Altered pedunculopontine pathways in freezing of gait: a diffusion tensor imaging study based on dopaminergic degeneration status.

backgroundFreezing of gait (FOG), a transient cessation of walking, is commonly observed in various neurodegenerative diseases and linked to pedunculopontine nucleus (PPN) pathway dysfunction. However, it remains unclear whether PPN pathway alterations differ depending on the presence of dopaminergic degeneration (DD).

objectivesTo investigate differences in PPN pathway in FOG patients with and without DD, classified using FP-CIT PET.

methodsSixteen FOG patients over 70 years old (10 with DD + and 6 without DD-) and 20 age-matched controls underwent diffusion tensor imaging (DTI). Preprocessing included denoising, removing Gibbs artifact, bias correction, and eddy current correction, registered to MNI standard space using MRTRIX 3 and FSL. Quantitative parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and tract volume were extracted with a PPN-to-ROI mask covering 9 regions of interest. Group comparisons were performed using tract density and region-specific analyses.

resultsRegardless of dopaminergic degeneration, FOG patients exhibited reduced tract volume and increased MD, AD, and RD in bilateral caudate nucleus (CN), globus pallidus external, globus pallidus internal, putamen, subthalamic nucleus, primary motor cortex (M1), dorsal/ventral motor cortex (PMd/PMv), and supplementary motor area (SMA). FA in left M1, PMd, PMv, SMA, and right CN were significantly lower in FOG patients than HC. No significant differences were found between DD + FOG and DD-FOG groups.

conclusionsPPN pathway degeneration is associated with FOG regardless of dopaminergic degeneration, highlighting PPN pathway dysfunction as a key mechanism in FOG.