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The Sound of Music
In unraveling the puzzle of how music affects the human brain, neurologists may help broaden music’s healing potential.
by Beverly Ballaro

Mark Jude Tramo

When the Beatles invaded his hometown to make their debut on the “Ed Sullivan Show,” seven-year-old Mark Jude Tramo found himself captivated. By then, his own precocious musical abilities had caught the eye of a talent scout. At the 1964–65 World’s Fair, Tramo played classic rock ’n’ roll on electric guitar for the crowds. By nine, he was performing as a folk guitarist at Catholic churches. In high school he was writing songs. And he produced his first musical show—a rock musical—at seventeen.

While earning his undergraduate and medical degrees, Tramo played in a rock group whose demo landed him and his bandmates a coveted audition at RCA Records. But RCA’s offer arrived the same week that Tramo matched in neurology at his first-choice hospital. “Given the vagaries of making it in the music industry,” says Tramo, “the choice was clear, but heart-wrenching.”

The recording industry’s loss became the medical profession’s gain. When Tramo saw that a new science, dedicated to understanding music perception and cognition, was on the horizon, he seized an opportunity to combine two passions. During his residency, it occurred to him that the new digital technologies he was using to record music could facilitate neuroscientific studies of musical timbre recognition. And he realized that research into how humans perceive music could potentially contribute to new therapies in the realms of deafness, stroke rehabilitation, and palliative care.

To unlock the puzzle of how the brain processes tonal information, Tramo began working with stroke and split-brain patients. By analyzing which music-processing functions these people were unable to perform, he helped determine which regions of the brain are involved in certain music-related activities. Those studies inspired Tramo, with colleagues in the Harvard Program in Neuroscience, to develop an experimental model for the neural coding of pitch and harmony in the auditory cortex of primates.

The clinical applications that may one day arise out of such understanding are the driving force behind Harvard’s Institute for Music and Brain Science, which Tramo co-founded in 2002. The institute is dedicated to advancing knowledge about the neurobiological foundations of music and fighting diseases that impair the capacity to perceive, learn, and perform music. Its research also focuses on using music to treat children and adults with neurological and other diseases.

Music therapy, says Tramo, may benefit patients in every phase of life, beginning with premature infants. “Babies in neonatal ICUs are isolated in incubators,” he says. “They can’t see well and are subjected to an acoustically stressful environment because of all the monitor alarms going off.” Some studies suggest, he adds, that music can help premature infants gain weight faster, avoid cardiopulmonary distress, and leave the ICU sooner.

“The degree of neonatal music sensitivity is amazing,” says Tramo. “Babies can perceive sounds in the womb beginning at about the midpoint between conception and birth. By four months of age, they will respond to dissonant chords in music by squirming and turning away from the source.” Research, he adds, indicates that musical preferences are determined in part by environmental exposure. “It’s analogous to the way humans are born with a capacity for speech,” he explains. “Children quickly learn the ‘language’ of music for their particular culture.”

Yet infants also display preferences for certain musical features that cut across cultural boundaries. Whether based on seven notes, as in most Western music, or five notes, as in some Eastern traditions, Tramo adds, the music of all cultures relies on an octave structure that can be broken down into a limited subset of pitches that are consistent from one octave to the next. Babies have the auditory capacity to recognize octave similarity.

Infants are not the only potential beneficiaries of scientific insight into the way the brain responds to music, says Tramo. Tonal information processing studies may one day lead to applications in speech therapy and the treatment of dyslexia in older children. Adults, too, may benefit from mood induction therapy—the use of music to deal with chronic pain or to reduce the discomfort, anxiety, and depression that often accompany diseases such as cancer.

Some studies have suggested that exposure to music can modify the widely fluctuating blood pressure that many coronary bypass patients experience postoperatively. Other studies indicate that music can help calm aggressive behavior, a common problem with Alzheimer’s patients. And understanding how the ear and the brain process music can lead to the development of better hearing prostheses, cochlear implants, and other bionic devices that may alleviate deafness.

Although music therapy is already being used to help patients, Tramo acknowledges that “many of the data still fall into the realm of the anecdotal.” The lack of rigorous, controlled clinical studies has prevented music therapy from achieving the status of a treatment whose value is officially recognized within the medical profession and covered by insurance companies.

Tramo believes that the effects are there for the measuring. “We already understand much about how different parts of the brain ‘talk’ to each other,” he says. “We know, for example, that the relationship between sounds and emotions has an anatomical basis. The nerve cells in the auditory cortex connect to the nerve cells in the medial temporal cortex, which controls memory and emotions. Those nerve cells, in turn, connect to other parts of the brain that regulate heart rate, blood pressure, and immune response. So, a broad connectivity is at work.”

Amid his quest to bring clarity to these kinds of scientific issues, Tramo has not completely forsaken his artistic vocation—some of his recordings are getting airplay on a 1970s rock radio show, and a record label has expressed interest in re-releasing an album he recorded years ago. He is now working on a digital re-mastering of the material.

But Tramo is devoting most of his energy over the next few years to developing The Institute for Music and Brain Science, studying music perception in stroke and epilepsy patients, and, with colleagues, “cracking the neural code for pitch and harmony” in the primate auditory cortex. And he is writing a book about music, medicine, and neuroscience. “At this point,” he laughs, “I think it’s safe to say that my rock ’n’ roll days are over.”

 

Anne Blood

In his 1697 play The Mourning Bride, William Congreve celebrated music’s extraordinary power to shape our spirits and sentiments: “Music hath charms to soothe a savage breast, to soften rocks, or bend a knotted oak.” More than two centuries later, Lewis Thomas ’37 offered a perspective more cerebral than visceral but one nonetheless enamored of music’s mysterious effects. “Music is the effort we make to explain to ourselves how our brains work,” Thomas wrote. “We listen to Bach transfixed because this is listening to a human mind.”

The emotional impact of music has come to fascinate a new generation of researchers like Anne Blood, instructor in neurology at HMS, who found herself intrigued by this puzzle while a graduate student living in Los Angeles, the heart of the recording industry. So, while a postdoctoral fellow at McGill University, Blood decided to subject art to the scrutiny of modern scientific tools. With colleagues, she designed and conducted brain-imaging studies aimed at illuminating the origins of music’s power to sway listeners’ moods, both positively and negatively.

To assess which areas of the brain come into play when listeners experience an unpleasant emotional response to music, Blood exposed a group of test subjects to a series of recordings that steadily increased the degree of dissonance. But the first order of business was to ensure that the subjects would, indeed, find the clashing sounds sufficiently unpleasant.

To this end, Blood chose non-musicians as test subjects. She also took care to exclude from the study aficionados of jazz, which characteristically relies on a complex interplay of harmonic tension and resolution.

“It’s quite common for trained musicians to develop a taste for dissonance,” Blood explains. “The pleasure that many people derive from dissonance is not so much the jarring contrast between two particular notes, but the resolution of that tension into consonance as well as the pleasurable, suspenseful anticipation of that resolution. In the music we used in our study, the dissonance never resolved.”

Music historians, in fact, have demonstrated how both the Western definition and perception of harmony have evolved over time. For medieval musicians, harmony consisted of simple two-note combinations. During the Renaissance, three-note chords emerged, and the Romantic Era saw the expansion of chords into four-part harmonies. Modern composers further expanded the meaning of harmony; contemporary listeners now enjoy dissonant chords whose instability would have struck earlier audiences as unbearable. When Blood finally previewed the most dissonant test tape for a colleague, she was gratified by her colleague’s assurance that it was so awful, “it nearly made her feel sick to her stomach.”

When Blood correlated brain activity with a dissonance level that increased continuously, she made a discovery that contrasted with previous findings. Listening to dissonant sounds did not change activity in the parts of the brain that typically light up in response to other sensory stimuli such as visual cues. Instead, as the music increased in unpleasantness, an area on the right side of the brain indicated by other studies to be important to memory and anxiety—the parahippocampal gyrus—became active.

Blood had more striking findings in store when she recruited a fresh set of test subjects for a study designed to examine the impact of positive emotional responses to music. This time, she chose ten trained musicians, knowing that the likelihood of evoking a powerful emotional response to music would be higher for someone with a lifelong passion for the art. Specifically, Blood wanted to analyze what goes on in the brains of listeners while they are experiencing a powerful emotional reaction indicated by the physiological sensation of getting shivers down the spine.

“The tricky part, of course,” says Blood, “is that, while people from various backgrounds and cultures report a euphoric response to music that uniformly involves sensations of tingling and chills, the music that evokes such a response differs from individual to individual.” To solve this problem, Blood asked each musician in the study to select his or her own piece of music. Her only stipulation was that the piece had to be purely instrumental, since the brain will inevitably respond to human voices or vocal cues. Her subjects’ choices ranged from the mournful strains of a Barber string piece to the lush orchestration of a Rachmaninoff concerto, although Blood points out that other types of music outside the classical genre can also evoke the same response.

An analysis of the results revealed a pattern of brain response quite distinct from what Blood and her colleagues had observed in their study of unpleasant emotional responses to dissonance. The experience of listening to pleasant music, she discovered, did not evoke responses in the parahippocampal gyrus.

Instead, during their positive, spine-tingling experience of feeling moved, Blood’s musician subjects all exhibited increased activities in areas such as the ventral striatum, amygdala, and dorsal midbrain areas—regions of the brain associated with motivation and reward. “This was quite striking,” Blood says, “because these subcortical parts of the brain are connected with more basic, instinctive impulses and cravings that all animals exhibit. They are mostly reserved for survival-oriented tasks such as eating and reproduction. These are the same neural pathways that typically show a lot of activity in the presence of sexual arousal, for example, or addictive drugs. And yet, clearly, music is not necessary for physical survival or the perpetuation of the species.”

Researchers are still debating why Barber’s ethereal Adagio for Strings should light up the same region of the brain turned on by earthier drives for food or sex. “Humans are highly evolved,” says Blood, “but evolution has left us with a number of primitive emotional systems. It may be that the more evolved parts of our brains somehow patch into the evolutionarily older parts and link to them abstract, higher-level cognitive processes, such as listening to music.”

It may take years before scientists arrive, if they ever do, at a definitive answer to the question of why humans have developed such a strong neurobiological basis for the appreciation of music. “Fortunately, the implications of this capacity are not nearly as mysterious,” says Blood. “If music can stimulate areas of the brain linked to such intensely positive emotions, this lends scientific weight to the popular intuition that music may offer significant mental and physical health benefits.”

 

Gottfried Schlaug

For Gottfried Schlaug, associate professor of neurology at HMS, confirming the astonishing human capacity for neuroplasticity means dispelling the notion that the brains of all musically talented people come preprogrammed with an aptitude for music. “I’ve been happy to discover that, for the most part, musicianship and the chance to excel at playing a musical instrument are not predetermined by heredity,” says Schlaug. “To think that musical potential is already limited at birth would be quite depressing for all of us who believe in the enormous potential of the brain to grow and mature based on experiences.”

Yet, Schlaug cautions, it would be a mistake to discount completely the role of genes in the expression of certain musical abilities, such as absolute pitch. Some families have an increased incidence of this ability—as do 35 percent of Japanese musicians and a roughly similar proportion of Asian American musicians (compared with only 10 to 18 percent of their Caucasian counterparts). Researchers, he says, are still trying to differentiate the impact of early music exposure from potential genetic effects. Age at commencement of musical training is one strong factor in the expression of the absolute pitch phenotype, says Schlaug, adding that other factors may include a particular brain anatomy that is commonly found in musicians with perfect pitch.

But, Schlaug notes, cultural factors may be at work as well. Some researchers suspect that the tonal nature of some Asian languages may lend some of their speakers a more nuanced perception of pitch. Others have pointed to the rigorous early musical education programs that are more common in some Asian countries than in Western nations. “In addition,” Schlaug says, “these programs tend to rely on teaching philosophies, such as the Suzuki method, that strongly emphasize learning music through listening rather than through reading notation.”

Although the extent to which genes underlie absolute pitch remains a mystery, one conclusion of Schlaug’s research is unambiguous: the experience of playing music alters the human brain in profound ways. “The idea that experiences can shape the brain in ways that we can actually measure is relatively new,” he says.

This realization came about when Schlaug compared adult musicians with non-musicians. He was seeking any behavioral differences between the two groups, as well as functional and structural brain dissimilarities. He identified not only a number of characteristic differences in the motor and sensory regions of the musicians’ brains, but also pronounced changes in the brain regions responsible for translating visual-spatial information into motor commands.

In particular, areas in the superior parietal region and in the lateral inferior temporal region showed significant differences between the two groups. Differences were also seen in the cerebellum, where auditory and motor functions become integrated. The musicians’ brains, Schlaug discovered, were bigger in certain, well-delineated brain regions than their non-musical counterparts’ brains. Moreover, the degree of difference in the musicians’ brains correlated with the intensity and duration of their musical training.

To understand when and how these changes take place, Schlaug and colleagues are conducting a longitudinal study of more than 75 children between the ages of five and seven. The children in the experimental group are taking piano or string instrument lessons; the control group’s only exposure to music comes as part of their ordinary school curriculum. The researchers plan to follow the children for at least three years, taking annual brain images and subjecting them to various behavioral and cognitive tests.

Although he has completed only the first year of the study, Schlaug is already seeing, in brain images of the child musicians, differences in the same regions that music transforms in their adult counterparts. He and his colleagues are also tracking any possible transfer effects that instrumental training might have on the children’s overall IQs, reasoning abilities, and verbal, visual-spatial, math, motor, and auditory skills.

At first glance, it might seem counterintuitive that a child’s ability to bow the violin might also enhance parts of the brain connected to visual-spatial skills. But Schlaug points out that these two realms may be more related than they first appear.

“To play the violin requires the ability to read musical notes,” he says, “and then the player’s brain has to translate that visual-spatial and time information into specific motor commands. Similar operations might be taking place when someone is assembling a jigsaw puzzle. So, it’s easy to see how parts of the brain that are involved in music processing might also become better at other tasks that require a similar processing.” Brain-based sharing also takes place between music and language processing tasks, he adds, so that instrumental practice, singing, and rhythmic games may strengthen verbal skills.

“We’re learning,” says Schlaug, “that the human brain is remarkably plastic and highly responsive to early experiences.” At the same time, it is also possible, he notes, that “certain learned behaviors rather than music-specific factors may account for the improved performances of musician children in a variety of realms. In general, musicians learn how to be attentive and disciplined. Their musical training may produce improvements in other areas not so much because of specific brain changes but because it makes them particularly adept at learning how to learn.”

Applying this new knowledge to therapeutic opportunities is Schlaug’s ultimate goal. “The next step,” he says, “is to think about how we can use music to alter the brains of people whose diseases might respond to such changes.” To this end, one of Schlaug’s postdoctoral fellows, Katie Overy, is testing whether the phonological skills of dyslexic children may respond positively to certain musical components.

Schlaug is also overseeing a study focused on melodic intervention therapy—a way of helping stroke patients with aphasia to regain, through music, the ability to speak. Although singing and speaking do share some brain pathways, Schlaug says, they are sufficiently separate so that these patients can still sing even though they can’t talk. “We know the intervention works,” Schlaug says, “the question now is to figure out how it works and to see where such understanding can help us develop new ways to improve the lives of even more people.”

Roy Hamilton

The phenomenon of perfect pitch has long intrigued scientists curious about the interplay of genetics and experience in shaping the human brain. For Roy Hamilton ’01, the discovery that blind musicians exhibit absolute pitch at startlingly higher rates than their sighted counterparts came about by two accidents, one cruel and one happy.

The first accident took place some 50 years ago when a number of premature infants received excessive doses of oxygen in their incubators. This exposure caused a displacement of the tissue in their eyes, resulting in the condition known as retrolental fibroplasias, which rendered them totally, permanently blind.

The second twist of fate occurred while Hamilton, now a neurology resident at the University of Pennsylvania, and colleagues were doing research with 46 of these blind subjects in the Beth Israel Deaconess Medical Center laboratories of HMS faculty members Gottfried Schlaug and Alvaro Pascual-Leone. Hamilton was focusing on the role of cortical plasticity in producing the superior tactile acuity that many blind people display. Yet in the course of interviewing his subjects, he stumbled across claims of perfect pitch by a remarkable number of them. And when Hamilton put his subjects to the test, the results bore out the accuracy of their self-assessments.

Against All Odds

What made the results all the more striking, Hamilton says, is that “the phenomenon of perfect pitch is exceedingly rare.” Among the sighted general population, absolute pitch occurs on the order of less than one in 1,500 people. The rarity of this ability may reflect, says Hamilton, what most studies have indicated: that early exposure to musical training seems to be a prerequisite for perfect pitch in most sighted individuals.

If people are not exposed to musical training by the age of 11, they almost never go on to exhibit perfect pitch. By contrast, among musicians who go on to receive Western musical conservatory training, the rate hovers around 18 percent.

To no one’s surprise, the nine blind research subjects who reported no musical background did not have absolute pitch. But 12 out of the 21 subjects who had received some musical training—an astonishing 57 percent—did display this talent. And Hamilton was even more intrigued to learn that this startling percentage existed even though the average age at which members of his blind cohort had begun musical training was eight years, four months—much later than the average training onset age of sighted musicians—and some of his subjects were as old as 14 before they first picked up a musical instrument.

“The fact that these blind musicians were still able to develop perfect pitch at two or three times the rate of prevalence among sighted musicians clearly suggests that something unique is going on with blind people,” Hamilton says. “The challenge now is to figure out how their brains differ, both functionally and morphologically.”

Some Stars Are Born

The idea that the brains of sighted and blind people are not identically wired is not new. It has long been known, for example, that sighted people have great difficulty in mastering Braille. What has not been as clear is how much of the distinction is tied to genetic factors and how much to experiential factors. Absolute pitch, says Hamilton, does appear to have a genetic component.

The chances of perfect pitch existing in identical twins, for example, are higher than they are for non-identical twins. Studies have also confirmed a significantly higher incidence of absolute pitch in certain racial and ethnic groups. Asian populations, for example, seem to have elevated rates of perfect pitch compared with non-Asian populations. And, what’s more, these higher rates appear to exist independent of the musical scale or environment in which people from those populations are trained.

In the case of the subjects in Hamilton’s study, however, the link between blindness and absolute pitch ability had to be explained in other than genetic terms; all of the subjects in this study had been born sighted but became blind shortly after birth.

Amazing Grace

A clue as to what non-genetic factors might explain the amazing rate of absolute pitch ability in Hamilton’s blind subjects came from previous brain-imaging studies comparing sighted musicians with non-musicians. In those studies, researchers had discovered a pattern of anomaly: while some degree of asymmetry normally exists between the left and right hemispheres of the brain in all sighted people—with the left side being larger—this asymmetry is significantly exaggerated in sighted people with perfect pitch.

Yet, in blind musicians graced with absolute pitch, Hamilton says, this characteristic asymmetry doesn’t appear as pronounced. “This suggests,” he explains, “that if you are blind due to a peripheral cause, such as retrolental fibroplasias, and you’ve managed to develop absolute pitch ability, the mechanism by which you’ve done so may differ from that employed by the brains of sighted musicians with absolute pitch.”

The leading theory as to what that mechanism might be, Hamilton says, is predicated on the idea of compensation. Some researchers believe that, in blind people, the area of the brain that would normally be used for vision gets co-opted for non-visual tasks, such as music. Functional brain imaging appears to bear this theory out, in that tasks such as sound localization and pitch discrimination seem to increase activity levels in the visual cortex. The dramatically enhanced haptic acuity of such individuals, Hamilton adds, may similarly hinge on a co-opting of the occipital lobe.

“It’s really not surprising,” Hamilton says, “that this might be the case. Think about it—a whopping 40 percent of the cortex in a normal human brain is devoted to one sense: vision. To lose this particular sense delivers a greater blow than the loss of any other. The brain’s remarkable ability to reallocate the sizable assets normally dedicated to sight goes a long way toward enriching the lives of blind people.”

Beverly Ballaro was associate editor of the Harvard Medical Alumni Bulletin from 2000 to 2005; before that, she served as assistant editor for one year.

This article appeared in the Autumn 2003 issue of the Harvard Medical Alumni Bulletin.

Photo caption for last image in story: A number of well-known blind musicians, including Ray Charles, have had perfect pitch.

Photos: Justin Ide (Tramo); Liza Green (Blood and Schlaug); James Wasserman (Hamilton); Bettmann/Corbis (Ray Charles)