Exploring Altered Cortical Activity Using High-Density Multi-Electrode Arrays

Abstract

Altered cortical activity has been associated with several brain states including those following radiation therapy (RT), as well as diseased brain states such as epilepsy. These states often result in activation patterns within neural networks that possess unique spatiotemporal dynamics such as propagating waves. They have also been associated with altered neural activity and a variety of cognitive deficits; however, the network dynamics underlying these changes remain poorly understood. We aimed to explore and compare the neural dynamics of irradiated cortical networks to epileptiform networks which produced a series of spiral waves. We used a large-scale high-density multi-electrode array (hd-MEA) to investigate the network-level neural dynamics underlying both pathological brain states. To induce an epileptic brain state, we applied a pro-epileptiform solution consisting of 4-Aminopyridine (4-AP), increased extracellular potassium, and decreased extracellular magnesium to a subset of acute prefrontal cortex (PFC) slices from rats. Subsequently, we were able to examine the characteristics of spiral waves that propagated across the networks in our slices. These spiral waves possessed stereotypical features whereby they rotated around a fixed center of mass, had a broad distribution of instantaneous phases across electrodes and showed increased complexity compared to baseline networks. We then trained a deep generative adversarial network (GAN) to capture the key aspects of the spiral waves in order to produce novel exemplars of these otherwise rare events. We subsequently irradiated healthy PFC slices with a series of doses ranging from 20 to 100 Gy to examine the acute effects of radiation on cortical networks. We found an increase in the firing rate and density of functional connectivity within the irradiated slices. In comparison, the pro-epileptiform networks showed an increase in firing rate and the strength of the functional connections amongst neurons, but a lower density of connections due to the spatially localized nature of spiral waves. These differences in functional connectivity highlight the fact that these represent distinct brain states, and that RT is not merely inducing an epileptic state. Finally, we stained a subset of our irradiated slices with propidium iodide (PI) to quantify cell death and found a dose-dependent increase in apoptosis. Together, these results point to hd-MEAs as a promising tool for studying altered brain state dynamics, which can be used to help inform treatment protocols for both epilepsy and to minimize radiation-induced brain injuries.