Project 2 – Dr. Virendra Mishra

Freezing of Gait (FOG) in Parkinson's Disease (PD)

Virendra Mishra, PhD

Specific Aims:

Identify the structural and functional brain connectivity patterns in PD-FOG, PD-nFOG, and HC, and evaluate progression of FOG by:

  • Comparing the structural and functional connectivity brain patterns, both at baseline and longitudinally, between the FOG and nFOG PD subgroups;
  • Develop an unbiased estimator of tract-specific diffusion-derived measures and the fractional contribution of free-water (fiso) using a multi-shell high angular and spatial resolution diffusion MRI (dMRI), and further comparing these novel diffusion-derived voxelwise measures between the two groups to understand disease pathophysiology and progression;
  • Investigate the effect of levodopa on functional connectivity pattern in the PD subgroups; and
  • Combine the novel dMRI-derived measures with conventional structural MRI and resting state functional MRI (rs-fMRI) connectivity measures, and generate a subject-level score that is predictive of FOG progression.       

Establish a correlation between the multimodal MRI-derived measures and neuropsychological profile in each PD subgroup by:

  • Correlating the MRI-derived measures with neuropsychological assessments and clinical diagnostic tests within each PD subgroups;
  • Investigating the rs-fMRI connectivity brain patterns, and the association of these patterns with reference to changes in the neuropsychological profile with and without dopaminergic medication; and
  • Understanding the global shift in the correlation of network connectivity patterns with the neuropsychological profile within each of the PD subgroups.

Internal Mentor

Dietmar Cordes, PhD
Cleveland Clinic Lou Ruvo Center for Brain Health


Jeffrey L. Cummings, MD, ScD
Associate director of the Center for Neurodegeneration and Translational Neuroscience

External Mentor

Irene Litvan, MD
Irene Litvan, MD
Tasch Endowed Professor in Parkinson’s Disease Research