Functional changes during working memory in Huntington's disease: 30-month longitudinal data from the IMAGE-HD study.
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.
School of Psychology and Psychiatry, Monash University, Clayton, VIC, 3800, Australia.
Govinda R
GR
Poudel
Julie C
JC
Stout
D Juan F
DJ
Domínguez
Marcus A
MA
Gray
Louisa
L
Salmon
Andrew
A
Churchyard
Phyllis
P
Chua
Beth
B
Borowsky
Gary F
GF
Egan
Nellie
N
Georgiou-Karistianis
D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D001931:Brain Mapping; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000175:diagnosis / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology*; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011930:Reaction Time; D013223:Statistics as Topic; D013997:Time Factors
D010100:Oxygen