Crossed wiring of the mammalian brain began with early vertebrate vision

The crossed wiring of the mammalian brain, in which the right hemisphere handles the left side of the body, probably began as an inheritance from early vertebrate vision rather than as a survival advantage. That is the argument of Martin W. Wessendorf and Daniel Delie Wang of the University of Minnesota, in a hypothesis paper in Frontiers in Neuroanatomy.

The mechanism starts with the eye. Every vertebrate species reported, from lampreys and hagfish to humans, has an optic chiasm, the structure where visual fibers cross. Input from each visual field goes to the opposite optic tectum, a midbrain region called the superior colliculus in mammals. The authors conclude that the last common ancestor of vertebrates likely had both. They propose that the crossed visual map in the tectum served as a template. The tectum also receives touch and hearing inputs and sends out motor commands, so other sensory and motor systems aligned with it.

The design is a survey, not an experiment. The authors reviewed decades of comparative studies of brain circuits across fish, amphibians, reptiles, birds and mammals and looked for patterns in which animals share which traits. Their central finding is that vision is the most ancient crossed system. Other crossed circuits appear to have arrived later. According to the paper, the touch and pain pathways to the thalamus, the tectospinal tract and the rubrospinal tract, which are motor pathways running from the midbrain to the spinal cord, were likely present in the last common ancestor of tetrapods, the four-limbed vertebrates. The corticospinal tract, the main route from the cortex to the spinal cord, is unique to mammals, though the authors note a similar projection reported in some birds.

By the time mammals appeared, roughly 165 million years ago according to the authors, many major pathways were already crossed. An uncrossed neocortex would not have been impossible, but it would have required adding several extra crossings or rewiring existing circuits. That would likely have raised "wiring costs," meaning slower function, higher energy demands, or both. The "most economical way" for the neocortex to connect with existing circuits was to be crossed as well.

The corticospinal tract itself varies across species, which the authors take as a sign that its crossing is not strongly favored by natural selection. It is bilateral in goats and elephants and mostly uncrossed in hedgehogs and moles.

Many papers, dating back at least to the anatomist Santiago Ramón y Cajal, have speculated on the adaptive value of the crossed layout, but "to date none appears to have examined its evolutionary history." The authors review six earlier hypotheses, including that crossing strengthens the nervous system structurally, helps animals survive injury, solves an engineering problem in steering toward goals, or reflects an ancient twist in the body plan. They find each has weaknesses. A topological argument that crossings are needed to preserve spatial maps, for example, would imply that every mapped pathway must cross, which is not the case.

Wessendorf and Wang stress that their idea is a hypothesis. Their own list of predictions includes whether Cambrian fossils of early vertebrates preserve an optic tectum and chiasm, whether crocodilians and a wide range of birds have crossed telencephalic tracts to the spinal cord, and whether crossed wiring proves more efficient than plausible uncrossed alternatives.

The paper is Wessendorf and Wang, 2026, Frontiers in Neuroanatomy 20, doi 10.3389/fnana.2026.1937941.