Subspace-based Identification Algorithm for characterizing causal networks in resting brain.

The resting brain has been extensively investigated for low frequency synchrony between brain regions, namely Functional Connectivity (FC). However the other main stream of brain connectivity analysis that seeks causal interactions between brain regions, Effective Connectivity (EC), has been little explored. Inherent complexity of brain activities in resting-state, as observed in BOLD (Blood Oxygenation-Level Dependant) fluctuations, calls for exploratory methods for characterizing these causal networks. On the other hand, the inevitable effects that hemodynamic system imposes on causal inferences in fMRI data, lead us toward the methods in which causal inferences can take place in latent neuronal level, rather than observed BOLD time-series. To simultaneously satisfy these two concerns, in this paper, we introduce a novel state-space system identification approach for studying causal interactions among brain regions in the absence of explicit cognitive task. This algorithm is a geometrically inspired method for identification of stochastic systems, purely based on output observations. Using extensive simulations, three aspects of our proposed method are investigated: ability in discriminating existent interactions from non-existent ones, the effect of observation noise, and downsampling on algorithm performance. Our simulations demonstrate that Subspace-based Identification Algorithm (SIA) is sufficiently robust against above-mentioned factors, and can reliably uncover the underlying causal interactions of resting-state fMRI. Furthermore, in contrast to previously established state-space approaches in Effective Connectivity studies, this method is able to characterize causal networks with large number of brain regions. In addition, we utilized the proposed algorithm for identification of causal relationships underlying anti-correlation of default-mode and Dorsal Attention Networks during the rest, using fMRI. We observed that Default-Mode Network places in a higher order in hierarchical structure of brain functional networks compared to Dorsal Attention Networks.