Mapping Cortico-Striatal Connectivity onto the Cortical Surface: A New Tractography-Based Approach to Study Huntington Disease

Centre Hospitalier Universitaire Vaudois Lausanne – CHUV, UNIL, Switzerland
PLoS ONE (Impact Factor: 3.23). 02/2013; 8(2):e53135. DOI: 10.1371/journal.pone.0053135
Source: PubMed


Huntington disease (HD) is associated with early and severe damage to the basal ganglia and particularly the striatum. We investigated cortico-striatal connectivity modifications occurring in HD patients using a novel approach which focuses on the projection of the connectivity profile of the basal ganglia onto the cortex. This approach consists in computing, for each subcortical structure, surface connectivity measures representing its strength of connections to the cortex and comparing these measures across groups. In this study, we focused on Huntington disease as an application of this new approach. First, surface cortico-striatal connectivity measures of a group of healthy subjects were averaged in order to infer the "normal" connectivity profile of the striatum to the cortex. Second, a statistical analysis was performed from the surface connectivity measures of healthy subjects and HD patients in order to detect the cortical gyri presenting altered cortico-striatal connectivity in HD. Lastly, percentage differences of connectivity between healthy subjects and patients were inferred, for each nucleus of the striatum, from the connectivity measures of the cortical gyri presenting a significant connectivity difference between the two groups. These percentage differences characterize the axonal disruptions between the striatum and the cortex occurring in HD. We found selective region-specific degeneration of cortical connections predominating for associative and primary sensorimotor connections and with relative preservation of limbic connections. Our method can be used to infer novel connectivity-based markers of HD pathological process.

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Available from: Linda Marrakchi-Kacem
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    • "To our knowledge, reductions in subcortical–cortical structural connections have been shown in Huntington's disease subjects in comparison with healthy controls in four studies to date [Bohanna et al., 2011a,b; Kloppel et al., 2008; Marrakchi-Kacem et al., 2010; Marrakchi-Kacem et al., 2013] . Connections to associative [Marrakchi-Kacem et al., 2013] and sensorimotor [Bohanna et al., 2011a, 2011b; Marrakchi-Kacem et al., 2013] cortex appear particularly affected. Altered diffusion metrics within tractographygenerated white matter pathways have also been shown [Douaud et al., 2009; Dumas et al., 2012]. "
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    ABSTRACT: Huntington's disease is an incurable neurodegenerative disease caused by inheritance of an expanded cytosine-adenine-guanine (CAG) trinucleotide repeat within the Huntingtin gene. Extensive volume loss and altered diffusion metrics in the basal ganglia, cortex and white matter are seen when patients with Huntington's disease (HD) undergo structural imaging, suggesting that changes in basal ganglia-cortical structural connectivity occur. The aims of this study were to characterise altered patterns of basal ganglia-cortical structural connectivity with high anatomical precision in premanifest and early manifest HD, and to identify associations between structural connectivity and genetic or clinical markers of HD. 3-Tesla diffusion tensor magnetic resonance images were acquired from 14 early manifest HD subjects, 17 premanifest HD subjects and 18 controls. Voxel-based analyses of probabilistic tractography were used to quantify basal ganglia-cortical structural connections. Canonical variate analysis was used to demonstrate disease-associated patterns of altered connectivity and to test for associations between connectivity and genetic and clinical markers of HD; this is the first study in which such analyses have been used. Widespread changes were seen in basal ganglia-cortical structural connectivity in early manifest HD subjects; this has relevance for development of therapies targeting the striatum. Premanifest HD subjects had a pattern of connectivity more similar to that of controls, suggesting progressive change in connections over time. Associations between structural connectivity patterns and motor and cognitive markers of disease severity were present in early manifest subjects. Our data suggest the clinical phenotype in manifest HD may be at least partly a result of altered connectivity. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
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