Getting inside the child mind

When Dr. Tallie Z. Baram receives the 2013 Bernard Sachs Award at the Child Neurology Society’s annual meeting Nov. 1 in Austin, Texas, she will join a roster of such distinguished past honorees as current National Institutes of Health director Dr. Francis Collins.

The award is widely seen as the highest accolade in the field of children’s brain research and is considered the crowning achievement of a scientific career.

Baram, however, views it as something different: a springboard to what may prove to be her greatest contributions to our understanding of the early-life factors that affect the developing brain.

“Receiving the Sachs Award is rewarding and humbling, and I’m thankful for the recognition,” says the Danette Shepard Chair in Neurological Sciences at UC Irvine. “But, as Frank Sinatra sings, I believe the best is yet to come.”

In June, Baram got a $10 million Silvio O. Conte Center grant from the National Institute of Mental Health to establish an interdisciplinary program to explore how patterns and rhythms of maternal signals before and after birth may influence an infant’s vulnerability to cognitive and emotional problems during adolescence.

Conte Center grants are rarely bestowed, and only the most promising ideas to improve the diagnosis and treatment of mental health disorders receive funding. The center grant awarded to Baram is currently the only one of its kind in the University of California system.

“We want to help answer the question that’s been a topic of intense investigation for decades,” she says. “What happens during childhood that shapes the brain for life? This complex problem requires a multidisciplinary approach that involves both animal and human research. Here at UC Irvine, we’re applying principles of neurobiology to a strong human research program, and I believe that with the Conte Center funding, we can make innovative and major contributions to the solving of this crucial question.”

A large body of work has suggested that signals conveyed by a mother during fetal growth and the first few years after birth influence a baby’s development and lifelong cognitive and emotional functioning. Baram proposes that the patterns and rhythms of maternal signals, rather than their general quantity or quality, are the key properties that affect the developing brain.

“Rhythms and patterns are well known to influence individual synapses, or connections among brain cells,” she says. “They are also closely involved in the function of large sets of brain cells called brain networks. We believe that the patterns and rhythms – and especially their complexity and predictability versus fragmentation and unpredictability – shape the structure and function of the fetal and young child’s brain.”

To explore this, Baram recruited a UC Irvine team for her Conte Center on Brain Programming & Adolescent Vulnerabilities that will combine neurobiological and molecular research with animals, behavioral research with children, and neuroimaging and computational statistical analyses. The goal is to create a comprehensive picture of maternal influences, childhood cognitive and emotional development, and brain structure to help identify children who may be susceptible to adolescent mental health disorders and to help establish more effective treatments.

“This effort will link fundamental neuroscience to direct human clinical care in a very exciting and innovative way,” says Dr. Steven Small, the Dr. Stanley van den Noort Endowed Chair of Neurology who will oversee the Conte Center’s neuroimaging work. “It all reflects Tallie’s passion and abilities to take basic findings from the lab and apply them to new treatments. It’s the epitome of excellent translational research.”

Baram has been blazing new trails in pediatric neurology since receiving her Ph.D. from the Weizmann Institute of Science in Israel. After earning a medical degree at the University of Miami, she dedicated herself to exploring the developing brain and the factors that can trigger neurological disorders and later cognitive problems – all in the service of better treatments.

Her work has shed much light on how a child’s brain can become epileptic. Baram’s studies on brain effects of stress hormones in infantile spasms, a severe, rare form of early-life epilepsy, led to FDA approval of a potent therapy. Her group was the first to examine the link between long febrile seizures, a common type of childhood seizures that occur during fever, and subsequent adult epilepsy. Baram’s research has also focused on the effect of early-life stress on vulnerability to emotional and cognitive disorders later in life.

“Tallie is seen as an innovative researcher who takes child neurology problems from the bedside to the bench and back again,” says Dr. Ira Lott, professor emeritus of pediatrics who helped recruit her to UC Irvine in 1995. “It’s a reputation well-deserved.”

In her 18 years here, Baram has contributed to the backbone of translational neurosciences, a long-recognized strength of the university. She founded the UC Irvine Epilepsy Research Center and became the first woman to receive the American Epilepsy Society’s Epilepsy Research Recognition Award. She’s also one of three UC Irvine faculty members to get the Senator Jacob Javits Award in the Neurosciences, the federal government’s most prestigious prize for research into brain disorders.

Baram still finds time to enthusiastically mentor young physician-scientists – crucial to the ongoing preeminence of neurosciences at UC Irvine. One emerging neurologist, Dr. Daniela Bota with the UC Irvine Health Comprehensive Brain Tumor Program, says Baram’s guidance helped her integrate research into her clinical work. This led to Bota receiving a $1 million federal grant to study and treat “chemo brain,” a condition in which cancer patients experience problems with concentration, thinking and memory after chemotherapy.

“Tallie’s assistance was absolutely vital to the project and to my career,” Bota says. “Her mentoring is very important, because for women scientists, it can be difficult to find a proper mentor. She has inspired me to succeed and, in the future, to mentor the next generation.”

It’s that next generation that inspires Baram, especially with the Conte Center. While the federal funding for the program is for five to 10 years, she sees the work continuing far past the day she retires to focus on bringing classical music – with its rich, predictable and complex patterns and rhythms – to the brains of schoolchildren.

“The concept of early-life brain programming as an important influence on vulnerability and resilience later in life is crucial and huge. I am proud to contribute to studying this topic in a new way,” Baram says. “We’re just beginning.”