Date of Award

Fall 2014

Document Type

Dissertation

Degree Name

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

Department

Biomedical Engineering

First Advisor

Mesut Sahin

Second Advisor

Bharat Biswal

Third Advisor

Bryan J. Pfister

Fourth Advisor

Vijayalakshmi Santhakumar

Fifth Advisor

Kevin Pang

Abstract

Much of the cerebellar research has been conducted in anesthetized animals, particularly using ketamine/xylazine combination in rats, and yet the absolute impact of the anesthesia on the neural circuit remains unanswered . In the current study, spontaneous electrical activity and sensory evoked potentials from the cerebellar surface with chronically implanted, flexible-substrate, multielectrode arrays in rats were collected and analyzed with the motor cortex signals. The power spectra and the intercontact coherence plots of the spontaneous activity in the awake-quiet animals extended up to 800 Hz in the cerebellum and only up to 200 Hz in the motor cortex. Ketamine/xylazine anesthesia suppressed most of the activity in the cerebellar cortex, which was in clear contrast to the motor cortex. In the awake cerebellum, large coherence values were observed between contact pairs as far apart as ∼2 mm. Otherwise, there was not a discernable relation between the coherence and the intercontact distance. These results have suggested that the surface electrodes could provide much more detailed information about the state of neural circuits when they were used on the cerebellar cortex compared with the cerebral areas.

Findings in ketamine/xylazine treated rats by using micro ECoG signals extracted the baseline information in the cerebellum to investigate the altered electrophysiology in the damaged neural circuitry. The temporal course of excitability change in selected neural networks was used as a method to study traumatic brain injury (TBI). This research demonstrated the use of cerebellar evoked potentials (EPs), which was characterized in the first phase of the study, for monitoring the injury progression in a rat model of fluid percussion injury (FPI). A mechanical tap on the dorsal hand was used as a stimulus, and EPs were recorded from the paramedian lobule (PML) of the posterior cerebellum via multi-electrode arrays (MEA). Evoked response amplitudes (EPAs) were analyzed immediate after the injury and on a daily basis for one week thereafter. This data indicated a trend of consistently decreasing EPAs in all nine animals, losing as much as 75% of baseline amplitudes measured before the injury. Notably, it was highlighted that there was two particular time windows; the first 24 hours of injury in the acute period and day-3 to day-7 in the delayed period where the largest drops (~40% and 30%) were observed in the EPAs. Immunohistochemical analysis supported electrophysiological findings that there was severity dependent Purkinje cell (PC) loss under the implant site. Current research has presented the evidences that sensory evoked potentials recorded from the cerebellar surface can be a useful technique to monitor the course of cerebellar injury and identify the phases of injury progression even at mild levels.

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