A Very Spatial Brain Defect: Gene disorder blocks neural path for vision

Among its many unusual symptoms, the genetic disorder called Williams syndrome robs people of depth perception and the ability to visualize how different parts assemble into larger objects, as in a simple jigsaw puzzle.

An unusual scarcity of tissue in a small corner of the visual system underlies this particular problem in individuals with Williams syndrome, a new brain-imaging study finds. It appears that, at least with respect to vision, this genetic condition creates a slight defect in an otherwise typical brain.

In contrast, some researchers have proposed that a unique course of brain development occurs in Williams syndrome, which is linked to a missing, roughly 20-gene section of chromosome 7 (SN: 2/26/00, p. 142: Available to subscribers at Genes to Grow On).

“A very circumscribed abnormality of visual processing characterizes the brain in Williams syndrome,” says neuroscientist and study director Andreas Meyer-Lindenberg of the National Institute of Mental Health (NIMH) in Bethesda, Md. He cautions, however, that other symptoms of the disorder, such as extreme gregariousness toward strangers and difficulty understanding metaphors and other forms of abstract thought, may derive from much broader neural disruptions.

Meyer-Lindenberg and his NIMH colleagues describe their findings in the Sept. 2 Neuron.

The researchers tied vision difficulties in Williams syndrome to a shortage of neurons in part of the brain network that locates objects in space and discerns spatial relationships among objects. Another brain network that identifies different objects, as well as a region that receives nerve signals from the eyes, showed no impairment in Williams syndrome, the scientists say.

Meyer-Lindenberg’s team used functional magnetic resonance imaging (fMRI) to track blood flow throughout the brains of 13 adults with Williams syndrome and 11 adults with no genetic disorders. Both groups performed two tasks. One involved assessing whether pairs of puzzle pieces could fit together to form a square; the other required determining whether two images were situated at the same height on a computer screen.

Analyses of blood flow showed that the people with Williams syndrome had weaker neural activity in a marble-size section of the brain’s network for making spatial judgments. Scans of brain anatomy then revealed a deficit of tissue in an adjacent area of the same network among the volunteers with Williams syndrome. Impairment of that small area partially blocks transmission of visual information to the brain region that displays weak activity in fMRI images from those participants, Meyer-Lindenberg theorizes.

Although Williams syndrome usually includes mild-to-moderate mental retardation, all participants in the new study scored in the average range on intelligence tests. This removed the possibility that retardation-related processes in the brain somehow affected the visual systems of Williams syndrome volunteers.

Preliminary evidence from the same participants also links Williams syndrome to a lack of tissue in a frontal brain area already implicated in social behavior, including fear responses to strangers, the NIMH scientist says.

Although the neural basis of the social and intellectual profile of Williams syndrome remains poorly understood, Meyer-Lindenberg and his coworkers have clarified the syndrome’s visual-system defect, comments neuropsychologist Helen Tager-Flusberg of Boston University School of Medicine in an editorial published with the new study.