powerful in the modeling and analysis of continuous neural signals like EEG signals. However, those methods have not generally been well adapted to point processes. Here, we use our recent results on correlation distortions in multivariate Linear-Nonlinear-Poisson spiking neuron models to derive generalized Yule-Walker-type equations for fitting ‘‘hidden” Multivariate Autoregressive models. We use this new framework to perform Granger causality analysis in order to extract the directed information flow pattern in networks of simulated spiking neurons. We discuss the relative merits and limitations of the new method

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention

Causal Measures of Structure and Plasticity in Simulated and Living Neural Networks

A major goal of neuroscience is to understand the relationship between neural structures and their function. Recording of neural activity with arrays of electrodes is a primary tool employed toward this goal. However, the relationships among the neural activity recorded by these arrays are often highly complex making it problematic to accurately quantify a network's structural information and then relate that structure to its function. Current statistical methods including cross correlation and coherence have achieved only modest success in characterizing the structural connectivity. Over the last decade an alternative technique known as Granger causality is emerging within neuroscience. This technique, borrowed from the field of economics, provides a strong mathematical foundation based on linear auto-regression to detect and quantify “causal” relationships among different time series. This paper presents a combination of three Granger based analytical methods that can quickly provide a relatively complete representation of the causal structure within a neural network. These are a simple pairwise Granger causality metric, a conditional metric, and a little known computationally inexpensive subtractive conditional method. Each causal metric is first described and evaluated in a series of biologically plausible neural simulations. We then demonstrate how Granger causality can detect and quantify changes in the strength of those relationships during plasticity using 60 channel spike train data from an in vitro cortical network measured on a microelectrode array. We show that these metrics can not only detect the presence of causal relationships, they also provide crucial information about the strength and direction of that relationship, particularly when that relationship maybe changing during plasticity. Although we focus on the analysis of multichannel spike train data the metrics we describe are applicable to any stationary time series in which causal relationships among multiple measures is desired. These techniques can be especially useful when the interactions among those measures are highly complex, difficult to untangle, and maybe changing over time

A Granger Causality Measure for Point Process Models of Ensemble Neural Spiking Activity

The ability to identify directional interactions that occur among multiple neurons in the brain is crucial to an understanding of how groups of neurons cooperate in order to generate specific brain functions. However, an optimal method of assessing these interactions has not been established. Granger causality has proven to be an effective method for the analysis of the directional interactions between multiple sets of continuous-valued data, but cannot be applied to neural spike train recordings due to their discrete nature. This paper proposes a point process framework that enables Granger causality to be applied to point process data such as neural spike trains. The proposed framework uses the point process likelihood function to relate a neuron’s spiking probability to possible covariates, such as its own spiking history and the concurrent activity of simultaneously recorded neurons. Granger causality is assessed based on the relative reduction of the point process likelihood of one neuron obtained excluding one of its covariates compared to the likelihood obtained using all of its covariates. The method was tested on simulated data, and then applied to neural activity recorded from the primary motor cortex (MI) of a Felis catus subject. The interactions present in the simulated data were predicted with a high degree of accuracy, and when applied to the real neural data, the proposed method identified causal relationships between many of the recorded neurons. This paper proposes a novel method that successfully applies Granger causality to point process data, and has the potential to provide unique physiological insights when applied to neural spike trains.National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant R01-EB006385

Graphical modelling of multivariate time series

We introduce graphical time series models for the analysis of dynamic relationships among variables in multivariate time series. The modelling approach is based on the notion of strong Granger causality and can be applied to time series with non-linear dependencies. The models are derived from ordinary time series models by imposing constraints that are encoded by mixed graphs. In these graphs each component series is represented by a single vertex and directed edges indicate possible Granger-causal relationships between variables while undirected edges are used to map the contemporaneous dependence structure. We introduce various notions of Granger-causal Markov properties and discuss the relationships among them and to other Markov properties that can be applied in this context.Comment: 33 pages, 7 figures, to appear in Probability Theory and Related Field

Classification-based prediction of effective connectivity between timeseries with a realistic cortical network model

Effective connectivity measures the pattern of causal interactions between brain regions. Traditionally, these patterns of causality are inferred from brain recordings using either non-parametric, i.e., model-free, or parametric, i.e., model-based, approaches. The latter approaches, when based on biophysically plausible models, have the advantage that they may facilitate the interpretation of causality in terms of underlying neural mechanisms. Recent biophysically plausible neural network models of recurrent microcircuits have shown the ability to reproduce well the characteristics of real neural activity and can be applied to model interacting cortical circuits. Unfortunately, however, it is challenging to invert these models in order to estimate effective connectivity from observed data. Here, we propose to use a classification-based method to approximate the result of such complex model inversion. The classifier predicts the pattern of causal interactions given a multivariate timeseries as input. The classifier is trained on a large number of pairs of multivariate timeseries and the respective pattern of causal interactions, which are generated by simulation from the neural network model. In simulated experiments, we show that the proposed method is much more accurate in detecting the causal structure of timeseries than current best practice methods. Additionally, we present further results to characterize the validity of the neural network model and the ability of the classifier to adapt to the generative model of the data

Granger Causality for Compressively Sensed Sparse Signals

Compressed sensing is a scheme that allows for sparse signals to be acquired, transmitted and stored using far fewer measurements than done by conventional means employing Nyquist sampling theorem. Since many naturally occurring signals are sparse (in some domain), compressed sensing has rapidly seen popularity in a number of applied physics and engineering applications, particularly in designing signal and image acquisition strategies, e.g., magnetic resonance imaging, quantum state tomography, scanning tunneling microscopy, analog to digital conversion technologies. Contemporaneously, causal inference has become an important tool for the analysis and understanding of processes and their interactions in many disciplines of science, especially those dealing with complex systems. Direct causal analysis for compressively sensed data is required to avoid the task of reconstructing the compressed data. Also, for some sparse signals, such as for sparse temporal data, it may be difficult to discover causal relations directly using available data-driven/ model-free causality estimation techniques. In this work, we provide a mathematical proof that structured compressed sensing matrices, specifically Circulant and Toeplitz, preserve causal relationships in the compressed signal domain, as measured by Granger Causality. We then verify this theorem on a number of bivariate and multivariate coupled sparse signal simulations which are compressed using these matrices. We also demonstrate a real world application of network causal connectivity estimation from sparse neural spike train recordings from rat prefrontal cortex.Comment: Submitted to IEEE Transactions on Neural Networks and Learning System

Contour Integration via Cortical Interactions in Visual Cortex

The visual system possesses a remarkable ability to group fragmented line segments into coherent contours and to segregate them from background. This process, known as contour integration, is critical to identifying object boundaries in complex visual scenes, and thus particularly important for performing shape discrimination, image segmentation and ultimately object recognition. Current evidence supports the idea that long-range horizontal connections in early visual cortex contribute to the process of contour integration, but the underling cortical circuitry, particularly the top-down feedback influence from higher visual areas, is not fully understood. Throughout the thesis, we took computational approaches to systematically examine how contour information is represented across the network of cortical areas and the circuitry by which this information is encoded. Three closely related projects, each having new methods development and hypothesis testing, were performed to analyze and interpret a very large set of neural data. The data set consists of recently acquired multi-electrode multi-unit spikes and local field potentials (LFPs) simultaneously recorded in visual areas V1 and V4 of monkeys performing a visual contour detection task. In the first project, well-established Granger causality measure was extended to the analysis of spiking trains data, which enabled us to quantify the causal interactions within and between areas V1 and V4. Our findings provided clear evidence that there is a top-down V4 feedback influence upon early visual area V1 during contour integration. In the second project, we investigated whether the contour signals in V1 are derived from feedback inputs alone, or whether they are mediated by an intimate interaction between feedback and horizontal connections within V1. Conditional causality measure was developed to dissect the respective contributions of V1 horizontal connections and V4 feedback to contour grouping. Our results suggest that feedback and lateral connections closely interact to mediate the contour integration process. In the third project, a novel Granger causality measure was proposed for the analysis of mixed neural data of spikes and LFP. Spikes and LFP are generated by separate sources with distinct signal characteristics. A joint analysis of spikes and LFP was performed to address the fundamental question about how contour regulates cortical communication between individual neurons and local network activity. The results conform to the general input-output relationship between LFP and spikes within an area. Importantly, we found that contour-related causality is only observed from spikes to LFP, but not in the opposite direction. These findings suggest that Granger causality from spikes to LFP, rather than that from LFP to spikes, carries contour-related information. Taken together, these results indicate that cortical interactions underlie contour integration, thus contribute to a better understanding of the cortical circuitry for parsing visual images and for sensory processing in general. Given the increasing use of multi-electrode recordings in multiple cortical areas, the methodology developed in this thesis should also have a broad impact.Ph.D., Biomedical Engineering -- Drexel University, 201