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 “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.”
In the fMRI phase of the study, participants were scanned
while performing spatial tasks — matching geometric
objects, assembling puzzle-like pieces into a square, and
attending to the location of faces and houses. In each
case, only those with Williams Syndrome failed to activate
the “where” circuit, while the controls showed increased
activation in that circuit. The patients’ brains showed no
difference from controls on tasks that activated the
“what” circuit.
Using structural MRI, the researchers found a small region
early in the “where” circuit that lacked gray matter
(neuron bodies) in the Williams Syndrome participants. Its
location — conspicuously just before the functionally
abnormal areas — raised suspicions; and a path analysis
confirmed that the functional abnormalities could be
accounted for by defective input from this structurally
abnormal area. The researchers hypothesize that it is
likely the primary site of the visuospatial construction
deficit.