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

• Published in: NeuroImage clinical Vol. 12; no. C; pp. 806 - 814
• Main Authors: Coppen, Emma M., van der Grond, Jeroen, Hafkemeijer, Anne, Rombouts, Serge A.R.B., Roos, Raymund A.C
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2016; Elsevier
• Subjects: Adult; Aged; Brain - diagnostic imaging; Brain - pathology; Disease Progression; Female; Gray Matter - diagnostic imaging; Gray Matter - pathology; Grey matter; Humans; Huntington Disease - diagnostic imaging; Huntington Disease - pathology; Huntington's disease; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways - diagnostic imaging; Neural Pathways - pathology; Neuropsychological Tests; Radiology; Regular; Structural covariance networks; Structural MRI; Voxel-based morphometry; VBM; ICA; Grey matter; Voxel-based morphometry; CAG; Structural MRI; HTT; MNI; Huntington's disease; TFC; MMSE; TMT; TMS; HD; UHDRS; SDMT; Structural covariance networks; Huntingtin; Independent Component Analysis; Symbol Digit Modality Test; Total Functional Capacity; cytosine-adenine-guanine; Montreal Neurological Institute; Voxel-Based Morphometry; Unified Huntington's Disease Rating Scale; Mini Mental State Examination; Trail-Making Test; Total Motor Score; HTT, Huntingtin; UHDRS, Unified Huntington's Disease Rating Scale; HD, Huntington's disease; MNI, Montreal Neurological Institute; TMS, Total Motor Score; ICA, Independent Component Analysis; VBM, Voxel-Based Morphometry; TMT, Trail-Making Test; SDMT, Symbol Digit Modality Test; CAG, cytosine-adenine-guanine; TFC, Total Functional Capacity; MMSE, Mini Mental State Examination
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2016.10.009

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. We aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments. 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. 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. Our results suggest that structural covariance might be a sensitive approach to reveal early grey matter changes, especially for premanifest HD. •Identification of anatomical networks in Huntington's disease (HD).•Independent component analysis was used to examine structural covariance networks.•HD patients showed changes in subcortical and cortical covariance networks.•A network-based approach is sensitive to reveal early grey matter changes.