@article{f4aa00153ca94dfeb9575cabcd744ca8,
title = "Regional subcortical shape analysis in premanifest Huntington's disease",
abstract = "Huntington's disease (HD) involves preferential and progressive degeneration of striatum and other subcortical regions as well as regional cortical atrophy. It is caused by a CAG repeat expansion in the Huntingtin gene, and the longer the expansion the earlier the age of onset. Atrophy begins prior to manifest clinical signs and symptoms, and brain atrophy in premanifest expansion carriers can be studied. We employed a diffeomorphometric pipeline to contrast subcortical structures{\textquoteright} morphological properties in a control group with three disease groups representing different phases of premanifest HD (far, intermediate, and near to onset) as defined by the length of the CAG expansion and the participant's age (CAG-Age-Product). A total of 1,428 magnetic resonance image scans from 694 participants from the PREDICT-HD cohort were used. We found significant region-specific atrophies in all subcortical structures studied, with the estimated abnormality onset time varying from structure to structure. Heterogeneous shape abnormalities of caudate nuclei were present in premanifest HD participants estimated furthest from onset and putaminal shape abnormalities were present in participants intermediate to onset. Thalamic, hippocampal, and amygdalar shape abnormalities were present in participants nearest to onset. We assessed whether the estimated progression of subcortical pathology in premanifest HD tracked specific pathways. This is plausible for changes in basal ganglia circuits but probably not for changes in hippocampus and amygdala. The regional shape analyses conducted in this study provide useful insights into the effects of HD pathology in subcortical structures.",
keywords = "circuit, premanifest Huntington's disease, shape, subcortical structures, subregion",
author = "Xiaoying Tang and Ross, {Christopher A.} and Hans Johnson and Paulsen, {Jane S.} and Laurent Younes and Albin, {Roger L.} and Ratnanather, {J. Tilak} and Miller, {Michael I.}",
note = "Funding Information: National Institutes of Health, Grant/Award Numbers: NIH R01 EB008171, NIH R01 EB000975, NIH P41 EB015909, NIH P50 NS091856, NIH R21 NS088302; CHDI Foundation, Grant/Award Number: A3917; National Institute of Neurological Disorders and Stroke, Grant/Award Number: NS40068; National Key R&D Program of China, Grant/ Award Number: 2017YFC0112404; Shunde International Joint Research Institute Start-up Grant, Grant/Award Number: 20150306; National Natural Science Foundation of China, Grant/Award Number: NSFC 81501546 Funding Information: information National Institutes of Health, Grant/Award Numbers: NIH R01 EB008171, NIH R01 EB000975, NIH P41 EB015909, NIH P50 NS091856, NIH R21 NS088302; CHDI Foundation, Grant/Award Number: A3917; National Institute of Neurological Disorders and Stroke, Grant/Award Number: NS40068; National Key R&D Program of China, Grant/Award Number: 2017YFC0112404; Shunde International Joint Research Institute Start-up Grant, Grant/Award Number: 20150306; National Natural Science Foundation of China, Grant/Award Number: NSFC 81501546We acknowledge the contribution of all PREDICT-HD participants and sites who gave their time to be involved in this study. We would also like to acknowledge Jingyuan Li from Carnegie Mellon University for her contribution to the template sub-segmentation of the caudate and putamen. Xiaoying Tang is supported by the National Natural Science Foundation of China (NSFC 81501546), the SYSU-CMU Shunde International Joint Research Institute Start-up Grant (20150306), and the National Key R&D Program of China (2017YFC0112404). Michael I. Miller and Tilak Ratnanather are partially supported by NIH P41 EB015909, NIH R01 EB000975 and NIH R01 EB008171. PREDICT-HD and Jane S. Paulsen are supported by the National Institute of Neurological Disorders and Stroke (NS40068) and CHDI Foundation, Inc. (A3917). Roger Albin is supported by NIH R21 NS088302 and P50 NS091856. Michael I. Miller owns an equal share in Anatomyworks LLC. The terms of this arrangement have been reviewed and approved by the Johns Hopkins University, in accordance with its conflict of interest policy. Funding Information: We acknowledge the contribution of all PREDICT-HD participants and sites who gave their time to be involved in this study. We would also like to acknowledge Jingyuan Li from Carnegie Mellon University for her contribution to the template sub-segmentation of the caudate and putamen. Xiaoying Tang is supported by the National Natural Science Foundation of China (NSFC 81501546), the SYSU-CMU Shunde International Joint Research Institute Start-up Grant (20150306), and the National Key R&D Program of China (2017YFC0112404). Michael I. Miller and Tilak Ratnanather are partially supported by NIH P41 EB015909, NIH R01 EB000975 and NIH R01 EB008171. PREDICT-HD and Jane S. Paulsen are supported by the National Institute of Neurological Disorders and Stroke (NS40068) and CHDI Foundation, Inc. (A3917). Roger Albin is supported by NIH R21 NS088302 and P50 NS091856. Michael I. Miller owns an equal share in Anatomyworks LLC. The terms of this arrangement have been reviewed and approved by the Johns Hopkins University, in accordance with its conflict of interest policy. Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",
year = "2019",
month = apr,
day = "1",
doi = "10.1002/hbm.24456",
language = "English (US)",
volume = "40",
pages = "1419--1433",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley-Liss Inc.",
number = "5",
}