Journal article
Patterns of Co-Occurring Gray Matter Concentration Loss across the Huntington Disease Prodrome
Frontiers in neurology, Vol.7, pp.147-147
09/21/2016
DOI: 10.3389/fneur.2016.00147
PMCID: PMC5030293
PMID: 27708610
Abstract
Huntington disease (HD) is caused by an abnormally expanded cytosine–adenine–guanine (CAG) trinucleotide repeat in the
HTT gene. Age and CAG-expansion number are related to age at diagnosis and can be used to index disease progression. However, observed onset-age variability suggests that other factors also modulate progression. Indexing prodromal (pre-diagnosis) progression may highlight therapeutic targets by isolating the earliest-affected factors. We present the largest prodromal HD application of the univariate method voxel-based morphometry (VBM) and the first application of the multivariate method source-based morphometry (SBM) to, respectively, compare gray matter concentration (GMC) and capture co-occurring GMC patterns in control and prodromal participants. Using structural MRI data from 1050 (831 prodromal, 219 control) participants, we characterize control-prodromal, whole-brain GMC differences at various prodromal stages. Our results provide evidence for (1) regional co-occurrence and differential patterns of decline across the prodrome, with parietal and occipital differences commonly co-occurring, and frontal and temporal differences being relatively independent from one another, (2) fronto-striatal circuits being among the earliest and most consistently affected in the prodrome, (3) delayed degradation in some movement-related regions, with increasing subcortical and occipital differences with later progression, (4) an overall superior-to-inferior gradient of GMC reduction in frontal, parietal, and temporal lobes, and (5) the appropriateness of SBM for studying the prodromal HD population and its enhanced sensitivity to early prodromal and regionally concurrent differences.
Details
- Title: Subtitle
- Patterns of Co-Occurring Gray Matter Concentration Loss across the Huntington Disease Prodrome
- Creators
- Jennifer Ashley Ciarochi - Georgia State UniversityVince D Calhoun - University of New Mexico HospitalSpencer Lourens - University of IowaJeffrey D Long - University of IowaHans J Johnson - University of IowaH. Jeremy Bockholt - University of IowaJingyu Liu - Mind Research NetworkSergey M Plis - Mind Research NetworkJane S Paulsen - University of IowaJessica A Turner - Georgia State UniversityPREDICT-HD Investigators and Coordinators of the Huntington Study Group
- Resource Type
- Journal article
- Publication Details
- Frontiers in neurology, Vol.7, pp.147-147
- DOI
- 10.3389/fneur.2016.00147
- PMID
- 27708610
- PMCID
- PMC5030293
- NLM abbreviation
- Front Neurol
- ISSN
- 1664-2295
- eISSN
- 1664-2295
- Publisher
- Frontiers Media S.A
- Grant note
- A3917, 6266 / CHDI Foundation 1U01NS082074, 5R01NS040068, 5R01NS054893, 1U01NS082086, 1U01NS082083, 1U01NS082085 / National Institutes of Health
- Language
- English
- Date published
- 09/21/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Psychiatry; Psychological and Brain Sciences; Biostatistics
- Record Identifier
- 9984185372802771
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