A NEUROANATOMY OF FLAVOUR G.

Neil Martin
With nearly every bite I take, in the back of my mind there looms the same nagging question: Who is having all the fun? Is it my brain or is it really me? Jeffrey Steingarten, It Mustve Been Something I Ate hat vexed Steingarten was unusual. In his gastronomic best-seller, he recounts how he discovered a mysterious research paper describing a Swiss political journalist who had suffered a stroke and who consequently developed an extraordinarily attentive interest in good food. Before the stroke, the patient was indifferent to food; after the stroke, he seemed to show the punctiliousness of Larousse and Escoffier. He developed what was, to all intents and purposes, a Gourmand Syndrome. The neuroscientists who scanned the patients brain discovered a lesion an area of damage in the right hemisphere or side of the brain. This worried Steingarten. Was his own gourmandery attributable to, well, brain damage or, at the very least, mild neural dysfunction? Eating disorders resulting from brain injury are quite rare, although they are easy to induce experimentally (by deliberately damaging brain regions in non-human subjects). Eating disorders that would be considered unusual are even rarer. Picas Disease, for example, involves a pathological craving for highly unsuitable foods. Other types of neurological injury can result in phantageusia (experiencing imaginary tastes, phantoms), phantosmia (experiencing smell phantoms), dysgeusia (distorted taste sensitivity), dysosmia or cacosmia (distorted olfactory perception and the perception of smells as unpleasant, respectively). These disorders have common causes: head injury, respiratory illness and so on. Developing a (previously absent) Pangean interest in food, 58

though, is uncommon. The researchers who studied the patient that sparked Steingartens cerebral quest went on to discover that 36 of their patients showed similarly pathological cravings for high-quality food. To put his mind at rest, Steingarten had his own brain scanned and found that there was slight scarring to the right side of his brain (and slightly enlarged ventricles, the cavities inside the brain). This, however, is not unusual. Many of us have more or less of a particular part of the brain: there is often considerable variability in neuroanatomy from person to person. But it left Steingarten wondering whether his neurons dictated his obsession. There is a sizeable body of good scientific research to demonstrate that certain regions of the human and non-human primate brain are more involved than others in the process of eating, and in appreciating flavour. This research has emerged not only from experimental animal work (where the activity in individual brain cells is recorded directly via strands of electrodes) but also from studies of humans, using fairly sophisticated neuroimaging machines: expensive hulks of equipment that record activity surrounding active neurons while a person is engaged in some task such as sniffing, tasting, swallowing, thinking, reading and so on. This research suggests that one specific region mediates human response to the sensory properties of food and another to the hedonic or emotional quality of food (whether we find it pleasant or unpleasant). It also suggests that one region may be the place where smell and taste converge: where the human brain processes flavour. In his chapter on smell and taste in A Kipper With My Tea, Alan Davidson, after several pages of entertaining aperus about smell and taste, ended by being defeated by describing flavour. He wrote: At this point, it will be apparent that if tastes are married to aromas, as they are to produce flavours, the whole problem of the description becomes even more difficult. And here I stop. But we can re-commence the journey that Davidson prematurely concluded. Food flavour has been defined as the combination of olfactory 59

(smell) and gustatory (taste) sensations, although many sensory scientists also include mouth feel/texture and food temperature as important factors in flavour. Smell and taste are the Titans of flavour and are chemosenses: their receptors respond to molecules. Common misunderstandings arise from not knowing much about the chemosenses, especially the sense of smell. Not for nothing is it known as the Cinderella of the senses. If people are asked to select which sense they find least important, the sense of smell is routinely regarded as the least important of the five (Martin, 1999; Martin et al, 2001). It is, in fact, responsible for 80 per cent of food flavour, a fact that is largely unknown and elicits a degree of disbelief.
SMELL: A USERS GUIDE

The nose has two openings or nares which allow airborne molecules to enter. These nares, called anterior nares, are those we know as our nostrils. Another set of nares, called posterior nares or choana, are found at the back of the throat. Molecules, therefore, have two ways of reaching olfactory receptors: through the nostrils or through the back of the throat. The back of the throat also contains nasopharyngeal receptors which can pick up odour molecules. This is why a person can pinch their nose and still be able to identify an odour of a food placed on a spoon near the entrance of the mouth when he or she is breathing in. Slurping without swallowing also produces good olfactory reception and chewing liquids (such as wine) is oenologically advantageous because it releases more volatile molecules from the drink. If olfactory receptors fail to work (as they do when we have a cold or flu) we are unable to identify food. We are able to perceive a foods taste whether it is salty, bitter and so on but not its smell. This arrangement suggested to Moncreiff (1967) that if a persons eyes and nose were closed , they may not be able to distinguish between two very different foods. Apple and onion, for example, ought to be indistinguishable because the principal olfactory route is closed. Although the olfactory system is 60

malleable, it is not that malleable. In an experiment published in 1939, Kahn found that people could distinguish between red wine and unsweetened black coffee because the red wine felt lighter and lacked coffees astringency; between raw apple and potato because one tasted sour; and between tomato and orange for the same reason. Diluted raspberry juice and sweetened milk, however, were indistinguishable. Similarly, so were milk with sugar and milk with vanilla sugar. The olfactory receptors lie in a gloop of mucosa inside and at the top of the nose, just behind and above the bridge. In humans, they occupy around a few centimeters squared; in dogs, they occupy a relatively larger surface area. The mucosa serves the useful purpose of filtering undesirable molecules and foreign bodies. It also contains a mesh of tissue called cilia which contain the olfactory receptors. These receptors send signals onward to structures called the olfactory bulbs. The bulbs look like very small deflated balloons and are located under the front of the brain above the eye sockets. Because of their positioning, Varney (1995, cited in Callahan and Hinkebein, 1999) has likened them to two wet match sticks on a cheese grater. These organs are responsible for the first analysis of olfactory information; this is where olfactory sensation elides into perception. From the bulbs onwards, signals are sent to various regions of the brain, including the olfactory nerve, parts of the brains large surface (the cortex) and regions beneath this surface, including a structure called the thalamus. The thalamus is the brains relay station for all incoming sensory information. It projects to two other important structures: the hippocampus, a structure involved in memory formation, and the amygdala, a mysterious little structure that seems to be involved in monitoring the environment for danger or stimuli that are best avoided (amongst other functions). It, for example, is involved in the conditioning of fear, and people with damaged amygdalae cannot recognize expressions of fear in faces or voices. The hippocampus and amygdala are two structures in what is called the limbic system: a collection of structures beneath the cortex which are largely 61

involved in basic motivation (hunger, sex, thirst and so on). They also formed what was once called the rhinencephalon or smell brain, a term that is no longer used. Confusingly, odour molecules also stimulate another of the brains cranial nerves: the trigeminus. This, the fifth and largest cranial nerve, extends across the face and responds to chemical stimulation: the lachrymal response to peeling onions and the flooring effect of a whiff of ammonia are attributable to stimulation of the trigeminus. Almost every odour is thought to stimulate the trigeminus (because of the molecules) but only one odour is thought to stimulate the olfactory nerve without trigeminal stimulation (vanilla and nobody knows why). The trigeminal nerve sends signals contralaterally. That is, stimulation of the left side of the nerve activates the right side of the brain, and stimulation of the right side activates the left side. The olfactory nerve operates ipsilaterally: it does not cross over like the trigeminus. Left stimulation, therefore, leads to signals being sent to the left side of the brain. What happens to olfactory information at the level of the brain is more interesting, largely because we are not exactly sure what happens. This curio is returned to later.
ONE NOSTRIL OR TWO? Because the olfactory systems direction is ipsilateral, some early research into the sensitivity of each nostril concluded that one might be more receptive than another. For example, an odour presented to the left nostril might be named more quickly than one presented to the right because the left hemisphere holds the areas responsible for speech and language processing. Similarly, the right hemispheres reputation as the hemisphere for emotion (a reputation that is almost completely without foundation) was thought to result in odours being responded to more emotionally if they were presented to the right nostril. Evidence for both propositions is mixed, however, and one reason for the inconsistency may be that it is not the nostril stimulated that is important but the air-flow to that nostril.

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Recent research has shown that the flow of air in one nostril is greater than that in the other because of swelling inside the nose. However, this asymmetrical difference in air-flow changes every few hours: it switches from left to right and back again (Sobel et al, 1999). This means that the perception of an odour depends on the degree of air-flow through the nostril at that time. In this way, odour perception in one nostril can be less or more potent than that found in the other. Most brain research with human participants involves birhinal stimulation (the odour is presented to both nostrils). What few studies, until recently, have considered is that the act of smelling is also a motor act: it involves sniffing and this sniffing determines the strength of the smell we perceive. Two recent studies have attempted to unpack the effect of sniffing from the effect of smelling at the neural level. These studies suggest that different regions in the brain mediate the two types of activity. In one study, nine men and eight women smelled either low or high concentration levels of vanillin or propionic acid (which stimulates the trigeminus) or they smelled unscented air (Sobel et al, 1998a). Both odours produced activation in both hemispheres of the brain towards the back and at the sides (the temporal lobes) and this activation increased with increased odour concentration. When participants sniffed unscented air, however, activation in a different brain region (the cerebellum) was found. This structure is important for motor control and it allows us to maintain our sense of balance. Research is also beginning to show that it plays a role in thinking and in reading-disorders but its principal function seems to be a motor one. In a related experiment, Sobel et al (1998b) found that two odours were also associated with activation at the side and front of the tip of the brain. The researchers proposed that this area thus represented the primary olfactory cortex in humans, an area that has been well described in animals but poorly studied in humans. They also suggest that the claimed olfactory deficits in Parkinsons Disease patients reported in the literature may not actually reflect a deficit in smelling but in sniffing: in these 63

patients, the inability to engage effectively in a motor behaviour, such as smelling, may result in less of the odour being processed.
TASTE: A USERS GUIDE

We know as much about the neurophysiology of taste as we do odour: some, but not much. Tastes primary role is to warn the gut of what it is about to receive. Like smell, it seems like more of a danger warning signal device than a sense for pleasure. Taste appears to be an easy sense to manipulate. Studies have shown that if infants are fed sweetened water at six months, they will prefer sweetened water at a year and a half (those not fed sweetened water find it too sweet six months later); a similar phenomenon is seen when infants salt intake is modified. This has suggested to some people that we are not that genetically programmed to respond to taste and that environment can shape our perception of taste in very marked ways. Around 70 per cent of children on chemotherapy reported a flavour aversion to a previously-liked food once the nausea-inducing treatment had started, for example. The one taste which does seem to be genetically hard-wired is bitterness. Recent research has shown that taste cells may respond to different bitter tastes differently 65 per cent of cells responded to one type of bitter stimulus, 25 per cent to two and 7 per cent to three (Caicedo and Roper, 2001) which suggests that there is not a general response to bitterness but that there is some specificity in the system. Receptors for taste lie on the tongue and around parts of the mouth. Unlike the historical portrayal in many textbooks, there is no clear demarcation of taste on the tongue. Sweet isnt exclusively and invariably localized in the tip of the tongue, for example. The picture is a lot more complicated. Different parts of the tongue can sense sweetness, saltiness, bitterness, sourness and umami (more on umami later). There are between 2,000 to 10,000 taste buds, clustered in fifties on little processes called papillae. These turn over every few days so that the taste receptors you have today will not be the ones you will use next week (the supporting cells on the tongue divide). The buds are 64

covered in skin cells except for an outer pore. The bud contains hair-like filaments called microvilli: these send gustatory information to, ultimately, the brain. A food mixed in saliva on the tongue will stimulate the taste receptors which, in turn, fire signals to the brain via three cranial nerves. The front two-thirds of the tongue project to the facial nerve; the back of the tongue to the cranial nerve and other parts of the mouth to the vagus nerve. Nerve fibres called axons then forward the signal to a part of the brain stem (at the base of the brain, where most cranial nerves originate), then to the sensory relay station (thalamus) and then to two regions on the surface of the brain. These two brain regions are thought to be the ones responsible for perceiving flavour and the evidence for this in humans has come from neuroimaging research.
NEUROIMAGING: A BRIEF TUTORIAL

Neuroimaging studies measure, broadly, either brain metabolism and glucose consumption (using Positron Emission Tomography/ PET) or blood flow (using functional Magnetic Resonance Imaging/fMRI). The general principle behind both techniques is that active neurons expend greater energy and, therefore, attract greater blood flow and oxygen (which is available to functionally active cells and may or may not be used by them) than do inactive cells. Because PET and fMRI scanners measure the take-up of glucose or oxygen in functionally active neurons, they are regarded as measures of brain activation (although, strictly, they do not measure the activity of brain cells). Other neuroimaging techniques include Computerised Tomography (CT) and Magnetic Resonance Imaging (MRI) but these measure brain structure rather than neural or neurophysiological function (Martin, 1998a, 2003). The brain is conventionally divided into four neurogeographical regions called lobes. The anterior third, and the most developed, is the frontal lobe. Using neuroimaging techniques, studies have found that one area in the frontal lobe responds to the sensory properties of the taste of food; another, nearby area 65

Premotor Cortex Prefrontal Cortex

Precentral Cortex

Orbitofrontal Cortex

A view of the left side of a human brain. The frontal lobe occupies the area in front of the black line in the middle. The orbitofrontal cortex, the area suggested as the brains flavour centre, is located at the tip of the frontal lobe.

appears to be active when we make a psychological response to food such as perceiving its pleasantness. Many of the studies of the taste cortex and its response to the pleasantness of food have arisen from behavioural experiments investigating a familiar food-related phenomenon sensory-specific satiety.
CLUES TO FLAVOUR: SENSORY-SPECIFIC SATIETY

Sensory-specific satiety refers to the decrease in the pleasantness and consumption of specific food after eating it to satiety. The satiety is sensory-specific because individuals may become sated eating foods of specific tastes, shapes, sizes and textures but not foods of different taste, shape, size and texture (E.T. Rolls et al., 66

1986). This phenomenon explains why, if we eat a meal composed of a variety of specific foods, we eat more of it because there is greater sensory stimulation available from a varied meal (say, a bowl of soup, sausages, egg and bacon, and chocolate mousse) than a big plate of sausages. Sensory-specific satiety also has survival value because if we become bored with eating one food but not another, this increases the likelihood of a variety of foods being eaten. Much of the work on sensory-specific satiety has been conducted by Edmund and Barbara Rolls and their colleagues from the Universities of Oxford, England, and Pennsylvania State, USA. A common finding in SSS research is that if a food is eaten to satiety, then a second course of the same food will result in a reduction in intake of around 50 per cent (B.J. Rolls et al., 1981). In the Rolls early experiments, all foods with the exception of roast beef produced sensory-specific satiety. In one experiment, participants ate either a four-course meal of sausages, bread and butter, chocolate dessert and bananas or ate only one of these foods to satiety. The researchers found that consumption was 60 per cent higher when foods were presented together than when presented singly, in one course (B.J. Rolls et al., 1986). At a postsatiety tasting session, those foods presented singly were also rated as less pleasant than those eaten as part of a four-course meal (B.J. Rolls et al., 1984). Even colour and shape influence the amount of food eaten. When a variety of pasta shapes and sandwich fillings were presented for consumption, more was eaten than when only one pasta shape or one filling was presented. Similarly, more food was eaten when it varied in colour than if it was just one colour (B.J. Rolls et al., 1982). Sensory-specific satiety is unrelated to the calorific or nutritional content of the food. Rolls and Rolls (1997) found that even when participants chewed a food for as long as possible but were instructed not to swallow, they showed evidence of sensoryspecific satiety. Participants regarded the food they chewed until they were fed up with it, as unpleasant but they rated an unmasticated food as comparatively pleasant. 67

Even the smell of eaten food is regarded as less pleasant when the food is eaten to satiety, whereas the odour of unconsumed food remains unaffected. In an experiment where participants were asked to rate the pleasantness of the odours of banana, satsuma, fish paste, chicken and rose-water before and after consuming bananas and chicken to satiety, the pleasantness of chicken and banana odours (but not other foods) declined significantly after satiety (Rolls and Rolls, 1997). Curiously, the mechanism underlying sensory-specific satiety may also underlie the pleasure we receive from the taste of food.
TASTE AND THE BRAIN

Studies have shown that when macaque monkeys are fed glucose, neurons in a region in the front of the brain the primary taste cortex become highly responsive. Neurons in a nearby area the secondary taste cortex are also activated. However, when the monkey is fed the glucose to satiety, the responsiveness of the second area decreases. When the monkey is fed a food which it has not previously eaten (such as blackcurrant juice), neurons in this second area become responsive again. Similarly, when the monkey is fed blackcurrant juice to satiety and is then presented with (previously uneaten) glucose the same pattern of responsiveness and non-responsiveness is seen in this taste area. The increase and decrease in the activity of taste neurons is also found when the monkeys see the food they have eaten to satiety. Critchley and Rolls (1996) found that the responsiveness of 7 out of 9 neurons decreased to blackcurrant juice after eating it to satiety but that 8 out of 9 neurons also decreased when the monkey saw the food. When we eat food to satiety, it still has a flavour and it still imparts a psychological effect but we find it less pleasant. There are only so many sausages we can eat in one session but we will happily consider a bowl of ice-cream after becoming sated on ground pork. Current neuroimaging research suggests that the primary and secondary taste cortices are active when a person tastes a food (but does not eat to satiety). However, as satiety deve68

lops, activation in the primary taste cortex remains fairly stable but activation in the secondary taste cortex decreases. What this suggests is that one region in the brain responds to the sensory qualities of food (taste, texture, smell) but another, more sophisticated, area is responsible for our hedonic response to food. The part which responds to the sensory properties of food the primary taste cortex occupies an area towards the back of the frontal lobe. The secondary taste cortex occupies a part of the frontal lobe called the orbitofrontal cortex (OFC). Psychologically, the OFC is a very interesting region. It is considered to be the region of the brain that is responsible for the inhibition of inappropriate social and emotional behaviour. Damage to this region causes a panoply of social gaffes and problems: patients have difficulty ordering sequences of events, have difficulty in following sequential instructions and, frequently, report becoming more coarse, careless and thoughtless than they were before the injury. It is as if the damage has snapped the rope that tied the box that contained the thoughts and behaviours regarded as unacceptable. Pertinently, damage to this region also leads patients to forget important steps when following recipes (Fortin, Godbout & Braun, 2003). Like all other brain regions, however, the OFC is also involved in other behaviours (such as memory), but its role in emotion and pleasure is one of the more interesting. Neuroimaging has allowed researchers to investigate whether it responds to the taste of various foods and drinks including water, fat, umami and chocolate.
WATER

Like food when we are hungry, water is pleasant when we are thirsty. Similarly, when our thirst is slaked, the pleasantness of water wanes. The limited research available suggests that the same brain regions that become more or less active during satiety to food are similarly more/less active when water is drunk to satiety. Neurons in the primary and secondary taste cortices in macaque monkeys respond to water when the monkey is thirsty but activity in the secondary taste cortex decreases when the 69

monkey has drunk to satiety. De Araujo et al (2003a) recently described an experiment in which a group of participants drank water to satiety as an fMRI scanner measured participants brain response throughout. They found that the sensation of water in the mouth was initially associated with activity in the primary taste cortex and the OFC; this activity in the primary taste cortex remained stable even when the participants thirst was slaked. When the water had been drunk to satiety, however, activation in the OFC decreased. This decrease correlated with ratings of the waters pleasantness: as the water became less and less pleasant, activation in the OFC decreased. Kringelbach et al (2003) also used fMRI to measure changes in activity in the OFC as participants drank chocolate milk or tomato juice to satiety. The typical OFC decrease was found when chocolate or tomato was ingested to satiety, highlighting the role of this region in mediating satiety.
FAT

Fat is an important food for a myriad of reasons, some of which are health-related. Fat consists of triglycerides and free fatty acids (FFA) such as saturated, monosaturated and polyunsaturated (the three classes of FFA). All natural oils, such as sunflower oil and coconut oil, consist of triglycerides and contain few FFAs. FFAs are often used as flavour enhancers and to create artifical flavours. The flavour of blue-mould cheese derives partly from the volatilty of FFAs. Foods that are high in fat may not produce the same degree of satiety/reduction in hunger that foods high in carbohydrate or protein do. Importantly, for the phenomenology of eating, fat adds texture to foods. Its contribution to mouth-feel, as sensory scientists describe it, is very important and leads to foods being described as creamy, smooth, juicy, viscous or greasy (or combinations thereof). An interesting question that arises from this oleagenous function is whether the pleasure we receive from fatty foods is due to the actual fat content or to the texture. To try and answer this, a group of psychologists at Oxford 70

University recorded the activity of single neurons in the taste cortices of macaque monkeys as the animals tasted a food that was viscous but contained no fat, and fatty foods that were viscous (Verhagen et al, 2003). The group found that a set of neurons responded to the texture of fat and a separate set responded to the viscosity of the food (which contained no fat). This finding suggests that two separate regions of the OFC respond to aspects of fatty food: one which mediates the response to fat (what we might call the neurochemical response) and another which mediates the response to the texture of fat (its viscosity).
UMAMI

The fifth taste, first reported in 1909 by Ikeda, is found in various foods such as meat, mushrooms, some fish, cheese and tomatoes (as well as human breast milk). The chemicals glutamate and 5nucleotides are probably the components in these foods that make up the umami taste. Other, chemical, examples of stimuli that create the umami taste are: monosodium L-glutamate (MSG), GMP and inopsine 5-monophosphate (IMP). It was once thought that umami worked by enhancing the flavour of other tastes. To some extent, it does, but it also exists as a distinctive taste in its own right. Experiments in the 1960s and 70s found that adding the taste of umami to a variety of foods did not lower or increase the thresholds of other tastes: if umami was added, salty tastes were not perceived as more or less salty. Studies of primates indicate that specific neurons in the primary taste cortex respond to umami (MSG) but not to other tastes (such as glucose, quinine, hydrogen chloride or sodium chloride, the classical gustatory tetralogy). Neurons that respond to glutamate respond relatively poorly during the perception of salt (Rolls and Baylis, 1994). This suggests that umami may be as well represented in the brain as the other four tastes, although this idea remains controversial. Neurons in the secondary taste cortex/OFC that are responsive to umami become unresponsive when the food with this taste is eaten to satiety. Even a picture of the syringe which delivered the umami 71

produces a decrease in these neurons in primates who have eaten glutamate to satiety. In a recent neuroimaging study where people were fed MSG, IMP , glucose or a combination of MSG and IMP, the umami tastes activated similar areas to glucose: the prototypical taste areas (de Araujo et al, 2003b). However, when the two umami components were combined, activation in the front of the OFC increased, highlighting an important feature of umami: its components are synergistic. If you add one to another, the taste is stronger (Rifkin and Bartoshuk, 1980).
CHOCOLATE

When we eat a chunk of chocolate, we usually want another, then another. Eventually, however, we will lose interest in eating any more because the reward value of the food is reduced: we dont receive any pleasure from eating it any more. Given the research described earlier, we might expect to see changes in activation in the OFC as the chocolate becomes less pleasant to eat. In a recent PET study, volunteers ate chocolate to satiety as the scanner measured brain activation (Small et al, 2001). Participants first ate a chunk of chocolate, rated it for pleasantness and were then asked if they would like another. If they did, they were given another piece and asked to rate its pleasantness. This continued until the participant indicated that he or she had eaten enough chocolate. The researchers found that when participants ate chocolate they judged as pleasant, there was increased blood flow in a collection of brain regions including: areas beneath the corpus callosum (the band of fibres that connects the two sides or hemispheres of the brain), a part of the OFC (called the caudomedial OFC), and three other regions. When participants were sated, blood flow increased in a different part of the OFC (the caudolateral OFC) and another region (one also involved in the ability to recall landmarks). The researchers suggest that brain activation seen during ingestion of chocolate reflects two different systems which, in 72

turn, mediate two different aspects of behaviour: approach and withdrawal. When the brain responds to a reward positively, it activates the part of the OFC and another region implicated in reward and found in the frontal cortex (the insula). This reflects an approach behaviour because we tend to approach things we like and this generates a positive emotion. When the brain responds to non-reward or stimuli that do not provide an opportunity for reward (such as food we no longer want to eat), brain regions involved in withdrawal are recruited. These are involved in withdrawal because we tend to withdraw from stimuli we dont like and we find such stimuli unpleasant (or at the very least, do not find them pleasant). This is an interesting hypothesis because it is in keeping with a current model of emotion which argues that the frontal cortex is the region that becomes active during the experience of positive and negative emotion: the left frontal part becomes active when we experience positive emotion; the right frontal part becomes relatively active (and left becomes less active) when we experience negative emotion. This hypothesis is muddied slightly by the behaviour of one sense: the sense of smell. Studies like these examine the role of the brain in responding to pleasant food that is eaten to such an extent that it becomes less pleasant. Would a categorically unpleasant taste result in a reduction in the same frontal brain area as that which becomes less active as a food is eaten to satiety? Research is, oddly, sparse and what there is is inconclusive. One PET study found that the left OFC and amygdala were active during the perception of an aversive taste (highly salted water) but this activation was not seen consistently. In another study, glucose and salt both activated parts of the OFC (and the amygdala). The only general conclusion we can draw from these studies, therefore, is that if we taste a food that is distinctively pleasant or unpleasant, this perception is associated with increases in the part of the brain that responds to the taste of food and to feelings of satiety.

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SMELL AND THE BRAIN

The current research on the neurophysiology of smell in humans has been guided by studies of the effect of brain damage on olfactory perception. These studies highlight the role of the temporal, and more often the orbitofrontal, cortex in peoples ability to identify and detect smell. Damage to the right temporal and orbitofrontal cortices results in impaired odour memory (Jones-Gotman and Zatorre, 1993). Discriminating between odours becomes difficult when lesions are made to the same areas. If the frontal lobe is removed during surgery (to excise a tumour, for example), the ability to identify an odour will be relatively preserved if the OFC is spared but will be impaired if it is not. In one of the first neuroimaging experiments of odour perception in humans, Yousem et al (1997) exposed five men to the un-food-like odours of eugenol, geraniol and methyl salycilitate (what they referred to as olfactory odours) and ylang ylang, patchouli and rosemary oil (trigeminal odours). They found that the olfactory odours activated the right OFC but the response decreased with repeated stimulation. Trigeminal stimulation and repeated testing with the olfactory odours activated different parts of the brain, including the temporal lobe. The heterogeneity of brain response is common in studies of odour: Smelling activates a range of brain regions, some more potently than others. Levy et al (1998) compared brain activation in eight patients with decreased sensitivity to smell (hyposmia) and 17 healthy participants while they smelled pungent pyridine, l-menthone (peppermint) or amyl acetate (banana). Activation in healthy participants was found in the back of the OFC and the temporal lobe; similar activation was also seen in the hyposmic individuals but not as significantly as that seen in the healthy group. The greatest decrease was found in patients who detected but did not recognize the odours and this was found in the frontal lobe. Studies using odours that are relevant to cuisine have focused on how the brain responds to pleasant and unpleasant smells.

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WHERE THE BRAIN PROCESSES UNPLEASANT AND PLEASANT ODOUR

In an experiment where researchers had participants smelling the odour of banana and peppermint or simply imagining these smells, both sides of the OFC and the temporal cortex were activated. Activation during actual smelling, however, was greater than that seen during imagination, which suggests that similar areas are used for both activities but that the degree of involvement is greater during actual perception. Studies of individuals who experience smell and taste phantoms show greater activation during actual smelling and tasting than when they experience their imaginary smells and tastes. In a different study, left brain activation was greater than right when imagining and smelling the odours of peppermint and banana. A sex difference was found when participants smelled an unpleasant odour, however: rightsided activation was more common in men when they smelled pyridine. Greater activation has also been observed in younger participants (24-year-olds) than older individuals (73-year-olds) frontal lobe and related regions when these people smelled. The link between the frontal lobe and pleasant smells was highlighted in another of Rolls experiments (E.T. Rolls et al 2003). His group presented men and women with a range of pleasant and unpleasant smells and recorded brain activation as these odours were smelled. Pleasant smells were associated with activation in a part of the OFC we know responds in monkeys when they receive a reward for making an appropriate response. Different regions (the cingulate cortex) were activated by unpleasant and pleasant odours. In experiments by others, increases in the amygdala were found as odours increased in intensity. Really offensive odours were associated with significant activity in the amygdala and the left OFC. Mild to moderate aversive odours were only associated with increased activation in the OFC. This would suggest that the perception of a really potent odour such as Devils Dung (asafoetida) or of a fetid cheese such as the Stinking Bishop, will activate this small, subcortical structure, possibly because it is responsible for monitoring and responding to stimuli in the environment that are emotionally 75

very powerful and may need to be assessed for the harm that they could do. The brain, of course, is an electrical organ and we can measure its electrical behaviour either by recording from individual neurons/groups of neurons using minute electrodes or by recording from millions of neurons using 1 cm diameter electrodes placed on the scalp. When the electrodes detect electrical activity, this is fed through software that generates a brain wave or electroencephalogram (EEG). This EEG is conventionally divided into 4 wavebands or frequencies: from slowest and largest to fastest and smallest, these are delta, theta, alpha and beta. Alpha is the dominant, resting adult EEG, best seen in people who are relaxed and have their eyes closed. No one quite knows what EEGs and changes in the EEG frequencies represent, but some frequencies appear to change more reliably than others under certain conditions. The most obvious of these is the change to slow wave EEG during deep sleep. However, the EEG also responds to sensory stimulation, including odour. Moncrieff (1962) observed that almost all of the odours, apart from ylang ylang, presented in his experiment were associated with a general reduction in alpha activity. More recent studies have found that odours either reduce EEG alpha or theta activity or leave them, and other frequencies, unchanged (Lorig and Schwartz, 1988; Klemm et al, 1992). In one study using three different odours and four electrodes, greater decreases in activity were found in the theta frequency, especially in right frontal and left posterior areas, when people smelled the odour of spiced apple than the odour of lavender (Lorig and Schwartz, 1988). Other authors have reported selective increases in theta activity during exposure to birch tar, jasmine, lavender and lemon (Klemm et al, 1992). In two experiments comparing the human brains response to real and artificial food odours, Martin (1998b) found that theta activity was significantly lowered when people smelled the odour of chocolate (compared to baked beans, rotting pork, coffee or steam). Increases in theta activity are seen when people concen76

trate on challenging intellectual tasks and when people try and remember material (that they later successfully recall). When tasks are easy, or when people are distracted from these tasks, theta activity decreases. The smell of chocolate in this experiment seemed to be associated with a reduction in a type of EEG frequency that usually characterizes attention. Given that the odour of chocolate was rated the most pleasant and relaxing (and, therefore, generated distraction and a lack of concentration), this would make theoretical sense.
SMELL AND TASTE: WHERE DO THEY CONVERGE? What we seem to have learned so far from all the neuroimaging data and the studies of neural activity in monkeys is that the most likely locus of food flavour perception in the brain is the frontal lobe. Of course, this apparently exhaustive (but actually relatively brief, given the number of studies published) review of the brain mechanisms underlying taste and smell has been just that: a review of taste and smell. But, as we have seen from the studies of fat, touch is also an important determinant of food flavour. As the studies of satiety showed, visual stimulation is additionally important, although this is perhaps a more important contributor to hunger and satiety than it is to food flavour per se. What is intriguing, however, is that the key area involved in smell and taste the OFC appears to contain neurons that are unimodal and multimodal. That is, they are either responsive to one type of sensory stimulation (smell or taste only, say) or to more than one (such as smell and taste or taste and vision). Extensive studies are rare, but one very provocative study found that in the OFC taste area, 34 per cent of neurons were responsive to a stimuluss taste only, 13 per cent were responsive to its smell and 21 per cent to its appearance (Rolls and Baylis, 1994). However, 13 per cent also responded to smell and appearance, 13 per cent to taste and smell and 5 per cent to smell and appearance. All of these neurons were in close proximity. This arrangement although based on a study of a very small number of neurons suggests that there are brain cells that

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appear to respond only to taste and smell (and these are important responses) and nearby cells that undertake an interactive, multi-sensory role. Significantly, there were fewer bi-modal neurons (those that respond to smell and taste) in the primary taste cortex the area that responds to the sensory aspects of food than in the OFC. This finding, again, seems to highlight the importance of this region to a more sophisticated analysis of food perception. Perhaps, this is the region where smell and taste sensations are combined to produce the effect we call flavour. Could this be the region where the perception of the smell and taste of muffins, hollandaise, ham and poached eggs combine to provide the luxurious and unmistakeable flavour of eggs Benedict?
CODA

This guide to the neuroanatomy of flavour has limited itself to that domain: neuroanatomy. There are other topics, such as the role of brain regions involved in hunger, the system or systems involved in triggering hunger and in regulating glucose levels (which seem to trigger hunger), and the neurotransmitters involved in taste and smell perception, that go beyond this review. These are large areas in their own right and deserve other articles to themselves. This guide is also cautiously titled, A neuroanatomy rather than The neuroanatomy because every scientific discovery is subject to potential contradiction and revision. The curious, and most illuminating, contribution of this area of the study of food perception is its ability to show us the human brains response while a person smells, tastes and ingests food. Traditionally, studies of smell and taste have been slow to emerge relative to the sense of vision, which dominates neuroimaging studies of the senses. Possibly, this is because there is a more pressing need to understand the sense of vision than those of olfaction and gustation. Blindness is a more significant and common psychological blight than is anosmia, for example. But there is a growing caucus of researchers interested in finding out more about how we perceive food flavour and how the brain converts the sensory signals it receives into the impressions 78

and feelings we experience; in how the neuroanatomy is converted into psychology. Weve come a long way since 1892 when one of psychologys founding fathers, William James, said of the food lovers prized possessions: Taste, smell, as well as hunger, thirst, nausea and other so-called common sensations need not be touched onas almost nothing of psychological interest is known concerning them. Over a hundred years on, however, we know a considerable amount about them. Chefs such as Heston Blumenthal, Ferran Adria and Herv This are exploiting psychological and other types of scientific research to create new, psychologically challenging eating experiences. Commenting on the phenomenon whereby sugar can bring out the flavour of certain savoury nuts such as almonds and pistachios, for example, Blumenthal concluded, All that remains to find out is if theres real chemistry going on here, or if its all in the mind. Which, in a way, is where we came in.

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