Network Desynchronization with Sine Waves: from Synchrony to Asynchrony by Periodic Stimulation.

Understanding how brain stimulation interacts with the brain's internal dynamics is crucial for developing effective neuromodulation protocols. Here we explore the effects of exogenous alternating current (AC) fields across various amplitudes and frequencies on cortical slices expressing spontaneous slow oscillations. Cortical network entrainment occurs within an Arnold tongue-like region centered at the endogenous frequency. However, slightly detuned periodic stimulation of higher frequency leads to a desynchronized regime, revealing a novel approach for disrupting pathological synchronicity. The introduction of an additional direct current (DC) offset expands the modulatory ranges, facilitating the achievement of either entrainment or desynchronization, depending on the DC offset's polarity. The experimental observations are quantitatively reproduced by a computational model of spiking neurons, suggesting that the interaction between nonlinear oscillators can predict the network's response to AC fields. Besides an improved understanding of cortical dynamics and its interaction with exogenous electric fields, a robust protocol with potential clinical applications in pathological conditions is presented.