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Prefrontal Cortex White Matter Tracts in Prodromal Huntington Disease

Institution:
1Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
2EPI Athena, INRIA Sophia Antipolis-Méditerranée, Sophia Antipolis, France.
Publisher:
Wiley
Publication Date:
Oct-2015
Journal:
Hum Brain Mapp
Volume Number:
36
Issue Number:
10
Pages:
3717-32
Citation:
Hum Brain Mapp. 2015 Oct;36(10):3717-32.
PubMed ID:
26179962
PMCID:
PMC4583330
Appears in Collections:
NA-MIC, SLICER
Sponsors:
R01 NS040068/NS/NINDS NIH HHS/United States
R01 NS054893/NS/NINDS NIH HHS/United States
S10 RR023392/RR/NCRR NIH HHS/United States
U54 EB005149/EB/NIBIB NIH HHS/United States
Generated Citation:
Matsui J.T., Vaidya J.G., Wassermann D., Kim R.E., Magnotta V.A., Johnson H.J., Paulsen J.S. Prefrontal Cortex White Matter Tracts in Prodromal Huntington Disease. Hum Brain Mapp. 2015 Oct;36(10):3717-32. PMID: 26179962. PMCID: PMC4583330.
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Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large-scale analysis using multisite diffusion-weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT-HD study collected imaging and neuropsychological data on gene-positive HD participants without a clinical diagnosis (i.e., prodromal) and gene-negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto-occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG-age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long-range tracts essential for cross-region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage.

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