The authors claim that there exists a surprising and pervasive degree of geometric regularity in the long-range neuronal trajectories in the brain. They report that throughout the brain’s white matter is to be found a grid-like pattern of fibers crossing at right angles. The brain’s superhighways, the authors tell us, form a three dimensional analog of the streets and avenues in New York City, running at right angles to each other. Note that this does not tell us about individual neurons: even if neuronal processes group together on grid-like highways during part of their journey across the brain, that does not tell us how different parts of the brain are connected (just as one needs to know more than which highways to travel on when visiting a friend living in a different city). Nevertheless, for something as complicated as the human brain, all regularities are welcome news.
It is worth examining critically the novelty and nature of these striking claims. The paper offers no numerical quantification of the prevalence of these putative grid-like patterns in the brain (eg, what fraction of the white matter shows grid patterns – or, what is the degree to which such a pattern occurs at some given point of the brain), but contents itself with attractive visualizations. For example, we think of the Corpus Callosum as running laterally, joining the two brain hemispheres; to what extent are fibers running front-to-back, or up-down embedded into the Corpus Callosum? It is also important to remember that the method is indirect, and the results have not been validated using the “ground truth” of postmortem neuroanatomy. That there are regularities in fiber pathways of the brain, and even the qualitative presence of criss-crossing patterns, was previously known from myelin stained brain sections: what this current paper quantitatively adds to that prior understanding, is not yet clear.
In fact, bundles of fibers, running at right angles to each other in three orthogonal directions, were already described more than a century ago, as can be seen in this illustration from “Anatomie des Centres Nerveux” (1895) by Joseph Jules Dejerine. This Weigert stained section of the human brain shows neatly organized fibers of the Cingulum (horizontal), the Corpus Callosum (vertical), and the Corona Radiata (Couronne Rayonnante in the French text) perpendicular to the page. We haven’t come that far from Dejerine as far as the wiring of the human brain is concerned: this is what the late Francis Crick and Ted Jones, termed “The Backwardness of Human Neuroanatomy.”
We need a real technical breakthrough that allows us to trace neurons across the postmortem human brain. Meanwhile, following Darwin, we can learn something about human brains by studying non-human animals. Even there, we suffer from a substantial knowledge gap. The complete genomes of multiple species have been mapped, but we don’t have similarly complete maps of brain circuits. Recently, I joined with colleagues in calling for an effort to close this gap with systematic circuit mapping projects in multiple species. I am engaged in such a project myself to systematically map the circuits of the mouse brain using histological methods, and related efforts are under way elsewhere. These are early days: to get at the full complexity even of mouse brain circuits will require significantly more resources than we are devoting to it now. To do something at the same scale for the human brain is a challenge that is as daunting today as it was to set sail for an unknown continent, hundreds of years ago. There are still some real frontiers left for us to breach.