Structure and Dynamics of Large-Scale Cognitive Networks in Huntington's Disease
Aracil-Bolaños, Ignacio (Institut d'Investigació Biomèdica Sant Pau)
Martinez-Horta, Saul (Institut d'Investigació Biomèdica Sant Pau)
González-de-Echávarri, José María (Institut Hospital del Mar d'Investigacions Mèdiques)
Sampedro, Frederic (Institut d'Investigació Biomèdica Sant Pau)
Pérez-Pérez, Jesús (Institut d'Investigació Biomèdica Sant Pau)
Horta, Andrea (Institut d'Investigació Biomèdica Sant Pau)
Campolongo, Antonia (Institut d'Investigació Biomèdica Sant Pau)
Izquierdo, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Gómez-Ansón, Beatriz (Universitat Autònoma de Barcelona. Departament de Medicina)
Pagonabarraga Mora, Javier (Institut d'Investigació Biomèdica Sant Pau)
Kulisevsky, Jaime (Institut d'Investigació Biomèdica Sant Pau)

Date:	2021
Abstract:	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 = −2. 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 = −2. 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.
Grants:	Fundació la Marató de TV3 20142910 Instituto de Salud Carlos III CM19/00156 Instituto de Salud Carlos III PI14/02058 Instituto de Salud Carlos III PI17/001885
Note:	Altres ajuts: acords transformatius de la UAB
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cognition ; Huntington's ; Functional MRI
Published in:	Movement Disorders, 2021 , ISSN 1531-8257

DOI: 10.1002/mds.28839
PMID: 34752656

11 p, 2.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles