title: Prefrontal cortex white matter tracts in prodromal Huntington disease.
abstract: Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large-scale analysis using multisite diffusion-weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT-HD study collected imaging and neuropsychological data on gene-positive HD participants without a clinical diagnosis (i.e., prodromal) and gene-negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto-occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG-age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long-range tracts essential for cross-region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. Hum Brain Mapp 36:3717-3732, 2015. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa.|John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.
authors.forename: Joy T
authors.initials: JT
authors.lastname: Matsui
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Jatin G
authors.initials: JG
authors.lastname: Vaidya
authors.affiliation: EPI Athena, INRIA Sophia Antipolis-Méditerranée, Sophia Antipolis, France.
authors.forename: Demian
authors.initials: D
authors.lastname: Wassermann
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Regina Eunyoung
authors.initials: RE
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa.|Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.|Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, Iowa.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Magnotta
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa.|Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, Iowa.|Department of Electrical and Computer Engineering, College of Engineering, University of Iowa, Iowa City, Iowa.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, Iowa.|Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.|Department of Psychology, University of Iowa, Iowa City, Iowa.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
mesh_terms: D000328:Adult; D016880:Anisotropy; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D056324:Diffusion Tensor Imaging; D004522:Educational Status; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000473:pathology*; D011336:Probability; D011569:Psychiatric Status Rating Scales; D012091:Repetitive Sequences, Nucleic Acid; D066127:White Matter / Q000473:pathology*
keywords: Huntington's disease; cross-sectional analysis; diffusion tensor imaging; diffusion tractography; diffusion weighted MRI; multicenter studies; prefrontal cortex