Multimodal MRI analysis of the corpus callosum reveals white matter differences in presymptomatic and early Huntington's disease

M. Di Paola, E. Luders, A. Cherubini, C. Sanchez-Castaneda, P. M. Thompson, A. W. Toga, C. Caltagirone, S. Orobello, F. Elifani, F. Squitieri, U. Sabatini

Research output: Contribution to journalArticlepeer-review


Recent magnetic resonance imaging (MRI) studies suggest that abnormalities in Huntington's disease (HD) extend to white matter (WM) tracts in early HD and even in presymptomatic stages. Thus, changes of the corpus callosum (CC) may reflect various aspects of HD pathogenesis. We recruited 17 HD patients, 17 pre-HD subjects, and 34 healthy age-matched controls. Three-dimensional anatomical MRI and diffusion tensor images of the brain were acquired on a 3T scanner. Combining region-of-interest analyses, voxel-based morphometry, and tract-based spatial statistics, we investigated callosal thickness, WM density, fractional anisotropy, and radial and axial diffusivities. Compared with controls, pre-HD subjects showed reductions of the isthmus, likely due to myelin damage. Compared with pre-HD subjects, HD patients showed reductions of isthmus and body, with axonal damage confined to the body. Compared with controls, HD patients had significantly decreased callosal measures in extended regions across almost the entire CC. At this disease stage, both myelin and axonal damage are detectable. Supplementary multiple regression analyses revealed that WM reduction density in the isthmus as well as Disease Burden scores allowed to predict the "HD development" index. While callosal changes seem to proceed in a posterior-to-anterior direction as the diseases progresses, this observation requires validation in future longitudinal investigations.

Original languageEnglish
Pages (from-to)2858-2866
Number of pages9
JournalCerebral Cortex
Issue number12
Publication statusPublished - Dec 2012


  • axonal demyelination
  • diffusion tensor imaging
  • region of interest
  • voxel-based morphometry
  • Wallerian degeneration
  • white matter changes

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Multimodal MRI analysis of the corpus callosum reveals white matter differences in presymptomatic and early Huntington's disease'. Together they form a unique fingerprint.

Cite this