Functional changes during working memory in Huntington’s disease: 30-month longitudinal data from the IMAGE-HD study
- 565 Downloads
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.
- Georgiou-Karistianis N, Gray MA, Domínguez D JF, Dymowski AR, Bohanna I, Johnston LA, Churchyard A, Chua P, Stout JC et al (2013) Automated differentiation of pre-diagnosis Huntington’s disease from healthy control individuals based on quadratic discriminant analysis of the basal ganglia: the IMAGE-HD study. Neurobiol Dis 51:82–92PubMedCrossRefGoogle Scholar
- Hacker C, Perlmutter J, Criswell S, Ances B, Snyder A (2012) Resting state functional connectivity of the striatum in Parkinson’s disease. BrainGoogle Scholar
- Nelson HE, Willison J, Owen AM (1992) National adult reading test, 2nd edition. Int J Geriatr Psychiatry 7:533Google Scholar
- Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D, Kennard C, Hicks SL, Fox NC et al (2009) Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 8:791–801PubMedCentralPubMedCrossRefGoogle Scholar
- Tabrizi SJ, Scahill RI, Durr A, Roos RA, Leavitt BR, Jones R, Landwehrmeyer GB, Fox NC, Johnson H et al (2011) Biological and clinical changes in premanifest and early stage Huntington’s disease in the TRACK-HD study: the 12-month longitudinal analysis. Lancet Neurol 10:31–42PubMedCrossRefGoogle Scholar