This drawing dates from around 1510, although Leonardo had first started looking at human skulls in 1499, when he got access to human cadavers from the hospital of Santa Maria Novella in Florence. He used innovative techniques, such as injecting molten wax, to locate and draw the cavities around the brain in the bones of the cranium.

In common with many people at the time, he was keen to find the seat of the human soul. The spine was thought to be the most likely location. Leonardo showed that the brain and spine were connected but never identified where the human soul lies. He disputed the belief - then widely held - that sperm were produced in the marrow of the spinal column.

The sketch is one of the Windsor Folios, part of the Royal Collection, held at Windsor.