Transfer Entropy as a Measure of Brain Connectivity: A Critical Analysis With the Help of Neural Mass Models

Objective: Assessing brain connectivity from electrophysiological signals is of great relevance in neuroscience, but results are still debated and depend crucially on how connectivity is defined and on mathematical instruments utilized. Aim of this work is to assess the capacity of bivariate Transfer Entropy (TE) to evaluate connectivity, using data generated from simple neural mass models of connected Regions of Interest (ROIs). Approach: Signals simulating mean field potentials were generated assuming two, three or four ROIs, connected via excitatory or by-synaptic inhibitory links. We investigated whether the presence of a statistically significant connection can be detected and if connection strength can be quantified. Main Results: Results suggest that TE can reliably estimate the strength of connectivity if neural populations work in their linear regions, and if the epoch lengths are longer than 10 s. In case of multivariate networks, some spurious connections can emerge (i.e., a statistically significant TE even in the absence of a true connection); however, quite a good correlation between TE and synaptic strength is still preserved. Moreover, TE appears more robust for distal regions (longer delays) compared with proximal regions (smaller delays): an approximate a priori knowledge on this delay can improve the procedure. Finally, non-linear phenomena affect the assessment of connectivity, since they may significantly reduce TE estimation: information transmission between two ROIs may be weak, due to non-linear phenomena, even if a strong causal connection is present. Significance: Changes in functional connectivity during different tasks or brain conditions, might not always reflect a true change in the connecting network, but rather a change in information transmission. A limitation of the work is the use of bivariate TE. In perspective, the use of multivariate TE can improve estimation and reduce some of the problems encountered in the present study.