Brain controllability: Not a slam dunk yet.

In our recent article [1] published in this journal we provide quantitative evidence to show that there are warnings and caveats in the way Gu and collaborators [2] define controllability of brain networks and measure the contribution of each of its nodes. The comment by Pasqualetti et al. [3] confirms the need to go beyond the methodology and approach presented in Gu et al.'s original work. In fact, they recognize that "the source of confusion is due to the fact that assessing controllability via numerical analysis typically leads to ill-conditioned problems, and thus often generates results that are difficult to interpret". This is indeed the first warning we discussed in [1]: our work was not meant to prove that brain networks are not controllable from one node, rather we wished to highlight that the one node controllability framework and all consequent results were not properly justified based on the methodology presented in Gu et al. [2]. We used in our work the same method of Gu et al. not because we believe it is the best methodology, but because we extensively investigated it with the aim of replicating, testing, and extending their results. The warning and caveats we have proposed are the results of this investigation. Indeed, on the basis of our controllability analyses of multiple human brain networks datasets, we concluded: "The λ(W) are statistically compatible with zero and thus the associated controllability Gramian cannot be inverted. These results show that it is not possible to infer one node controllability of the brain numerically". Hence both groups agree that one node controllability cannot be inferred numerically.