Higher cognitive functions, like language and visual processing, havelong been thought to reside primarily in the brain's cerebrum. But abody of research in premature infants at Children's Hospital Boston isdocumenting an important role for the cerebellum -- previously thoughtto be principally involved in motor coordination -- and shows thatcerebellar injury can have far-reaching developmental consequences.
The latest study, in the October issue of Pediatrics, alsodemonstrates that the cerebrum and cerebellum are tightlyinterconnected. Sophisticated MRI imaging of 74 preterm infants' brainsrevealed that when there was injury to the cerebrum, the cerebellumfailed to grow to a normal size. When the cerebral injury was confinedto one side, it was the opposite cerebellar hemisphere that failed togrow normally. The reverse was also true: when injury occurred in onecerebellar hemisphere, the opposite cerebral hemisphere was smallerthan normal.
"There seems to be an important developmental link between thecerebrum and the cerebellum," says Catherine Limperopoulos, PhD, inChildren's Department of Neurology, the study's lead author. "We'refinding that the two structures modulate each other's growth anddevelopment. The way the brain forms connections between structures maybe as important as the injury itself."
As neuroimaging becomes more sophisticated, cerebellar injury isincreasingly recognized as a complication of premature birth. Improvedsurvival of fragile preemies, coupled with a surge in premature births,has left more and more families to deal with the damage to theirbabies' brains -- including cerebellar damage.
In March, Limperopoulos and colleagues published a study in Pediatricsshowing that the cerebellum grows rapidly late in gestation -- muchfaster than the cerebral hemispheres -- and that premature birtharrests this surge in development. In another study, published inPediatrics in September, they found that the incidence of cerebellarhemorrhage in extremely premature infants rose significantly, by about44 percent a year, from 1998 through 2002 -- an increase they attributeto improved survival and improved diagnostic techniques. By 2002,cerebellar hemorrhage was identified in 15 percent of surviving infantsweighing less than 750 grams.
"Until recently, cerebellar injury was underrecognized," saysLimperopoulos. "Doctors downplayed it, saying, 'Oh, maybe Johnny willbe a little clumsy.' Our research has made us aware that cerebellarinjury is not a benign finding. We now know to look for it, and cancounsel families that their children are likely to have deficits thatextend beyond motor, and that may benefit from early intervention."
A study presented mid-September, at the American Academy of CerebralPalsy and Developmental Medicine meeting, documents the magnitude ofthese problems. Limperopoulos and colleagues compared 31 toddlers, bornprematurely and identified at birth as having cerebellar hemorrhage(but no cerebral injury) with 31 controls who were also bornprematurely, but whose brain imaging studies were normal. In additionto motor problems, over half the children with cerebellar injury hadfunctional limitations in daily living, communication, andsocialization skills, compared with only 3 percent of controls.Sixty-one percent, versus 3 percent of controls, had globaldevelopmental delays. Deficits included delays in both expressive andreceptive language, visual reception delays, and impaired social andbehavioral function.
Limperopoulos and colleagues continue to follow children who wereidentified at birth as having cerebellar injury. The children undergo abattery of wide-ranging developmental tests including assessment ofmotor, cognitive, language, social and behavioral skills and tests offunctional abilities in self-care and day-to-day activities.Comprehensive MRI studies are paying particular attention to structuralconnections between the cerebrum and cerebellum -- how the nerve fibersrun 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 bestindicator of how a child will do."
Children's Hospital Boston is home to the world's largest researchenterprise based at a pediatric medical center, where its discoverieshave benefited both children and adults since 1869. More than 500scientists, including eight members of the National Academy ofSciences, nine members of the Institute of Medicine and 10 members ofthe Howard Hughes Medical Institute comprise Children's researchcommunity. Founded as a 20-bed hospital for children, Children'sHospital Boston today is a 347-bed comprehensive center for pediatricand adolescent health care. Children's also is the primary pediatricteaching affiliate of Harvard Medical School. For more informationvisit: http://www.childrenshospital.org/research/.
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