Abstract
E11 Compensation in Huntington’s disease
Journal of neurology, neurosurgery and psychiatry, Vol.89(Suppl 1), p.A39
09/01/2018
DOI: 10.1136/jnnp-2018-EHDN.105
Abstract
Background Compensation accounts for the dissociation between pathology and absence of behavioural change during premanifest stages of Huntington’s disease (HD). Despite neuronal loss, individuals with premanifest HD function at a level similar to that of a healthy population. Neural mechanisms underlying compensation, however, are generally poorly understood due to the lack of an operational definition of compensation. Here, we describe the first example of the modelling and empirical testing of compensation in HD. Aims We hypothesise that compensation occurs where increased brain activation is required to maintain normal levels of behaviour until pathology becomes too severe. A compensatory relationship is thus characterised by non-linear longitudinal trajectories of brain activity and behaviour as disease load increases linearly across sequential phases of disease progression. Methods We tested our model in a large cohort of premanifest and early HD gene-carriers from the TrackOn-HD study. Focusing on both cognitive and motor networks, brain activity was measured using task and resting-state fMRI, volumetric loss by structural MRI and behaviour by task performance. Compensation was tested for across three sequential phases of disease progression. Results Maintained global cognition was associated with increased effective connectivity between the left and right dorsolateral prefrontal cortex, an important region for cognitive processing, while maintained motor performance was associated with increased connectivity between bilateral premotor cortex. Conclusions Our empirical findings demonstrate theoretically-defined compensation in HD in networks central to the HD phenotype and can now be used to test both cross-sectional and longitudinal compensation in other neurodegenerative disease with similar patterns to HD.
Details
- Title: Subtitle
- E11 Compensation in Huntington’s disease
- Creators
- Sarah Gregory - Wellcome Centre for Human NeuroimagingJeffrey D Long - University of IowaStefan Kloppel - University of FreiburgAdeel Razi - University of Engineering and Technology LahoreElisa Scheller - University of FreiburgLora Minkova - University of FreiburgEileanoir B Johnson - UCL Institute of NeurologyAlexandra Durr - Université Paris CitéRaymund AC Roos - Leiden University Medical CenterBlair R Leavitt - University of British ColumbiaJames A Mills - University of IowaJulie C Stout - Monash UniversityRachael I Scahill - UCL Institute of NeurologySarah J Tabrizi - UCL Institute of NeurologyGeraint Rees - Wellcome Centre for Human Neuroimaging
- Resource Type
- Abstract
- Publication Details
- Journal of neurology, neurosurgery and psychiatry, Vol.89(Suppl 1), p.A39
- Publisher
- BMJ Publishing Group LTD
- DOI
- 10.1136/jnnp-2018-EHDN.105
- ISSN
- 0022-3050
- eISSN
- 1468-330X
- Language
- English
- Date published
- 09/01/2018
- Academic Unit
- Biostatistics; Psychiatry
- Record Identifier
- 9984281759202771
Metrics
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