Date of Award

5-31-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

Mesut Sahin

Second Advisor

Eric J. Lang

Third Advisor

Sergei Adamovich

Fourth Advisor

Bart Krekelberg

Fifth Advisor

Gail Forrest

Abstract

Non-invasive brain stimulation (NIBS) techniques garner significant interest due to their potential to offer instantaneous and region-specific treatments to neurological disorders. The cerebellum is one of the target sites for NIBS methods due to its central role in motor and cognitive functions. Among several modulation techniques, transcranial electric stimulations (tEs), in particular, transcranial direct and alternating current stimulations (tDCs/tACs), and low intensity focused ultrasound stimulation (LIFUS) show encouraging outcomes in clinical applications. tDCs and tACs are favored due to their low cost and accessibility while LIFUS offers high spatial resolution and deeper penetration without affecting the surrounding structures. In order to better understand the underlying mechanism of these methods in the cerebellum, animal studies are needed since these experiments require invasive surgeries. The goal of this study is to investigate the response of cerebellar PCs to electric and ultrasound stimulation in an animal model.

The first objective is to measure the electric field (e-field) distribution inside the brain parenchyma since e-field is the main parameter that determines the local effects of electrical stimulation. The results of this part show that e-field decays exponentially through horizontal and vertical directions from the stimulating electrode and scattered by the skin up to 80%. Then, tACS and tDCS are applied to the cerebellar cortex respectively while recording the extracellular spike activity from the cerebellar PCs. The activity of PCs is important because they generate the sole output from the cerebellar cortex, which in turn modifies the output of the deep cerebellar nuclei (DCN). The results of this part demonstrate that the direction of e-field is highly correlated with the level of modulation measured on the PCs. Applying the e-field parallel to the dendritic tree of the PCs generates the highest modulation level. Our data show that PCs have a characteristic response to both DC and AC fields, including entrainment of the simple spike activity at high frequencies. Our findings for the LIFUS also show that spike timing of PCs is strongly entrained with the pulsed ultrasound stimulation, and the level of the entrainment is inversely correlated with the pulse width.

In summary, the low intensity electric and ultrasound stimulation are able to effectively modulate the PC activity in the cerebellar cortex. This warrants research to further look into the mechanism of tES and LIFUS acting on the cerebellar cortex at the cellular level.

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