PhD Proposal: Vivek J. Khandwala

Developing Techniques for Quantifying the Therapeutic Efficacy of Deep Brain Stimulation

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder occurring in middle-aged and elderly populations. Characterizing the movement kinematics and muscle activation patterns that are associated with Parkinson’s disease is a critical step in the development of criteria that can be used in the evaluation of disease progression and the therapeutic efficacy of the preferred treatment option, deep brain stimulation (DBS). However, the effects of normal aging-related movement pathologies need to be dissociated from PD-related pathologies in order to successfully accomplish this. Numerous studies have shown that performance of voluntary movements slows with normal aging. The underlying mechanisms for such changes can be cognitive, motor, or a combination thereof. Therefore, the goal of the current study is to characterize voluntary movements as a function of: 1) normal aging, 2) Parkinson’s disease and 3) during treatment of PD with DBS. A series of button pressing tasks that incorporate multisensory cues, remembered endpoint locations, and variable planning times will be used to dissociate cognitive, memory, and motor components of voluntary movements for quantitative comparison as a function of age, disease, and stimulation state. We hypothesize that movement planning and execution will be negatively impacted by aging. We postulate that these changes will become manifest as decrements in spatiotemporal variables, kinematic variables, performance variables and muscle activation patterns. We predict that PD subjects will implement movement strategies that avoid multi-joint movements with resultant increases in reaction and movement times. We further expect to observe greater variability in muscle activation patterns accompanied by co-contraction of the proximal and distal musculature. PD patients in the on-stim condition will increase the frequency of multi-joint movements, increased movement velocity, and reductions in reaction and movement times. We further predict that DBS will alter EMG patterns with less variability and fewer co-contractions. To test these hypotheses, we analyze EMG patterns, spatiotemporal and kinematic data from 3D motion traces of young (n=10, age range 18-40), middle aged (n=10, age range 40-60), elderly (n=10, age range 60-85) subjects and PD patients with bilateral DBS implantation (n = 10) in both the stimulation states.