Multielectrode Interactions with the Normal and Epileptic Brain Public

Abstract

Multielectrode recordings provide the unique ability to observe the brain's dynamics at
multiple scales and from multiple locations. Using multielectrode arrays, I have carried
out several investigations of both the normal and epileptic brain, and developed new
technology to more easily interact with neural tissue.
First, using dissociated cultures of cortical neurons, I used a template-matching
algorithm to uncover evidence of precisely timed repeating sequences of neuronal action
potentials. These sequences, which have been observed in the intact brain and brain
slices, are a potential mechanism of neural information processing.
My other experiments involved freely moving animals. Based on prior work with cell
cultures, it is believed that closed-loop brain stimulation can suppress epileptiform
activity in animals with seizures. Before this hypothesis could be tested, I had to develop
a new recording and stimulation system capable of closed-loop microstimulation, along
with new signal processing algorithms to improve the data we observed. The resulting
system, NeuroRighter, is a freely available, open source platform with several advantages
over existing commercial systems (none of which is capable of closed-loop stimulation).
With the new recording and stimulation system in place, I was able to characterize in
detail the field potential and action potential dynamics underlying interictal spikes and
seizures in the tetanus toxin model of temporal lobe epilepsy. Specifically, I found
evidence of high-frequency oscillations in this model, which were restricted to interictal
spikes and commensurate with entrained bursts of multiunit activity.
While distributed stimulation was ultimately ineffective at suppressing seizures and
epileptiform bursting with the parameters we tested, we were nevertheless able to
control neural activity in epileptic animals in novel ways. In particular, we provided the
first evidence that high-frequency oscillations could be directly evoked with
microstimulation. Such stimulation has potential applications in presurgical screening
for epileptiform onset zones.

Table of Contents

Acknowledgements ............................................................................................................... vi
Brief Table of Contents ......................................................................................................... xi
Table of Contents ................................................................................................................ xiii
Table of Figures ................................................................................................................ xxiii
Chapter 1 Introduction .......................................................................................................... 1
Chapter 2 Precisely Timed Spatiotemporal Patterns of Neural Activity in Dissociated Cortical Cultures ................................................................................................................. 16
Chapter 3 Distributed Microstimulation for Epilepsy ...................................................... 38
Chapter 4 A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts ......................... 43
Chapter 5 Closed-loop Multielectrode Stimulator with Simultaneous Recording in Awake, Behaving Animals .................................................................................................. 92
Chapter 6 Common Median Referencing for Improved Action Potential Detection with Multielectrode Arrays ........................................................................................................ 119
Chapter 7 Seizures and Interictal Spikes are Altered by Distributed Microstimulation131
Chapter 8 Presence and production of high-frequency oscillations in the tetanus toxin model of epilepsy ............................................................................................................... 143
Chapter 9 Observations of the Effects of Microstimulation in the Rodent Hippocampus ........................................................................................................................................... 159
Appendix A NeuroRighter: Closed-loop Multielectrode Stimulation and Recording for Freely Moving Animals and Cell Cultures ....................................................................... 185
Appendix B NeuroRighter Construction Manual ............................................................ 199
Appendix C NeuroRighter User's Manual ....................................................................... 236
Appendix D SCB-68 Quick Reference Labels ................................................................... 271
References .......................................................................................................................... 274

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Engineering, Biomedical Biology, Neuroscience
Mot-clé	closed-loop multielectrode epilepsy stimulation microstimulation rat microelectrode seizure
Committee Chair / Thesis Advisor	Gross, Robert, Emory University Potter, Steve M, Emory University
Committee Members	Rainnie, Donald, Emory University Buffalo, Elizabeth, Emory University Litt, Brian, University of Pennsylvania Dingledine, Raymond J, Emory University

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