Background The earliest brain changes in Huntington’s disease (HD) are characterised by loss of caudate volume and surrounding white matter occurring early in the premanifest stage, with more extensive loss seen in manifest disease. Consistent with this, diffusion tractography reveals loss of structural connectivity between the basal ganglia and cortex.
Aims We sought to reveal how structural connectivity loss affects brain networks and how these changes relate to the clinical deficits seen in the premanifest and manifest stages of HD.
Methods Using diffusion tractography and graph theoretical analysis we constructed brain networks for 38 manifest HD individuals, 50 premanifest individuals and 47 healthy controls. Network segregation and integration were assessed using clustering coefficient and average path length respectively. Changes in connectivity to brain regions were assessed using degree. Correlations were performed between graph theory metrics and cognitive and motor variables.
Results Premanifest HD showed increased network segregation compared to controls, while manifest HD revealed increased segregation and loss of network integration compared to both premanifest and controls. Reduced degree was seen in the caudate bilaterally and left anterior cingulate in premanifest HD compared to controls, while numerous regions showed a reduction in degree in manifest disease compared to controls. Unified HD rating scale total motor score, emotion recognition and indirect circle tracing correlated with degree (predominantly in the frontal regions), clustering coefficient and average path length.
Conclusions Breakdown of the structural brain network occurs in premanifest HD, and to a greater extent in manifest HD. These changes relate to the cognitive and motor deficits seen early in the disease.
- Brain network
- diffusion tractography