Altered resting-state connectivity in Huntington's Disease

Authors

  • Cornelius J. Werner,

    1. Department of Neurology, RWTH Aachen University, Aachen, Germany
    2. JARA BRAIN – Translational Brain Medicine, Jülich and Aachen, Germany
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  • Imis Dogan,

    1. Department of Neurology, RWTH Aachen University, Aachen, Germany
    2. Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany
    3. JARA BRAIN – Translational Brain Medicine, Jülich and Aachen, Germany
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  • Christian Saß,

    1. Department of Neurology, RWTH Aachen University, Aachen, Germany
    2. Department of Neurology, Asklepios Hospital Hamburg, Hamburg, Germany
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  • Shahram Mirzazade,

    1. Department of Neurology, RWTH Aachen University, Aachen, Germany
    2. Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany
    3. JARA BRAIN – Translational Brain Medicine, Jülich and Aachen, Germany
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  • Johannes Schiefer,

    1. Department of Neurology, RWTH Aachen University, Aachen, Germany
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  • N. Jon Shah,

    1. Department of Neurology, RWTH Aachen University, Aachen, Germany
    2. Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany
    3. JARA BRAIN – Translational Brain Medicine, Jülich and Aachen, Germany
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  • Jörg B. Schulz,

    1. Department of Neurology, RWTH Aachen University, Aachen, Germany
    2. JARA BRAIN – Translational Brain Medicine, Jülich and Aachen, Germany
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  • Kathrin Reetz

    Corresponding author
    1. Department of Neurology, RWTH Aachen University, Aachen, Germany
    2. Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany
    3. JARA BRAIN – Translational Brain Medicine, Jülich and Aachen, Germany
    • Correspondence to: Kathrin Reetz, Department of Neurology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany. E-mail: kreetz@ukaachen.de

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  • The authors contributed equally to this work.

  • The study was approved by the Ethics committee of the Medicine Faculty of the RWTH Aachen University, and conducted in agreement with the Declaration of Helsinki. All participants gave written informed consent.

Abstract

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Using resting-state fMRI (rs-fMRI) we investigated the functional integrity of resting-state networks (RSN) in HD. 17 HD and 19 matched control participants were examined at a 3 Tesla MR scanner. After controlling for structural degeneration by means of voxel-based morphometry, task-free rs-fMRI data were analyzed using Independent Component Analysis (ICA) and a dual-regression approach in the context of genetic and clinical parameters. Further, we evaluated HD-related differences in interregional connectivity between networks. RSN analysis showed a significant increase in intrinsic functional connectivity in the HD sample compared with controls, including the thalamus, striatum, prefrontal, premotor, and parietal maps. A subset of the Default Mode Network (DMN) was also affected. In the HD cohort, motor impairment correlated with higher network connectivity in mainly motor and parietal cortices. Deteriorating total functional capacity was additionally associated with higher connectivity in the striatum, thalamus, insular and frontal areas. This pattern of increased activity in intrinsic functional networks might suggest a reduced ability of intra-network differentiation with clinical disease progression in HD. Finally, results showed reduced long-range connectivity between parietal ICA components in HD compared to controls, indicating impaired functional coupling between interregional networks in HD. Our data demonstrates that functional connectivity is profoundly altered in HD, both within and between RSN. Rs-fMRI analysis may provide additional valuable insights into neuronal dysfunctions beyond HD-related structural degeneration and disruptions of functional circuits in HD. Hum Brain Mapp 35:2582–2593, 2014. © 2013 Wiley Periodicals, Inc.

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