Journal article
Detection of Motor Changes in Huntington's Disease Using Dynamic Causal Modeling
Frontiers in human neuroscience, Vol.9, pp.634-634
11/25/2015
DOI: 10.3389/fnhum.2015.00634
PMCID: PMC4658414
PMID: 26635585
Abstract
Deficits in motor functioning are one of the hallmarks of Huntington's disease (HD), a genetically caused neurodegenerative disorder. We applied functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to assess changes that occur with disease progression in the neural circuitry of key areas associated with executive and cognitive aspects of motor control. Seventy-seven healthy controls, 62 pre-symptomatic HD gene carriers (preHD), and 16 patients with manifest HD symptoms (earlyHD) performed a motor finger-tapping fMRI task with systematically varying speed and complexity. DCM was used to assess the causal interactions among seven pre-defined regions of interest, comprising primary motor cortex, supplementary motor area (SMA), dorsal premotor cortex, and superior parietal cortex. To capture heterogeneity among HD gene carriers, DCM parameters were entered into a hierarchical cluster analysis using Ward's method and squared Euclidian distance as a measure of similarity. After applying Bonferroni correction for the number of tests, DCM analysis revealed a group difference that was not present in the conventional fMRI analysis. We found an inhibitory effect of complexity on the connection from parietal to premotor areas in preHD, which became excitatory in earlyHD and correlated with putamen atrophy. While speed of finger movements did not modulate the connection from caudal to pre-SMA in controls and preHD, this connection became strongly negative in earlyHD. This second effect did not survive correction for multiple comparisons. Hierarchical clustering separated the gene mutation carriers into three clusters that also differed significantly between these two connections and thereby confirmed their relevance. DCM proved useful in identifying group differences that would have remained undetected by standard analyses and may aid in the investigation of between-subject heterogeneity.
Details
- Title: Subtitle
- Detection of Motor Changes in Huntington's Disease Using Dynamic Causal Modeling
- Creators
- Lora Minkova - Department of Psychiatry and Psychotherapy, University Medical Center Freiburg Freiburg Brain Imaging Center, University Medical Center Freiburg Laboratory for Biological and Personality Psychology, Department of Psychology, University of FreiburgElisa Scheller - Department of Psychiatry and Psychotherapy, University Medical Center Freiburg Freiburg Brain Imaging Center, University Medical Center FreiburgJessica Peter - Department of Psychiatry and Psychotherapy, University Medical Center Freiburg Freiburg Brain Imaging Center, University Medical Center FreiburgAhmed Abdulkadir - Freiburg Brain Imaging Center, University Medical Center Freiburg Department of Computer Science, University of FreiburgChristoph P Kaller - Freiburg Brain Imaging Center, University Medical Center Freiburg Department of Neurology, University Medical Center Freiburg BrainLinks-BrainTools Cluster of Excellence, University of FreiburgRaymund A Roos - Department of Neurology, Leiden University Medical CentreAlexandra Durr - Department of Genetics and Cytogenetics, Pitié-Salpêtrière University HospitalBlair R Leavitt - Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British ColumbiaSarah J Tabrizi - Department of Neurodegenerative Disease, Institute of Neurology, University College LondonStefan Klöppel - Department of Psychiatry and Psychotherapy, University Medical Center Freiburg Freiburg Brain Imaging Center, University Medical Center Freiburg Department of Neurology, University Medical Center FreiburgTrackOn-HD Investigators
- Contributors
- Hans J Johnson (Contributor) - University of Iowa, Electrical and Computer Engineering
- Resource Type
- Journal article
- Publication Details
- Frontiers in human neuroscience, Vol.9, pp.634-634
- DOI
- 10.3389/fnhum.2015.00634
- PMID
- 26635585
- PMCID
- PMC4658414
- NLM abbreviation
- Front Hum Neurosci
- ISSN
- 1662-5161
- eISSN
- 1662-5161
- Publisher
- Frontiers Media S.A
- Grant note
- Albert-Ludwigs-Universität Freiburg Deutsche Forschungsgemeinschaft CHDI Foundation
- Language
- English
- Date published
- 11/25/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Psychiatry; The Iowa Institute for Biomedical Imaging; The Iowa Initiative for Artificial Intelligence; Iowa Informatics Initiative
- Record Identifier
- 9984221629402771
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