A loud shirt. A gravelly voice. Purple prose. The merging of the senses, called synesthesia, is a literary device that makes for vivid imagery. But in a neurological condition with the same name, a single perception can involve a second, linked sense that most people would not experience. "Synesthetes" may taste chocolate when hearing a song or see numbers as colors. The reason, new research suggests, may be that the brain cells in the area responsible for the secondary, or extra, sense—for instance, the chocolate taste—are overly active. In addition to shedding light on an unusual mode of perception, the findings could lead to treatments for brain disorders—showing ways to reduce hallucinations, for example, or correcting various types of impaired perception that can follow a stroke.
Synesthesia can occur early in life due to the explosive growth of a young child's brain, explains neuroscientist Devin Terhune of the University of Oxford in the United Kingdom. Normally, as the child grows older and brain circuits are refined, the linkages break up. But in synesthetes, for some reason, the secondary sense persists throughout life.
The simplest explanation, Terhune and his colleagues believe, is that neurons in the area responsible for the extra sense are more responsive, or "excitable," than usual, strengthening a sensory association that the person wouldn't normally be aware of. The investigators tested their hypothesis with a technique called transcranial magnetic stimulation, which, as the name suggests, stimulates a specific part of the brain with a weak magnetic field applied to the scalp.
The researchers worked with six people who had "grapheme-color synesthesia,"—the most common form of the condition, in which letters or numbers are perceived in certain colors  (the number 2 in turquoise or the letter S in magenta, for example)—and six "normal" controls. Each participant received stimulation on the scalp near an area called the primary visual cortex until they saw a flash of light known as a phosphene.
The investigators reasoned that if the synesthetes did have highly excitable neurons in the visual cortex, they would need less stimulation than the control subjects to see the phosphene. The suspicion proved correct: in fact, people without synesthesia required three times as much stimulation to reliably evoke the phosphene , the team reports online today in Current Biology.
"The idea that synesthesia results from region-specific hyperexcitability is novel," Terhune says. "But it's consistent with the dominant view that synesthesia is due to cross-connectivity between different brain areas. One possibility is that these highly excitable neurons might help produce the extra connections."
In a second phase of the experiment, the investigators used varying amounts of electrical stimulation (called transcranial direct-current stimulation, or TDCS) to either lessen or increase the synesthetes' color experience. Terhune says that although the vast majority of synesthetes are happy with their condition, the ability to alter neuronal excitability might lead to treatments for unwanted hallucinations, such as those that occur with schizophrenia, or to turn up brain activity in patients who have suffered a stroke or have brain damage.
By targeting specific areas to enhance the synesthetes' perceptions, the finding adds to a growing amount of research that uses brain stimulation to improve mental performance in general. Study co-author Roi Cohen Kadosh, who heads up Terhune's lab at Oxford, has already shown that TDCS can boost math skills  in adults for up to 6 months. "The long-term use of electrical stimulation releases brain chemicals involved in learning and memory," he says. "But it only enhances work that's already being done, like giving a runner an energy drink. You can't just zap your brain and become smart."
"This a great study. It's the first to use TDCS to enhance synesthetic experiences," says Peter Weiss-Blankenhorn of the Research Centre Jülich in Germany, via e-mail. He adds that future studies could combine TDCS with imaging techniques to confirm the authors' speculation that the cells' excitability helps build the networks that result in synesthesia. Such a study could change the activity level of key neurons, then use imaging techniques to see whether the synesthesia networks were affected, Weiss-Blankenhorn says.
Regarding the use of TDCS to improve mental performance, cognitive neuroscientist Michael Banissy of Goldsmiths, University of London, comments via e-mail: "It's an exciting avenue for future research, but caution is needed before we start using it for everyone to improve their performance. Brain stimulation needs to be done by people who are trained in using it appropriately."
Or as Cohen Kadosh puts it, "Don't try this at home."