Cortico-striatal-brainstem structural connectivity patterns in in Parkinson’s disease with and without freezing of gait

Virendra Mishra¹, Ece Bayram¹, Karthik Sreenivasan¹, Xiaowei Zhuang¹, Zhengshi Yang¹, Christopher Bird¹, Irene Litvan², Sarah J Banks¹, Dietmar Cordes¹, Brent Bluett¹

Background and Objective: Freezing of gait in Parkinson’s disease (PD) is a poorly understood phenomenon which frequently causes falls. To better understand this phenomenon, we evaluated structural connectivity in PD patients with freezing of gait (PD-FOG), compared to PD patients without freezing of gait (PD-nFOG), and healthy controls (HC).

Methods: Age, gender, and education-matched 10 HC, 9 PD-FOG, and 10 PD-nFOG were recruited at our center. PD-FOG and PD-nFOG were also matched on disease duration and severity. 71 direction diffusion-weighted MRI and 8 non-diffusion encoded b0 images were acquired on a 3T Siemens Skyra scanner with three-shell (500s/mm², 1000s/mm², and 2500s/mm²). 1 b0 image was acquired with opposite phase-encode to correct for eddy-current distortion. Deterministic tracking was conducted using TrackVis between 15 bilateral regions comprising of the cortical, striatal, and brainstem regions. A symmetric structural connectivity matrix was generated by weighting the number of streamlines between the ROIs by the average fractional anisotropy (FA) of the streamlines, and the number of voxels through which the streamlines pass normalized by the total number of available voxels and fiber length. Streamline length less than 10mm were discarded. Cohen’s d (effect-size) map was obtained for each comparison between HC, PD-FOG, and PD-nFOG, and only those connectivity having high d (d>0.8) were retained.

Results: Our study revealed impaired structural connectivity among premotor area, mesencephalic locomotor area, ventral striatum, and locus coeruleus between PD-FOG and PD-nFOG.

Discussion and Conclusions: PD-FOG is due in part to impaired structural connectivity between midbrain locomotor regions and cortical structures.

Acknowledgements: This study was supported by IDeA award from NIH under grant number 5P20GM109025.