Direct neural stimulation has recently become a standard therapy for neurological disorders such as Parkinson's Disease, Essential Tremors, and Dystonia. Currently, deep brain electro-stimulation and neuro-pharmaceutical treatments are the dominant therapeutic options available to the public. As our understanding of brain function and neurological diseases improves, we are able to develop more advanced neuromodulation techniques. These methods could become viable treatment solutions for treating brain dysfunction. Optogenetics, first introduced by a research team led by Karl Deisseroth at Stanford University, has proved to be a versatile technique with remarkable potential to be used in treatments for brain disorders, dysfunction, and injuries. Optogenetics makes use of light-gated ion channels and pumps, originally derived from certain types of algae or bacteria, to bi-directionally modulate the activity of neurons in mammals. By adopting new advances in the field of optics and photonics, including high-speed high-resolution spatial light modulators, solid-state lasers, and ultra-low noise photodetectors, we can build sophisticated devices which allow precise and resolute optical patterning in both the spatial and temporal domains.
In this thesis, I present an optogenetic brain-machine interface that offers high spatiotemporal neuromodulation functionality. The incorporation of imaging and sensing devices of neural activity into the system allowed us to run multiple independent experiments. These optogenetic experiments include closed-loop modulation of multiple areas of tissue, investigating the causal relationship between neural activity and blood flow, and quantifying the relationship between neural activity and cell metabolism.
To understand light to brain tissue interaction in a rat brain, a device has been developed which allows one to extract the optical properties throughout the tissue. Utilizing this data, Monte Carlo software was used to predict light distribution within the brain. This has far reaching effects for the future use of optogenetics. Our approach will allow the investigator the ability to precisely understand how introduced light will be distributed within the rat brain where light-gated ion channels have been genetically expressed. This becomes noticeably important when attempting to determine which areas of the brain tissue will and won't be modulated by the introduced light.
Due to the many advantages optogenetics inherently provides, it is a rising prospect for novel neuromodulation therapies. With continued research and development of devices, we could create new therapies for disabilities that arise from dysfunction of the human brain.
|Commitee:||Helmstetter, Fred, Law, Chiu-Tai|
|School:||The University of Wisconsin - Milwaukee|
|School Location:||United States -- Wisconsin|
|Source:||MAI 54/03M(E), Masters Abstracts International|
|Subjects:||Neurosciences, Biomedical engineering, Electrical engineering|
|Keywords:||Brain-machine interface, Digital micromirror device, Electrocorticography, Fluorescence imaging, Neuromodulation, Optogenetics|
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