title: Patterns of Co-Occurring Gray Matter Concentration Loss across the Huntington Disease Prodrome.
abstract: Huntington disease (HD) is caused by an abnormally expanded cytosine-adenine-guanine (CAG) trinucleotide repeat in theHTTgene. 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.
authors.affiliation: Neuroscience Institute, Georgia State University , Atlanta, GA , USA.
authors.forename: Jennifer Ashley
authors.initials: JA
authors.lastname: Ciarochi
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Department of Psychiatry, University of Iowa , Iowa City, IA , USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Lourens
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Long
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA; Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry, University of Iowa , Iowa City, IA , USA.
authors.forename: H Jeremy
authors.initials: HJ
authors.lastname: Bockholt
authors.affiliation: The Mind Research Network , Albuquerque, NM , USA.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Mind Research Network , Albuquerque, NM , USA.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Plis
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA; Department of Neurology, University of Iowa, Iowa City, IA, USA; Department of Psychology, University of Iowa, Iowa City, IA, USA.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
authors.affiliation: Neuroscience Institute, Georgia State University, Atlanta, GA, USA; The Mind Research Network, Albuquerque, NM, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Turner
keywords: disease progression; gray matter concentration; humans; magnetic resonance imaging; movement disorders; multivariate methods; prodromal symptoms