Functional changes during working memory in Huntington’s disease: 30-month longitudinal data from the IMAGE-HD study
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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.
KeywordsFunctional connectivity fMRI Huntington’s disease Longitudinal Working memory
We would like to acknowledge the contribution of all the participants who took part in this study. We are also grateful to the CHDI Foundation Inc. New York (USA) (Grant Number A: 3433) and to the National Health and Medical Research Council (NHMRC) (Grant Number: 606650), for their support in funding this research. This research was supported by the VLSCI’s Life Sciences Computation Centre; a collaboration between Melbourne, Monash and La Trobe Universities and an initiative of the Victorian Government, Australia. We also thank the Royal Children’s Hospital for the use of their 3T MR scanner. GFE is a Principal NHMRC Research Fellow.
Conflict of interest
All authors reported no biomedical financial interests or potential conflicts of interest.
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