Project 2 - Dr. Virendra Mishra

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.