by Jessleen K. Kanwal
figures by Brad Wierbowski

Imagine for a moment that you are unable to taste or smell anything.  For many patients undergoing chemotherapy, this is an everyday reality of their daily fight against cancer.  Chemotherapy kills fast-growing cells in the body in an effort to eradicate tumors.  Taste receptor cells located on our tongue are also fast-growing, regenerating every 2 weeks.  Thus, while chemotherapy kills cancer cells, healthy taste receptor cells also die off.  The end result is that many foods patients once enjoyed end up tasting metallic or flavorless [1,2].  This can lead to depression or excessive weight loss at a time when patients most need a healthy diet and lots of nutrients to recover from the effects of strong radiation.

Unfortunately, the loss of taste or smell and the subsequent side effects are symptoms commonly found not only in cancer patients, but also in patients with other medical conditions such as epilepsy, brain injury, stroke, multiple sclerosis, Alzheimer’s, Parkinson’s, or other neurological disorders [2].  Could we use science to somehow re-engineer their skewed or missing perception of “flavor”?

What is flavor and how can we manipulate it?

Taste is just one component of our perception of flavor.  Flavor, originally thought to depend on the combined sensation of both the taste and smell of a food, actually stems from the combined stimulation of all five of our senses.  The study of how our brain perceives flavor has sparked the formation of a new area of science called neurogastronomy.  Neurogastronomy brings together chefs, neuroscientists, behavioral psychologists, and biochemists in an effort to study how all of our senses stimulate the brain while we eat and how this knowledge can be used to make us perceive food differently [3].

Imagine that you come across a piece of pecan pie on the dining room table.  You see a double layered, crisply cut triangular wedge containing golden brown pie-filling topped with a layer of perfectly roasted pecans.  The visual appearance alone may be enough to draw you towards the food.  As you sink your teeth into the pie, sugar molecules bind to sweet receptors on the taste buds of your tongue, which then activate sweet responsive areas in the gustatory cortex – the perceptual taste center of your brain.

However, a large part of the pie flavor also comes from its smell.  There are two types of smell: orthonasal and retronasal.  When you sniff something from a distance, such as the whiff of pecans as you stand several feet away from the pie, you are performing orthonasal smelling.  Retronasal smelling occurs when you swallow food.  As you close your mouth and exhale through your nose, a puff of air is pushed past olfactory receptor neurons in your nose [4].  Chemicals that are released from the food as you chew activate these olfactory receptor cells, which then send signals to the brain giving you an “odor image” of the delicious aroma of freshly baked pecans (Figure 1).

As you continue to chew on the pie, the cracking sound you hear as you bite into the crunchy pecans also contributes to how sweet you perceive the flavor.  Eating different foods produces sounds of varying frequencies, which is measured in Hertz (Hz).  For instance, crunching on raw carrots produces a frequency of about 1–2 kilohertz (kHz, 1kHz = 1,000 Hz), whereas eating crispy flatbread produces more than 5 kHz [3].  For comparison, the sound of a man’s deep voice tends to have a much lower frequency of about 130 Hz and the sound of a crying baby is around 3.5 kHz [5].   Recent research has shown that high frequency sounds enhance the sweetness in food, while low frequency sounds bring out the bitterness [6].

Lastly, as pieces of the pecan pie churn through your mouth the soft gooey texture of the pie filling mixed with a few chunky crisp pecans may provide the perfect balance of soft to hard texture to further contribute to your perception of the pie’s sweet flavor.  Several studies have found that as food hardness decreases, perceived flavor intensity increases [7].

Surprisingly, even how food is served alters the perception of its flavor.  For example, rough spoons create the sensation of saltiness without any added sodium.  Food served on specifically colored plates and desserts shaped in a rounded, as opposed to rectangular, form can naturally boost the perception of sweetness [8].  So, it is likely that the pecan pie would taste sweeter if you ate it off of a white plate as opposed to a black one, and if it were presented as a circular piece instead of a triangular one [9].  Information about the pie from each of the senses are combined in higher order cortical brain regions to give the full pecan pie flavor (Figure 1).

What can neurogastronomy do?

Many of America’s largest food companies pump excess sugar, salt, and fat into packaged and processed foods to enhance flavor and optimize consumer bliss at the cost of their health [10,11].  However, understanding how non-taste-related sensations impact flavor could drive healthy eating without any additional cost.  A healthier diet would reduce or curb the growing obesity epidemic and the risks affiliated with being obese, such as artery disease, type 2 diabetes, hypertension, and heart attacks [11].  Furthermore, neurogastronomy findings are already being incorporated in some restaurants to enhance the dining experience.

For instance, the restaurant The Fat Duck in England serves a seafood dish called “Sounds of the Sea” that comes complete with sand, foam, seaweed, a conch shell, and a pair of iPod headphones.  Part of the dining experience involves using the headphones to first hear the sounds of the waves and seagulls before eating, which customers claim makes the fish taste fresher and better [6].

In addition, neurogastronomy studies may help patients who have lost the ability to taste or smell.  This challenge was already put to the test at the first international neurogastronomy conference held at the University of Kentucky in November of 2015.  At this conference, top chefs competed to create the perfect dish that would best appeal to all of the senses of two chemotherapy patients [2].

By building on knowledge about how textures, smells, appearances, and sounds of food affect flavor perception, the chefs were able to create highly enjoyable dishes for both patients [2].  Thus, science is starting to uncover how all of our senses contribute and work together to give us the perception of flavor.  In the future, we may be able to entice kids to love broccoli by presenting it together within a perfect combination of color, texture, sound, and smell.

Virtual taste

Now, imagine the possibilities if we could go a step further and trick our brains into thinking that spinach tastes like chocolate.  What if it were possible to make foods taste better by manipulating neural signals in our brain rather than modifying the ingredients within foods or even stimulating the right combination of senses to enhance flavor?

Although direct neural modifications to change taste perception are still far from fruition in humans, recent research in taste processing has discovered ways to make this possible in rodents.

Most of us are taught in school that we perceive five basic tastes — sweet, sour, salty, bitter, and umami (savory) — with our tongue, which sends signals to our brain “telling” us what we have just tasted.  However, recent findings from Dr. Charles Zuker’s research group at Columbia University have found that the tongue may not be necessary for our internal perception of taste.

This research was led by Dr. Yueqing Peng and performed on mice, a commonly used mammalian model system.  Mice, like humans, have taste receptor cells on their tongue, which upon activation send information to specific areas of the gustatory cortex, the major taste center in the brain.  Within the gustatory cortex, there are two spatially distinct subregions that receive, encode, and represent either sweet or bitter stimuli (Figure 2a) [12].  The scientists discovered that it is possible to manipulate an animal’s taste perception and associated behavioral actions by selectively activating these “sweet” or “bitter” subregions of the brain [13].

In their study, researchers trained thirsty mice to lick from a waterspout upon hearing an auditory tone.  Normally, mice lick faster if the water is sweetened with sugar and lick slower if the water is mixed with a bitter compound such as quinine (Figure 2b).  In the experiment, mice were genetically modified to express an ion channel that activates neurons located in the bitter subregion of the brain upon blue light stimulation (Figure 2c).  Thus, using this technique called optogenetics, researchers could shine blue light onto the brain and observe how activating these “bitter” neurons changes mouse licking behavior.

They found that exciting the cells in this bitter subregion significantly slowed down the licking, even wheh the spout delivered pure water.  Thus, activation of this brain region made mice perceive the water as tasting bitter.  In fact, the thirsty mice found the water so aversive that licking the waterspout would sometimes even elicit strong taste-rejection responses, such as gagging and attempts to rid the mouth of the non-existent bitter taste.  Conversely, stimulating only sweet-responsive neurons in the gustatory cortex significantly increased water-licking behavior, suggesting that activation of this brain region made mice perceive the pure water as tasting sweet (Figure 2d).

The researchers then went even further and tested whether activation of neurons in the sweet subregion could make mice perceive bitter water to be attractive.  Sure enough, mice licked bitter water faster if their sweet-responsive neurons were simultaneously activated, using blue light. Conversely, activating bitter-responsive neurons made mice dislike the sweet water (Figure 2d).

These findings indicate that activation of certain brain regions is able to change a mouse’s behavior, and thus its perception of the substance it is tasting.  When asked to interpret the results of the study, Dr. Zuker explains that ”taste, the way you and I think of it, is ultimately in the brain.  Dedicated taste receptors in the tongue detect sweet or bitter and so on, but it’s the brain that affords meaning to these chemicals” [14].

Thus, tricking our brains to taste something sweet while actually eating something bitter may no longer be pure science fiction.  It is now foreseeable that one day we could simply change which region of our brain is active while eating spinach in order to mimic the flavor of a sweet chocolate bar.  Until then, we can be sure to engage all of our senses as we eat— using the right sounds, smells, textures, and appearances to boost that sweet flavor into every meal.

Jessleen K. Kanwal is a Ph.D. candidate in the Neuroscience Program at Harvard University.

References

1. Neurogastronomy: How our brains perceive the flavor of food.” ScienceDaily. ScienceDaily, 18 November 2015
2. Allison Perry and Laura Dawahare. Food, Flavor and Science: Neurogastronomy Symposium Begins Pursuit of Solutions for the Taste Impaired.” University of Kentucky News, 15 November 2015
3. Susmita Baral. Neurogastronomy 101: The Science of Taste Perception. Eater, 18 October 2015
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10. Ashley Welsh. How the food industry manipulates taste buds with ‘salt sugar fat’. CBS News, May 2015.
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12. Peng, Y., Gillis-Smith, S., Jin, H., Trankener, D., Ryba, N. J. & Zuker, C. S. Sweet and bitter taste in the brain of awake behaving animals. Nature (2015).
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14. Harrsion Wein. How taste is perceived in the brain. NIH, December 2015.