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Prefrontal executive function associated coupling relates to Huntington's disease stage.

Abstract
Huntington's disease (HD) is a neurodegenerative disease caused by cytosine-adenine-guanine (CAG)-repeat expansion in the huntingtin (HTT) gene. Early changes that may precede clinical manifestation of movement disorder include executive dysfunction. The aim of this study was to identify functional network correlates of impaired higher cognitive functioning in relation to HD stage. Blood-oxygenation-level-dependent (BOLD) functional-magnetic resonance imaging (fMRI) and structural-MRI were performed in 53 subjects with the HD-mutation (41 prodromals, 12 early affected) and 52 controls. Disease stage was estimated for each subject with HD-mutation based on age, length of the CAG-repeat expansion mutation and also putaminal atrophy. The Tower of London test was administered with three levels of complexity during fMRI as a challenge of executive function. Functional brain networks of interest were identified based on cortical gray matter voxel-clusters with significantly enhanced task-related functional coupling to the medial prefrontal cortex (MPFC) area. While prodromal HD-subjects showed similar performance levels as controls, multivariate analysis of task-related functional coupling to the MPFC identified reduced connectivity in prodromal and early manifest HD-subjects for a cluster including mainly parts of the left premotor area. Secondary testing indicated a significant moderator effect for task complexity on group differences and on the degree of correlation to measures of HD stage. Our data suggest that impaired premotor-MPFC coupling reflects HD stage related dysfunction of cognitive systems involved in executive function and may be present in prodromal HD-subjects that are still cognitively normal. Additional longitudinal studies may reveal temporal relationships between impaired task-related premotor-MPFC coupling and other brain changes in HD.
AuthorsPaul G Unschuld, Xinyang Liu, Megan Shanahan, Russell L Margolis, Susan S Bassett, Jason Brandt, David J Schretlen, Graham W Redgrave, Jun Hua, Christoph Hock, Sarah A Reading, Peter C M van Zijl, James J Pekar, Christopher A Ross
JournalCortex; a journal devoted to the study of the nervous system and behavior (Cortex) 2013 Nov-Dec Vol. 49 Issue 10 Pg. 2661-73 ISSN: 1973-8102 [Electronic] Italy
PMID23906595 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 Elsevier Ltd. All rights reserved.
Chemical References
  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Oxygen
Topics
  • Adult
  • Brain Mapping
  • Disease Progression
  • Executive Function (physiology)
  • Female
  • Functional Laterality (physiology)
  • Humans
  • Huntingtin Protein
  • Huntington Disease (physiopathology, psychology)
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net (physiopathology)
  • Nerve Tissue Proteins (genetics)
  • Neuropsychological Tests
  • Oxygen (blood)
  • Prefrontal Cortex (physiopathology)
  • Psychomotor Performance (physiology)
  • Reaction Time (physiology)

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