Brain Advance Access originally published online on September 13, 2007
Brain 2007 130(11):2845-2857; doi:10.1093/brain/awm210
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dorsolateral prefrontal cortex dysfunction in presymptomatic Huntington's disease: evidence from event-related fMRI
1Department of Psychiatry and 2Department of Neurology, University of Ulm, Leimgrubenweg 12, 89075 Ulm, Germany
Correspondence to: Robert Christian Wolf, Department of Psychiatry III, University of Ulm, Leimgrubenweg 12-14, 89075 Ulm, Germany E-mail: christian.wolf{at}uni-ulm.de
Evidence from magnetic resonance imaging (MRI) suggests early structural and functional brain changes in individuals with the Huntington's disease (HD) gene mutation who are presymptomatic for the motor symptoms of the disorder (pre-HD subjects). The objective of this study was to investigate the functional neuroanatomy of verbal working memory (WM) in pre-HD subjects. By means of event-related functional MRI, we studied healthy controls (n = 16) and pre-HD subjects (n = 16) with a parametric WM paradigm comprising three different WM load levels. Voxel-based morphometry (VBM) was used to control potentially confounding brain atrophy. Although WM performance did not significantly differ between pre-HD subjects and healthy controls, pre-HD subjects showed a significantly decreased activation of the left dorsolateral prefrontal cortex (DLPFC) at intermediate and high WM load levels only. This region was not affected by early cortical atrophy, as revealed by VBM. Pre-HD individuals close to the onset of motor symptoms showed an increased activation of the left inferior parietal lobule and the right superior frontal gyrus compared with both pre-HD subjects far from symptom onset and healthy controls. In addition, the activation level in the left DLPFC was positively correlated with the UHDRS cognitive subscore in pre-HD subjects. Our findings demonstrate that early functional brain changes in pre-HD subjects may occur in the DLPFC before manifest cortical atrophy, and support a role of this region in the expression of clinical symptoms. Compensatory brain responses in pre-HD individuals may occur with closer proximity to the onset of manifest clinical symptoms.
Key Words: Huntington's disease; presymptomatic; working memory; prefrontal cortex; functional MRI; VBM
Abbreviations: DLPFC, dorsolateral prefrontal cortex; HD, Huntington's disease; fMRI, functional magnetic resonance imaging; VBM, voxel-based morphometry
Received April 24, 2007. Revised July 1, 2007. Accepted August 9, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Kloppel, B. Draganski, H. R. Siebner, S. J. Tabrizi, C. Weiller, and R. S. J. Frackowiak Functional compensation of motor function in pre-symptomatic Huntington's disease Brain, June 1, 2009; 132(6): 1624 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Muhlau, A.M. Wohlschlager, C. Gaser, M. Valet, A. Weindl, S. Nunnemann, A. Peinemann, T. Etgen, and R. Ilg Voxel-Based Morphometry in Individual Patients: A Pilot Study in Early Huntington Disease AJNR Am. J. Neuroradiol., March 1, 2009; 30(3): 539 - 543. [Abstract] [Full Text] [PDF]
|
|