Synesthetes can taste numbers, feel colors or have other sensations triggered by sensations. Studies of their brains could provide clues for neurological disorders.

If you ask Emma Anders about the number five, she’ll tell you that it’s red. She’ll also tell you that five is a mischievous, self-centered brat — like a kid throwing a temper tantrum at a party.

“Two is yellow, three is purple, four is an intense sky blue,” says the 21-year old student at UC San Diego. “An eight is very noble and kind of held together, almost like a parent figure to five. Nine is a brown-haired guy, and he’s pretty calm — but he’s really into seven.”

For most people, a number is simply an arithmetical value that represents a quantity. But for Anders, it is also a thing that has a particular color and an entire suite of personality traits. And it’s not just numbers — she also ascribes colors to flavors and smells. (Vaseline, for instance, smells burgundy, and a green apple tastes yellowish-orange.)

This is the world of synesthesia, a perceptual phenomenon in which one sense kindles sensation in another. The condition, which is harmless, is caused by increased connectivity between areas of the brain that are normally separated. As a result, when Anders sees a five, the region of her brain that perceives colors is stimulated along with the region that processes numbers.

Other synesthetes see colors when they hear music, taste words before they say them or feel textures on their fingertips when they discern the flavors of particular foods. Virtually any combination between the senses is possible in the 1% to 4% of people who have inherited the condition.

No one is trying to cure synesthesia — in fact, most synesthetes will tell you they love their synesthetic experiences and would never want to lose them. But scientists have begun studying people like Anders in hopes that what they discover about the way their brains are wired will provide clues for understanding other neurological disorders, like autism and schizophrenia.

“We’re using the synesthetic brain as a model for neural hyper-connectivity,” says Steffie Tomson, a neuroscientist at Baylor College of Medicine in Houston. “What we’re learning is that there are very specific delicate relationships between different regions of the brain that can cause it to function normally — or to tweak.”

Scientists have been aware of synesthesia for more than 100 years, but only in the last decade or so has it been considered more than a strange quirk. Recent advances in neuroimaging have allowed researchers to visualize what’s going on inside a synesthete’s brain when it makes its unconventional connections. The Internet has inspired the creation of online tests that have gathered data from tens of thousands of synesthetes throughout the world. And genetic sequencing has enabled scientists to come closer to pinpointing the genes that cause this condition.

David Brang, a UC San Diego neuroscientist, says nature provides a strong hint that the brains of synesthetes may have some kind of cognitive advantage. The genes for synesthesia appear to be dominant, and family trees depict the trait marching through the bloodline. This high degree of heritability suggests the genetic mutation that causes synesthesia provides some significant evolutionary benefit.

Brang’s hypothesis is that the benefit is related to creativity, enhanced perception and overall smarts. So far, studies have found that so-called colored sequence synesthetes (who experience color when they see numbers or letters) have a heightened ability to discriminate between similar colors, while mirror-touch synesthetes (who experience touch sensations when watching another person touch themselves) are more sensitive to touch in general.

The search for the genes that trigger synesthesia is underway in David Eagleman’s lab at Baylor College of Medicine, where Tomson works. Eagleman calls this nascent field “perceptual genomics,” or the study of how specific genes influence how people experience the world.

“I see in synesthesia a really good inroad into understanding the brain in general and consciousness in particular,” says Eagleman, who has identified a region on chromosome 16 that is linked to colored sequence synesthesia. “Here we have a condition where some small change, presumably a very tight genetic change, causes the internal experience to be completely different from someone else’s.”

The study of synesthesia has helped shift the way scientists think about the brain. In the past, they have focused on matching different areas with specific functions; now, the entire organ is viewed as a tapestry of interwoven connections.

“The whole system is a giant network,” Eagleman says. “It’s no longer sufficient to think about single areas in isolation.”

Like synesthesia, many neurological disorders — such as schizophrenia, autism,Alzheimer’s disease, depression and epilepsy — have been linked to abnormal communication between brain regions. The hope is that as neuroscientists learn about how the connections in the synesthetic brain differ from those in normal brains, they will also gain insight into how these differences develop — and how they sometimes manifest as harmful disorders.

“We’re trying to understand how a different activity pattern in your brain can change the way you perceive reality,” says Tomson, pointing out that studying disorders such as depression or schizophrenia in people who already have the disorder can be tricky. Not only are the network properties of these illnesses more complex than the relatively simple circuitry involved with synesthesia, but patients are often on medication, which makes it impossible to tell how their brains would function on their own.

“Synesthesia is a perfect model because we have a healthy brain that has some kind of perceptual tweak that changes the relationship between various regions of the brain,” she says

Researchers in Eagleman’s lab are also studying sensory processing dysfunction (SPD), which is a hallmark characteristic of autism. People with this disorder have temper tantrums and other extreme reactions when exposed to particular tastes, sounds, textures or other stimuli.

The prevailing idea is that people with SPD experience certain stimuli as louder or more intense than normal. But Eagleman’s studies of synesthesia have caused him to look at individuals with SPD in a different way.

“I think that what they’re experiencing is a form of synesthesia where instead of some sense connecting to their color area, it’s connecting to an area involving pain or aversion or nausea,” Eagleman says. “If that’s true, what we’re doing in synesthesia will give us an actual molecular target for helping that.”

Synaesthesia – crossovers in the senses

Nabokov experienced colour with each sound, Kandinsky heard music with a splash of paint, both had synaesthesia, a rare neurological condition which causes the senses to intertwine.

he Nobel Prize winning physicist Richard Feynman reported seeing equations in colour. The artist Wassily Kandinsky tried to re-create the visual equivalent of a symphony in each of his paintings. And Vladimir Nabokov wrote, “One hears a sound but recollects a hue, invisible the hands that touch your heartstrings. / Not music the reverberations within; they are of light. / Sounds that are colored, and enigmatic sonnet addressed to you.”

All had synaesthesia, a harmless neurological condition in which activity in one sensory modality, such as vision or hearing, evokes automatic and involuntary perceptual experiences in another, due to increased cross-talk between the sensory pathways in the brain.

“It’s generally agreed that there’s cross-activation, so that activity in sensory area A will activate area B,” says David Eagleman of the Baylor College of Medicine, “but we don’t know whether it’s due to a difference in wiring or in the chemical cocktail.” Eagleman chaired a symposium at the annual meeting of the Society for Neuroscience in San Diego earlier this week, in which he and others presented the latest findings about the condition.

Once thought to be extremely rare, synaesthesia is now believed to affect between 1 and 4% of the population. Several years ago, Eagleman and his colleagues set up a website, containing a battery of tests to objectively verify synaesthetic experiences, and to date more that 9,000 synaesthetes have registered on the site.

Self-reports on the website reveal that there are over 100 different forms of synaesthesia, and these can be clustered into 5 main groups. In the most common form of the condition, letters, numbers and units of time such as weeks and months evoke the experience of colour; in others, sounds evoke smells, tastes or sensations of touch; in yet others, pain, touch, temperature, orgasms and emotions evoke colours.

Some synaesthetes taste shapes or the textures of objects on their tongue, while others, with the recently described mirror-touch synaesthesia, experience tactile sensations when they observe others being touched.

Synaesthetes can be broadly divided into two groups. “Projector” synaesthetes experience these cross-activated perceptions in the external world, whereas “associators”, experience them only in the mind’s eye. And there are two main hypotheses to explain the neural basis of this increased sensory cross-talk. According to one, there is increased connectivity between normally distinct sensory pathways, because of greater neuronal outgrowth during brain development, or because exuberant connections were not properly “pruned”. According to the other, the sensory cross-talk occurs because of a lack of proper inhibition.

That synaesthesia can be induced by drugs such as LSD, and that synaesthetic experiences can wax and wane with, for example, changes in mood, suggests a role for inhibitory processes mediated by the neurotransmitter GABA, but the two hypotheses are not mutually exclusive, and there is also evidence for the other.

Romke Rouw of the University of Amsterdam described experiments showing structural differences between the brains of synaesthetes and non-synaesthetes. Using a technique called diffusion tensor imaging, Rouw and her colleagues have shown that some synaesthetes have increased connectivity between adjacent regions on the ventral surface (or underside) of the temporal lobe, areas which are involved in processing texture, colour and form.

Rouw’s group has also shown that some synaesthetes exhibit increased activation in the superior parietal cortex, which is known to contain neurons that integrate different types of sensory information. Using another neuroimaging technique called voxel-based morphometry, they also found that some synaesthetes have increased grey matter volume in this region, and that associators, but not projectors, have more grey matter in the hippocampus, a part of the brain involved in memory.

Danko Nikolić of the Max Planck Institute for Brain Research in Frankfurt pointed out that concepts can trigger synaesthetic experiences too. For example, grapheme-colour synaesthetes experience the colours associated with the number 7 when presented with 5 + 2. The same letter can also evoke different synaesthetic experiences according to its context – the grapheme “0”, for example, evokes one colour when presented in a sequence of letters and another when presented in a sequence of numbers.

Nikolić even described two professional swimmers for whom different swimming styles evoke different colours. So in some synaesthetes, concepts and meanings also give rise to concrete perceptual experiences. Nikolić
suggests that this should be thought of as “ideaesthesia”, or sensing ideas.

Studying synaesthesia can teach us about how sensory systems normally work, but they may also tell us something about the processes underlying sensory disturbances. According to Michael Banissy of the Institute of Cognitive Neuroscience in London, nearly one third of amputees report mirror-touch sensations in their missing limbs. He has also shown that mirror-touch synaesthetes outperform non-synaesthetes in facial recognition tasks, because they appear to be more empathetic.

One focus of Eagleman’s synaesthesia research is what he called “perceptual genomics”, or the identification of genes involved in the condition. He says it’s possible that hundreds of genes are involved, and that these are likely to encode proteins with diverse functions, from GABA channels that mediate inhibitory neurotranismission, to axon guidance molecules involved in the initial wiring the brain. They have already identified a hotspot on chromosome 16, which seems to harbour a number of genes involved in synaesthesia.

“There are 300 genes in the hotspot,” says Steffi Tomson, a graduate student in Eagleman’s lab who is involved in the gene hunt. “100 of those are expressed in the brain, and we’re focusing on those.” And the fact that synaesthesia runs in families will help to identify the genes involved. “Now we’re selecting more families,” Tomson adds, “and have just submitted two synaesthetes for full exome sequencing. We’re also going to look at the neural networks involved in synaesthesia, to try to understand how they are organised.”

 

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