Regional subcortical shape analysis in premanifest Huntington's disease

Xiaoying Tang, Christopher A Ross, Hans Johnson, Jane S. Paulsen, Laurent Younes, Roger L. Albin, J. Tilak Ratnanather, Michael I. Miller

Research output: Contribution to journalArticle

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’ 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.

Original languageEnglish (US)
JournalHuman Brain Mapping
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Huntington Disease
Atrophy
Pathology
Caudate Nucleus
Amygdala
Basal Ganglia
Age of Onset
Signs and Symptoms
Hippocampus
Magnetic Resonance Spectroscopy
Control Groups
Brain
Genes

Keywords

  • circuit
  • premanifest Huntington's disease
  • shape
  • subcortical structures
  • subregion

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology

Cite this

Tang, X., Ross, C. A., Johnson, H., Paulsen, J. S., Younes, L., Albin, R. L., ... Miller, M. I. (Accepted/In press). Regional subcortical shape analysis in premanifest Huntington's disease. Human Brain Mapping. https://doi.org/10.1002/hbm.24456

Regional subcortical shape analysis in premanifest Huntington's disease. / Tang, Xiaoying; Ross, Christopher A; Johnson, Hans; Paulsen, Jane S.; Younes, Laurent; Albin, Roger L.; Ratnanather, J. Tilak; Miller, Michael I.

In: Human Brain Mapping, 01.01.2018.

Research output: Contribution to journalArticle

Tang, X, Ross, CA, Johnson, H, Paulsen, JS, Younes, L, Albin, RL, Ratnanather, JT & Miller, MI 2018, 'Regional subcortical shape analysis in premanifest Huntington's disease', Human Brain Mapping. https://doi.org/10.1002/hbm.24456
Tang, Xiaoying ; Ross, Christopher A ; Johnson, Hans ; Paulsen, Jane S. ; Younes, Laurent ; Albin, Roger L. ; Ratnanather, J. Tilak ; Miller, Michael I. / Regional subcortical shape analysis in premanifest Huntington's disease. In: Human Brain Mapping. 2018.
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