Specific patterns of brain alterations underlie distinct clinical profiles in Huntington's disease
Garcia-Gorro, Clara (Universitat de Barcelona. Departament de Cognició, Desenvolupament i Psicologia de l'Educació)
Llera, A. (Radboud University Medical Centre. Centre for Cognitive Neuroimaging)
Martínez-Horta, Saul (Institut d'Investigació Biomèdica Sant Pau)
Pérez-Pérez, Jesús (Institut d'Investigació Biomèdica Sant Pau)
Kulisevsky, Jaime (Institut d'Investigació Biomèdica Sant Pau)
Rodriguez Dechicha, Nadia (Hospital Duran i Reynals (Barcelona))
Vaquer Ricart, Irene (Hospital Duran i Reynals (Barcelona))
Subira, Susana (Universitat Autònoma de Barcelona. Departament de Psicologia Clínica i de la Salut)
Calopa, Matilde (Hospital Universitari de Bellvitge)
Muñoz García, José Esteban (Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut)
Santacruz, Pilar (Hospital Clínic i Provincial de Barcelona)
Ruiz-Idiago, J. (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Mareca, Celia (Hospital Mare de Deu de la Mercè)
Beckmann, Christian F. (Donders Institute for Brain. Cognition and Behaviour. Department of Cognitive Neuroscience. Radboud University Medical Center)
Diego Balaguer, Ruth de (Institució Catalana de Recerca i Estudis Avançats)
Camara Mancha, Estela (Institut d'Investigació Biomèdica de Bellvitge)

Data:	2019
Resum:	Huntington's disease (HD) is a genetic neurodegenerative disease which involves a triad of motor, cognitive and psychiatric disturbances. However, there is great variability in the prominence of each type of symptom across individuals. The neurobiological basis of such variability remains poorly understood but would be crucial for better tailored treatments. Multivariate multimodal neuroimaging approaches have been successful in disentangling these profiles in other disorders. Thus we applied for the first time such approach to HD. We studied the relationship between HD symptom domains and multimodal measures sensitive to grey and white matter structural alterations. Forty-three HD gene carriers (23 manifest and 20 premanifest individuals) were scanned and underwent behavioural assessments evaluating motor, cognitive and psychiatric domains. We conducted a multimodal analysis integrating different structural neuroimaging modalities measuring grey matter volume, cortical thickness and white matter diffusion indices - fractional anisotropy and radial diffusivity. All neuroimaging measures were entered into a linked independent component analysis in order to obtain multimodal components reflecting common inter-subject variation across imaging modalities. The relationship between multimodal neuroimaging independent components and behavioural measures was analysed using multiple linear regression. We found that cognitive and motor symptoms shared a common neurobiological basis, whereas the psychiatric domain presented a differentiated neural signature. Behavioural measures of different symptom domains correlated with different neuroimaging components, both the brain regions involved and the neuroimaging modalities most prominently associated with each type of symptom showing differences. More severe cognitive and motor signs together were associated with a multimodal component consisting in a pattern of reduced grey matter, cortical thickness and white matter integrity in cognitive and motor related networks. In contrast, depressive symptoms were associated with a component mainly characterised by reduced cortical thickness pattern in limbic and paralimbic regions. In conclusion, using a multivariate multimodal approach we were able to disentangle the neurobiological substrates of two distinct symptom profiles in HD: one characterised by cognitive and motor features dissociated from a psychiatric profile. These results open a new view on a disease classically considered as a uniform entity and initiates a new avenue for further research considering these qualitative individual differences.
Ajuts:	Agencia Estatal de Investigación BFU2017-87109-P Instituto de Salud Carlos III CP13-00225 Instituto de Salud Carlos III PI14-00834
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Clinical profiles ; Data fusion ; Huntington's disease ; Linked ICA ; Neurodegeneration ; Structural MRI
Publicat a:	NeuroImage. Clinical, Vol. 23 (2019) , p. 101900, ISSN 2213-1582

DOI: 10.1016/j.nicl.2019.101900
PMID: 31255947

11 p, 1.3 MB

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