Date of Award

Spring 2015

Degree Type


Degree Name

Doctor of Philosophy (PhD)


Biomedical Engineering

First Advisor

Pedro Irazoqui

Committee Chair

Pedro Irazoqui

Committee Member 1

Edward Bartlett

Committee Member 2

Riyi Shi

Committee Member 3

Robert Worth

Committee Member 4

John Jefferys


Electrical stimulation has been successful in treating patients who suffer from neurologic and neuropsychiatric disorders that are resistant to standard treatments. For deep brain stimulation (DBS), its official approved use has been limited to mainly motor disorders, such as Parkinson's disease and essential tremor. Alcohol use disorder, and addictive disorders in general, is a prevalent condition that is difficult to treat long-term. To determine whether DBS can reduce alcohol drinking in animals, voluntary alcohol consumption of alcohol-preferring rats before, during, and after stimulation of the nucleus accumbens shell were compared. Intake levels in the low stimulus intensity group (n=3, 100&mgr;A current) decreased by as much as 43% during stimulation, but the effect did not persist. In the high stimulus intensity group (n=4, 200&mgr;A current), alcohol intake decreased as much as 59%, and the effect was sustained. These results demonstrate the potent, reversible effects of DBS.^ Left vagus nerve stimulation (VNS) is approved for treating epilepsy and depression. However, the standard method of determining stimulus parameters is imprecise, and the patient responses are highly variable. I developed a method of designing custom stimulus waveforms and assessing the nerve response to optimize stimulation selectivity and efficiency. VNS experiments were performed in rats aiming to increase the selectivity of slow nerve fibers while assessing activation efficiency. When producing 50% of maximal activation of slow fibers, customized stimuli were able to activate as low as 12.8% of fast fibers, while the lowest for standard rectangular waveforms was 35.0% (n=4-6 animals). However, the stimulus with the highest selectivity requires 19.6nC of charge per stimulus phase, while the rectangular stimulus required only 13.2nC.^ Right VNS is currently under clinical investigation for preventing sudden unexpected death in epilepsy and for treating heart failure. Activation of the right vagal parasympathetic fibers led to waveform-independent reductions in heart rate, ejection ratio, and stroke volume. Customized stimulus design with response feedback produces reproducible and predictable patterns of nerve activation and physiological effects, which will lead to more consistent patient responses.