Neurogastronomy: How the Brain Creates Flavor and Why It Matters

The most important ultimate function of the human brain flavor system is making the right choices in consuming healthy or unhealthy food. The key to making these choices lies in the decision-making mechanisms of our brains, which only recently have begun to be recognized. Interest in these mechanisms has merged with the interests of economists, who for many years have realized that people make economic choices that are based on their value judgments about what they like. I first became aware of this when my father, Geoffrey Shepherd, wrote an article about it in 1956. This merging of interests of neuroscientists and economists has given rise to a new field called neuroeconomics, a term coined by Paul Glimcher in his book Decisions, Uncertainty, and the Brain: The Science of Neuroeconomics.

We have already met elements of the decision system in considering emotions and in the actions of dopamine on the subsystems we have studied thus far (chapter 19), as well as on the factors that lead to obesity (chapter 21). We bring them together here to enable us to enlarge the human brain flavor system to include the mechanisms that determine whether we eat in healthy, and flavor-fulfilling, ways.

One of the molecules that is key to how our brains work is the neurotransmitter dopamine, which was introduced when we discussed emotions in chapter 19. The largest population of dopamine-containing neurons is in the midbrain—far away, you might think, from the highest levels of brain activity. However, from this vantage point these neurons send their axons throughout the brain. Some of them go to the striatum, a large region under the cerebral cortex that is involved in planning, initiating, and carrying out movements as well as in various motivational states; we have already met the striatum in chapter 19 as part of the system of habits for food cravings. Most people have heard about these dopamine cells because of their role in Parkinson’s disease, in which the degeneration of these cells and their subsequent loss of input to the striatum results in progressive paralysis.

The other important concentration of dopamine neurons is located in what is called the ventral tegmental area (VTA). These cells connect widely in the brain. Especially relevant to the flavor system are parts of the striatum, the prefrontal cortex (including the orbitofrontal cortex), the insular cortex (where smell and taste are combined), the nucleus accumbens, the amygdala, and the hippocampus. These VTA–dopamine connections form what is called the reward system of the brain. The experiments providing evidence for this have been carried out in rats, monkeys, and humans and often involve the subjects working for rewards of fruit juice, so the subjects essentially are motivated by the images of retronasal smell and flavor.

We have already met Wolfram Schultz in chapter 19 as a leader in studying these dopamine reward systems. In a typical experiment in his laboratory, a monkey explores for hidden food; when a hidden bit of cookie or another food is touched, the dopamine cells release a burst of impulses. In another type of experiment, the dopamine neurons fire a burst of impulses when the monkey is stimulated by the reward of water or fruit juice. The dopamine neurons fire to any rewarding stimulus (discriminating between the stimuli is done by the sensory systems). In his early experiments the cells did not respond to aversive stimuli, such as water that was too salty; the reward needed to be pleasurable. Recently some responses to aversive stimuli have also been found. Of special interest is the fact that dopamine neurons fire to conditioning stimuli, such as a light that signals a future reward. This means they are able to predict future rewards. This ability constitutes one of the highest cognitive functions of the brain. The dopamine neurons do this through their modulation of the cells in the orbitofrontal cortex that are involved in planning future actions. Which brings us back to the human brain flavor system.

These functions modulated by dopamine are important for all sensory systems, but especially so for flavor. The dopamine fibers not only connect from the midbrain to the olfactory cortex, where they can modulate the formation of odor images and odor objects there, but also to the orbitofrontal cortex. In addition, in the olfactory bulb there are dopamine-containing interneurons (some of the periglomerular cells), so that dopamine can be involved in the shaping of the initial smell images in the glomerular layer. Another connection between smell and dopamine is found in the neurodegenerative diseases such as Parkinson’s and Alzheimer’s; an early sign of these diseases is a decline in smell sensitivity.

Through its role in reward systems in the brain, dopamine is also involved in the brain mechanisms underlying drug addiction. The way it works appears to be as follows. After dopamine is released to activate the reward neurons in the striatum and cerebral cortex, there are cell mechanisms for its reuptake to terminate its action. Cocaine blocks this reuptake, amplifying and prolonging dopamine’s action, bringing on the addictive state. Some drugs also increase long-term potentiation at synapses where the excitatory neurotransmitter glutamate is released. Nicotine has been shown to have this effect. It also has a direct stimulatory effect on dopamine cells. There are thus multiple mechanisms for amplifying the reward system. Because of the inherent plasticity induced in brain cells by their activity, these actions tend to be self-prolonging. These addictive effects brought on by drug actions are present in food cravings, as we saw in chapter 19, and were a motivating hypothesis for the early study of food cravings. As we shall see, it is becoming an organizing principle for understanding overeating.

Because the dopamine cells have such widespread actions in the brain, it is important to know where they get their inputs. Some of them come from the same areas to which they project, completing feedback loops that can maintain their activity. The other main inputs come from the core of the brain that is often called the reticular system because it is not a specific region but rather a kind of network of cells that stretches from the center of the brain stem into the depths of the forebrain. It is an ancient system, present in all vertebrates and expanded in the human. The cells have long dendrites, as if they are reaching out to receive and integrate many inputs from different brain regions. The key point is that their inputs come from within the brain, just as their outputs stay within the brain, so it is an entirely internal system.

This reticular system is the unknown workhorse of the brain. It is rather like the USB slot on your computer, ready to accept a wide range of input devices and connect them to the desired output. The inputs may come from the hypothalamus to stimulate or terminate feeding; they may signal different emotional or motivational states from the prefrontal cortex or the nucleus accumbens, a deep brain region or from different sensory systems, including those involved in flavor. The VTA neurons, with their own long dendrites, integrate these signals and transmit them through release of dopamine, in many cases back onto the same regions that have sent them their inputs. In this way, both the reticular system and the dopamine neurons are concerned with the significance and expectation of sensory inputs or motor outcomes rather than with discrimination among them. The fact that significance and expectation are embedded so deeply in our brains further explains how difficult it is to change the link between flavors and our cravings for them.

We are now in a position to incorporate all the elements of the human brain flavor system into the new field of neuroeconomics. This reflects the fact that economists have realized that the reason people attach economic value to a particular product is to be found not only in the product but even more so in the way an individual places personal value on the product—in essence, the way a person gives it a reward value. An example from recent studies illustrates this new field as it applies to decisions about flavors.

Todd Hare, Colin Camerer, and Antonio Rangel at the California Institute of Technology wished to know how we make choices, and postulated that the brain has mechanisms for making optimal choices between alternatives. It had previously been shown that a value signal for making choices arises in the ventromedial area of the prefrontal cortex, in the frontal lobe, which as we have seen is concerned with higher cognitive functions. They hypothesized that this area must be under control by another area, the dorsolateral prefrontal cortex, which had been shown to be involved in various higher functions, including cognitive control of decision making. They were particularly interested in food choices, and set up experiments to study the brains of people on diets. Tests were first carried out to separate the subjects into two groups, those who demonstrated self-control and those who lacked self-control. The self-controllers chose foods that were healthy, the non-self-controllers chose foods that tended to be unhealthy.

The investigators then put the subjects in a brain scanner and carried out functional brain imaging while the subjects made their choices. They first found that activity in the ventromedial area was correlated with the subject’s goal values, whether healthy or not. The activity was correlated with healthy ratings by the self-controllers but not by the non-self-controllers. The dorsolateral area was more active during successful self-control trials. And the dorsolateral and ventromedial areas were both active during self-control trials.

The authors make the interesting suggestion that the ventromedial area originally evolved to assign a short-term value to a food, such as flavor in this case, and the dorsolateral area developed subsequently to reflect long-term considerations, such as healthiness. The dorsolateral area has wide connections with other higher-cognitive brain areas, which the authors suggest may be why general intelligence and emotional control are involved in self-control in decision-making. In final summary, Hare, Camerer, and Rangel observe:

A synthesis of the brain systems involved in food choices has been made recently by Nora Volkow, Gene-Jack Wang, and Ruben Baler. Volkow has impeccable credentials for this task. She is a long-time student of drug addiction, as well as director of the National Institute on Drug Abuse (NIDA). As we saw in chapter 19, research on addiction is providing valuable insights into the brain mechanisms that are active in both drug craving and “images of desire” for food. This similarity has led Volkow in recent years to build on this background to propose a model for the different brain systems involved in food choice and healthy versus unhealthy eating (figure 22.1). This puts the basic elements of the model of the human brain flavor system presented in chapter 18 (see figure 18.2) into the more dynamic form of a control system.

The dynamic control model pictured in the figure consists of four main parts. It begins with saliency, a psychologist’s term for how strong and attractive a sensory stimulus is. Saliency includes the irresistible salty, sugary, fatty, high-calorie density of fast foods; the smells of coffee and chocolate; and the balanced attractiveness of the flavors of traditional cuisines around the world. These reflect the array of sensory inputs shown in figure 18.2 as well as how much reward value they have as assessed by the brain mechanisms in the orbitofrontal cortex and related areas.

FIGURE 22.1 Schematic representation of the sensory control system in the human

This diagram was developed originally to depict the sensory control system as seen in drug addiction and is here applied to the control of eating.

(Adapted from N. D. Volkow, G.-J. Wang, and R. D. Baler, Reward, dopamine, and the control of food intake: Implications for obesity, Trends in Cognitive Science 15 [2011]: 37–45)

These inputs go to three main subsystems. One is the memory subsystem, which stores the conditioned preferences by learning of the individual. Second is the motivational drive subsystem that determines how much an individual desires or “craves” a kind of food. And third is the subsystem for inhibitory control, emotional regulation, and executive function, providing the top–down cognitive control of choice. Figure 22.1 shows that normally the executive function is strong. In the terms of the study by Hare, Camerer, and Rangel, people with this strong executive function are those with normal self-control.

By contrast, these systems and their interactions appear to be disrupted in obese individuals. As shown in figure 22.1, for them, saliency is powerful, in many cases overpowering, with strong inputs to all the systems. The learned memories of these overly attractive stimuli, the drive they elicit, and the input to the control subsystem are all increased. There is also a new direct input from the learned memories of the craved foods to the control subsystem. But in these individuals, the control subsystem is decreased. As a result, the increased drive from the salient stimuli is only weakly opposed by the inhibitory executive control. There is thus, in the terms of Hare and colleagues, a lack of self-control, and the person experiences a drive for the craved food that cannot be adequately resisted.

This model provides a useful focus for future experiments. The authors point out that other factors are involved, such as circuits that regulate mood and circuits for internal awareness. There is also the highly complex system of regulation of gut hormones, circulating levels of leptins and ghrelins, and other body hormones. And there is the critical role of language in human food choices.

We end by returning to our original question: what is it that makes the flavor of a given food irresistible? Recall the experiments on food cravings that we reviewed in chapter 19. In reviewing those studies in 2009, Marci Pelchat notes: “Thus, this work supports the common substrate hypothesis for food and drug cravings. The prominent representation of memory and sensory integration structures in this study is consistent with the central role of sensory memory in the experience of food cravings. It is as if, when craving, one has a sensory template of what has to be eaten to satisfy the craving.”

This brings us full circle back to the steps along the way we have covered of how the brain creates flavor: the sensory representation of odor images and odor objects—the “sensory template”—in memory circuits in the olfactory pathway; the integration with the other sensory representations in multiple areas of the cerebral cortex; the formation of images of desire by those interacting areas; and the magnification of those desires by activity in emotional circuits beyond the control by the decision-making centers of the brain. The diagrams of the human brain flavor action system (see figure 18.2) and of food addiction control (see figure 22.1) identify some of the hidden brain systems and their mechanisms that need to be taken into account in any public strategy to encourage healthful eating.