期刊
FRONTIERS IN NEUROLOGY
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2016.00147
关键词
disease progression; gray matter concentration; humans; magnetic resonance imaging; movement disorders; multivariate methods; prodromal symptoms
资金
- National Institutes of Health, National Institute of Neurological Disorders and Stroke [1U01NS082074]
- NIH/NINDS grant [5R01NS040068]
- CHDI Foundation, Inc. [A3917, 6266]
- Cognitive and Functional Brain Changes in Preclinical Huntington Disease (HD) [5R01NS054893]
- 4D Shape Analysis for Modeling Spatiotemporal Change Trajectories in Huntington's [1U01NS082086]
- Functional Connectivity in Premanifest Huntington's Disease [1U01NS082083]
- Basal Ganglia Shape Analysis and Circuitry in Huntington Disease [1U01NS082085]
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.
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