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Multicenter Study
. 2015 Oct;36(10):3717-32.
doi: 10.1002/hbm.22835. Epub 2015 Jul 14.

Prefrontal Cortex White Matter Tracts in Prodromal Huntington Disease

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Free PMC article
Multicenter Study

Prefrontal Cortex White Matter Tracts in Prodromal Huntington Disease

Joy T Matsui et al. Hum Brain Mapp. .
Free PMC article

Abstract

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. Hum Brain Mapp 36:3717-3732, 2015. © 2015 Wiley Periodicals, Inc.

Keywords: Huntington's disease; cross-sectional analysis; diffusion tensor imaging; diffusion tractography; diffusion weighted MRI; multicenter studies; prefrontal cortex.

Conflict of interest statement

Conflict of interest: Jane S. Paulsen has served on an advisory board for Lundbeck, LLC and has a consulting agreement with ProPhase, LLC.

Figures

Figure I
Figure I
T1-weighted (top) and DTI (bottom) templates that are encoded with color maps.
Figure II
Figure II
White matter tracts extending to the prefrontal cortex that were examined in this study are highlighted with different colors: left uncinate fasciculus (light blue), right uncinate fasciculus (dark blue), anatomical prefrontal white matter tracts of the corpus callosum (yellow), left inferior fronto-occipital fasciculus (light red), right inferior fronto-occipital fasciculus (dark red), left anterior thalamic radiations (light green), and right anterior thalamic radiations (dark green).
Figure III
Figure III
Percentages of voxels in each tract skeleton containing significant differences in diffusion tensor image scalars between controls and CAG-age product (CAP) groups. These results were acquired with the threshold-free cluster enhancement method at 50,000 permutations and corrected with false discovery rate at a criterion of q < 0.05 for left (l) and right (r). More details are shown in Figure IV and Figure V. Abbreviations: PFCC, anatomical prefrontal WM tracts of the corpus callosum; ATR(l), anterior thalamic radiations left; ATR(r), anterior thalamic radiations right; IFO(l), inferior fronto-occipital fasciculus left; IFO(r), inferior fronto-occipital fasciculus right; UNC(l), uncinate fasciculus left; UNC(r), uncinate fasciculus right; FA, fractional anisotropy; AD, axial diffusivity; RD, radial diffusivity; MD, mean diffusivity.
Figure IV
Figure IV
Detailed differences in diffusion tensor image scalars between control and High CAG-age product (CAP) groups. Plots of mean diffusion tensor image scalars across tract skeleton voxels that contained significant differences between Control and High CAG-age product (CAP) groups for each participant. These results were acquired with the threshold-free cluster enhancement method at 50,000 permutations and corrected with false discovery rate at a criterion of q < 0.05 for left (l) and right (r). Abbreviations: PFCC, anatomical prefrontal WM tracts of the corpus callosum; ATR(l), anterior thalamic radiations left; ATR(r), anterior thalamic radiations right; IFO(l), inferior fronto-occipital fasciculus left; IFO(r), inferior fronto-occipital fasciculus right; UNC(l), uncinate fasciculus left; UNC(r), uncinate fasciculus right; FA, fractional anisotropy; AD, axial diffusivity; RD, radial diffusivity; MD, mean diffusivity.
Figure V
Figure V
Detailed differences in diffusion tensor image scalars between control and Medium CAG-age product (CAP) groups. Plots of mean diffusion tensor image scalars across tract skeleton voxels that contained significant differences between control and Medium CAG-age product (CAP) groups for each participant. These results were acquired with the threshold-free cluster enhancement method at 50,000 permutations and corrected with false discovery rate at a criterion of q < 0.05 for left (l) and right (r). Abbreviations: PFCC, anatomical prefrontal WM tracts of the corpus callosum; ATR(l), anterior thalamic radiations left; ATR(r), anterior thalamic radiations right; IFO(l), inferior fronto-occipital fasciculus left; IFO(r), inferior fronto-occipital fasciculus right; AD, axial diffusivity; MD, mean diffusivity; RD, radial diffusivity; Med, medium.
Figure VI
Figure VI
Percentages of voxels in each tract skeleton containing significant correlations between diffusion tensor image scalars and cognitive variables that showed decreased anisotropy was related to cognitive decline for prodromal Huntington disease participants. These results were acquired with the threshold-free cluster enhancement method with 50,000 permutations and corrected with false discovery rate at a criterion of q < 0.05. Abbreviations: TMTA, Trail Making Test A; TMTB, Trail Making Test B; SDMT, Symbol Digit Modalities Test; S Word, Stroop Color and Word Test – word condition; S Color, Stroop Color and Word Test – color condition; PFCC, anatomical prefrontal WM tracts of the corpus callosum; ATR(l), anterior thalamic radiations left; ATR(r), anterior thalamic radiations right; IFO(l), inferior fronto-occipital fasciculus left; IFO(r), inferior fronto-occipital fasciculus right; UNC(l), uncinate fasciculus left; UNC(r), uncinate fasciculus right; FA, fractional anisotropy; AD, axial diffusivity; RD, radial diffusivity; MD, mean diffusivity.

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