From correlation to causation: Estimating effective connectivity from zero-lag covariances of brain signals.

Knowing brain connectivity is of great importance both in basic research and for clinical applications. We are proposing a method to infer directed connectivity from zero-lag covariances of neuronal activity recorded at multiple sites. This allows us to identify causal relations that are reflected in neuronal population activity. To derive our strategy, we assume a generic linear model of interacting continuous variables, the components of which represent the activity of local neuronal populations. The suggested method for inferring connectivity from recorded signals exploits the fact that the covariance matrix derived from the observed activity contains information about the existence, the direction and the sign of connections. Assuming a sparsely coupled network, we disambiguate the underlying causal structure via L1-minimization, which is known to prefer sparse solutions. In general, this method is suited to infer effective connectivity from resting state data of various types. We show that our method is applicable over a broad range of structural parameters regarding network size and connection probability of the network. We also explored parameters affecting its activity dynamics, like the eigenvalue spectrum. Also, based on the simulation of suitable Ornstein-Uhlenbeck processes to model BOLD dynamics, we show that with our method it is possible to estimate directed connectivity from zero-lag covariances derived from such signals. In this study, we consider measurement noise and unobserved nodes as additional confounding factors. Furthermore, we investigate the amount of data required for a reliable estimate. Additionally, we apply the proposed method on full-brain resting-state fast fMRI datasets. The resulting network exhibits a tendency for close-by areas being connected as well as inter-hemispheric connections between corresponding areas. In addition, we found that a surprisingly large fraction of more than one third of all identified connections were of inhibitory nature.