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Diffusion Tensor Imaging in Huntington’s disease reveals distinct patterns of white matter degeneration associated with motor and cognitive deficits

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Abstract

White matter (WM) degeneration is an important feature of Huntington’s disease (HD) neuropathology. To investigate WM degeneration we used Diffusion Tensor Imaging and Tract-Based Spatial Statistics to compare Fractional Anisotropy, Mean Diffusivity (MD), parallel diffusivity and perpendicular diffusivity (λ⊥) in WM throughout the whole brain in 17 clinically diagnosed HD patients and 16 matched controls. Significant WM diffusivity abnormalities were identified primarily in the corpus callosum (CC) and external/extreme capsules in HD patients compared to controls. Significant correlations were observed between motor symptoms and MD in the CC body, and between global cognitive impairment and λ⊥ in the CC genu. Probabilistic tractography from these regions revealed degeneration of functionally relevant interhemispheric WM tracts. Our findings suggest that WM degeneration within interhemispheric pathways plays an important role in the deterioration of cognitive and motor function in HD patients, and that improved understanding of WM pathology early in the disease is required.

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Abbreviations

HD:

Huntington’s disease

WM:

White matter

DTI:

Diffusion Tensor Imaging

TBSS:

Tract-Based Spatial Statistics

FA:

Fractional Anisotropy

λ⊥:

Perpendicular diffusivity

λ||:

Parallel diffusivity

MD:

Mean Diffusivity

ROI:

Region-of-interest

UHDRS:

Unified Huntington’s Disease Rating Scale

MMSE:

Mini Mental State Examination

BDI:

Beck Depression Inventory

CAG:

Cytosine-adenine-guanine

YSD:

Years since diagnosis

NART:

National Adult Reading Test

TR:

Repetition time

TE:

Echo time

FDT:

FMRIBs Diffusion Toolbox

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Acknowledgements

This study was funded by grant number 234247 from the National Health and Medical Research Council (Australia). We sincerely thank all participants for their time and effort. We also thank the Brain Research Institute (Austin Hospital) for the use of the 3T GE scanner. This study was carried out at School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Victoria 3800, Australia. IB is supported by an Australian Rotary Health scholarship.

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Authors and Affiliations

  1. Howard Florey Institute, Florey Neuroscience Institutes, Parkville, Victoria, Australia

    India Bohanna, Hamed Asadi, Leigh Johnston & Gary Egan

  2. Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia

    India Bohanna, Hamed Asadi & Gary Egan

  3. Experimental Neuropsychology Research Unit, School of Psychology and Psychiatry, Monash University, Clayton, Victoria, 3800, Australia

    Nellie Georgiou-Karistianis & Anusha Sritharan

  4. Department of Electrical and Electronic Engineering, University of Melbourne, Parkville, Victoria, Australia

    Leigh Johnston

  5. Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia

    Andrew Churchyard

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  1. India Bohanna
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  2. Nellie Georgiou-Karistianis
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  3. Anusha Sritharan
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  4. Hamed Asadi
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  5. Leigh Johnston
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  7. Gary Egan
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Correspondence to Nellie Georgiou-Karistianis.

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Supplementary Fig. 1

The ability of TBSS to identify the white matter tract skeleton in controls and both mild and moderate HD patients. The image clearly demonstrates the ability of the automated TBSS method to identify the major white matter pathways. (JPEG 128 kb)

High resolution image (TIFF 1907 kb)

Supplementary Fig. 2

Effect of using different thresholds on the group tract maps in HD patients, in (A) tracts from the ROI where MMSE and λ^ were correlated; and (B) tracts from the ROI where UHDRS and MD were correlated. Images show pathways present in between 5.9% (1/17) and 100% (17/17) of HD patients. A final threshold of 47% (8/17) was chosen to identify pathways that were common amongst individuals while still allowing the variability amongst individuals to be represented. (JPEG 3377 kb)

High resolution image (TIFF 9561 kb)

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Bohanna, I., Georgiou-Karistianis, N., Sritharan, A. et al. Diffusion Tensor Imaging in Huntington’s disease reveals distinct patterns of white matter degeneration associated with motor and cognitive deficits. Brain Imaging and Behavior 5, 171–180 (2011). https://doi.org/10.1007/s11682-011-9121-8

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