Background The default-mode network (DMN) is a set of brain regions which shows greater activity during rest relative to a cognitive task. Altered function of this network has been associated with a decline of cognition in several neurodegenerative diseases and related at-risk conditions. In Huntington's disease (HD), an autosomal dominant inherited neurodegenerative disorder, several studies so far have shown abnormal brain activation patterns even in preclinical carriers of the HD disease gene mutation (preHD). To date, however, the functional integrity of the DMN has not been addressed in this population.

Aims The aim of this study was to study the functional connectivity of the DMN in 18 preHD individuals and 18 healthy controls during cognitive performance.

Methods Participants underwent functional MRI during an attention task, and a group independent component analysis was applied to identify spatiotemporally distinct patterns of two DMN subcomponents.

Results Compared to controls, preHD individuals showed lower component-specific connectivity in the anterior medial prefrontal cortex (aMPFC), the left inferior parietal (lIPL) and the posterior cingulate cortex (p<0.05, cluster-corrected). Connectivity between the two DMN components was increased in preHD compared to controls. Furthermore, connectivity of the aMPFC was correlated with CAG repeat length, whereas lPL connectivity was correlated with cognitive measures.

Conclusions These results highlight the biomarker-potential of DMN connectivity in preHD, and suggest a possible role of DMN function in maintaining optimal cognitive performance. Future longitudinal studies could consider using DMN for tracking disease-progression and disease-related cognitive decline.