Local and global microstructural and functional thalamomotor connectivity alterations in Parkinson’s disease following motor learning

Diffusion tensor imaging (DTI) is a sensitive method for detecting white-matter alterations in Parkinson's disease (PD) and is increasingly used to capture short-term learning-induced plasticity. However, evidence for such effects in PD remains limited. In this pilot study, 32 levodopa-treated patients were randomized to a three-week digital intervention or placebo app, examining motor learning neuroplasticity. The active intervention involved a digital spatial navigation protocol combining egocentric and allocentric strategies with multisensory-deprivation principles, alongside psychological and rehabilitation modules. Neuroimaging demonstrated increased fractional anisotropy in the right ventrolateral posterior (VLp) thalamus and strengthened functional connectivity between the VLp and precentral gyrus (PreCG), both preliminary associated with improvements in motor performance. Graph-theory analysis indicated increased local efficiency in PreCG and adjacent motor networks, suggesting enhanced structural integration. Collectively, these findings raise the possibility of region-specific short-term plasticity in PD, and support DTI's sensitivity to detect clinically meaningful training-related white-matter adaptations beyond the effects of dopaminergic therapy. Replication in larger, adequately powered samples is needed to confirm these findings.