Elsevier

NeuroImage: Clinical

Volume 9, 2015, Pages 32-43
NeuroImage: Clinical

Dynamics of the connectome in Huntington's disease: A longitudinal diffusion MRI study

https://doi.org/10.1016/j.nicl.2015.07.003Get rights and content
Under a Creative Commons license
open access

Highlights

  • Investigates characteristics of the connectome in Huntington's disease (HD).

  • HD patients showed longitudinal changes in their structural connectome.

  • Connectome dynamics correlated with changes in clinical and cognitive measures.

  • Connectomics provides novel insights into compensatory strategies of the diseased brain.

Abstract

Objectives

To longitudinally investigate the connectome in different stages of Huntington's disease (HD) by applying graph theoretical analysis to diffusion MRI data.

Experimental design

We constructed weighted structural networks and calculated their topological properties. Twenty-two premanifest (preHD), 10 early manifest HD and 24 healthy controls completed baseline and 2 year follow-up scans. We stratified the preHD group based on their predicted years to disease onset into a far (preHD-A) and near (preHD-B) to disease onset group. We collected clinical and behavioural measures per assessment time point.

Principle observations

We found a significant reduction over time in nodal betweenness centrality both in the early manifest HD and preHD-B groups as compared to the preHD-A and control groups, suggesting a decrease of importance of specific nodes to overall network organization in these groups (FDR adjusted ps < 0.05). Additionally, we found a significant longitudinal decrease of the clustering coefficient in preHD when compared to healthy controls (FDR adjusted p < 0.05), which can be interpreted as a reduced capacity for internodal information processing at the local level. Furthermore, we demonstrated dynamic changes to hub-status loss and gain both in preHD and early manifest HD. Finally, we found significant cross-sectional as well as longitudinal relationships between graph metrics and clinical and neurocognitive measures.

Conclusions

This study demonstrates divergent longitudinal changes to the connectome in (pre) HD compared to healthy controls. This provides novel insights into structural correlates associated with clinical and cognitive functions in HD and possible compensatory mechanisms at play in preHD.

Key words

Graph theoretical analysis
Executive control
Orbitofrontal cortex
Hubs
TRACK-HD
Longitudinal biomarker

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1

These authors contributed equally to this work.