Advisors
Steve M. Potter, PhD (Georgia Institute of Technology)
Robert E. Gross, M.D., PhD (Emory University)

Thesis Committee
Joseph R. Manns, PhD (Emory University)
Maysam Ghovanloo, PhD (Georgia Institute of Technology)
Pamela Bhatti, PhD (Georgia Institute of Technology)

Epilepsy is a debilitating, chronic illness affecting nearly one in 100 Americans and accounting for 1% of the world’s burden of disease. For one-third of the patients, complete seizure control is unattainable even with a combination of medications. Surgically resecting the affected brain area(s) while being effective in stopping seizures in these patients is precluded in the majority due to risk to memory and other vital functions. Vagus Nerve stimulation, where the vagus nerve having projection to the brain stem nuclei is unilaterally stimulated by an implanted pulse generator remains the only FDA approved electrical stimulation treatment for epilepsy. Medtronic’s SANTE (Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy) and Neuropace’s RNS (Responsive Nerve Stimulation) recently completed clinical trials are now awaiting FDA approval. These three techniques have shown that electrical stimulation has great potential for significantly reducing seizures in epilepsy. However, most brain stimulation techniques use a single macroelectrode (1.27 mm in diameter) for stimulation. We propose that using an array of microelectrodes distributed throughout the epileptic focus might be more effective in controlling seizures when compared to the single macroelectrode approach.

Commercially available microelectrode arrays have high impedances due to their low surface area and small tip diameters. Lowering the electrode impedance, but preserving the small diameter, would provide a number of advantages, including reduced stimulation voltages, reduced stimulation artifacts and improved signal-to-noise ratio. Impedance reductions can be achieved by electroplating the MEAs with platinum (Pt) black, which increases the surface area but has little effect on the physical extent of the electrodes. However, because of the low durability of Pt black plating, this method has not been popular for chronic use. In Aim 1 of my thesis, I have shown that performing electroplating under ultrasonic vibrations – sonicoplating – significantly (p<0.05) improves the durability of electroplated Pt black. In Aim 2 of my thesis, I will study the radius of neuronal activation with electrical stimulation performed through unplated microelectrodes (33 µm), sonicoplated microelectrodes (33 µm) and macroelectrodes (150 µm) using c-Fos staining to detect neuronal activity. Preliminary results show that macroelectrodes activate ~21 neurons in 50 µm sections of the hippocampus whereas unplated microelectrodes activate ~5 neurons and sonicoplated microelectrodes activate ~10 neurons in voltage controlled electrical stimulation studies in anesthetized rats. Hence by using an array of 16 sonicoplated microelectrodes >7 times net neuronal activation can be achieved when compared to single macroelectrode stimulation, while causing lesser tissue damage. In Aim 3 of my thesis, I will use sonicoplated 16-microelectrode arrays to perform hippocampal electrical stimulation in the tetanus toxin rat model of temporal lobe epilepsy. From spontaneous local field potential recordings of control and epileptic rats, I have identified that epileptic rats have significant reduction (p<0.0001) in theta oscillations during exploratory behavior. Through preliminary studies I have shown that distributed asynchronous microstimulation at theta frequencies is effective in reducing seizure frequency (p<0.05), while higher stimulation frequencies tended to increase seizure frequency indicating that the effect is stimulation frequency specific. Closed-loop electrical stimulation where electrical stimulation is performed on seizure detection is currently being explored.