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One of the charms of the world's most famous painting is that she appears radiant one moment and then serious and sardonic the next.
Now scientists claim to have come up with an answer to her changing moods - our eyes are sending mixed signals to the brain.
They believe Mona Lisa's smile depends on what cells in the retina pick up the image and what channel the image is transmitted through in the brain.
Sometimes one channel wins over the other, and you see the smile, sometimes others take over and you do not see the smile.
Different cells in the eye are designed to pick up different colours, contrasts, backgrounds and foregrounds. Some deal with central vision while others with peripheral.
Depending on what cells picks up the image first depends on what channel they are sent to the brian for interpreting.
These channels encode data about an object's size, clarity, brightness and location in the visual field.
"Sometimes one channel wins over the other, and you see the smile, sometimes others take over and you don't see the smile," said Dr Luis Martinez Otero, a neuroscientist at Institute of Neuroscience in Alicante, Spain, who conducted the study, told New Scie