• Emma M Coppen, Jeroen van der Grond, Anne Hafkemeijer, Serge A R B Rombouts, and Raymund A C Roos.
• Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
• Neuroimage Clin. 2016 Jan 1; 12: 806-814.

BackgroundProgressive 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.ObjectivesWe aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments.MethodsStructural 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.ResultsPremanifest 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.ConclusionOur results suggest that structural covariance might be a sensitive approach to reveal early grey matter changes, especially for premanifest HD.

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