Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical "disconnection".
The corpus callosum (CC) is the major conduit for information transfer between the cerebral hemispheres and plays an integral role in relaying sensory, motor and cognitive information between homologous cortical regions. The majority of fibers that make up the CC arise from large pyramidal neurons in layers III and V, which project contra-laterally. These neurons degenerate in Huntington's disease (HD) in a topographically and temporally selective way. Since any focus of cortical degeneration could be expected to secondarily de-afferent homologous regions of cortex, we hypothesized that regionally selective cortical degeneration would be reflected in regionally selective degeneration of the CC. We used conventional T1-weighted, diffusion tensor imaging (DTI), and a modified corpus callosum segmentation scheme to examine the CC in healthy controls, huntingtin gene-carriers and symptomatic HD subjects. We measured mid-sagittal callosal cross-sectional thickness and several DTI parameters, including fractional anisotropy (FA), which reflects the degree of white matter organization, radial diffusivity, a suggested index of myelin integrity, and axial diffusivity, a suggested index of axonal damage of the CC. We found a topologically selective pattern of alterations in these measures in pre-manifest subjects that were more extensive in early symptomatic HD subjects and that correlated with performance on distinct cognitive measures, suggesting an important role for disrupted inter-hemispheric transfer in the clinical symptoms of HD. Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing.
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. rosas@helix.mgh.harvard.edu
H Diana
HD
Rosas
Stephanie Y
SY
Lee
Alexander C
AC
Bender
Alexandra K
AK
Zaleta
Mark
M
Vangel
Peng
P
Yu
Bruce
B
Fischl
Vasanth
V
Pappu
Christina
C
Onorato
Jang-Ho
JH
Cha
David H
DH
Salat
Steven M
SM
Hersch
D000328:Adult; D003337:Corpus Callosum / Q000473:pathology*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*