Neural and behavioral responses to deep brain stimulation of the subthalamic nucleus

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Title Neural and behavioral responses to deep brain stimulation of the subthalamic nucleus
Publication Type dissertation
School or College College of Engineering
Department Biomedical Engineering
Author Anderson, Collin
Date 2016
Description Parkinson's Disease (PD) motor symptoms, characterized most commonly by bradykinesia, akinesia, rigidity, and tremor, are brought about through the degeneration of dopaminergic neurons in the substantia nigra pars compacta, which leads to changes in electrophysiological activity throughout the basal ganglia. These symptoms are often effectively treated in the early stages of the disease by dopamine replacement therapies. However, as the disease progresses, the therapeutic window of pharmacological approaches reduces and patients develop significant side effects, even under minimally effective doses. When the disease reaches this stage, surgical therapies, such as high-frequency deep brain stimulation (DBS), are considered. DBS of the subthalamic nucleus partially treats the motor symptoms of PD and has been implemented to treat PD over 50,000 times worldwide, but its mechanisms are unclear. In this work, we set out to advance the understanding of the mechanisms, function, and malfunction of DBS as a treatment for PD, keeping in mind the idea that DBS treats PD symptoms without restoring basal ganglia neural activity to that seen under healthy conditions. First, we demonstrated that neuronal information directed from the basal ganglia to the thalamus is pathologically increased in the parkinsonian condition and reduced by DBS in a standard 6-OHDA rat model of PD. Next, we developed a rodent model of DBSs role in the exacerbation of hypokinetic dysarthria, providing a framework for the study of this poorly understood side effect of DBS. Finally, we found that DBS creates action suppression deficits independently from a parkinsonian state, and that PD creates apathy that is not rescued by DBS. Our specific results led to the interpretation that DBS, in its current form, might inherently create side effects that are largely unavoidable. Our work fits into the following overarching idea. DBS successfully treats some motor symptoms of PD through the reduction of pathological information transmission. However, the fact that reducing pathological information does not restore neural activity to that present under healthy conditions underlies some of its failures to improve certain symptoms, as well as its exacerbations and side effects.
Type Text
Publisher University of Utah
Subject Deep Brain Stimulation; Information Theory; Parkinson's Disease
Dissertation Name Doctor of Philosophy
Language eng
Rights Management ©Collin Anderson
Format application/pdf
Format Medium application/pdf
Format Extent 4,934,953 bytes
Identifier etd3/id/4143
ARK ark:/87278/s6tf35pm
Setname ir_etd
ID 197690
Reference URL https://collections.lib.utah.edu/ark:/87278/s6tf35pm
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