Brain folding shapes the branching pattern of the middle cerebral artery.

The folds of the brain offer a particular challenge for the subarachnoid vascular grid. The primitive blood vessels that occupy this space, when the brain is flat, have to adapt to an everchanging geometry while constructing an efficient network. Surprisingly, the result is a non-redundant arterial system easily challenged by acute occlusions. Here, we generalize the optimal network building principles of a flat surface growing into a folded configuration and generate an ideal middle cerebral artery (MCA) configuration that can be directly compared with the normal brain anatomy. We then describe how the Sylvian fissure (the fold in which the MCA is buried) is formed during development and use our findings to account for the differences between the ideal and the actual shaping pattern of the MCA. Our results reveal that folding dynamics condition the development of arterial anastomosis yielding a network without loops and poor response to acute occlusions.