Image-HD: The use of FMRI during performance of spatial working memory and cognitive flexibility in Huntington's disease.

Abstract

Background: IMAGE-HD is a multi-modal neuroimaging study incorporating the use of structural, microstructural, and functional imaging, together with clinical and neuropsychological correlates. Our aim was to assess the cognitive changes during pre-diagnosis HD. Method(s): Seventeen pre-diagnosis HD (five males/ 12 females, mean age 44.7 +/- 9.8 years), 14 symptomatic HD (11 males/ three females, mean age 50.9 +/- 7.6 years), and 17 controls (seven males/ 10 females, mean age 45.2 +/- 12.4 years) underwent fMRI using a 3T scanner. BOLD signal activation was examined during spatial working memory (N-back) and cognitive flexibility (set/response shifting) tasks. Imaging data was thresholded using clusters determined by Z >2.3 and an (uncorrected) cluster significance threshold of p<0.05. Result(s): Spatial working memory: In pre-diagnosis HD, compared to controls, BOLD signal was significantly decreased in the anterior cingulate, caudate, putamen, parietal and dorsolateral prefrontal cortex (DLPFC). Conversely, Symptomatic HD showed significant increases in the areas described above, compared to both pre-diagnosis HD and controls. Cognitive flexibility: During attention shifting, pre-diagnosis HD showed significantly increased activation in anterior cingulate and precuneus, and a significant decrease in inferior temporal gyrus, compared to controls. Compared to symptomatic HD, prediagnosis HD showed significantly increased activation in caudate, putamen and M1, and a significant decrease in anterior cingulate and DLPFC. Behavioural data did not significantly differ between groups. Conclusion(s): The variable activation patterns indicate crucial time points during the neurodegenerative process of HD, involving onset or worsening of more than one pathological process (axon or myelin degeneration, neuronal dysfunction or death). This would explain the complex pattern of increased/ decreased activation between groups, also influenced by task type.