Dataset Information

Intact sensory-motor network structure and function in far from onset premanifest Huntington's disease.

ABSTRACT: Structural and functional changes attributable to the neurodegenerative process in Huntington's disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (11 preHD, 22 controls) as well as electrophysiological measurements (12 preHD, 13 controls). There were no significant differences in white matter macro- and microstructure between far from onset preHD participants and controls. Functional connectivity in a basal ganglia-thalamic and motor networks, all measures of the motor efferent and sensory afferent pathways as well as sensory-motor integration were also similar in far from onset preHD and controls. With the methods used in far from onset preHD sensory-motor neural macro- or micro-structure and brain function were similar to healthy controls. This suggests that any observable structural and functional change in preHD nearer to onset, or in manifest HD, at least using comparable techniques such as in this study, most likely reflects an ongoing neurodegenerative process.

SUBMITTER: Gorges M

PROVIDER: S-EPMC5339687 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Intact sensory-motor network structure and function in far from onset premanifest Huntington's disease.

Gorges Martin M Müller Hans-Peter HP Mayer Isabella Maria Sophie IM Grupe Gesa Sophie GS Kammer Thomas T Grön Georg G Kassubek Jan J Landwehrmeyer G Bernhard GB Wolf Robert Christian RC Orth Michael M

Scientific reports 20170307

Structural and functional changes attributable to the neurodegenerative process in Huntington's disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imagin ...[more]

PMID: 28266655

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Project description:The initial stages of neurodegeneration are commonly marked by normal levels of cognitive and motor performance despite the presence of structural brain pathology. Compensation is widely assumed to account for this preserved behaviour, but despite the apparent simplicity of such a concept, it has proven incredibly difficult to demonstrate such a phenomenon and distinguish it from disease-related pathology. Recently, we developed a model of compensation whereby brain activation, behaviour and pathology, components key to understanding compensation, have specific longitudinal trajectories over three phases of progression. Here, we empirically validate our explicit mathematical model by testing for the presence of compensation over time in neurodegeneration. Huntington's disease is an ideal model for examining longitudinal compensation in neurodegeneration as it is both monogenic and fully penetrant, so disease progression and potential compensation can be monitored many years prior to diagnosis. We defined our conditions for compensation as non-linear longitudinal trajectories of brain activity and performance in the presence of linear neuronal degeneration and applied our model of compensation to a large longitudinal cohort of premanifest and early-stage Huntington's disease patients from the multisite Track-On HD study. Focusing on cognitive and motor networks, we integrated progressive volume loss, task and resting state functional MRI and cognitive and motor behaviour across three sequential phases of neurodegenerative disease progression, adjusted for genetic disease load. Multivariate linear mixed models were fitted and trajectories for each variable tested. Our conceptualization of compensation was partially realized across certain motor and cognitive networks at differing levels. We found several significant network trends that were more complex than that hypothesized in our model. These trends suggest changes to our theoretical model where the network effects are delayed relative to performance effects. There was evidence of compensation primarily in the prefrontal component of the cognitive network, with increased effective connectivity between the left and right dorsolateral prefrontal cortex. Having developed an operational model for the explicit testing of longitudinal compensation in neurodegeneration, it appears that general patterns of our framework are consistent with the empirical data. With the proposed modifications, our operational model of compensation can be used to test for both cross-sectional and longitudinal compensation in neurodegenerative disease with similar patterns to Huntington's disease.

Dataset Information

Intact sensory-motor network structure and function in far from onset premanifest Huntington's disease.

Publications

Intact sensory-motor network structure and function in far from onset premanifest Huntington's disease.

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