Can White Matter Tract Measures Predict Post-DBS Recovery in Patients with Parkinson’s Disease

19 

Abstract Submission 

Ivan Campbell¹, Brad Caron², Harrison Walker³, Benjamin Hill¹, Virendra Mishra⁴

¹University of South Alabama, Mobile, AL, ²Department of Psychology, University of Texas at Austin, Austin, TX, ³University of Alabama at Birmingham, Birmingham, AL, ⁴The University of Alabama at Birmingham, Birmingham, AL

Ivan Campbell  
University of South Alabama
Mobile, AL

Brad Caron  
Department of Psychology, University of Texas at Austin
Austin, TX

Harrison Walker, MD  
University of Alabama at Birmingham
Birmingham, AL

Benjamin Hill, PhD  
University of South Alabama
Mobile, AL

Virendra Mishra  
The University of Alabama at Birmingham
Birmingham, AL

Deep Brain Stimulation (DBS) is a neurosurgical procedure typically used in the treatment of Parkinson's disease (PD) and its related motoric dysfunction. While it is highly efficacious, (Bratsos, 2018) there is variability in response to implantation, with some patients improving more than others. Previous research has shown that stimulation of white matter (WM) tracts surrounding the targeted structure (specifically the subthalamic nucleus) may be implicated in the therapeutic effect of DBS. (Abdulbaki, 2021) Therefore, we hypothesize that variability in outcome post-DBS could be explained by the WM measures.

We selected 8 random patients with PD who underwent DBS surgery at The University of Alabama at Birmingham (UAB). We collected Unified Parkinson's Disease Rating Scale (UPDRS)-III, both before DBS and 12-month post DBS in every patient. Additionally, we collected conventional 30 directions diffusion weighted MRI (dMRI) data on a 3T MRI at a b-value of 1000s/mm2 before the surgery. All MRI processing was performed using the cloud-platform for reproducible neuroimaging analyses known as brainlife.io (Hayashi & Caron et al, 2023). Structural MRI images were segmented into tissue-types (gray-matter, white-matter) for tracking using the brainlife.io app.239, and cortical parcellations were generated using Freesurfer implemented as brainlife.io app.664. Diffusion MRI data was preprocessed using QSIPrep (Cieslak et al, 2021) implemented as brainlife.io app.246. Anatomically constrained tractography (Smith et al, 2012) implemented as brainlife app.297 was used to simulate white matter fiber pathways. Resulting tractograms were then segmented into 3 bi-hemisphere tracts (motor thalamic, spino-thalamic, and thalamico-cerebellar tracts) using a custom version of the white matter query language (Bullock et al, 2019) implemented as brainlife.io app.188. Measures of macrostructure (streamline count, midpoint density) were estimated using custom MatLAB code implemented as brainlife.io app.189. The diffusion tensor model (DTI) was used to estimate measures of microstructure along each tract using brainlife.io app.297 and app.361 for model fitting and tract profilometry (Yeatman et al, 2012) respectively. Along-the-tract measures such as fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity, fiber count, fiber density, and number of streamlines were extracted for each patient and used in linear regression via Jamovi to predict change in UPDRS-III from before and after DBS implantation.

Due to limited sample size (n=8), no significant results at a level of pcorr<.05 were obtained. However, multiple results trended toward significance. The midpoint density of the left motor thalamic tract (r=.694, p=.056), and the axial diffusivity of the right motor thalamic tract (r=.652, p=.08) showed the strongest effect size of correlation for improvement in UPDRS-III.

While evidence is limited due to the small sample size available at the time of the analysis, these results point to a potential link between white matter tract measurements and response to DBS implantation, and warrant further investigation.

Deep Brain Stimulation ¹

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ²

Diffusion MRI Modeling and Analysis

Motor Behavior Other

Subcortical Structures

Aging

Cerebellum

Degenerative Disease

DISORDERS

Motor

Movement Disorder

Sub-Cortical

Thalamus

Tractography

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC