Objective: Our objective was to correlate pedunculopontine nucleus (PPN) connectivity with quantitative gait metrics in Parkinson’s disease (PD) using diffusion tensor imaging (DTI).

Background: Gait impairment in PD is likely caused by degeneration in multiple brain circuits, including the basal ganglia, thalamus, amygdala, and PPN. While the PPN is an important locomotion center, the integrity of PPN networks is under-studied and may be a useful marker to predict gait dysfunction in PD. DTI can assess microstructural changes by measuring fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD).

Method: Twenty-one PD patients and 15 controls were recruited. DTI data were processed using FSL v6.0, and tractography was performed using the PPN as a seed of interest for cortical and subcortical target structures. Total tract volume, mean FA, MD, RD, and AD values for each tract were analyzed. Quantitative gait metrics and other clinical tests were recorded in subjects’ medication ON and OFF states, and were used to determine if specific features of gait dysfunction in PD were related to PPN connectivity.

Results: The PPN showed widespread connections to cortical targets (superior and middle frontal gyri, anterior cingulate, pre-SMA, SMA and pre- and postcentral gyri), subcortical structures (thalamus, basal ganglia, and cerebellum), and the spinal cord.

There were no differences in DTI parameters between PD and controls in the left hemisphere. In the right hemisphere, differences between PD and control were seen in tract volume (PPN to S1 and pre-SMA), MD (PPN to caudate, PMd, SMA and amygdala), RD (PPN to SMA and amygdala), and AD (PPN to caudate and amygdala).

With Pearson correlation analysis between right hemispheric tract parameters and gait metrics, moderate-strong correlations were found between MD in tracts to amygdala and velocity and stride length when OFF; RD and AD in tracts to amygdala and stride length when OFF; RD in tracts to caudate and stride length when OFF; and tract volume in tracts to S1 and pre-SMA and cadence and stride time when ON.

Conclusion: Our data suggest that PPN networks with connections to S1, pre-SMA, amygdala, and caudate are important in gait control in PD with hemispheric lateralization. The contribution to gait control is through dopamine-dependent and independent pathways.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tractography-analysis-of-the-pedunculopontine-nucleus-correlates-with-gait-impairment-in-parkinsons-disease/