Striato-cortical connectivity patterns predict clinical profiles in Huntington's disease
Paepe, Audrey E. de (Institut d'Investigació Biomèdica de Bellvitge)
Bikou, Vasiliki (Institut d'Investigació Biomèdica de Bellvitge)
Turan, Eylül (Katholieke Universiteit te Leuven (1970- ))
Perez Bellido, Alexis (Universitat Autònoma de Barcelona. Departament de Psicologia Bàsica, Evolutiva i de l'Educació)
Garcia-Gorro, Clara (Institut d'Investigació Biomèdica de Bellvitge)
Rodriguez Dechicha, Nadia (Hestia Health Duran i Reynals (Hospitalet de Llobregat, Catalunya))
Vaquer Ricart, Irene (Hestia Health Duran i Reynals (Hospitalet de Llobregat, Catalunya))
Calopa, Matilde (Hospital Universitari de Bellvitge)
Diego Balaguer, Ruth de (Institut d'Investigació Biomèdica de Bellvitge)
Camara Mancha, Estela (Institut d'Investigació Biomèdica de Bellvitge)

Data:	2025
Descripció:	9 pàg.
Resum:	BACKGROUND: Huntington's disease is an inherited neurodegenerative disorder affecting striato-cortical circuits, with significant heterogeneity in the severity and progression of symptoms and neurodegenerative patterns. OBJECTIVES: To identify how distinct functional striato-cortical connectivity signatures may predict clinical profiles in Huntington's disease. METHODS: Thirty-eight Huntington's disease gene expansion carriers underwent cross-sectional motor, cognitive, and behavioral assessments and multimodal MRI. Principal component analysis was employed to characterize Huntington's disease clinical profiles. Next, seed-based whole-brain functional connectivity maps were derived for three basal ganglia seeds (caudate nucleus, putamen, nucleus accumbens) to delineate cortico-striatal connections. Multiple linear regressions assessed relationships between resulting clinical profiles and seed-based resting-state functional connectivity maps. Finally, basal ganglia gray matter volumes were examined in relation to clinical profiles and connectivity. RESULTS: Principal component analysis identified two main clinical profiles in Huntington's disease: motor-cognitive and behavioral. Multiple linear regression models revealed distinct functional neural signatures associated with each profile. Motor-cognitive symptoms related with a divergent connectivity pattern, specifically decreased connectivity between the caudate and putamen with executive and premotor areas, in contrast to increased connectivity between the ventral nucleus accumbens and executive network regions. Meanwhile, the behavioral profile was linked to decreased connectivity in limbic networks. Basal ganglia atrophy was associated with increased nucleus accumbens-cortical connectivity as well as motor-cognitive symptom severity. CONCLUSIONS: Distinct Huntington's disease clinical profiles can be characterized by predominantly motor-cognitive or behavioral disturbances, each related with unique functional and structural brain signatures. This substantiates that striato-cortical circuits exhibit functional interaction and potential reorganization.
Ajuts:	Instituto de Salud Carlos III FORT23/00032 Ministerio de Economía y Competitividad PI14/00834 Generalitat de Catalunya 2021/SGR-00352 Agencia Estatal de Investigación PID2020-114518RB-I00 Agencia Estatal de Investigación BFU2017-87109-P
Drets:	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, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Huntington's disease ; Individual differences ; Clinical profiles ; rs-fMRI ; Principal component analysis
Publicat a:	NeuroImage. Clinical, Vol. 46 (2025) , art. 103788, ISSN 2213-1582

DOI: 10.1016/j.nicl.2025.103788
PMID: 40279872

9 p, 5.1 MB

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