Background In Huntington’s disease (HD), cerebral white matter changes have been reported in a number of studies using diffusion tensor imaging (DTI) or T1-weighted magnetic resonance imaging (MRI). A key question is how brain structure – both grey and white matter – influences brain function. Intrinsic functional connectivity MRI (ifcMRI) investigates intrinsic connectivity networks (ICN), i.e., brain regions which are active when the brain does not engage in a functional task. The objective of our study is to integrate structural data (assessed by DTI) with ifcMRI changes in order to obtain a comprehensive picture of structural and functional changes with an emphasis on motor and basal ganglia thalamic networks.

Methods Thirty-three early stage HD subjects (HD – TFC stage 1 and 2) and 25 age- and gender-matched healthy control subjects were included in the study. All participants underwent MRI on a 3T scanner with T1w, DTI and ifcMRI sequences. DTI and ifcMRI data analyses were performed in a standardised manner using the Tensor Imaging and Fibre Tracking (TIFT) software for complementary DTI fibre tracking (FT) and ifcMRI data analysis.

For motor network ifcMRI analyses the dominant M1 was used as seed, for basal ganglia-thalamic network the thalamus was used. In addition, the cortico-spinal tract (CST) and the thalamocortical pathway were used for comparisons at the group level.

Results At the group level, we confirm microstructural changes identified in previous DTI studies in HD. These include an increase of FA values in the basal ganglia, and FA reductions in the external and internal capsule, in parts of the thalamus, and in subcortical white matter. Within the motor ICN, the insula was less connected in HD than controls. For the basal ganglia-thalamic ICN connectivity differed in the insula and the basal ganglia between HD and controls in both hemispheres..

Conclusion The integration of structural connectivity, assessed by DTI FT and functional connectivity, assessed by ifcMRI revealed that the insula was less connected as a part of two different networks, the motor and the basal ganglia-thalamic networks. This suggests that abnormal connectivity of the insula may be relevant in the emergence of signs of HD.

Acknowledgement This work was partially supported by the European Union under the Seventh Framework programme – PADDINGTON Project, Grant Agreement No. 261358, and the European Huntington’s Disease Network (EHDN), project 070 – PADDINGTON.