Episode 39 – Neurons, Double-Crossed

Why does the right side of the brain control the left side of the body (and vice versa)?

In this episode, we investigated one of the great mysteries in biology: why are our brains cross-wired? Specifically, why does the right side of the brain control the left side of the body, and vice versa?

It’s worth mentioning up-front that everything discussed below is theoretical and unprovable. With that said, observation about crossed fibers date back to at least Hippocrates or the Hippocratic authors. He (or they) observed a curious pattern in traumatic head injury patients: if a patient had a right-sided head injury and developed focal seizures, the convulsion would affect the left side of the body. Similarly, a left-sided head injury would lead to right-sided focal seizures.

To understand these observations – and those which followed – a brief review of the sensory and motor nervous system is in order. The nervous system has three main functions:

  1. Sensory output = visual or tactile sensation
  2. Integration = brain and spinal cord
  3. Motor output = muscles of our limbs

The visual, tactile sensory, and motor pathways all cross the midline by way of decussations, which is the technical term for the point when nerve fibers cross the midline. These include the ascending tactile sensory tracts that cross in the spinal cord, for example, as well as the optic chiasm in the brain.

The person who offered some of the earliest and best explanations for this findings was Ramon Y Cajal. As a pathologist and neuro-anatomist he made foundational histological observations about the structure and function of the central nervous system (CNS) and shared the 1906 Nobel prize for physiology and medicine with Camillo Golgi. But Cajal also made detailed anatomic drawings of the central nervous system, showing the arborization of nerves and, of course, how neuronal tracks cross the midline.

Not surprisingly Cajal spent a tremendous amount of time, essentially his whole career,  studying the central nervous system and noticing and mapping lots and lots of detail. In 1898, he happened to be studying the optic chiasm, which transmits visual inputs from the eyes to the brain. He noticed and questioned a curious thing: the right half of the world, or visual field to be more specific, is “seen” by the left half of the brain, and the left half of the world is seen by the right half the brain. In other words, why does the opposite side of the brain process a given half of the visual field? As he said at the time “One of the most obscure issues in biology is, no doubt, to determine to what extent the organism benefits from the singular phenomenon of the decussation”. He wondered, wouldn’t it have been a simpler setup for each side of the brain to process its own side of the visual field? He therefore reasoned that this more complex arrangement that we and our ancient animal ancestors evolved to have must serve a purpose or provide us with some advantage.

Given the central importance of the visual tracts in Cajal’s hypothesis, briefly reviewing the anatomy may be helpful. First, light passes through the rounded cornea and lens of the eye. In doing so it gets bent and inverted by the time it gets to the retina, so light hitting the retina is upside down and backwards. Crossing of the optic tracts actually allows for the image to be reverted to a correct orientation prior to being processed in the visual cortex. 

Crossing of the visual inputs in the optic chiasm allows our brains to correctly interpret the spatial setup of the world around us. We need our optic tracts to cross to accurately perceive the world around us. If you took the example of reading the word “DANGER”, with DAN in the right visual field and GER in the left visual field, if the optic tracts didn’t cross then our brains would actually flip those and read GER-DAN. Because of the way that our curved corneas and lenses flip and invert visual inputs, without crossing we would have a hard time accurately navigating the world. 

Recall that the right retina sends tracts to both the right and left visual cortices and vice versa. This is important to allow for depth perception and stereoscopic vision. We need stereoscopic vision to use fine motor skills (e.g., tying tiny knots in the operating room or repairing a watch).

Cajal noted the necessity of having visual tracts cross, and then projected that onto the rest of the central nervous system. His reasoning went like this: if the visual tracts cross then sensory tracts must also cross. You wouldn’t want the right half of the brain handling visual input from the left side of the visual field, but the left half of the brain handling tactile sensory input from the left side of the body. It’s important for all of the sensory input for each half of the world to be processed and integrated by only one side of the brain. So sensory input has to cross the midline for that system to work cohesively.

This video shows a newly-sighted girl integrating sight and touch for the first time in her life in a fascinating case report.

Cajal took his theory to its next logical conclusion. If sensory input crosses the midline then motor output must also cross. He theorized that crossing the midline evolved eons ago in limbed vertebrates to ensure that the right half of the brain (and vice versa) responds to the left side of the world in every way – whether visual, tactile, or motor. 

One might imagine this as an evolutionarily advantageous development that occurred in more advanced, limbed vertebrates. If you look at limbless vertebrates, such as fish, they perceive a threatening stimulus on the left sides of their bodies in their right brain, but use muscles on the right side of their bodies to move away from the threat. This is the exact opposite of what more advanced limbed vertebrates do. We use the left sides of our bodies to move away from a left-sided threat. And it turns out that the corticospinal motor tracts, which cross the midline and mediate this threat response, are phylogenetically younger, meaning they evolved later,  supporting the idea that crossing evolved as a way to coordinate visual, tactile, and motor input and output in limbed vertebrates.

There are a number of interesting clinical correlates. First, there are several congenital syndromes associated with abnormal or disrupted motor neuronal decussations. These include Klippel-Feil syndrome and X-linked Kallmann syndrome, and they can present with a really fascinating neurological finding called mirror movements, which are unintended, involuntary movements on one side of the body that mirror voluntary movements on the opposite of the body. So if someone went to catch a baseball with their left hand, their right hand would also move to catch the ball, involuntarily.

An even more extreme congenital abnormality with motor neuron crossing is seen in the concisely named Horizontal Gaze Palsy and Progressive Scoliosis syndrome, or (HGPS). These patients have mutations in the Robo family of receptors, which bind a protein called Slit. Slit is important in mediating the crossing of motor neuron tracts. So a mutation in Robo leads to a situation where motor neuron tracts don’t cross at all and the right side of the brain controls the right side of the body. Their sensory and visual  tracts do cross, though, and interestingly they have normal sensorimotor function aside from the clinical features from which the syndrome is named, namely scoliosis and a horizontal gaze palsy.

The last clinical point also involves embryogenesis. It turns out that melanin is crucial for ensuring the correct routing of optic tracts during fetal development. Recall that under normal circumstances, each retina sends visual tracts to both sides of the brain, which allows for stereoscopic vision and depth perception.

Albinism is a group of genetic disorders that is characterized by the inability to make melanin. The visual tracts of those with albinism only send input to one side of the brain per eye (e.g. left eye to right brain). So their optic tracts do cross but only send visual input to the opposite side of the brain. As a result, patients with albinism often lack stereoscopic vision, and thus often have chronic nystagmus and difficulties with depth perception.

Take Home Points

  1. Ramon Y Cajal developed a theory for why the central nervous system crosses the midline.
  2. Visual tracts cross to revert inverted retinal images and allows for depth perception and fine motor skills.
  3. Cajal theorized that tactile sensory & motor tracts must also therefore cross so the brain handles all sensory input and motor output from the same side of the world around us.


Click here to obtain AMA PRA Category 1 Credits™ (1.00 hours), Non-Physician Attendance (1.00 hours), or ABIM MOC Part 2 (1.00 hours).

Listen to the episode


Credits & Citation

◾️Episode and show notes written by Avi Cooper and Tony Breu
◾️Audio edited by Clair Morgan of nodderly.com

Cooper AZ, Breu AC, Abrams HR. Neurons, Double-Crossed The Curious Clinicians Podcast. December 8, 2021

Image credit: https://www.nytimes.com/2017/02/17/science/santiago-ramon-y-cajal-beautiful-brain.html

Published by Tony Breu

Tony Breu, MD is an internist/hospitalist who loves asking ‘why’?

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