Abstract
An improved understanding of the mechanisms underlying neuromodulatory approaches to mitigate seizure onset is needed to identify clinical targets for the treatment of epilepsy. Using a Wilson-Cowan-motivated network of inhibitory and excitatory populations, we examined the role played by intrinsic and extrinsic stimuli on the network's predisposition to sudden transitions into oscillatory dynamics, similar to the transition to the seizure state. Our joint computational and mathematical analyses revealed that such stimuli, be they noisy or periodic in nature, exert a stabilizing influence on network responses, disrupting the development of such oscillations. Based on a combination of numerical simulations and mean-field analyses, our results suggest that high variance and/or high frequency stimulation waveforms can prevent multi-stability, a mathematical harbinger of sudden changes in network dynamics. By tuning the neurons' responses to input, stimuli stabilize network dynamics away from these transitions. Furthermore, our research shows that such stabilization of neural activity occurs through a selective recruitment of inhibitory cells, providing a theoretical undergird for the known key role these cells play in both the healthy and diseased brain. Taken together, these findings provide new vistas on neuromodulatory approaches to stabilize neural microcircuit activity.