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Abstract:
Abstract: Fragile X syndrome (fraX) is a neurogenetic
disorder that is the most common heritable cause of
neurodevelopmental disability. FraX results from trinucleotide
expansion within, and consequent silencing of the FMR-1 gene
leading to reduced FMR-1 protein (FMRP) levels in the brain.
Prominent components of the neuropsychological profile include
impairments in visuospatial processing and executive function. We
used functional magnetic resonance imaging to examine visuospatial
working memory (WM) in 10 females with fraX and 15 normal females
(ages 10 - 22) using standard 1-back and 2-back tasks. Brain
activation was examined in four regions of the cortex known to play
a role in WM: middle and inferior frontal gyri, superior parietal
lobule, and supramarginal gyrus. Relative to controls, fraX
subjects showed significantly reduced performance for the 2-back
task. Whereas control subjects showed increased activation in all
brain regions between the 1-back and 2-back tasks, fraX subjects
showed little change in activation between the two tasks.
Significant correlations were found between FMRP and activation in
the right inferior and bilateral middle frontal gyri and the
bilateral supramarginal gyri. These findings suggest that fraX
subjects are unable to modulate activation in the prefrontal and
parietal cortex in response to increasing WM load, and that these
deficits are related to decreased FMRP expression.
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