Specific patterns of brain alterations underlie distinct clinical profiles in Huntington's disease
Por:
Garcia-Gorro, C, Llera, A, Martinez-Horta, S, Perez-Perez, J, Kulisevsky, J, Rodriguez-Dechicha, N, Vaquer, I, Subira, S, Calopa, M, Munoz, E, Santacruz, P, Ruiz-Idiago, J, Mareca, C, Beckmann, CF, De Diego-Balaguer, R, Camara, E
Publicada:
1 ene 2019
Resumen:
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.
Filiaciones:
Garcia-Gorro, C:
IDIBELL Inst Invest Biomed Bellvitge, Cognit & Brain Plast Unit, Lhospitalet De Llobregat, Barcelona, Spain
Univ Barcelona, Dept Cognit Dev & Educ Psychol, Barcelona, Spain
Llera, A:
Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimagirg, Nijmegen, Netherlands
Martinez-Horta, S:
Hosp Santa Creu & Sant Pau, IIB St Pau, Biomed Res Inst St Pau, Movement Disorders Unit,Dept Neurol, Barcelona, Spain
Carlos III Inst, Ctr Networked Biomed Res Neurodegenerat Dis, CIBERNED, Madrid, Spain
Perez-Perez, J:
Hosp Santa Creu & Sant Pau, IIB St Pau, Biomed Res Inst St Pau, Movement Disorders Unit,Dept Neurol, Barcelona, Spain
Carlos III Inst, Ctr Networked Biomed Res Neurodegenerat Dis, CIBERNED, Madrid, Spain
Kulisevsky, J:
Hosp Santa Creu & Sant Pau, IIB St Pau, Biomed Res Inst St Pau, Movement Disorders Unit,Dept Neurol, Barcelona, Spain
Carlos III Inst, Ctr Networked Biomed Res Neurodegenerat Dis, CIBERNED, Madrid, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Rodriguez-Dechicha, N:
Hosp Duran & Reynals, Hestia Duran & Reynals, Lhospitalet De Llobregat, Barcelona, Spain
Vaquer, I:
Hosp Duran & Reynals, Hestia Duran & Reynals, Lhospitalet De Llobregat, Barcelona, Spain
Subira, S:
Hosp Duran & Reynals, Hestia Duran & Reynals, Lhospitalet De Llobregat, Barcelona, Spain
Univ Autonoma Barcelona, Dept Clin & Hlth Psychol, Barcelona, Spain
Calopa, M:
Hosp Univ Bellvitge, Neurol Serv, Movement Disorders Unit, Barcelona, Spain
Munoz, E:
Hosp Clin Barcelona, Movement Disorders Unit, Neurol Serv, Barcelona, Spain
IDIBAPS, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain
Univ Barcelona, Fac Med, Barcelona, Spain
Santacruz, P:
Hosp Clin Barcelona, Movement Disorders Unit, Neurol Serv, Barcelona, Spain
Ruiz-Idiago, J:
Hosp Mare de Deu Merce, Barcelona, Spain
Univ Autonoma Barcelona, Dept Psychiat & Forens Med, Barcelona, Spain
Mareca, C:
Hosp Mare de Deu Merce, Barcelona, Spain
Beckmann, CF:
Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimagirg, Nijmegen, Netherlands
Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands
De Diego-Balaguer, R:
IDIBELL Inst Invest Biomed Bellvitge, Cognit & Brain Plast Unit, Lhospitalet De Llobregat, Barcelona, Spain
Univ Barcelona, Dept Cognit Dev & Educ Psychol, Barcelona, Spain
Univ Barcelona, Inst Neurosci, Barcelona, Spain
ICREA, Catalan Inst Res & Adv Studies, Barcelona, Spain
Cognit & Brain Plast Unit, Feixa Llarga S-N, Barcelona 08907, Spain
Camara, E:
IDIBELL Inst Invest Biomed Bellvitge, Cognit & Brain Plast Unit, Lhospitalet De Llobregat, Barcelona, Spain
Gold, Green Published
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