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Estimation of Directed Effective Connectivity from fMRI Functional Connectivity Hints at Asymmetries of Cortical Connectome

Matthieu Gilson, Ruben Moreno-Bote, Adrián Ponce-Alvarez, Petra Ritter and Gustavo Deco

PLOS Computational Biology, 2016, vol. 12, issue 3, 1-30

Abstract: The brain exhibits complex spatio-temporal patterns of activity. This phenomenon is governed by an interplay between the internal neural dynamics of cortical areas and their connectivity. Uncovering this complex relationship has raised much interest, both for theory and the interpretation of experimental data (e.g., fMRI recordings) using dynamical models. Here we focus on the so-called inverse problem: the inference of network parameters in a cortical model to reproduce empirically observed activity. Although it has received a lot of interest, recovering directed connectivity for large networks has been rather unsuccessful so far. The present study specifically addresses this point for a noise-diffusion network model. We develop a Lyapunov optimization that iteratively tunes the network connectivity in order to reproduce second-order moments of the node activity, or functional connectivity. We show theoretically and numerically that the use of covariances with both zero and non-zero time shifts is the key to infer directed connectivity. The first main theoretical finding is that an accurate estimation of the underlying network connectivity requires that the time shift for covariances is matched with the time constant of the dynamical system. In addition to the network connectivity, we also adjust the intrinsic noise received by each network node. The framework is applied to experimental fMRI data recorded for subjects at rest. Diffusion-weighted MRI data provide an estimate of anatomical connections, which is incorporated to constrain the cortical model. The empirical covariance structure is reproduced faithfully, especially its temporal component (i.e., time-shifted covariances) in addition to the spatial component that is usually the focus of studies. We find that the cortical interactions, referred to as effective connectivity, in the tuned model are not reciprocal. In particular, hubs are either receptors or feeders: they do not exhibit both strong incoming and outgoing connections. Our results sets a quantitative ground to explore the propagation of activity in the cortex.Author Summary: The study of interactions between different cortical regions at rest or during a task has considerably developed in the past decades thanks to progress in non-invasive imaging techniques, such as fMRI, EEG and MEG. These techniques have revealed that distant cortical areas exhibit specific correlated activity during the resting state, also called functional connectivity (FC). Moreover, recent studies have highlighted the possible role of white-matter projections between cortical regions in shaping these activity patterns. This structural connectivity (SC) can be estimated using MRI, which measures the probability for two areas to be connected via the density of neural fibers. However, this does not provide the strengths of dynamical interactions. Many methods have thus been developed to estimate the connectivity between neural populations in the cortex that is hypothesized to shape FC. The strengths of these dynamical interactions are called effective connectivity (EC). We use a cortical model that combines information from Diffusion-weighted MRI (dwMRI) and fMRI in order to estimate EC. We demonstrate theoretically that directed C can be inferred using time-shifted covariances. The key point of our method is the use of temporal information from FC at the scale of the whole network. Applying our model on experimental fMRI data at rest, we estimate the asymmetry of intracortical connectivity. Obtaining an accurate EC estimate is essential to analyze its graph properties, such as hubs. In particular, directed connectivity links to the asymmetry between input and output EC strengths of each node, which characterizes feeder and receiver hubs in the cortical network.

Date: 2016
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Citations: View citations in EconPapers (4)

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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1004762

DOI: 10.1371/journal.pcbi.1004762

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