Neuropsychological and neuroimaging changes have been observed in
individuals with the Huntington's disease (HD) gene expansion prior
to the onset of manifest HD. This cross-sectional fMRI study of
preclinical HD (pre-HD) individuals was conducted to determine if
functional brain changes precede deficits in behavioral performance and
striatal atrophy. Twenty-six pre-HD and 13 demographically matched healthy
participants performed a time reproduction task while undergoing fMRI
scanning. Pre-HD participants were divided into two groups (n =
13 each): FAR (>12 years to estimated onset [YEO] of manifest
HD) and CLOSE (<12 YEO). The CLOSE group demonstrated behavioral
deficits, striatal atrophy, and reduced neural activation in the left
putamen, SMA, left anterior insula and right inferior frontal gyrus. The
FAR group showed reduced neural activation in the right anterior cingulate
and right anterior insula. The FAR group also demonstrated
increased neural activation in the left sensorimotor, left medial
frontal gyrus, left precentral gyrus, bilateral superior temporal gyri and
right cerebellum. The fMRI changes in the FAR group occurred in the
relative absence of striatal atrophy and behavioral performance deficits.
These results suggest that fMRI is sensitive to neural dysfunction
occurring more than 12 years prior to the estimated onset of manifest HD.
(JINS, 2007, 13, 758–769.)