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. 2013 Mar 14:2:377-84.
doi: 10.1016/j.nicl.2013.03.001. eCollection 2013.

Reduced functional brain connectivity prior to and after disease onset in Huntington's disease

Eve M Dumas  1 , Simon J A van den Bogaard, Ellen P Hart, Roelof P Soeter, Mark A van Buchem, Jeroen van der Grond, Serge A R B Rombouts, Raymund A C Roos; TRACK-HD investigator group
Affiliations

Reduced functional brain connectivity prior to and after disease onset in Huntington's disease

Eve M Dumas et al. Neuroimage Clin. .

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).

Discussion: 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.

Keywords: Functional connectivity; Huntington's disease; Premanifest gene carriers; Resting state fMRI.

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Figures

Fig. 1
Fig. 1
Group comparisons of functional brain connectivity shown in three orientations. Green areas show the voxels encompassing the network of interest (NOI) with which the connectivity decreases are present. Blue–light blue areas show the areas of reduced connectivity with the NOI between premanifest gene carriers and controls, red–yellow areas show the areas of reduced connectivity with the NOI between early manifest HD and controls. Some areas of blue and red overlap is present, here the functional connectivity is reduced in both premanifest and manifest HD.
Fig. 2
Fig. 2
Structural voxelwise covariate differences between groups. Red–yellow areas show the areas of differences in grey matter probability between early manifest HD and controls. Blue–light blue areas of structural differences between early manifest HD and premanifest gene carriers. No areas of differences in the voxel-based probability maps where found between premanifest gene carriers and controls.
See this image and copyright information in PMC

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