Albert Galaburda, MD
Landau Professor of Neurology
Harvard Medical School
Professor of Neurology
Beth Israel Deaconess Medical Center

MRRC Project(s)

P01 HD33113 01
Williams Syndrome: Bridging Cognition and Gene
PI, Project V: Brain Cytoarchitectonic Characterization

Learning disabilities affect an appreciable portion of the childhood population and the biological tendencies are not outgrown, such that the handicap often continues into adult life. We have concentrated on two learning disabilities: Developmental Dyslexia (DD) and Williams Syndrome (WMS).

DD represents primarily a disorder of language processing, observed most obviously in, but not restricted to, written language. We have focused our work on defining the brain systems involved in the perceptual and cognitive problems seen in this disorder and the relationships among them during development. For this work we have been guided by observations made on human autopsy brains, some of which observations have been implemented in animal models, where causal mechanisms can be studied. DD subjects exhibit difficulties with temporal processing of rapidly changing sounds. Yet, this difficulty is not easily seen in spoken language production or comprehension, but only in reading and writing. This finding implies a separate involvement of systems capable of cognitive processes upon phonologies, so-called metaphonological processes. We have contrasted involvement of systems involved in perception with those involved in cognitive and meta-cognitive functions. We have engaged in a multilevel approach using architectonics, histometry, connectivity, cellular electrophysiology, immunohistochemistry, behavior, and evoked potentials, some through collaborations with other laboratories.

Williams Syndrome (WMS) provides an opportunity to correlate genes and behaviors. WMS results from a hemizygous deletion in the region of chromosome 7q11.23, spanning approximately 20 genes between FZD9, on the centromeric end, and GTF2I, on the telomeric end. In addition to specific involvement of musculoskeletal and organ systems, related in part to the absence of elastin, patients with WMS show a striking fractionation of their cognitive profile, with remarkable sparing of language and social functions, but impaired visuo-spatial abilities and face processing. The discovery of partial deletions is helping to assign specific roles to the different genes involved, with a recent realization that GTF2I and GTF2IRD may be important contributors to the visuo-spatial deficits. This work represents a collaboration of our laboratory and others with expertise in cognitive psychology, clinical electrophysiology, structural and functional neuroimaging, genetics, and neuroanatomy.