Whole-brain estimates of directed connectivity for human connectomics.

Connectomics is essential for understanding large-scale brain networks but requires that individual connection estimates are neurobiologically interpretable. In particular, a principle of brain organization is that reciprocal connections between cortical areas are functionally asymmetric. This is a challenge for fMRI-based connectomics in humans where only undirected functional connectivity estimates are routinely available. By contrast, whole-brain estimates of effective (directed) connectivity are computationally challenging, and emerging methods require empirical validation. Here, using a motor task at 7T, we demonstrate that a novel generative model can infer known connectivity features in a whole-brain network (>200 regions, >40,000 connections) highly efficiently. Furthermore, graph-theoretical analyses of directed connectivity estimates identify functional roles of motor areas more accurately than undirected functional connectivity estimates. These results, which can be achieved in an entirely unsupervised manner, demonstrate the feasibility of inferring directed connections in whole-brain networks and open new avenues for human connectomics.

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Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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Declaration of Competing Interest We confirm that there are no conflicts of interest associated with this publication and that there has been no financial support for this work that could have influenced its outcome. Further, we confirm that the manuscript has been read and approved by all authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We further confirm that any aspect of the work covered in this manuscript that has involved human subjects has been conducted with the ethical approval of all relevant bodies. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submission of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author.