Early grey matter changes in structural covariance networks in Huntington's disease

Abstract

Background: Progressive subcortical changes are known to occur in Huntington's disease (HD), a hereditary neurodegenerative disorder. Less is known about the occurrence and cohesion of whole brain grey matter changes in HD.

Objectives: We aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments.

Methods: Structural magnetic resonance imaging data of premanifest HD (n = 30), HD patients (n = 30) and controls (n = 30) was used to identify ten structural covariance networks based on a novel technique using the co-variation of grey matter with independent component analysis in FSL. Group differences were studied controlling for age and gender. To explore whether our approach is effective in examining grey matter changes, regional voxel-based analysis was additionally performed.

Results: Premanifest HD and HD patients showed decreased network integrity in two networks compared to controls. One network included the caudate nucleus, precuneous and anterior cingulate cortex (in HD p < 0.001, in pre-HD p = 0.003). One other network contained the hippocampus, premotor, sensorimotor, and insular cortices (in HD p < 0.001, in pre-HD p = 0.023). Additionally, in HD patients only, decreased network integrity was observed in a network including the lingual gyrus, intracalcarine, cuneal, and lateral occipital cortices (p = 0.032). Changes in network integrity were significantly associated with scores of motor and neuropsychological assessments. In premanifest HD, voxel-based analyses showed pronounced volume loss in the basal ganglia, but less prominent in cortical regions.

Conclusion: Our results suggest that structural covariance might be a sensitive approach to reveal early grey matter changes, especially for premanifest HD.

Keywords: CAG, cytosine-adenine-guanine; Grey matter; HD, Huntington's disease; HTT, Huntingtin; Huntington's disease; ICA, Independent Component Analysis; MMSE, Mini Mental State Examination; MNI, Montreal Neurological Institute; SDMT, Symbol Digit Modality Test; Structural MRI; Structural covariance networks; TFC, Total Functional Capacity; TMS, Total Motor Score; TMT, Trail-Making Test; UHDRS, Unified Huntington's Disease Rating Scale; VBM, Voxel-Based Morphometry; Voxel-based morphometry.

Fig. 1

Regional grey matter volume changes in HD. Voxel-based morphometric analysis showed regional grey matter volume changes in premanifest gene carriers (A) and Huntington's disease patients (B) compared to controls. The grey matter changes are overlaid on sagittal, transversal and coronal slices of MNI-152 standard T1-weigthed images. Corresponding MNI x-, y- and z-coordinates are displayed. The threshold for display is p < 0.05 (corrected using familywise error). The color scale bar represents T-scores.

Fig. 2

Overview of structural covariance networks. The ten identified anatomical networks are based on the structural covariance of grey matter among all participants. The networks are overlaid on sagittal, transversal and coronal slices of MNI-152 standard T1-weigthed images.