Functional changes during working memory in Huntington's disease: 30-month longitudinal data from the IMAGE-HD study

Govinda Poudel, Julie C Stout, Juan F Dominguez, Marcus Gray, Louisa Salmon, Andrew J Churchyard, Phyllis Chua, Beth Borowsky, Gary Francis Egan, Nellie Georgiou-Karistianis

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52 Citations (Scopus)

Abstract

We characterized 30-month longitudinal change in functional activation and connectivity during working memory in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease (HD). In a case-control longitudinal study (baseline, 18 months, and 30 months), we compared change in fMRI activity over time during working memory in 22 pre-HD, 11 symp-HD, and 20 control participants. Outcome measures were BOLD (blood-oxygen-level-dependent) activity during 1-BACK and 2-BACK working memory and functional connectivity between dorsolateral prefrontal cortex (DLPFC) and caudate. Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK in the left DLPFC and medial frontal cortex, and further increased activation during 2-BACK in the bilateral caudate, putamen, and temporal cortex. Longitudinal change in symp-HD was not significantly different from controls. Longitudinal changes in pre-HD were associated with disease burden and years to onset. The pre-HD group showed longitudinal decreased functional connectivity between left DLPFC and caudate during both 1-BACK and 2-BACK performance. We provide an evidence for longitudinal changes in BOLD activity during working memory prior to clinical manifestations of HD. The ability to increase activation in the prefrontal cortex over time may represent an early compensatory response during the premanifest stage, which may reflect an early marker for clinically relevant functional changes in HD.

Original languageEnglish
Pages (from-to)501-512
Number of pages12
JournalBrain Structure and Function
Volume220
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • fMRI
  • Functional connectivity
  • Huntington’s disease
  • Longitudinal
  • Working memory

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