title: Major Superficial White Matter Abnormalities in Huntington's Disease.
abstract: BACKGROUND
  The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes.
  
  
  METHODS
  Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease.
  
  
  RESULTS
  There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001).
  
  
  CONCLUSIONS
  This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease.
authors.affiliation: Morphology and Morphometry for NeuroImaging Lab, Clinical and Behavioural Neurology Department, IRCCS Fondazione Santa LuciaRome, Italy; Neuroscience Department, University of Rome "Tor Vergata"Rome, Italy.
authors.forename: Owen R
authors.initials: OR
authors.lastname: Phillips
authors.affiliation: Ahmanson Lovelace Brain Mapping Center, Neurology, University of California Los Angeles Los Angeles, CA, USA.
authors.forename: Shantanu H
authors.initials: SH
authors.lastname: Joshi
authors.affiliation: IRCCS Casa Sollievo della SofferenzaSan Giovanni Rotondo, Italy; CSS-MendelRome, Italy; Lega Italiana Ricerca Huntington FoundationRome, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
authors.affiliation: Radiology Department, IRCCS Santa Lucia FoundationRome, Italy; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, IDIBAPSBarcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sanchez-Castaneda
authors.affiliation: Ahmanson Lovelace Brain Mapping Center, Neurology, University of California Los Angeles Los Angeles, CA, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Narr
authors.affiliation: Ahmanson Lovelace Brain Mapping Center, Neurology, University of California Los Angeles Los Angeles, CA, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Shattuck
authors.affiliation: Neuroscience Department, University of Rome "Tor Vergata"Rome, Italy; Clinical and Behavioural Neurology Department, IRCCS Fondazione Santa LuciaRome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Radiology Department, IRCCS Santa Lucia FoundationRome, Italy; Neuroradiology, University of Magna GraeciaCatanzaro, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Sabatini
authors.affiliation: Morphology and Morphometry for NeuroImaging Lab, Clinical and Behavioural Neurology Department, IRCCS Fondazione Santa LuciaRome, Italy; Human Studies Department, Libera Università Maria SS. Assunta (LUMSA)Rome, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Di Paola
keywords: CAG repeat length; DTI diffusion; Huntington's disease; MRI; intracortical myelin; movement disorders; oligodendrocyte; white matter