Important developmental link between the cerebrum and the cerebellum

Higher cognitive functions, like language and visual processing, have long been thought to reside primarily in the brain's cerebrum. But a body of research in premature infants at Children's Hospital Boston is documenting an important role for the cerebellum - previously thought to be principally involved in motor coordination - and shows that cerebellar injury can have far-reaching developmental consequences.

The latest study, in the October issue of Pediatrics, also demonstrates that the cerebrum and cerebellum are tightly interconnected. Sophisticated MRI imaging of 74 preterm infants' brains revealed that when there was injury to the cerebrum, the cerebellum failed to grow to a normal size. When the cerebral injury was confined to one side, it was the opposite cerebellar hemisphere that failed to grow normally. The reverse was also true: when injury occurred in one cerebellar hemisphere, the opposite cerebral hemisphere was smaller than normal.

"There seems to be an important developmental link between the cerebrum and the cerebellum," says Catherine Limperopoulos, PhD, in Children's Department of Neurology, the study's lead author. "We're finding that the two structures modulate each other's growth and development. The way the brain forms connections between structures may be as important as the injury itself."

As neuroimaging becomes more sophisticated, cerebellar injury is increasingly recognized as a complication of premature birth. Improved survival of fragile preemies, coupled with a surge in premature births, has left more and more families to deal with the damage to their babies' brains - including cerebellar damage.

In March, Limperopoulos and colleagues published a study in Pediatrics showing that the cerebellum grows rapidly late in gestation - much faster than the cerebral hemispheres - and that premature birth arrests this surge in development. In another study, published in Pediatrics in September, they found that the incidence of cerebellar hemorrhage in extremely premature infants rose significantly, by about 44 percent a year, from 1998 through 2002 - an increase they attribute to improved survival and improved diagnostic techniques. By 2002, cerebellar hemorrhage was identified in 15 percent of surviving infants weighing less than 750 grams.

"Until recently, cerebellar injury was underrecognized," says Limperopoulos. "Doctors downplayed it, saying, 'Oh, maybe Johnny will be a little clumsy.' Our research has made us aware that cerebellar injury is not a benign finding. We now know to look for it, and can counsel families that their children are likely to have deficits that extend beyond motor, and that may benefit from early intervention."

A study presented mid-September, at the American Academy of Cerebral Palsy and Developmental Medicine meeting, documents the magnitude of these problems. Limperopoulos and colleagues compared 31 toddlers, born prematurely and identified at birth as having cerebellar hemorrhage (but no cerebral injury) with 31 controls who were also born prematurely, but whose brain imaging studies were normal. In addition to motor problems, over half the children with cerebellar injury had functional limitations in daily living, communication, and socialization skills, compared with only 3 percent of controls. Sixty-one percent, versus 3 percent of controls, had global developmental delays. Deficits included delays in both expressive and receptive language, visual reception delays, and impaired social and behavioral function.

Limperopoulos and colleagues continue to follow children who were identified at birth as having cerebellar injury. The children undergo a battery of wide-ranging developmental tests including assessment of motor, cognitive, language, social and behavioral skills and tests of functional abilities in self-care and day-to-day activities. Comprehensive MRI studies are paying particular attention to structural connections between the cerebrum and cerebellum - how the nerve fibers run and connect, and where they might be disrupted.

"We want to understand what happens over time," Limperopoulos says. "The way the brain adapts and reorganizes after injury may be the best indicator of how a child will do."