3-D MRI scan rendering of the brains white matter (nerve fibers), showing small area (yellow) found to lack grey matter in people with Williams Syndrome. Impaired input from this area is thought to have resulted in lack of activation in downstream parts of the circuit, which processes locations of objects, when participants performed visual-spatial tasks, such as paying attention to locations of faces and houses (red), assembling puzzle-like pieces and matching geometric objects (blue). Overlap regions are shown in purple. Source: Shane Kippenhan, Ph.D.,
NIMH Clinical Brain Disorders Branch
The structurally abnormal site is obscured within the cortexs folds in this full rendering of the brain, showing the functionally abnormal circuit. Source: Shane Kippenhan, Ph.D., NIMH Clinical Brain Disorders Branch
Using brain imaging, neuroscientists at the NIH’s National Institute of Mental Health (NIMH) have pinpointed the site of a defect in a brain circuit associated with a specific thinking deficit. Their study demonstrates how a rare genetic disorder, Williams Syndrome, can offer clues as to how genetic flaws may translate into cognitive symptoms in more common and complex major mental disorders. Andreas Meyer-Lindenberg, M.D., Karen Berman, M.D., and colleagues, traced the thinking deficit to a circuit at the back of the brain that processes locations of objects in the visual field. The researchers report on their Magnetic Resonance Imaging (MRI) study in the September 2, 2004 Neuron.
The study focused on the inability to visualize an object as a set of parts and then construct a replica, as in assembling a puzzle – a key cognitive deficit experienced by people with Williams Syndrome. In addition to this visuospatial construction deficit, people with Williams Syndrome also tend to be overly friendly and anxious and often have mental retardation and learning disabilities. Compared to most mental disorders, which are thought to involve complex interactions between multiple genes and environmental triggers, the genetic basis of Williams Syndrome is remarkably well understood. People with the disorder lack about 21 genes in a particular part of chromosome 7.
"Williams Syndrome yields a unique opportunity to study how genes influence our ability to construct our social and spatial worlds," said NIMH Director Thomas Insel, M.D. "By studying people with this disorder, we can discover how genetic mutations change not only molecular and cellular processes, but lead to differences in the brain circuitry for complex aspects of cognition."
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