System Design of a Closed-Loop Vagus Nerve Stimulator Comprising a Wearable EEG Recorder and an Implantable Pulse Generator

Closed-loop vagus nerve stimulators (VNSs) are used to treat refractory epilepsy (RE) and provide an alternative treatment modality with fewer side effects for RE. This work proposes a closed-loop VNS that senses the scalp EEG via a wearable EEG recorder (WER) and stimulates the vagus nerve via an implantable VNS (IVNS), the combination of which is referred to as a “HybridVNS”. First, the architecture and system control (by an App) of the HybridVNS are presented. Next, discrete component implementations of its key building blocks including the multichannel preamplifier, pulse generator and wireless power link are provided. Further, a 4-channel preamplifier magnifies the recorded EEG signals, and each channel consists of a capacitively coupled instrumentation amplifier (CCIA) cascaded by a 2nd-order low pass filter. The measured gain and the input-referred noise (IRN) of the preamplifier are 45.8 dB and 4.9 ${\mu}$ V _rms (1 Hz–200 Hz), respectively. We propose a switched-resistor array pulse generator for constant-current stimulation, and a novel distance-frequency adaptive inductive coupling link (DFAICL) to automatically tune the resonance frequency. A maximum wireless power transmission efficiency of 17% is achieved in the DFAICL when the supply power is 30dBm and the distance is 20 mm at 2 MHz. Finally, we demonstrate that in the WER, the onset of an epileptic seizure can be detected by a threshold of coastline length (294 ${\mu}$ V) combined with a threshold of slope (7.3 ${\mu}$ V/ms) within a unit time segment (780 ms), which provides an average accuracy of 88.2%. The feasibility of the IVNS was tested in an acute rodent epilepsy experiment. However, the closed-loop experiment was not conducted.