Structure and Dynamics of Large‐Scale Cognitive Networks in Huntington's Disease

Abstract

A BS TRACT: Background: Huntington's disease is a neurodegenerative disorder characterized by clinical alterations in the motor, behavioral, and cognitive domains. However, the structure and disruptions to large-scale brain cognitive networks have not yet been established. Objective: We aimed to profile changes in large-scale cognitive networks in premanifest and symptomatic patients with Huntington's disease. Methods: We prospectively recruited premanifest and symptomatic Huntington's disease mutation carriers as well as healthy controls. Clinical and sociodemographic data were obtained from all participants, and resting-state functional connectivity data, using both time-averaged and dynamic functional connectivity, was acquired from whole-brain and cognitively oriented brain parcellations. Results: A total of 64 gene mutation carriers and 23 healthy controls were included; 21 patients with Huntington's disease were classified as premanifest and 43 as symptomatic Huntington's disease. Compared with healthy controls, patients with Huntington's disease showed decreased network connectivity within the posterior hubs of the default-mode network and the medial prefrontal cortex, changes that correlated with cognitive (t = 2.25, P = 0.01) and disease burden scores (t = À2.42, P = 0.009). The salience network showed decreased functional connectivity between insular and supramarginal cortices and also correlated with cognitive (t = 2.11, P = 0.02) and disease burden scores (t = À2.35, P = 0.01). Dynamic analyses showed that network variability was decreased for default-central executive networks, a feature already present in premanifest mutation carriers (dynamic factor 8, P = 0.02). Conclusions: Huntington's disease shows an early and widespread disruption of large-scale cognitive networks. Importantly, these changes are related to cognitive and disease burden scores, and novel dynamic functional analyses uncovered subtler network changes even in the premanifest stages.

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“…For chorea, 12 articles were included, ( Sanchez-Castaneda et al, 2017 , Sarappa et al, 2017 , Dumas et al, 2013 , Aracil-Bolaños et al, 2022 , Gargouri et al, 2016 , Liu et al, 2016 , Muller et al, 2016 , Wolf et al, 2015 , Wolf et al, 2014 , Werner et al, 2014 , Quarantelli et al, 2013 , Poudel et al, 2014 ) all concerning Huntington’s disease (HD) and well-matched for age and gender. The number of patients per study varied from 10 to 43.…”

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