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Summer Lecture Series Provokes Young Minds

By Rich McManus

Images of human brains — rendered in vibrant, nearly tie-dye color — were one of the attractions for an audience of summer interns attending Dr. Judith Rapoport's offering in the "Research at the Frontier" seminar for youngsters June 24 in Masur Auditorium. The eight-part series, sponsored by the Office of Education, highlights the variety and depth of NIH's intramural program and features leading researchers and institute directors.

Rapoport, who is chief of NIMH's Child Psychiatry Branch, gave the series' second talk on "The Adolescent Brain" before an audience not too far removed from that phase of human development. Focusing on normal vs. abnormal brain development, Rapoport showed how advances in technology — both anatomic and functional magnetic resonance imaging, which can "light up" areas of the brain in relation to age, treatment or response to controlled stimuli — can lead to therapeutic insights.

Rapoport and her colleagues have taken advantage not only of technology, but also of a cohort of human subjects whom they've been able to image and study for years on end — from toddlers to people in their 30s. "Longitudinal prospective studies have been very useful in child psychiatry," she said. Her lab has been able to literally track the development of brains as they mature through the years, tracing specific anatomical changes.

Comparing brain weight to body weight in different species, Rapoport and colleagues discovered that humans are not quite kings of the hill; "The porpoise and the elephant have beat us out," she reported. But there seems to be "relatively little correlation between brain size and ability — bigger isn't necessarily better."

NIMH studies have shown that cortical brain regions develop at different rates. "The temporal lobe matures later than other parts of the brain," Rapoport said. And the cerebellum — what she termed "the small brain behind the brain" — reaches full size and matures far later than other brain regions.

Creating maps of the cortex based on the sum of many images gathered over many years, Dr. Jay Giedd and Rapoport have been able to demonstrate graphically that synaptic growth proceeds from the rear to the front in a "gradual wave of change."

Examining the "heritability" of brain structures, she has found that some regions appear to be under more genetic control than others, and that the simple passage of time can prompt different regions to activate, as if they were on timers of some sort. What has emerged from the decidedly unstatic movies of brain development is that "as you age, you get to resemble your biological parents in brain structure over time."

Other researchers had previously discovered differences among male and female brains: the male brain tends to be somewhat larger, but in females, the gray/white matter ratio is higher. Also, development curves in female brains tend to peak earlier than in males.

Particularly useful to Rapoport's team have been studies of childhood-onset schizophrenia (COS), a rare variant of a major disorder that normally manifests in people who are around age 20 or older. While the illness is extremely rare in those under age 13, Rapoport has been able to recruit a cadre of some 75 children with COS whom she has been able to study from 1991 to the present. There appears to be some genetic link between COS and Crohn's disease, a digestive disorder, she has found. Also, the back-to-front wave of development in normal brains seems to be mimicked, at least directionally, in COS patients, who experience loss, rather than gain, of function in a wave "that starts at the back of the brain then moves forward to cover the entire brain...This is probably an exaggeration of a normal pattern of development."

In patients with COS, and in those with attention-deficit hyperactivity disorder (ADHD), Rapoport has found a variety of anxiety/emotional problems linked more closely to morphological changes in the brain. Insights from such imaging are expected to come more quickly as technology gets more sophisticated, she suggested.

"We have gained an unprecedented ability to dissect brain pathways and genetic/environmental determinants of clinically relevant behavior," she said.

Future talks in the series, held Tuesdays from noon to 1 p.m. in Masur Auditorium, Bldg. 10, include: July 29, "Biomedical Imaging in the Post-Genomic Era: Opportunities and Challenges," by Dr. King Li, associate director, radiology and imaging sciences, Clinical Center; and Aug. 5, "Imaging the Addictive Brain," by Dr. Nora Volkow, director, National Institute on Drug Abuse.

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