Proportional-Integral Controller-Based Deep Brain Stimulation Strategy for Controlling Excitatory-Inhibitory Network Synchronization.

Deep brain stimulation (DBS) has emerged as a potential therapy for disrupting pathological synchronous firing patterns of neurons and restoring healthy oscillations in many brain disorders when pharmacological interventions fail. However, existing DBS devices require extensive clinical interventions in tuning stimulation parameters over the treatment period. In our previous works, we developed a novel neurostimulation motif, referred to as "Forced Temporal Spike-Time Stimulation" (FTSTS), which can reliably and robustly desynchronize the excessively synchronized excitatory-inhibitory (E-I) networks by harnessing E-to-I synaptic plasticity. However, our FTSTS protocol was an open loop and required us to manually titrate the FTSTS parameters, such as amplitude, frequency, and pulse width. In this work, we close the DBS loop by developing a proportional-integral (PI) controller-based FTSTS strategy to tune the stimulation amplitude. Using an E-I network model, we perform the spectral analysis of spiking data to determine the correlation between the network synchrony and the mean population firing rate of E and I neurons. We systematically investigate the stimulation parameter space to investigate the effects of amplitude and frequency on the mean firing rate of E and I neurons. We design a PI controller to tune the stimulation amplitude using the mean firing rate of I neurons as a feedback signal. We demonstrate the feasibility of our approach in controlling the neuronal synchronization in the E-I network consisting of 400 E and 100 I neurons through various case studies.