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Speci fi c patterns of brain alterations underlie distinct clinical pro fi les in Huntington ' s disease
| Content Provider | Semantic Scholar |
|---|---|
| Author | Garcia-Gorroa, Clara Llerac, Alberto Martinez-Hortad, Saul Perez-Perezd, Jesus Kulisevskyd, Jaime Rodriguez-Dechichag, Nadia Vaquerg, Irene Subirag, Susana Calopai, Matilde Muñozj, Esteban Santacruzj, Pilar Ruiz-Idiagom, Jesus Marecam, Celia Beckmannc, Christian F. Diego-Balaguera, Ruth De Camaraa, Estela |
| Copyright Year | 2019 |
| Abstract | 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 https://doi.org/10.1016/j.nicl.2019.101900 Received 29 April 2019; Received in revised form 11 June 2019 Abbreviations: ACC, anterior cingulate cortex; CC, corpus callosum; CST, corticospinal tract; CT, cortical thickness; FA, fractional anisotropy; ICA, independent component analysis; IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; OFC, orbitofrontal cortex; PBA-s, problem behaviours assessment short version; RD, radial diffusivity; SDMT, symbol digit modality tests; SLF, superior longitudinal fasciculus; SMA, supplementary motor area; TMT, trail making test; UF, uncinated fasciculus; UHDRS, unified Huntington's disease rating scale; VBM, voxel based morphometry ⁎ Corresponding author at: Cognition and Brain Plasticity Unit, L'Hospitalet de Llobregat (Barcelona), IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), Spain; Department of Cognition, Development and Educational Psychology, University of Barcelona, Barcelona, Spain E-mail address: ruth.dediego@ub.edu (R. de Diego-Balaguer). 1 The authors contributed equally to this work 2 Lead contact: Ruth de Diego-Balaguer, 'Cognition and Brain Plasticity Unit, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. NeuroImage: Clinical 23 (2019) 101900 Available online 15 June 2019 2213-1582/ © 2019 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). T 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. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://brainvitge.org/website/wp-content/uploads/2019/07/GarciaGorro_NeuroImage-Clinical_2019.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
