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

Paul G. Unschuld, Xinyang Liu, Megan Shanahan, Russell Louis Margolis, Susan Bassett, Jason Brandt, David Schretlen, Graham Redgrave, Jun Hua, Christoph Hock, Sarah A. Reading, Peter C Van Zijl, James J Pekar, Christopher A Ross

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2661-2673
Number of pages13
JournalCortex
Volume49
Issue number10
DOIs
StatePublished - Nov 2013

Fingerprint

Huntington Disease
Executive Function
Cytosine
Guanine
Adenine
Prefrontal Cortex
Mutation
Magnetic Resonance Imaging
Movement Disorders
Motor Cortex
Neurodegenerative Diseases
Atrophy
Multivariate Analysis
Brain
Genes

Keywords

  • Cognition
  • Cortical networks
  • Executive function
  • FMRI
  • Functional connectivity
  • Huntington's disease
  • Neurodegeneration

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Arts and Humanities (miscellaneous)
  • Developmental and Educational Psychology

Cite this

Prefrontal executive function associated coupling relates to Huntington's disease stage. / Unschuld, Paul G.; Liu, Xinyang; Shanahan, Megan; Margolis, Russell Louis; Bassett, Susan; Brandt, Jason; Schretlen, David; Redgrave, Graham; Hua, Jun; Hock, Christoph; Reading, Sarah A.; Van Zijl, Peter C; Pekar, James J; Ross, Christopher A.

In: Cortex, Vol. 49, No. 10, 11.2013, p. 2661-2673.

Research output: Contribution to journalArticle

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