RESEARCH AUGUST/SEPTEMBER 2018 BY SUSAN FITZGERALD What is Synesthesia? Synesthesia, a neurologic condition in which one sense activates another, may help researchers understand how and why we perceive reality.

Alex Louis, a 13-year-old from Tarrytown, NY, experiences musical notes as colors. A is dark green, E is brown, and G-sharp is deep blue. The vibrate tone of his mom's cell phone, a G note, is yellow.

Illustration by Bratislav Milenkovic Alex never thought twice about the colorful way he processes music. But one day his school band director happened to mention to him and his mother that some kids with perfect pitch, like Alex, have synesthesia, a condition in which they see different colors depending on the notes they hear.

The band director wasn't aware Alex had synesthesia. Alex wasn't either. Or at least he didn't realize that what he was experiencing was out of the ordinary. "Doesn't everybody do that?" he recalls asking the band director.

Unusual Occurrence In reality, synesthesia is a fairly rare neurologic phenomenon in which the brain processes data in several senses at once—one sense activates another unrelated sense, and they are experienced simultaneously. About 4 percent of the population has synesthesia, according to a 2013 study in Frontiers in Psychology. Alex says he has always heard music in colors, also known as sound-to-color synesthesia, or chromesthesia, an ability invisible to those around him.

Other people with synesthesia may perceive numbers or letters as certain colors regardless of what color they happen to be printed in (grapheme-color synesthesia), or they may "taste" certain words (lexical-gustatory synesthesia). For instance, in the same 2013 study in Frontiers in Psychology, a research subject said she tasted potato chips when she heard the word "woman."

Synesthesia is thought to be more common in people with autism (Alex has been diagnosed with pervasive developmental disorder-not otherwise specified, a form of autism with milder symptoms), and in creative people, including artists, musicians, and poets.

Living with Synesthesia In his memoir Born on a Blue Day, writer Daniel Tammet describes how synesthesia affects his world. "The number one, for example, is a brilliant and bright white, like someone shining a flashlight into my eyes. Five is a clap of thunder or the sound of waves crashing against rocks. Thirty-seven is lumpy, like porridge, while 89 reminds me of falling snow," writes Tammet, who also has savant syndrome, a condition characterized by an extraordinary ability to memorize minute details or rapidly calculate numbers.

The molecular mechanism underlying synesthesia is not known, but the condition is thought to be caused by differences in cortical wiring that emerge during the development of connective pathways, probably in early childhood.

Dierent Wiring "In the infant brain everything is connected. Then, the excess connections are pruned away by genes that lead to specialized modules, for example, for color and number shape," explains neuroscientist Vilayanur Ramachandran, MBBS, PhD, distinguished professor in the psychology department and neuroscience program at University of California, San Diego (UCSD) and director of the Center for Brain and Cognition at UCSD. If, due to genetic mutations, no pruning occurs, it can result in hyperconnectivity, or cross-activation, between neuronal tracts that control different senses.

Dr. Ramachandran has been studying synesthesia for more than a decade, in part because he finds the phenomenon fascinating and in part because understanding the basis of the condition could help explain normal brain development.

Dr. Ramachandran has written about different variations of synesthesia, including one referred to as "calendar synesthesia," in which people actually see a physical calendar in front of them when they think about prior or future dates. When the person looks to the right, the calendar fades on the left, and vice versa. He has also written about mirror-touch synesthesia, in which a person feels what someone else is experiencing just by observing it. "Someone else gets pinched and you say 'ouch,'" he says. "Or you giggle uncontrollably when you see someone being tickled."

A Long History Reports of synesthesia-like behavior go back hundreds of years, but it was attributed to various causes, including an overactive imagination, mental illness, or drug-induced hallucinations. Synesthesia was formally documented in the late 1800s. More recently, scientists have taken a renewed interest in the condition, using PET scans and functional MRI images to look for differences in brain structure and connectivity.

Genetic Mutation DNA sequencing is uncovering possible genetic causes of the condition. In a study published earlier this year in Proceedings of the National Academy of Sciences, a research team from the Netherlands and the United Kingdom identified 37 gene variants of interest in three multigenerational families with different manifestations of sound-color synesthesia, although none were found in all three families. "Some of these genes have been shown to play a role in the development of new connections between brain cells, a process known as axogenesis," says Edward Hubbard, PhD, a University of Wisconsin-Madison neuroscientist who edited the report and studies synesthesia at his lab.

"Normally we look at it as having two different things out there, like a color or a sound, and we want to know how the brain combines information from multiple senses," he says. "In synesthesia, the brain takes in information from one sense, but generates two experiences."

Additional Insights Dr. Hubbard hopes that understanding what happens in the brains of people with synesthesia will provide insights into how children learn concepts such as numbers and letters. More generally, he believes it could help us understand how brain processes allow us to have conscious experiences in the first place. "Why are we aware of the world around us, as opposed to not?"

To find research subjects, Dr. Hubbard often goes to large lecture halls on campus and describes the condition. Invariably, a few students will approach him afterwards, saying they never talk about their synesthesia for fear of being considered strange. In some cases, they discovered a parent has the same quirk.

A Fun Gi Regardless of what is eventually revealed about synesthesia, no one suggests the condition needs to be fixed. Alex Louis has heard music in colors for as long as he can remember. In addition to playing the drums, guitar, bass, and ukulele in his school band, he likes to sing and act. In fact, he recently performed with the national touring company of the musical School of Rock. He hears the show's song "Stick It to the Man" as brownish red, which turns into sea green as the tune shifts keys.

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"It seems like his autism has left him with some amazing gifts," Alex's mom, Pamela, says. Alex, too, sees only an upside to his ability to hear music as colors, noting that he sometimes describes the colors to his friends, who are always impressed. " [Having synesthesia] is pretty good," he says. On second thought, "It's cool. It's fun."

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