Research Abstracts Online
January 2010 - March 2011
University of Minnesota Twin Cities
PI: Timothy J. Ebner
Mechanisms and Control of Movement Disorders: Ataxia and Parkinson's Disease
These researchers are using MSI for two projects. The first involves a novel form of neural activation of the cerebellar cortex that was discovered in the Ebner laboratory using optical imaging methods in vivo. This activation process, called "spreading acidification and depression” (SAD), is hypothesized to underlie the channelopathy of episodic ataxia type 1. The cellular mechanisms of SAD remain unclear. In order to understand these mechanisms, this group has developed a computational model of SAD based on direct activation of the parallel fibers through addition of extra synaptic glutamate. The model uses the geometry of the cerebellar cortex determined through measurements of extrasynaptic diffusion of glutamate in the cerebellar cortex released from local synapses. The model has several free parameters, such as tissue volume, the glutamate activation threshold, and the synaptic release delay. The researchers are performing a systematic sweep of the free parameter space to characterize the model and compare it with the experimental results.
The second project investigates deep brain stimulation (DBS), which has provided relief for many patients with medically refractory movement disorders. While the mechanisms involved are not entirely understood, studies have shown that high-frequency DBS in the subthalamic nucleus or globus pallidus interna reduces the severity of the motor impairments in Parkinson’s disease in both humans and monkeys. A limitation of present DBS approaches is the lack of any feedback to control the stimulation and optimize the therapeutic outcome. Not only is there no on-line feedback to control stimulation, feedback control is also lacking to optimize the site of stimulation based on the abnormal signals recorded at the electrode contacts. In a behaving, nonhuman primate model of Parkinson’s disease, this study tests whether the effectiveness of DBS can be improved by delivering the stimulation in the STN at the site with the maximal electrical activity and using feedback-control techniques driven by internal motor cortical signals.
Claudia Hendrix, Research Associate
Laurentiu S. Popa, Graduate Student
Kasen Riemersma, Staff