Introduction In a recent functional MRI study we investigated the integrity of resting-state networks (RSN) in Huntington’s disease (HD) and reported significant increases in intrinsic functional connectivity including the thalamus, striatum, prefrontal, premotor and parietal maps.1 The aim of the present study was to follow up these findings and to assess RSN changes in HD longitudinally.
Methods Ten HD patients (3 pre-, 7 manifest) and ten controls matched for age and gender underwent 3T MRI at two visits (mean scan interval HD: 22 ± 4 months; controls: 25 ± 6). Resting-state data were analysed using independent component analysis and subsequent dual-regression.2,3 Structural changes were analysed by means of voxel-based morphometry (VBM).
Results Patients did not show substantial clinical decline over time. VBM revealed HD-typical striatal and cortical atrophy at both time-points, but no group-by-time interaction. RSN analysis at baseline showed increased intrinsic connectivity in HD compared to controls in striatal and fronto-striatal components. Longitudinally, we found group-by-time interactions showing an attenuation of the increased coherence mainly in fronto-striatal RSN in HD. Functional connectivity drop-off was more pronounced in HD stages II-III, whereas premanifest subjects were more stable over time. Baseline striatal volumes correlated negatively with the difference in functional connectivity over time, indicating that patients with more pronounced atrophy seem to have a higher drop-off from baseline to follow-up.
Conclusions The pattern of increased intrinsic connectivity in HD might suggest a reduced ability of intra-network differentiation and potential functional compensatory mechanisms. As disease pathology progresses over time increased neural coupling seems to attenuate, possibly due to progression of cell degeneration. The prognostic value of our findings needs to be evaluated in a larger sample in the context of clinical and structural decline.
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