PMID- 23906595
OWN - NLM
STAT- MEDLINE
DCOM- 20140730
LR  - 20220309
IS  - 1973-8102 (Electronic)
IS  - 0010-9452 (Linking)
VI  - 49
IP  - 10
DP  - 2013 Nov-Dec
TI  - Prefrontal executive function associated coupling relates to Huntington's disease 
      stage.
PG  - 2661-73
LID - S0010-9452(13)00162-7 [pii]
LID - 10.1016/j.cortex.2013.05.015 [doi]
AB  - 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.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Unschuld, Paul G
AU  - Unschuld PG
AD  - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School 
      of Medicine, Baltimore, MD, USA; Division of Psychiatry Research and 
      Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland. Electronic 
      address: paul.unschuld@uzh.ch.
FAU - Liu, Xinyang
AU  - Liu X
FAU - Shanahan, Megan
AU  - Shanahan M
FAU - Margolis, Russell L
AU  - Margolis RL
FAU - Bassett, Susan S
AU  - Bassett SS
FAU - Brandt, Jason
AU  - Brandt J
FAU - Schretlen, David J
AU  - Schretlen DJ
FAU - Redgrave, Graham W
AU  - Redgrave GW
FAU - Hua, Jun
AU  - Hua J
FAU - Hock, Christoph
AU  - Hock C
FAU - Reading, Sarah A
AU  - Reading SA
FAU - van Zijl, Peter C M
AU  - van Zijl PC
FAU - Pekar, James J
AU  - Pekar JJ
FAU - Ross, Christopher A
AU  - Ross CA
LA  - eng
GR  - NS16375/NS/NINDS NIH HHS/United States
GR  - P41-EB015909/EB/NIBIB NIH HHS/United States
GR  - P50AG005146/AG/NIA NIH HHS/United States
GR  - T32MH015330/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130626
PL  - Italy
TA  - Cortex
JT  - Cortex; a journal devoted to the study of the nervous system and behavior
JID - 0100725
RN  - 0 (HTT protein, human)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Nerve Tissue Proteins)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adult
MH  - Brain Mapping
MH  - Disease Progression
MH  - Executive Function/*physiology
MH  - Female
MH  - Functional Laterality/physiology
MH  - Humans
MH  - Huntingtin Protein
MH  - Huntington Disease/physiopathology/*psychology
MH  - Image Processing, Computer-Assisted
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Nerve Net/physiopathology
MH  - Nerve Tissue Proteins/genetics
MH  - Neuropsychological Tests
MH  - Oxygen/blood
MH  - Prefrontal Cortex/*physiopathology
MH  - Psychomotor Performance/physiology
MH  - Reaction Time/physiology
OTO - NOTNLM
OT  - Cognition
OT  - Cortical networks
OT  - Executive function
OT  - Functional connectivity
OT  - Huntington's disease
OT  - Neurodegeneration
OT  - fMRI
EDAT- 2013/08/03 06:00
MHDA- 2014/07/31 06:00
CRDT- 2013/08/03 06:00
PHST- 2013/02/26 00:00 [received]
PHST- 2013/05/06 00:00 [revised]
PHST- 2013/05/26 00:00 [accepted]
PHST- 2013/08/03 06:00 [entrez]
PHST- 2013/08/03 06:00 [pubmed]
PHST- 2014/07/31 06:00 [medline]
AID - S0010-9452(13)00162-7 [pii]
AID - 10.1016/j.cortex.2013.05.015 [doi]
PST - ppublish
SO  - Cortex. 2013 Nov-Dec;49(10):2661-73. doi: 10.1016/j.cortex.2013.05.015. Epub 2013 
      Jun 26.