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D19 Longitudinal changes in functional connectivity of cortico-basal ganglia networks in manifest and premanifest huntington’s disease
  1. Fatma Gargouri1,2,
  2. Arnaud Messé3,4,
  3. Vincent Perlbarg1,4,5,
  4. Romain Valabregue1,2,
  5. Peter McColgan6,
  6. Lydia Yahia-Cherif1,2,
  7. Sara Fernandez-Vidal1,2,
  8. Ahmed Ben Hamida7,
  9. Habib Benali4,
  10. Sarah Tabrizi6,
  11. Alexandra Durr2,8,
  12. Stéphane Lehéricy1,2,9,10
  1. 1Institut du Cerveau et de la Moelle épinière – ICM, Centre de NeuroImagerie de Recherche – CENIR, Paris, France
  2. 2Institut du Cerveau et de la Moelle épinière – ICM, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France
  3. 3Department of Computational Neuroscience, University Medical Centre Eppendorf, Hamburg University, Germany
  4. 4Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, Inserm UMR_S 1146, Laboratoire d’Imagerie Biomédicale, Paris, France
  5. 5Institut du Cerveau et de la Moelle épinière – ICM, Bioinformatics and Biostatistics platform – ICONICS, Paris, France
  6. 6Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
  7. 7Advanced Technologies for Medicine and Signals –ATMS, Ecole Nationale d’Ingénieurs de Sfax –ENIS, Sfax Université, Tunisia
  8. 8Department of Genetics, APHP, University Hospital Pitié-Salpêtrière, Paris, France
  9. 9ICM Team Control of Normal and Abnormal Movement
  10. 10Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

Abstract

Background In Huntington’s disease (HD), there is neuronal loss in distributed brain regions predominating in the basal ganglia but also present in the cortex. Functional imaging studies at rest have reported reduced long-range functional connectivity within motor areas as well as associative areas of the frontal and parietal lobes, the basal ganglia and the default mode network. Changes in functional connectivity over time in longitudinal studies in HD and preHD is less known although two studies did not find significant changes in connectivity over one- to three-year periods.

Aims We evaluated the changes in functional organisation within the sensorimotor, associative and limbic cortico-basal ganglia networks in preHD and HD patients compared with controls using resting-state fMRI (rs-fMRI) and graph theory over a two-year period.

Methods We acquired structural MRI and rs-fMRI in three visits one year apart, in 18 adult HD patients, 24 preHD and 18 gender- and age-matched healthy volunteers from the TRACK-HD study. We inferred topological changes in functional connectivity between 182 regions within cortico-basal ganglia networks using graph theory measures.

Results We found significant differences for global graph theory measures in HD but not in preHD. The average shortest path length (L) decreased, which indicated a change toward the random network topology. HD patients also demonstrated increases in degree k, reduced betweeness centrality bc and reduced clustering C. Changes predominated in the sensorimotor network for bc and C and were observed in all circuits for k. Hubs were reduced in preHD and no longer detectable in HD in the sensorimotor and associative networks.

Conclusion PreHD is characterised by progressive decrease in hub organisation, and these changes aggravate in HD patients with changes in local metrics.

  • resting-state fMRI
  • graph theory
  • longitudinal changes

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