The sweet smell of purple

New Scientist, 13 August 1994

Muriel still remembers when her father painted the family house. The paint was white. But it smelled unmistakably blue. Then there's Kristen, who tastes words, complete with texture and temperature. Often the spelling affects the flavour. 'Lori', for instance, tastes like a pencil eraser, but 'Laurie' tastes lemony.

These two women have synaesthesia, which means that their senses mingle. A stimulus to one sense gives rise to entirely unexpected responses in others. A scent, in Muriel's case, triggers not only smell but colour. Grass might smell purple - or roses grey. The taste of chocolate might bring on a prickly feeling, of pins jabbing into flesh. Sounds, too, evoke colours and shapes. One synaesthetic can picture the green loops of a helicopter's drone; another is assaulted with red daggers on hearing a bell.

Most people with the condition - there are an estimated one in 25 000 - simply hear letters, numbers and words in colour. To them, it is a natural, unobtrusive part of life, like seeing. Synaesthetics aren't impaired, don't 'suffer' and for the most part enjoy their little gift. Amusing and quaint though it is, synaesthesia, neurologists agree, is rather unimportant - at least, it would be if it hadn't fired a debate that goes to the core of how the brain works.

The problem is that synaesthesia is not easily explained. How does this sensory mix-up happen? And where in the brain does it take place? According to the widely-accepted view, the various functions of the brain, senses included, are handled in specialised neural 'modules' - theoretical constructs which make it easier to understand how the brain works. And each module consists of a number of areas of the brain wired together by neural pathways. Information to do with hearing, for instance, is processed in one module, while vision is processed in another.

The neural pathways involved in this division of labour are believed to centre on the cortex, the sheet of tissue that forms the outer shell of the brain's two distinctive hemispheres. The unusually large size of the cortex in humans compared to other animals suggests that it is the seat of the rational thinking that sets humans apart from other creatures; in other words, that it is the human brain's 'highest' and most sophisticated structure.

But synaesthesia seems to defy this segregation: at least two senses are interacting. When Muriel 'smells' the colour of paint, does the activity take place in the brain's 'smell centre' or in the module for vision? Or somewhere else? Is there something special about her brain or could any old brain do this? Or could it be that ideas of modularity and cortical supremacy are off the mark?

A team of psychologists and neurologists in London, headed by Simon Baron-Cohen of the Institute of Psychiatry, has been looking at the condition for six years. They have come to the tentative conclusion that the brains of synaesthetics are biologically distinct. 'In people with synaesthesia,' suggests John Harrison, a neuropsychologist at Charing Cross Hospital and a leading member of the team, 'perhaps unusual pathways link centres of the brain that process auditory inputs to areas processing vision.' In other words, their brains are cross-wired. 'It's a perfectly good explanation.'

But not according to an American neurologist. Richard Cytowic of Capitol Neurology, a private clinic in Washington DC, says that explaining synaesthesia within the standard view of the brain is like explaining the orbit of Mars by adding another 'sphere' to accommodate the theory that the Universe is Earth-centred. Modules do not exist structurally. So why, asks Cytowic, are researchers going out of their way to protect them? Why invent 'special pathways' to explain synaesthesia? Why should hypothetical modules drive experimentation? It is phenomenology, he believes, which should drive theory. 'The fact is that the current model can't explain it,' he insists. 'So that model has to be questioned.'

The brains of synaesthetics, Cytowic proposes, may not be fundamentally different at all. Synaesthesia may instead be telling us something new about human brain physiology. Far from being a hierarchy, dominated by a 'rational' cortex where functions such as sensory perception are localised and separated, the human brain may be a much more integrated and democratic unit.

In trying to explain synaesthesia and sensory perception, says Cytowic, researchers in the past have placed too little emphasis on the limbic, or 'emotional', brain. This is a collection of neural structures that lies buried beneath the cortex and has strong channels of communication with other parts of the brain and with hormonal systems. Cytowic believes the limbic system not only has a hand in coordinating communication in the brain, but also determines the salience of the information being processed. Far from being subordinate to the cortex, the limbic system is central to human brain function. He calls this revised model, largely based on the ideas of other neurologists, the 'multiplex' brain. And the quest to explain synaes-thesia, he says, has helped to unveil it.

Scarlet trumpets

Synaesthesia has been a popular medical mystery for almost 300 years. John Locke, the 17th-century philosopher, knew a blind man who described scarlet, a colour he'd never seen, as ' . . . the sound of a trumpet'. An 18th-century English ophthalmologist noted a blind patient who claimed to 'hear' colour. The first systematic study was done by the geneticist Francis Galton, of University College London, at the end of the last century, when he compiled the reported experiences of a number of synaesthetics. Then, for almost a hundred years, with scientists lacking the tools to discover more, synaesthesia fell out of fashion.

Cytowic first encountered synaesthesia in 1980 when he met Michael Watson, a man who boasted of coloured orgasms and could taste the points of a lemony flavour. Vaguely familiar with the condition - from long hours spent in mouldy medical school libraries - Cytowic's curiosity was piqued. The joint mission of doctor and subject to understand synaesthesia forms the backbone of Cytowic's second book on the subject, The Man Who Tasted Shapes. It also prompted him to turn his back on orthodox brain physiology

Just a few years later, a 76-year-old painter from Wales, Elizabeth Stewart-Jones, presented herself to the British Psychological Society. In an intriguing letter, she described her lifelong ability to hear words and sounds in colour. Each word in her vocabulary had its own distinct complexion. Simon Baron-Cohen invited her in for some tests - and has been leading mainstream British research on the condition ever since. He and his team believe that synaesthesia can be explained without overturning the 'division of labour' model of how the brain works.

Both sides agree that the condition is genuine and diagnosable. When Cytowic squirted flavoured liquids onto Michael Watson's tongue, for instance, the res-ponses were both vivid and consistent. Quinine always felt 'like polished wood' and Angostura bitters was 'an organic sphere with tendrils'. Similarly, one simple test with Stewart-Jones convinced Baron-Cohen that synaesthesia was real. He read out 103 words and letters and asked her to describe the colours they evoked. The word 'Moscow', she said, was darkish grey, with spinach-green and a pale blue in places. 'Daniel' was deep purple, blue and red and shiny. By contrast, the control subject gave simple and sometimes predictable responses: 'fridge', unsurprisingly, was white. When retested two weeks later, the control subject replied with 17 per cent accuracy. Stewart-Jones, on the other hand, after 10 weeks and with no prior warning, described every word exactly as she had the first time.

Baron-Cohen published his results in the journal Perception. When he reported the findings in an interview on Radio 4, over 200 women (and two men) wrote in, claiming to have syn-aesthesia - an astonishing response, given that it was a science programme with at least equal numbers of male and female listeners. Others responded to newspaper articles. Anecdotal evidence from this databank of people who claim to have synaesthesia - the London team has the names and details of nearly 600 to date - sketches a portrait of the condition.

Objects of ridicule

The majority of synaesthetics are female. Most have experienced their coloured words, sounds, smells, touches and what-not from as far back as they can remember, and the associations have remained consistent over time. Elizabeth Stewart-Jones's first name, for example, has always been the 'horrid glistening yellow' that it is today. The experiences are involuntary and cannot be suppressed. Synaesthetics don't actively try to taste the colour of spearmint; it just happens. Finally, synaesthetics tend to keep quiet about their sensory spillover. At first believing that everyone perceived the world in this multi-sensory way, most were shocked and embarrassed, some ridiculed, when they learnt otherwise.

Cytowic agrees with the overall sketch but says his sample group of about fifty have a number of other shared traits. Females dominate, he agrees, but by far less - perhaps three times - than the 10:1 prevalence Baron-Cohen and his colleagues suggest. A larger than average proportion, at least 10 per cent and perhaps more, are gay or lesbian, he finds. And there is a preponderance of non-righthandedness. Synaesthetics also tend to have extraordinary memories and they are inclined, he says, to 'unusual' experiences - like deja vu, precognitive dreams and clairvoyance. But they experience difficulties with maths and with finding their way around.

Both teams suspect that synaesthesia has a genetic basis, though evidence is far from conclusive. Baron-Cohen reports that a number of synaesthetics have relatives - every last one of them female - who share the trait.

The particular constellation of traits - difficulties with navigation and maths, the prevalence of females - could prove significant. Some scientists believe that even ordinary men and women show differences in their 'cerebral dominance' - that the left and right hemispheres of their brains have strengths and weaknesses that vary according to sex. Could synaesthesia reflect differences between male and female minds? Toss in the possibility that synaesthetics have a tendency to left-handedness and the puzzle becomes even more intriguing. Most familial traits associated with left-handedness - among them dyslexia and stuttering - are predominantly male. A female trait associated with lefthandedness, says Cytowic, 'is an unusual pattern'.

Though Baron-Cohen has not yet assessed the mathematical and navigation skills of synaesthetics and therefore cannot comment, he has inquired about lefthandedness. 'It would have a direct bearing on neural development,' he says. 'But we haven't found any evidence of it.'

Blood flow

'It's clear that the brains of synaesthetics operate differently,' says Cytowic. 'What we quibble over is the interpretation of this.' The central dispute is over what is happening in the brain when a person experiences synaesthesia. To help answer that question both Cytowic and the London group have turned to imaging blood flow in the brains of people with synaesthesia. Blood flow can be used as a measure of neural activity. Both sides are cautious about the reliability of brain imaging techniques - there is too much scope for error in measurement and interpretation - and tend to consider behavioural in-formation more compelling. Yet it has been brain imaging results that have polarised them most.

In 1981, with the help of David Stump, an expert in measuring brain metabolism, Cytowic induced a synaesthetic experience in Watson's brain using a technique called xenon inhalation. Watson inhaled radioactive xenon gas which quickly dissolved in his bloodstream. The xenon-saturated blood could then be tracked by detectors monitoring 16 different brain regions. The result was a series of snapshots of his brain metabolism. The presumption is that the greater the blood flow the greater the activity.

First, Cytowic and his colleagues established what Watson's brain looked like normally; then they induced synaes-thesia with fragrances such as spearmint and wintergreen; finally, the researchers augmented the synaesthesia by giving Watson a dose of amyl nitrite, a drug that enhances sensuality. What they discovered was astonishing: during synaes-thesia, both with and without the amyl boost, blood flow in the left hemisphere of Watson's brain was greatly reduced, falling as low as three times below an average person's lower limit. There was a slight but insignificant decrease in the right hemisphere. In parts of his cortex, it appeared that the blood didn't circulate at all.

These findings pushed Cytowic further towards the new model. Watson's sensory fusion, he concluded, had not taken place in the cortex, as the standard view might have predicted. Indeed, the left hemisphere of his cortex seemed to shut down during the experience. But while average cortical blood flow had dropped, the brain's overall blood flow had increased. Cytowic drew a bold conclusion: syn-aesthesia took place in the left side of the limbic system, a chunk of brain buried deep in the temporal lobe, and the seat of emotions and memory. If senses merged in the limbic brain, he reasoned, it no doubt played a far greater role in perception than traditional brain theory had so far allowed.

'It's just an idea,' he says, enjoying the ripple of controversy. But a bold idea indeed, considering that the experiment was conducted on only one individual - and an unusual one at that. The xenon inhalation process revealed that Michael Watson's resting blood flow was inhomogenous to begin with and that his hemispheric flow was not symmetrical, which it should be. Moreover, given that it could only measure activity in the cortex, observers would naturally assume that whatever was going on in Watson's brain was taking place in the limbic system. 'We would be cautious about generalising about that (the single case study),' comments Baron-Cohen.

Cytowic is among a growing number of neurologists who see the brain as a multiplex. Alongside the hard-wired circuitry of classical neuroanatomy, say proponents, there are additional channels of electrical and chemical communication. 'Volume transmission', as the usage of these additional channels has become known, is more lax, or 'leaky', than its more physically-contrained counterpart, 'wiring transmission', the brain chatter conducted by axons, synapses and dendrites.

In volume transmission, over fifty messenger molecules, among them hormones and peptides, transmit information through the extracellular fluid surrounding the nervous system, in what is in effect an alternative, chemical network of communication. This kind of transmission makes communication in the brain much more versatile than classically imagined. The speed of diffusion can be slow and the distances travelled long. Cytowic enjoys likening it to travelling along a railway track (wiring transmission) versus leaving the track and floating along unrestrained towards a target. Neural impulses do not flow in the strictly linear, hierarchical fashion traditionalists have long supposed. Rather, information travels in all sorts of ways and in unexpected directions. At the very heart of the process and regulating this cacophony of systems is the limbic brain.

Crossed pathways

The suggestion that the brain harbours some kind of coordination centre is not a new one. Antonio Damasio of the University of Iowa College of Medicine has suggested that recall is reconstructed from numerous fragments of memories, all stored separately within the cortex, but activated in an integrated way. This coordination site, perhaps located in the hippocampus, may even be allowing the brain to 'read' the sensory information that is packed away in the cortex.

Synaesthesia, Cytowic proposes, is an inside peep at this coordination process, which he believes takes place in the limbic brain. He offers the analogy of a television broadcast. Most people perceive only the final picture, but it's as though people with synaesthesia are tapping in prematurely and seeing the picture as it is being formed. The mixing of senses that occurs in the limbic system, he believes, is a 'fundamental mammalian attribute'.

'I believe that synaesthesia is actually a normal brain function in every one of us, but that its working reaches conscious awareness in only a handful,' he writes in his book. In most people, sensory crossovers occur as a normal part of perception without their knowledge. In people with synaesthesia, perception itself is bared to consciousness.

Such are the vagaries of science that about the time his book was being penned, the London team was conducting its own experiments on cerebral blood flow in people with synaesthesia. Its findings, using the more sophisticated positron emission tomography (PET), are somewhat at odds with those of Cytowic. As words and sounds were read aloud to 12 blindfolded subjects, PET scanners mapped the flow of radioactively-labelled blood. The six control subjects exhibited nothing unusual. Blood flow in the six synaesthetics, however, was anomalous: although sound had been the only stimulus, blood seemed to be flowing to areas of the cortex at the back of the head that specialise in vision - and in particular to regions believed to process information about colour. A paper detailing the experiment is currently being reviewed for publication.

The PET results seem to reinforce the idea that synaesthetics' brains harbour unusual neural pathways. Findings from an earlier behavioural test by the same team do so as well. In a test similar to the one given to Stewart-Jones, nine synaesthetics and nine controls were asked to describe the colours of 130 carefully-selected words and sounds. As predicted, controls scored low, around 37 per cent, after only one week, while one year later, the nine synaesthetics were over 92 per cent accurate. But they noted something interesting. Though there was little agreement about the colour of individual letters, three vowels were clearly exceptions: eight of the nine synaes-thetics saw 'i' as white to pale grey, 'o' as white and 'u' as yellow to light brown.

The consensus was striking. The point was further strengthened by the fact that the white 'o' was consistent historically; in 1883 Galton noted it in his group of subjects, as did Vladimir Nabokov of himself in 1966. That there should be consistency not only among subjects but across time suggests that the specialised neural pathways that become inadvertently crossed in synaesthesia are very particular ones.

The question now preoccupying the London team is whether this unusual connectivity develops specially during early life or is simply the relic of a system of pathways that would normally fade away. Research on infants by Daphne Maurer of the University of Toronto indicates that we may all be born with a sort of synaesthesia but grow out of it. Flashing a light in a newborn's eyes does not elicit a clear response from anything akin to a vision centre. Do the same to the average adult and blood clearly flows to the visual cortex. In studies of kittens and baby macaque, researchers have also found examples of neural connections between sensory pathways that disappear as the animals mature.

While other brains mature and segregate, Harrison speculates, the brains of people with synaesthesia retain childhood bonds. Perhaps from among many ways of processing data the synaesthetic's brain chooses fusion over discretion.

Where to from here? Both teams are interested in knowing how learning affects synaesthesia, and vice versa. The London group is launching a study on the pre-literate offspring of people with synaesthesia. They want to know why synaesthesia is so often letter-based, something acquired with literacy, as opposed to sound-based. 'It is counter-intuitive,' says Harrison, because we are exposed to sounds from birth.

'Learning alters the brain,' says Cytowic. Along with culture and environment, what we learn and how we learn, he believes, sets the context for perception. 'We've got perception inside-out,' he says. 'We are not passive receivers. The brain goes out and grabs information, and the limbic system decides what.' Inquiries into how we learn may help explain why only some people experience synaesthesia - or at least experience it strongly. For Cytowic questions whether a distinction should be made between the synaesthetics and non-synaesthetics. 'Perhaps there is a continuum,' he muses.

Living with coloured names

All your life you've enjoyed the scents of foods like roast turkey or oranges or rum sauce. Imagine your surprise if you were to discover that other people could merely taste them. You describe the distinct and powerful 'citrusy' smell of a lemon, but others can't fathom it. For them, lemons only have flavour. You can't believe it. Discovering synaesthesia can be a bit like this.

I was in my late teens when I found out - not so much that I had synaesthesia but that the others did not. I was discussing a short story with my high school English teacher, who wanted me to change the name of a main character. I protested. 'She needs a strong red name,' I said, appealing to reason. The issue of the name was suddenly dropped, and we turned instead to examining the way for me all letters and numbers were endowed with colour. I hadn't known it was unusual. Years went by before I learnt that this habit of mine had a name and, even more exciting, that other people experienced it too.

People ask questions like 'how many times have you experienced synaesthesia?', as though it were a rare psychic encounter, or 'how does it feel?', as though it caused pain. I experience synaesthesia any time words and numbers are around - the way most people detect a smell any time there is a scent in the air - and it feels every bit as natural. A more important question sometimes asked is 'how does it affect your daily life?'

In my case, with the most common and basic form of synaesthesia ('chromatic-graph-emic'), the effect is small. Occasionally, I am unfairly biased against people with 'weak coloured' names - Phil, Lydia, Iona - and in favour of 'strong' ones - Mark, Richard, Sarah. it also serves as an aide memoire: I can quickly commit telephone numbers to memory, can remember important page numbers weeks later and have always been a first-class speller. But for me it has unquestionably had its greatest impact as an ice-breaker: talk of synaesthesia can liven even the dullest of dinner parties.