Cortical myelination insights into the freezing of gait in Parkinson’s disease
Poster No:
227
Submission Type:
Abstract Submission
Authors:
Gaurav Rathi1, Jason Longhurst2, Zoltan Mari3, Virendra Mishra1
Institutions:
1University of Alabama at Birmingham, Birmingham, AL, 2Saint Louis University, St. Louis, MO, 3Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV
First Author:
Co-Author(s):
Introduction:
Freezing of Gait (FOG) is a debilitating motor symptom experienced by a subset of individuals with Parkinson's Disease (PD) (Moore et al., 2007; Nutt et al., 2011). Previous studies have established the relationships between gray matter (GM) and white matter (WM) changes with clinical and physical therapy (PT) variables in PD (Dadar et al., 2020; Terada et al., 2018). However, the potential of conventional MRI techniques and the use of T1-weighted/T2-weighted (T1w/T2w) ratio mapping, to assess cortical microstructural changes like cortical myelination (CM), while their associations with clinical and therapeutic variables remain largely underexplored (Uddin et al., 2019). Based on the previous reported studies on morphological changes in PD-FOG, we hypothesize that CM could show significant group-level differences, and correlates with clinical variables including Levodopa Equivalent Daily Dose (LEDD), Disease Duration (DDX), Unified Parkinson's Disease Rating Scale-III-ON (UPDRS-III-ON), the Freezing of Gait Questionnaire (FOG-Q) and 6 different PT variables (Longhurst et al., 2022), providing insights into its role in clinical outcomes and therapy efficacy.
Methods:
Our cross-sectional study included two groups: individuals with FOG (PD-FOG, n=15) and those without FOG (PD-nFOG, n=16). PD-FOG and PD-nFOG groups were classified based on clinical assessments and expert evaluations. High-resolution T1w MPRAGE and T2w SPACE MRI scans were acquired using a Siemens 3T Skyra scanner with an imaging parameter including voxel size=1.0mm³, and slice thickness=1.0mm. For T1w scans, rotation time [TR]=2300ms, echo time [TE]=2.96ms; for T2w scans, TR=3200ms, TE=412ms. T1w and T2w MRI data were preprocessed using the Human Connectome Project pipeline (https://www.humanconnectome.org/software/hcp-mr-pipelines). Motion correction, spatial normalization, and T1w/T2w ratio calculations were performed to derive CM maps for each hemisphere. Group-wise mean comparisons and the correlation analysis of T1w/T2w CM with clinical and PT variables were performed using PALM (Winkler et al., 2014) in FSL. Statistical significance was set at an uncorrected p-value<0.005.
Results:
In the mean comparison, PD-FOG exhibited significantly lower CM in both the left and right hemispheres compared to PD-nFOG (Figure 1). Correlation analysis revealed significant associations between CM and clinical variables, while one of them, UPDRS-III-ON showed the strongest correlations (Figure 2 (A), (B)). In both hemispheres, higher UPDRS-III-ON scores were consistently associated with lower CM in both PD-FOG and PD-nFOG groups, with slopes highlighting the robustness of these relationships. Significant correlations with CM were also observed in all 6 PT variables, but combined dual-task effects (cDTE) exhibited distinct patterns across hemispheres (Figure 2 (C), (D)). In the left hemisphere, cDTE was negatively correlated with CM in both PD-FOG and PD-nFOG groups, while in the right hemisphere, correlations varied. Positive correlations were observed between cDTE and CM in PD-nFOG, whereas negative correlations were evident in PD-FOG. The slope followed a similar trend, underscoring regional differences in CM and cDTE performance.
Conclusions:
This study highlights the potential of CM as a valuable imaging marker for distinguishing PD-FOG from PD-nFOG. Significant CM reductions were observed in multiple brain regions, including the lateral occipital, inferior parietal, and precuneus areas in both hemispheres, with specific cortical regions like the isthmus cingulate, superior frontal, and lingual cortices playing critical roles in the motor dysfunction associated with FOG. Future studies should integrate neuropsychological tests to further investigate the relationship between CM and motor or cognitive measures, enhancing diagnostic accuracy and guiding personalized treatment strategies for individuals with PD-FOG.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Motor Behavior:
Motor Planning and Execution 2
Keywords:
Data analysis
DISORDERS
Morphometrics
Movement Disorder
MRI
STRUCTURAL MRI
1|2Indicates the priority used for review
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Provide references using APA citation style.
10.1016/j.nicl.2020.102353
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