title: Reduced functional brain connectivity prior to and after disease onset in Huntington's disease.
abstract: BACKGROUND
  Huntington's disease (HD) is characterised by both regional and generalised neuronal cell loss in the brain. Investigating functional brain connectivity patterns in rest in HD has the potential to broaden the understanding of brain functionality in relation to disease progression. This study aims to establish whether brain connectivity during rest is different in premanifest and manifest HD as compared to controls.
  
  
  METHODS
  At the Leiden University Medical Centre study site of the TRACK-HD study, 20 early HD patients (disease stages 1 and 2), 28 premanifest gene carriers and 28 healthy controls underwent 3 T MRI scanning. Standard and high-resolution T1-weighted images and a resting state fMRI scan were acquired. Using FSL, group differences in resting state connectivity were examined for eight networks of interest using a dual regression method. With a voxelwise correction for localised atrophy, group differences in functional connectivity were examined.
  
  
  RESULTS
  Brain connectivity of the left middle frontal and pre-central gyrus, and right post central gyrus with the medial visual network was reduced in premanifest and manifest HD as compared to controls (0.05 > p > 0.0001). In manifest HD connectivity of numerous widespread brain regions with the default mode network and the executive control network were reduced (0.05 > p > 0.0001).
  
  
  CONCLUSIONS
  Brain regions that show reduced intrinsic functional connectivity are present in premanifest gene carriers and to a much larger extent in manifest HD patients. These differences are present even when the potential influence of atrophy is taken into account. Resting state fMRI could potentially be used for early disease detection in the premanifest phase of HD and for monitoring of disease modifying compounds.
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Eve M
authors.initials: EM
authors.lastname: Dumas
authors.forename: Simon J A
authors.initials: SJ
authors.lastname: van den Bogaard
authors.forename: Ellen P
authors.initials: EP
authors.lastname: Hart
authors.forename: Roelof P
authors.initials: RP
authors.lastname: Soeter
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
keywords: Functional connectivity; Huntington's disease; Premanifest gene carriers; Resting state fMRI