Neocortical morphometry in Huntington's disease: Indication of the coexistence of abnormal neurodevelopmental and neurodegenerative processes.
Jean-Francois Mangin, Denis Rivière, Edouard Duchesnay, Yann Cointepas, Véronique Gaura, Christophe Verny, Philippe Damier, Pierre Krystkowiak, Anne-Catherine Bachoud-Lévi, Philippe Hantraye, Philippe Remy, Gwenaëlle Douaud
Author Information
Jean-Francois Mangin: Université Paris-Saclay, CEA, CNRS, Baobab, Neurospin, Gif-sur-Yvette, France.
Denis Rivière: Université Paris-Saclay, CEA, CNRS, Baobab, Neurospin, Gif-sur-Yvette, France.
Edouard Duchesnay: Université Paris-Saclay, CEA, CNRS, Baobab, Neurospin, Gif-sur-Yvette, France.
Yann Cointepas: Université Paris-Saclay, CEA, CNRS, Baobab, Neurospin, Gif-sur-Yvette, France.
Véronique Gaura: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), MIRCen, France.
Christophe Verny: Centre national de référence des maladies neurogénétiques, Service de neurologie, CHU, 49000 Angers, France, UMR CNRS 6214 - INSERM U1083, France.
Philippe Damier: CHU Nantes, INSERM, CIC 0004, France.
Pierre Krystkowiak: Neurologie, CHU Amiens-Picardie, France.
Anne-Catherine Bachoud-Lévi: AP-HP, Hôpital Henri Mondor, Centre de Référence-Maladie de Huntington, France.
Philippe Hantraye: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, France.
Philippe Remy: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), MIRCen, France.
Gwenaëlle Douaud: Functional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom. Electronic address: gwenaelle.douaud@ndcn.ox.ac.uk.
Huntington's disease (HD) is an inherited, autosomal dominant disorder that is characteristically thought of as a degenerative disorder. Despite cellular and molecular grounds suggesting HD could also impact normal development, there has been scarce systems-level data obtained from in vivo human studies supporting this hypothesis. Sulcus-specific morphometry analysis may help disentangle the contribution of coexisting neurodegenerative and neurodevelopmental processes, but such an approach has never been used in HD. Here, we investigated cortical sulcal depth, related to degenerative process, as well as cortical sulcal length, related to developmental process, in early-stage HD and age-matched healthy controls. This morphometric analysis revealed significant differences in the HD participants compared with the healthy controls bilaterally in the central and intra-parietal sulcus, but also in the left intermediate frontal sulcus and calcarine fissure. As the primary visual cortex is not connected to the striatum, the latter result adds to the increasing in vivo evidence for primary cortical degeneration in HD. Those sulcal measures that differed between HD and healthy populations were mainly atrophy-related, showing shallower sulci in HD. Conversely, the sulcal morphometry also revealed a crucial difference in the imprint of the Sylvian fissure that could not be related to loss of grey matter volume: an absence of asymmetry in the length of this fissure in HD. Strong asymmetry in that cortical region is typically observed in healthy development. As the formation of the Sylvian fissure appears early in utero, and marked asymmetry is specifically found in this area of the neocortex in newborns, this novel finding likely indicates the foetal timing of a disease-specific, genetic interplay with neurodevelopment.
