We aimed to investigate the structural integrity of the Corpus Callosum in ET and ET with resting tremor (ETrt) patients compared to healthy controls using a multimodal MRI approach. We combined traditional group comparisons with data-driven clustering methods, to identify potential similarities and differences between these subtypes.

Some studies showed the involvement of CC in ET. CC is the largest commissural fiber bundles responsible for interconnecting the right and left hemispheres, facilitating communication between regions of opposite lobes. Neuroimaging findings might suggest that ET-plus could be associated with more widespread changes, involving large-scale brain networks, and a different involvement of right and left networks. CC could play a key role in these bi-hemispherical circuitry. Despite these advances, no study has evaluated any differences in the involvement of the CC, between the ET subtypes.

We enrolled 128 participants (63 ET, 38 ETrt, and 27 HC). We performed a multimodal MRI evaluation (thickness, mean diffusivity [MD], and fractional anisotropy [FA]) of the CC’s genu, body, and splenium, using different statistical approaches. We first performed a traditional group-based comparison, controlling for relevant covariates. Then, we used an unsupervised classification model based on MRI data to explore potential subgroup distinctions.

Our evaluation showed significant changes in structural parameters of CC in both ET and ETrt patients compared to HC, mainly represented by thickness reductions across all regions and MD increase in the body. Notably, we found no differences between the ET and ETrt groups. Clustering analysis reinforced this observation, placing ET and ETrt in a single cluster with similar abnormalities in all MRI parameters and clearly separating them from HC.

Despite their clinical differences, ET with and without resting tremor patients showed analogous macro- and microstructural changes in the CC, suggesting shared pathophysiological processes within this brain region.