Vanderbilt researchers seek a new kind of harmony as music unlocks the secrets of the mind

In college — well before she decided to become a neuroscientist, or even knew there was such a thing — Reyna Gordon studied opera singing. Her questions for the faculty, however, began drifting beyond melodies and appoggiaturas into the realm of science. Why does music make us feel such strong emotions? How does it work on us?

Nobody had answers. Yet the more intense the feelings a piece of music provoked, the more her curiosity grew. She tried to sing Anne's Aria from Stravinsky's The Rake's Progress, and it gave her fits because the words and their stresses didn't line up comfortably with the rhythm of the music. That produced a frustrating cognitive dissonance — and with it, a strange fascination. Why, she wondered, did language and musical meters produce such a powerful balm when they synced up, and distress when they didn't?

Those ruminations led Gordon where she is today — not to Noah Liff's center, but to Bill Wilkerson's.

click to enlarge [Reyna Gordon]

Reyna Gordon

The Bill Wilkerson Center at Vanderbilt University Medical Center houses one of the nation's top ear, nose and throat institutes. Singing stars come here to have their vocal chords repaired and leave signed gold records for a growing wall display. Top-flight surgeons remove throat cancers in these suites, and deaf children have their hearing restored with cutting-edge cochlear implants.

It's also one hub of a coordinated effort to make Vanderbilt a global center for understanding the dynamic interaction of music and the brain — a relationship that may prove pivotal in unlocking disorders that have stymied doctors, scientists and researchers for decades.

Gordon's terrain is a new Music Cognition Laboratory, a nascent enterprise whose name promises something a bit more high-tech than its current components: some mismatched furniture, cardboard boxes with consumer-grade audio gear, a dry-erase board with some scientific squiggles, a bouncy-ball office chair. Yet scientists across many disciplines — including Gordon, who holds a Ph.D. in neuroscience — have a mandate here to consider the same questions she asked herself more than a decade ago.

Brain science is exploding because of ever-improving imaging and time-mapping techniques. These have produced exciting and unexpected discoveries about music as a tool for better understanding and treating (or relieving) some widespread disabilities and illnesses: autism, PTSD, Alzheimer's disease, Parkinson's disease, learning disabilities, depression, pain management and other disorders and pathologies. The ancient, intuitive understanding that music heals is undergoing a thorough scientific examination.

The top medical research center in Nashville wants to lead it. Bolstering its initiative is a two-year, $200,000 grant creating a new Program for Music, Mind & Society at Vanderbilt. Its aim, according to one of the grant documents, is "to discover how music works, from the molecules and neurons that constitute the brain response to music, up through explorations of how music training changes the brain, therapeutic uses of music in clinical settings, ethnographic studies of the role of music in society, and arts policy grounded in scientific research."

The money and interest came from a much larger Trans-Institutional Program (or TIPs) fund that coordinates and accelerates work being done across disciplines and departments. Gordon says at least 14 different schools, colleges, departments and institutes are represented, including psychology, pharmacology, otolaryngology, electrical engineering, the Blair School of Music and arts policy.

While the money isn't enough to fund full-scale trials or experiments, it will support a new graduate seminar and visiting speaker series. It will fund pilot studies to leverage larger external grants in specific disciplines. And it will finance getting Vanderbilt's research efforts out of the campus bubble and into public events that educate about the cognitive and emotional impact of the city's chief cultural export.

click to enlarge [Ron Eavey]

Ron Eavey

"We've been stirring this pot with the university for a while," says Ron Eavey, director of the Wilkerson Center and chair of the VUMC Department of Otolaryngology. Besides being Gordon's mentor and boss, he's an enthusiastic believer in the power of interdisciplinary research and the potential for studying music cognition.

"We sense there's a lot of excitement" at the top levels of university governance, Eavey says. "The logic is compelling. How could we not do this?"

Along those lines, Vanderbilt sponsored open forums in the summers of 2014 and 2015 at Ingram Hall, the auditorium attached to the Blair School of Music. At the first one, musician Ben Folds held an onstage conversation with cognitive psychologist and former recording engineer/producer Daniel Levitin, the literal and figurative rock star of the burgeoning field of music neuroscience.

Levitin wrote the 2007 bestseller This Is Your Brain on Music, a well-received book that documented music's deep influence on just about every aspect of brain operation. Among the functions affected by music are perception of time, empathic communication, speech, long-term memory and visual processing. Science has proven that music activates our ancient limbic system, the seat of our deepest fears and emotions.

Levitin returned to Vanderbilt in August — not as a speaker or star, but as one of hundreds of researchers attending the national conference of the Society for Music Perception and Cognition. Hosting the conference in Nashville for the first time was yet another coup for the TIPs grant contingent.

"Vanderbilt has drawn together an impressive team of creative and rigorous scientists who are contributing in great ways to the neuroscience of musical behaviors," Levitin tells the Scene via email.

Behind the impetus to coordinate efforts at Vanderbilt is the sheer number of widely distributed and diverse research initiatives — including Gordon's. At a time when funding from the critical National Institutes of Health is more competitive than ever, Gordon may have landed Vanderbilt's first NIH grants explicitly devoted to music neuroscience research. She found a correlation between sensitivity to rhythmic nuances and more developed grammar skills in children with typical language development.

Combined with her prior published work, which focuses on the relationship between understanding rhythm and development of speech, this correlation suggests we have shared neural circuitry for rhythm and speech. Now Gordon is looking ahead, planning long-term studies where groups of kids with typical and impaired development of language are given rhythmic training to see if their grammar skills improve.

Other Vanderbilt professors are staking out their own terrain in the field. Randolph Blake, a psychology professor in the Vision Research Center, published NIH-funded research that used melodies and musical notation to show how our brains resolve conflicting visual signals. Marianne Ploger, a professor of music perception and cognition at the Blair School of Music, is applying neuroscientific insights to the teaching of music theory, particularly understanding musical intervals and harmonies. Ph.D. candidate Sara Lynn Beck, herself a songwriter, is investigating the degree to which group music-making makes children more social and cooperative in other activities.

Eavey applies a tapestry-and-loom comparison to the work being done across these fronts at Vanderbilt: many threads weaving together to form something whose patterns and colors aren't yet clear. But a closer look offers a sense of where the field is heading, and Vanderbilt with it.

click to enlarge [Mark Wallace - PHOTO: ERIC ENGLAND]

PHOTO: ERIC ENGLAND
Mark Wallace

Mark Wallace

As director of Vanderbilt's Brain Institute, Mark Wallace coordinates approximately $55 million of grant-funded research each year, involving faculty, staff and students in up to 22 different departments. This robust operation, one of the country's largest, offers plenty of bandwidth to add music to its portfolio of psychological research, he says.

Wallace specializes in multi-sensory input and processing. Visual and auditory signals are coordinated through timing cycles in our brains called oscillations. To study these, his lab is outfitted with acoustic isolation booths (named, with impeccable geek cred, for characters in The Lord of the Rings). Via video monitors and headphones, subjects are shown visual and audio cues that are often intentionally conflicting or out of sync. Over time, with multiple studies on varied populations, the lab's research is filling in a vast map of hidden patterns and mechanisms in the ways we hear and process sight and sound.

Wallace and his team have published original research proposing that the brain clocks that govern visual and auditory input in autistic children are profoundly out of sync. To autistic kids, Wallace says, people speaking can look like a badly dubbed movie; the time delay is worse for kids with more severe cases.

Yet for years, teachers and clinicians have tried to cajole autistic kids into making eye contact during conversations to improve their social function. In fact, Wallace says, they may need to look away to focus on the audio, because the visual discrepancy causes emotional distress. His research also shows that exterior sound and rhythm can influence those brain clocks through a process called entrainment.

"We now know there are disruptive oscillatory patterns in the brains of children with autism," Wallace says. "What I think is that music has an ability to reset [and] normalize those oscillations in a way that ultimately has cascading effects on their ability to process information about the world."

Wallace is working with Los Angeles-based composer Mike Garson, famous as David Bowie's longtime keyboard player, to develop "stimuli sets" (i.e., musical themes and cues) to entrain those brain clocks. Garson, who has seen music work wonders on his own autistic grandson, is also planning a trip to Nashville in April to perform his ambitious Suite for Healing at the Schermerhorn Symphony Center.

click to enlarge [Nicole Baganz - PHOTO: ERIC ENGLAND]

PHOTO: ERIC ENGLAND
Nicole Baganz

Nicole Baganz

Not far from Wallace's offices is the lab of his collaborator in all things music and mind, Nicole Baganz. Her space is a so-called wet lab, with refrigerators and freezers with biohazard decals, water baths and beakers. Next to her desk, which by luck has a sweeping view of downtown Nashville, there's a little bench-top device called a Belly Dancer. It gently swirls serotonin molecules through a gel so they settle for counting.

Serotonin preoccupies Baganz, a post-doctoral research fellow in the VUMC Department of Pharmacology. It's a neurotransmitter, a special molecule that leaps from one neuron to the next at the brain's unfathomable number of synaptic connections. Such molecules are the very medium of thought and emotion.

"The brain has over 100 different types of neurotransmitters," Baganz says. "They're secreted by neurons. And we're trying to figure out how these neurons project to different brain regions. So if you imagine a symphony of 100 players, harmony is like mental health. But if there's dissonance, which person in this 100-person orchestra is off? And in what way?"

Where scientists like Wallace and Gordon are examining patterns and relationships at a macro-to-middle level, Baganz is working at the micro or molecular level, seeking how and why those findings might be true and exploring their means of cause and effect. While she speaks in musical metaphors, her research so far has been narrowly focused on fundamental questions about neurotransmitters and their influence on development and genetics.

Some of her superiors are skeptical that she can directly integrate music into her purview. Compared to molecular results, music is hard to quantify or administer in a scientifically rigorous way. Baganz says she understands those concerns. But as other scientists discover provocative correlations or transformations, she counters that somebody has to zoom in and figure out the why and how.

"Few people have done the molecular or cellular work investigating how music can affect gene expression patterns and the chemicals involved in controlling mood," Baganz says. "There have been a very few studies, but nothing looking at the nuts and bolts."

That's what she hopes to explore. As one of the chief architects of the Music, Mind & Society Program's public interface, she organized the Ingram Hall public forums, and she's building another symposium around next spring's Mike Garson concert. She also writes and speaks about the explosive prospects for applying micro-level discoveries to the therapeutic use of music for the mentally ill. For those efforts, Baganz was just given a Next Generation Award from the Society for Neuroscience, the biggest association of its kind. That laurel should help her push her research in the direction she wants to go.

click to enlarge [David Zald - PHOTO: ERIC ENGLAND]

PHOTO: ERIC ENGLAND
David Zald

David Zald

A different neurotransmitter — dopamine — is much on the mind of psychology and psychiatry professor David Zald. Zald plays and records original music on a Chapman Stick, the electric tapping instrument made famous by King Crimson bass player Tony Levin, and about five years ago his interest in the fascinating pleasure-inducing molecule dopamine fused with his lifelong passion for music.

Zald has a vast research and teaching purview. But he's devoted significant time to surveying research on how dopamine helps us appreciate music. In a lengthy 2011 monograph that cites and interprets more than 100 papers, Zald and co-author Robert Zatorre conclude that "musical pleasure arises from an interaction between biologically ancient reward mechanisms and much more recently evolved cortical systems which are highly modifiable by individual experience and culture."

In other words, we clever humans have developed a tool to hack our own brains, getting the cortical areas (the regions responsible for complex thinking) to engage in an effortless minuet with our deeper animal brains. That tool is music. Other animals have similar dopamine systems, the authors write — but only humans, with our executive and intellectual capacities, can experience the music-dopamine cascade in music, something that happens when music tickles our sense of anticipation and resolution.

This can be as simple as arriving at the final home-base chord of a piece. But it's also an ongoing manipulation of listener expectations, arousal and prediction. This plays out in multiple brain regions, and Zald is interested in understanding the process better.

"Our biggest questions relate to how the rewards get built, how the anticipation gets built, and how this may interact at the level of the dopamine system," Zald says. He'd like to pursue that work with musical wrinkles to see what can be learned about addictions or compulsions. From a research point of view, he says, music is "very important because it does feed off our natural reward system, which is what gets engaged by a range of things like drugs of abuse and more pathological obsessions."

The implications for treatment of addiction are compelling — and not just a little ironic. In the 1960s, music was often associated with getting hooked on drugs. A half-century later, Zald suggests, given focused study, music may unlock some secrets to getting off of them.

click to enlarge [Elisabeth Dykens - PHOTO: ERIC ENGLAND]

PHOTO: ERIC ENGLAND
Elisabeth Dykens

Elisabeth Dykens

The longest-running initiative at the nexus of mind and music on Vanderbilt's campus is almost certainly research on Williams syndrome at the Vanderbilt Kennedy Center, which studies developmental disabilities. More than a decade ago, childhood psychiatrist Elisabeth Dykens was working with a patient with Williams syndrome, a rare genetic condition that involves a varied set of learning issues and, in most cases, an outsized affinity for music.

"I remember testing a little boy who wasn't that verbal, but he could drum a rhythm that blew me away," Dykens says. "I went, 'Hmmm, I want to understand this.' "

Because people with Williams are highly social, she envisioned a residential summer camp in Nashville where young adults could live in dorms and participate in a week of music-making in the city's studios. Not only could they work with professionals, she imagined a climax beyond the reach of many career musicians: a performance at the Grand Ole Opry.

In 2010 the Academy of Country Music came on board as a sponsor and supporter, and the result is what's now called the Lifting Lives Music Camp. Campers come with a wide range of musical abilities, but their joy is uniform as they shuttle around town, meeting with star artists and songwriters.

"They have such unusual auditory processing, so even someone who can't keep a tune wants to be around music all the time," Dykens says. "One of our campers two years ago was so overtaken emotionally by the symphony she had to leave the room."

Dykens was one of the lead applicants for the TIPs grant, arguing that interdisciplinary coordination is exactly what's needed. She points out that there is an excellent music therapy program for patients of Vanderbilt Children's Hospital but a lack of services for other patients undergoing psychiatric and psychological treatment, where arguably music could do even more good.

"This is a whole new frontier," Dykens says, "and I'm thrilled that Nashville and Vanderbilt are poised to lead the way."

click to enlarge [Jay Clayton - PHOTO: ERIC ENGLAND]

PHOTO: ERIC ENGLAND
Jay Clayton

Jay Clayton

Jay Clayton is an English professor and director of the Curb Center for Art, Enterprise and Public Policy, not a scientist. But he's delved further into the world of medicine than almost any of his humanities colleagues, landing the first NIH grant ever given to a literature scholar.

The aim of that multi-year project was to study ethical, cultural and social issues raised by the exploding field of genomics, the study of the function and structure of the genomes that make up the DNA in an organism's cells. As someone who's written about the ramifications of Mary Shelley's Frankenstein and Bruce Sterling's cyberpunk fiction, he's more than qualified to bring Curb to the TIPs neuroscience roundtable.

"It's not that we're looking to make contributions to a paper that a neuroscientist publishes in a neuroscience journal," Clayton says in the historic house that shelters the Curb Center on 18th Avenue South. "Curb's role is to foster studies and reflection pieces on the implications of the discoveries this grant makes about music's effect on psychology, on health and on special-needs populations."

It's relatively easy to imagine the health policy issues arising as music therapies prove themselves in clinical trials against existing standards of care and psychological medications. There will be implications for education, as musical techniques show results in learning. And at the cutting edge, there will be difficult conversations as scientists figure out how to profile people's subconscious minds or build robust human/computer interfaces.

"Neuroscience is really one of the most powerful new fields of scientific endeavor. It's a field of incredible promise, incredible hype and very high expectations," Clayton says. "All these issues around neuroscience have really thorny cultural dimensions. People have fears. Sometimes well grounded, and sometimes totally ungrounded. They have unrealistic hopes and expectations.

"Curb needs to be part of the conversation. We are the people that can help explain some of these cultural forces that are at work in shaping the public's understanding of science."

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