Basal ganglia network degeneration and cortical network compensation in Huntington's disease. (360G-Wellcome-103437_Z_13_Z)

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin gene. Neuronal degeneration occurs initially in the striatum and progresses to other subcortical and cortical structures. HD gene carriers may be split into pre-manifest or manifest groups based on the unified Huntington's disease rating scale total motor score. Extensive white matter loss occurs prior to the onset of overt motor symptoms in the pre-manifest stage. Aims: Us ing diffusion tractography in pre-manifest HD and controls, I will evaluate longitudinal change in structural basal ganglia connectivity. Differences in functional cortical and sub-cortical brain networks will be characterised using resting state fMRI. By combining tractography and resting state fMRI I will investigate the correspondence between functional and structural networks. Associations with symptomatology and disease burden will also be evaluated. Methods: Diffusion tractography and r esting state fMRI will be analysed using graph theory in 110 pre-manifest HD and 112 controls, at one time point. Basal ganglia connectivity will be assessed at two time points. Implications: Understanding how HD affects basal connectivity and brain networks will shed light on pathogenesis and compensatory mechanisms in HD and other neurodegenerative diseases.