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A genetic disorder yields insight into genes and cognition

02.09.2004


Researchers attempting to understand the stunningly complex machinery by which genes give rise to the brain often find invaluable clues in genetic disorders that affect brain structure and function.



Andreas Meyer-Lindenberg and his colleagues have gained just such clues by studying the brain function of sufferers of Williams syndrome (WS). This rare disorder, caused by the deletion of a specific chromosome segment, can cause mental retardation, physical abnormalities, and personality disorder. But most intriguing to Meyer-Lindenberg and his colleagues is that the disorder causes a specific inability to visualize an object as a set of parts--for example, to assemble a simple piece of furniture.

In brain-imaging studies of people with WS, the researchers sought to shed light on the neurological malfunction that underlies this inability. In particular, they sought to determine whether the functional disorder could reveal the "modularity" of the processing of visual information in the brain’s visual cortex.


The visual cortex is basically organized into two processing pathways--a ventral pathway that processes the identity of objects and a dorsal pathway that processes spatial information on them. Thus, reasoned the researchers, the weakness in "visuospatial construction" in people with WS likely lies in the dorsal pathway.

In their experiments, the researchers performed functional magnetic resonance imaging (fMRI) of the brains of 13 volunteers with WS, as they asked the volunteers to perform two perceptual tasks. Such fMRI imaging involves using harmless magnetic fields and radio waves to image blood flow in the brain, which reveals brain activity.

In one set of experiments, the researchers asked the subjects to determine whether sets of geometric shapes could be assembled into a square. In another, they asked the patients to concentrate on either the identity of images of faces or houses, or their location. In normal people, attention to identity would activate the ventral stream, and attention to location would activate the dorsal stream.

The fMRI images revealed that the people with WS showed significantly lower neural activity in the dorsal stream of the visual cortex.

Higher-resolution structural MRI imaging revealed a reduction in the volume of gray matter in an adjacent brain region. The researchers’ studies also showed that impaired input from this region could cause the reduced function.

The researchers concluded that "Our observations confirm a longstanding hypothesis about dorsal stream dysfunction in WS, demonstrate effects of a localized abnormality on visual information processing in humans, and define a systems-level phenotype for mapping genetic determinants of visuoconstructive function."

Such insights, they said, should help scientists trace the genetic origin and molecular causes of the disorder.

Heidi Hardman | EurekAlert!
Further information:
http://www.cell.com

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