Anti-kindling achieved by stimulation targeting slow synaptic dynamics

Different stimulation techniques are introduced which specifically modulate the slow synaptic dynamics in a neuronal network model of the subthalamic nucleus with activity dependent synaptic plasticity.

A modeling approach is utilized to investigate the effects of the different stimulation techniques. In particular, the short-term and long-term outcome is studied in a mathematical model for a population of bursting STN neurons subject to synaptic plasticity with symmetric spike timing characteristics. In our mathematical model in the absence of stimulation synchronized network states with strong connectivity (modeling disease states) as well as desynchronized states with weak connectivity (modeling healthy states) are stable.

We demonstrate that different stimulation techniques induce an anti-kindling by shifting the target population to a weakly connected, desynchronized state. Intriguingly, long-term anti-kindling can even be achieved although during stimulus delivery the neuronal synchrony hardly decreases or even slightly increases. The therapeutic index and the impact of inhibition, calculated to compare the different stimulation techniques, indicate that coordinated rest stimulation might be particularly robust and reliable.

The presented stimulation strategies and the results of our modeling study might have strong implications in the context of deep brain stimulation.