Epilepsy is the third most commonly diagnosed neurological disorder, afflicting 2.5 million people in the United States. Despite its pervasiveness, scientists are only just beginning to understand the mechanisms underlying seizures. Specifically, there is still very little known about the relationship between neuronal mechanisms underlying inter-ictal spikes – periodic, and brief bursts of neuronal activity – and seizures that occur during epilepsy.
This knowledge deficit can be attributed to current techniques for acquiring data on neuronal activities. Most electrophysiological studies at the cellular level are performed on isolated brain slices, which disrupt complex neural circuitry and generation of spontaneous seizures. In vivo studies in animal models of epilepsy are another means of acquiring data, but they almost exclusively use variations of conventional EEG recording, which record electrophysiological signals integrated over large areas neural tissue. There are very few in vivo studies of electrical activity at the scale of individual neurons in animal models, and even fewer in human patients with epilepsy.
We propose to use three modalities to analyze inter-ictal spikes and seizures at multiple scales: conventional electrocorticography (ECoG, intra-cranial EEG), micro-electrocorticography (micro-ECoG), and penetrating microelectrode arrays in human patients with epilepsy. Conventional ECoG electrodes will be used to record neural activity integrated over a wide cortical area. Nonpenetrating micro-ECoG grids resting on the surface of the cortex will be used to measure local field potentials (LFPs) generated by thousands of neurons. Penetrating, microelectrode arrays will record LFPs and action potentials (APs) of individual neurons.
Using this integrated approach, we will be able to determine how the activity of individual neurons and groups of neurons correlate with, and contribute to, inter-ictal spikes. Additionally, by examining neural activity across the array, it will be possible to determine how seizure activity propagates through the cerebral cortex at the microscopic level. By analyzing these multiscale signals individually, and by correlating them with each other, we hope to gain insight into the generation and propagation of seizures, and mechanistically link the activity of individual neurons and networks of neurons with established electrophysiologtical markers of seizures and epilepsy.
The numbered button-like electrodes are micro-ECoG electrodes used by surgeons to locate and then remove brain areas responsible for severe epileptic seizures.