| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Department of Neurology (Drs. Rosas and Hersch), Massachusetts General Hospital and Harvard Medical School, and Departments of Neurology, Pathology, and Psychiatry (Dr. Ferrante), Boston University School of Medicine; MGH-NMR Center (Drs. Rosas, Liu, Salat, van der Kouwe, Jenkins, Dale, and Fischl, M. Glessner), Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown; and Geriatric Research Education and Clinical Center (Dr. Ferrante), Bedford VA Medical Center, MA.
Address correspondence and reprint requests to Dr. H.D. Rosas, Department of Neurology, Massachusetts General Hospital, MGH East, Bldg. 114, Suite 2000, 114 16th Street, Charlestown, MA 02129-4404; e-mail: rosas{at}helix.mgh.harvard.edu
Background: Huntington’s disease (HD) is a fatal and progressive neurodegenerative disease that is accompanied by involuntary movements, cognitive dysfunction, and psychiatric symptoms. Although progressive striatal degeneration is known to occur, little is known about how the disease affects the cortex, including which cortical regions are affected, how degeneration proceeds, and the relationship of the cortical degeneration to clinical symptoms. The cortex has been difficult to study in neurodegenerative diseases primarily because of its complex folding patterns and regional variability; however, an understanding of how the cortex is affected by the disease may provide important new insights into it.
Methods: Novel automated surface reconstruction and high-resolution MR images of 11 patients with HD and 13 age-matched subjects were used to obtain cortical thickness measurements. The same analyses were performed on two postmortem brains to validate these methods.
Results: Regionally specific heterogeneous thinning of the cortical ribbon was found in subjects with HD. Thinning occurred early, differed among patients in different clinical stages of disease, and appeared to proceed from posterior to anterior cortical regions with disease progression. The sensorimotor region was statistically most affected. Measurements performed on MR images of autopsy brains analyzed similarly were within 0.25 mm of those obtained using traditional neuropathologic methods and were statistically indistinguishable.
Conclusions: The authors propose that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD. These measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications.
This article has been cited by other articles:
|
|
 |
|
  B. C. Dickerson, A. Bakkour, D. H. Salat, E. Feczko, J. Pacheco, D. N. Greve, F. Grodstein, C. I. Wright, D. Blacker, H. D. Rosas, et al. The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals Cereb Cortex, July 16, 2008; (2008) bhn113v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.M. Fjell, K.B. Walhovd, I. Amlien, A. Bjornerud, I. Reinvang, L. Gjerstad, T. Cappelen, F. Willoch, P. Due-Tonnessen, R. Grambaite, et al. Morphometric Changes in the Episodic Memory Network and Tau Pathologic Features Correlate with Memory Performance in Patients with Mild Cognitive Impairment AJNR Am. J. Neuroradiol., June 1, 2008; 29(6): 1183 - 1189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. Rosas, D. H. Salat, S. Y. Lee, A. K. Zaleta, V. Pappu, B. Fischl, D. Greve, N. Hevelone, and S. M. Hersch Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity Brain, April 1, 2008; 131(4): 1057 - 1068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Luo, H. Mizuta, and D. C. Rubinsztein p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and enhances toxicity Hum. Mol. Genet., March 15, 2008; 17(6): 895 - 905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kloppel, B. Draganski, C. V. Golding, C. Chu, Z. Nagy, P. A. Cook, S. L. Hicks, C. Kennard, D. C. Alexander, G. J. M. Parker, et al. White matter connections reflect changes in voluntary-guided saccades in pre-symptomatic Huntington's disease Brain, January 1, 2008; 131(1): 196 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Feigin, C. Tang, Y. Ma, P. Mattis, D. Zgaljardic, M. Guttman, J. S. Paulsen, V. Dhawan, and D. Eidelberg Thalamic metabolism and symptom onset in preclinical Huntington's disease Brain, November 1, 2007; 130(11): 2858 - 2867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Strand, Z. C. Baquet, A. K. Aragaki, P. Holmans, L. Yang, C. Cleren, M. F. Beal, L. Jones, C. Kooperberg, J. M. Olson, et al. Expression Profiling of Huntington's Disease Models Suggests That Brain-Derived Neurotrophic Factor Depletion Plays a Major Role in Striatal Degeneration J. Neurosci., October 24, 2007; 27(43): 11758 - 11768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Y. Heng, S. J. Tallaksen-Greene, P. J. Detloff, and R. L. Albin Longitudinal Evaluation of the Hdh(CAG)150 Knock-In Murine Model of Huntington's Disease J. Neurosci., August 22, 2007; 27(34): 8989 - 8998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Kipps, A. J. Duggins, E. A. McCusker, and A. J. Calder Disgust and Happiness Recognition Correlate with Anteroventral Insula and Amygdala Volume Respectively in Preclinical Huntington's Disease. J. Cogn. Neurosci., July 1, 2007; 19(7): 1206 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gomez-Anson, M. Alegret, E. Munoz, A. Sainz, G. C. Monte, and E. Tolosa Decreased frontal choline and neuropsychological performance in preclinical Huntington disease Neurology, March 20, 2007; 68(12): 906 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Goghari, K. Rehm, C. S. Carter, and A. W. MacDonald III Regionally Specific Cortical Thinning and Gray Matter Abnormalities in the Healthy Relatives of Schizophrenia Patients Cereb Cortex, February 1, 2007; 17(2): 415 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. I. Wright, D. Williams, E. Feczko, L. F. Barrett, B. C. Dickerson, C. E. Schwartz, and M. M. Wedig Neuroanatomical Correlates of Extraversion and Neuroticism Cereb Cortex, December 1, 2006; 16(12): 1809 - 1819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Schaechter, C. I. Moore, B. D. Connell, B. R. Rosen, and R. M. Dijkhuizen Structural and functional plasticity in the somatosensory cortex of chronic stroke patients Brain, October 1, 2006; 129(10): 2722 - 2733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hadjikhani, R. M. Joseph, J. Snyder, and H. Tager-Flusberg Anatomical Differences in the Mirror Neuron System and Social Cognition Network in Autism Cereb Cortex, September 1, 2006; 16(9): 1276 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Finke, P. Bublak, M. Dose, H. J. Muller, and W. X. Schneider Parameter-based assessment of spatial and non-spatial attentional deficits in Huntington's disease Brain, May 1, 2006; 129(5): 1137 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Brandt, B Shpritz, C A Munro, L Marsh, and A Rosenblatt Differential impairment of spatial location memory in Huntington's disease J. Neurol. Neurosurg. Psychiatry, November 1, 2005; 76(11): 1516 - 1519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Martinussen, B. Fischl, H. B. Larsson, J. Skranes, S. Kulseng, T. R. Vangberg, T. Vik, A.-M. Brubakk, O. Haraldseth, and A. M. Dale Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method Brain, November 1, 2005; 128(11): 2588 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
WCHD abstracts: poster programme J. Neurol. Neurosurg. Psychiatry, October 1, 2005; 76(suppl_4): A27 - A54. [Full Text] [PDF]
|
|
|
|
|
|
H. D. Rosas, N. D. Hevelone, A. K. Zaleta, D. N. Greve, D. H. Salat, and B. Fischl Regional cortical thinning in preclinical Huntington disease and its relationship to cognition Neurology, September 13, 2005; 65(5): 745 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Milad, B. T. Quinn, R. K. Pitman, S. P. Orr, B. Fischl, and S. L. Rauch Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory PNAS, July 26, 2005; 102(30): 10706 - 10711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Miller, M. F. Beg, C. Ceritoglu, and C. Stark Increasing the power of functional maps of the medial temporal lobe by using large deformation diffeomorphic metric mapping PNAS, July 5, 2005; 102(27): 9685 - 9690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Lerch, J. C. Pruessner, A. Zijdenbos, H. Hampel, S. J. Teipel, and A. C. Evans Focal Decline of Cortical Thickness in Alzheimer's Disease Identified by Computational Neuroanatomy Cereb Cortex, July 1, 2005; 15(7): 995 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kassubek, F. D. Juengling, D. Ecker, and G. B. Landwehrmeyer Thalamic Atrophy in Huntington's Disease Co-varies with Cognitive Performance: A Morphometric MRI Analysis Cereb Cortex, June 1, 2005; 15(6): 846 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C M Kipps, A J Duggins, N Mahant, L Gomes, J Ashburner, and E A McCusker Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study J. Neurol. Neurosurg. Psychiatry, May 1, 2005; 76(5): 650 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fennema-Notestine, S. L. Archibald, M. W. Jacobson, J. Corey-Bloom, J. S. Paulsen, G. M. Peavy, A. C. Gamst, J. M. Hamilton, D. P. Salmon, and T. L. Jernigan In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease Neurology, September 28, 2004; 63(6): 989 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mascalchi, F. Lolli, R. D. Nave, C. Tessa, R. Petralli, C. Gavazzi, L. S. Politi, M. Macucci, M. Filippi, and S. Piacentini Huntington Disease: Volumetric, Diffusion-weighted, and Magnetization Transfer MR Imaging of Brain Radiology, September 1, 2004; 232(3): 867 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Salat, R. L. Buckner, A. Z. Snyder, D. N. Greve, R. S.R. Desikan, E. Busa, J. C. Morris, A. M. Dale, and B. Fischl Thinning of the Cerebral Cortex in Aging Cereb Cortex, July 1, 2004; 14(7): 721 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Christie and J. C. Dalrymple-Alford A New Rat Model of the Human Serial Reaction Time Task: Contrasting Effects of Caudate and Hippocampal Lesions J. Neurosci., February 4, 2004; 24(5): 1034 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Kassubek, F D Juengling, T Kioschies, K Henkel, J Karitzky, B Kramer, D Ecker, J Andrich, C Saft, P Kraus, et al. Topography of cerebral atrophy in early Huntington's disease: a voxel based morphometric MRI study J. Neurol. Neurosurg. Psychiatry, February 1, 2004; 75(2): 213 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Miller, M. Hosakere, A. R. Barker, C. E. Priebe, N. Lee, J. T. Ratnanather, L. Wang, M. Gado, J. C. Morris, and J. G. Csernansky Labeled cortical mantle distance maps of the cingulate quantify differences between dementia of the Alzheimer type and healthy aging PNAS, December 9, 2003; 100(25): 15172 - 15177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Margolis and C. A. Ross Diagnosis of Huntington Disease Clin. Chem., October 1, 2003; 49(10): 1726 - 1732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Kuperberg, M. R. Broome, P. K. McGuire, A. S. David, M. Eddy, F. Ozawa, D. Goff, W. C. West, S. C. R. Williams, A. J. W. van der Kouwe, et al. Regionally Localized Thinning of the Cerebral Cortex in Schizophrenia Arch Gen Psychiatry, September 1, 2003; 60(9): 878 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sailer, B. Fischl, D. Salat, C. Tempelmann, M. A. Schonfeld, E. Busa, N. Bodammer, H.-J. Heinze, and A. Dale Focal thinning of the cerebral cortex in multiple sclerosis Brain, August 1, 2003; 126(8): 1734 - 1744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. Rosas, W. J. Koroshetz, Y. I. Chen, C. Skeuse, M. Vangel, M. E. Cudkowicz, K. Caplan, K. Marek, L. J. Seidman, N. Makris, et al. Evidence for more widespread cerebral pathology in early HD: An MRI-based morphometric analysis Neurology, May 27, 2003; 60(10): 1615 - 1620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Greenamyre and I. Shoulson We need something better, and we need it now: Fetal striatal transplantation in Huntington's disease? Neurology, March 12, 2002; 58(5): 675 - 676. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
