Trepanation has long had a place in the treatment of madness and brain injury. But as we see above in this detail from "The Extraction of the Stone of Madness" by Hieronymus Bosch (1450-1516), trepanation pops up -- at least in art history -- as a means to extract the Stone of Madness (AKA the Stone of Folly) from an afflicted patient's skull.
To be clear, most medical and art historians agree that the painting represents neither an actual surgical procedure nor a charlatan's scam. While the con artist interpretation is tempting ("Look, I've cured you of your madness and here's the stone I removed to prove it!), no historical sources from the period mention genuine or fraudulent stone operations.
Rather, it would seem Bosch was making a statement on the gullibility of the patient and the limits of medical understanding in the 1400s. In the same way that surgeons of the day removed bladder stones with appallingly high mortality rates, we see a barbarous, lunatic doctor attempting to remove such a stone from an even less-mastered region of human anatomy [source: Krischel, et al].
Still, the idea itself gained traction in the imagination. Stone removal surgeries popped up in theatrical performances in the Netherlands during the 15th and 16th-centuries. And above right we see Flemish painter Quentin Massys' 16th century painting "An Allegory of Folly," which clearly shows the Stone of Madness embedded in the fool's forehead.
And yet, according to a team of neurologists from the National Neurosciences Center in Kolkata, India, one possibility presents itself as a genuine stone of madness: cranial meningiomas.
A meningioma is a tumor that arises from the meninges, the membranes that surround your brain and spinal cord. Occurring just inside the skull, these spherical growths are often quite benign. But as described in a 2012 letter to Neurology India by Prasad Krishnan, et al, they can also result in irrelevant speech, forgetfulness and behavioral abnormalities such as disinhibition, emotional liability and talkativeness. The 65-year-old patient profiled in the letter underwent a craniotomy and gross total excision of the lesion, curing her of all the symptoms. In other words, surgeons removed the stone-like growth in her skull underpinning her abnormal mental state.
Of course this doesn't exactly back up the notion of real-life meningioma surgeries in the 15th century -- the earliest known written record of one doesn't emerge till the 17th century -- but it does provide some food for thought.
Now let's view the 2002 stop motion film "The Stone of Folly" by animator Jesse Rosensweet and sculptor Alastair Dickson: