Background While involuntary motor dysfunction is most commonly used as the hallmark of manifest Huntington's disease (HD), cognitive functions are known to decline decades before the presence of motor symptoms.
Aims We used a spatial working memory task (n-back) to investigate functional brain changes in presymptomatic HD (pre-HD) and early symptomatic HD (symp-HD), compared with controls, via fMRI.
Methods 35 pre-HD (UHDRS <5), 23 symp-HD (UHDRS ≥5) and 32 controls participated. During baseline (0-back), participants reported the location of the current stimulus, while the 1-back and 2-back conditions required report of stimulus location presented 1 or 2 screens back, respectively. Data were analysed with FSL's FEAT. FLAME was used to conduct group analyses. Z statistic images were thresholded at Z >2.3 and a corrected cluster significance of p<0.05.
Results No group differences across conditions for behavioural data. fMRI data revealed a common network of activity when comparing 1-back to 0-back conditions with groups displaying significant increases in middle frontal gyrus, insula, middle temporal gyri, precentral gyri, parietal lobe and cerebellum. Between group differences revealed significant increases in BOLD signal in the caudate and putamen, left insula and left superior temporal gyrus in controls compared with pre-HD. Compared with symp-HD, pre-HD showed significant increases in the DL-PFC and cerebellum. We subsequently performed time series analyses to assess per cent BOLD signal change over time during task performance. Differential patterns of brain activation over time were observed across groups in DL-PFC, thalamus, anterior cingulate, hippocampus, insula and caudate.
Conclusions Pre-HD, symp-HD and controls show differential patterns of both functional BOLD activation and per cent BOLD signal changes during task performance. Variable activation patterns indicate crucial time points during the neurodegenerative process of HD involving onset or worsening of more than one pathological process.
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