Huntington's disease (HD) is an inherited brain disorder characterized by progressive motor, cognitive and behavioral dysfunctions. It is caused by abnormally large trinucleotide cytosine-adenine-guanine (CAG) repeat expansions on exon 1 of the Huntingtin gene. CAG repeat length (CAG-RL) inversely correlates with an earlier age of onset. Region-based studies have shown that Huntington's disease gene mutation carriers (HDgmc) individuals (CAG-RL ≥ 36) present functional connectivity (FC) alterations in subcortical and default mode networks. In this analysis, we expand on previous HD studies by investigating associations between CAG-RL and connectivity in the whole brain, as well as between CAG dependent connectivity and motor and cognitive performances. We used group independent component analysis on resting-state fMRI scans of 261 individuals [183 HDgmc and 78 healthy controls (HC)] from the PREDICT-HD study, to obtain whole-brain resting state networks (RSNs). Regression analysis was applied within and between RSNs connectivity [functional network connectivity (FNC)] to identify CAG-RL associations.
Connectivity within the putamen RSN is negatively correlated with CAG-RL. The FNC between putamen and insula decreases with increasing CAG-RL, and also shows significant associations with motor and cognitive measures. The FNC between calcarine and middle frontal gyri increased with CAG-RL. In contrast, FNC in other visual networks declined with increasing CAG-RL. In addition to observed effects in subcortical areas known to be related to HD, our study identifies a strong presence of alterations in visual regions less commonly observed in previous reports and provides a step forward in understanding FNC dysfunction in HDgmc.
This research output has an Altmetric Attention Score of 54. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 June 2022.
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