Men enrolled several years ago in studies of two different high-blood pressure drugs quickly developed potent side effects, yet the drug trials were not halted. In fact, today both drugs are highly successful money makers for the drug companies, Pfizer and Upjohn Corporation. The reason: men found the side effects of both drugs tolerable—indeed, delightful. Miraculously, both drugs answered man's ancient quest to boost masculinity. One, Viagra, cured erectile dysfunction and the other, Rogaine, fostered hair growth on the scalps of balding men. Moreover, the scientists conducting the experiments hadn't a clue that these high-blood-pressure drugs would deliver such welcome benefits.
Such serendipity is one of the most welcome experiences in science. In addition to providing the thrill of surprise, serendipitous events signal that we have leaned something new. Sometimes this knowledge comes from the most unlikely sources, which is what happened to me.
The Case of the Noisy Eyeballs
My story of scientific providence begins with a bizarre medical symptom: noisy eyeballs. That’s right. My eyes were making a horrid grating noise whenever they moved—a noise that only I could hear. I had the great fortune of meeting one of the few people who could understand my symptoms: Josef Rauschecker, a professor of physiology and biophysics at Georgetown University , and one of the world’s authorities on the auditory cortex. He suggested that my noisy eyeballs were triggered by serotonin, a neurotransmitter in the brain. Rauschecker explained that his recent brain scans of people suffering from tinnitus, a constant ringing in the ears, show that a particular part of their brain—the nucleus accumbens—is smaller than normal. This nugget of nerve cells helps to regulate the flow of sensory information to the cerebral cortex via another major relay center, the thalamus.
In this sense, the nucleus accumbens is like a valve on a water faucet, as it prevents an overload of sensory input from reaching our conscious mind. Controlling the flow of information is important for attention and anxiety and for suppressing unwanted noise. That guy yapping on his cell phone, oblivious to the conversations around him, is an example of the nucleus accumbens in action. All he hears is the person talking on the phone; he is deaf to sounds in his other ear, because his nucleus accumbens shuts off the input to his auditory cortex. In contrast, people suffering from tinnitus are unable to shut off the irritating noise because of their feeble nucleus accumbens valve.
The same sensory shutoff function is also essential for sleep. Levels of serotonin, which modulates the activity of the nucleus accumbens, also fluctuate in the sleep-wake cycle, and serotonin is a well-known sleep aid. The sleep centers of the brain (raphe nuclei) connect to the nucleus accumbens. The emotional center of the brain (amygdala) also connects to it. Inputs to the nucleus accumbens from both the emotional and sleep centers of our brain explain why our sensations sharpen with arousal and stress but are blunted by sleepiness.
Normally, dysfunctional noise gets filtered out. For example, the thunderous sounds in our head caused by talking or chewing would disrupt hearing if they were not shut off before reaching the auditory cortex. In cases of people who have tinnitus, doctors may someday prescribe a small dose of selective serotonin reuptake inhibitor (SSRI) drugs—the same ones used for treating depression—a bit of serotonin or the diet supplement tryptophan, which the body uses to make serotonin.
Are Sulfites to Blame?
Last year, I wrote an article about my noisy eyeballs and serotonin for Scientific American Mind. I then began getting a steady stream of e-mails and letters from readers around the world admitting secretly to experiencing all manner of bizarre brain mix-ups.
Consider this letter from Joan (last name withheld), a hyperbaric nurse from Rhode Island: "I too can hear my eyeballs,” she writes. “However, it is not a loud noise, just a swishing back and forth when I move them and usually at night before sleep when it is quiet. I’m certain there are many more [such bodily noises]…we’re just not 'tuned in'!"
Joan is right. Charles Limb of the National Institute of Health tells me that some people hear their eyeballs not just at bedtime, but all the time! In this case, the noise is not imaginary; it is caused by the tugging of eye muscles. The skull bone between the inner ear canals and the brain is very thin, and in patients with this condition, disease or injury has perforated the thin shield, allowing the semicircular canals of the inner ear to bulge into the brain cavity. This extra hole in the head acts as a third ear tuned to internal sounds.
But perhaps the most exciting connection to emerge from the case of the noisy eyeballs came from Martin Kronberg, of Ottawa, Canada. A few months ago, I received a note from him: "Please find attached a paper that is about to be published in the journal Biosience Hypothesis,” he wrote. “The paper was significantly inspired by your article in Scientific American. Kronberg’s scientific paper suggests that sulfites could cause tinnitus by acting on the nucleus accumbens, a small cortical area located in the center of the brain.
Sulfites are used as antioxidants to prevent foods from turning brown and as preservatives to kill harmful microorganisms. In fact, I know, as an amateur wine maker, that the first step in making wine is to add sodium sulfite to kill the wild yeast on the grapes so that the juice can be inoculated with the preferred strain. Sulfites are used this way in many food products and sulfa drugs (sulfonamides) are also used as antibiotics.
So what do sulfites have to do with tinnitus and noisy eyeballs? Kronberg noticed that the enzymes blocked by sulfites in bacteria—this property is why sulfites are such powerful antiobiotics—have very similar chemical properties to the enzymes that help regulate the production of dopamine and serotonin, both of which are important neurotransmitters in the nucleus accumbens. In particular, Kronberg suggests that sulfites could impair the function of the enzyme making dopamine (dihydroxyphenylalanine), and also the enzyme tryptophane hydroxylase required for synthesis of melatonin and serotonin. If so, then sulfites might disrupt the normal functioning of the nucleus accumbens, and prevent it from properly regulating the flow of information.
Only time will tell if there is anything to this hypothesis springing from the curious cross pollination among the readers of Scientific American Mind, but it is wonderful to be doing science collaboratively and serendipitously. Who knew that my noisy eyeballs would one day lead to so many intriguing scientific ideas?
Are you a scientist? Have you recently read a peer-reviewed paper that you want to write about? Then contact Mind Matters editor Jonah Lehrer, the science writer behind the blog The Frontal Cortex and the book Proust Was a Neuroscientist. His next book, How We Decide, will be available in February 2009.