A Bidirectional Neuromodulation Technology for Nerve Recording and Stimulation

Abstract

Electrical nerve recording and stimulation technologies are critically needed to monitor and modulate nerve activity to treat a variety of neurological diseases. However, current neuromodulation technologies presented in the literature or commercially available products cannot support simultaneous recording and stimulation on the same nerve. To solve this problem, a new bidirectional neuromodulation system-on-chip (SoC) is proposed in this paper, which includes a frequency-shaping neural recorder and a fully integrated neural stimulator with charge balancing capability. In addition, auxiliary circuits consisting of power management and data transmission circuits are designed to provide the necessary power supply for the SoC and the bidirectional data communication between the SoC and an external computer via a universal serial bus (USB) interface, respectively. To achieve sufficient low input noise for sensing nerve activity at a sub-10 μ V range, several noise reduction techniques are developed in the neural recorder. The designed SoC was fabricated in a 0.18 μ m high-voltage Bipolar CMOS DMOS (BCD) process technology that was described in a previous publication and it has been recently tested in animal experiments that demonstrate the proposed SoC is capable of achieving reliable and simultaneous electrical stimulation and recording on the same nerve.

Keywords: bidirectional; closed-loop; neuromodulation; precision medicine; sciatic nerve; system-on-chip; vagus nerve.

Figure 1

An illustration of the proposed bidirectional neuromodulation system for nerve recording and stimulation experiments.

Figure 2

Block diagrams of the proposed neural recorder.

Figure 3

(a) Simplified functional block diagrams of one stimulator channel; (b) Examples of stimulation waveforms and patterns used in the experiments. Reproduced with permission from Anh Tuan Nguyen, A Programmable Fully Integrated Microstimulator for Neural Implants and Instrumentation; published by IEEE Biomedical Circuits and Systems Conference (BioCAS), 2016.

Figure 4

Block diagrams of the auxiliary circuits, which include a nano flash field-programmable gate array (FPGA), a universal serial bus (USB) interface chip, a voltage reference chip, and several voltage regulators.

Figure 5

Chip microphoto of the designed neural recorder and neural stimulator in a high-voltage 0.18 $\mathsf{\mu }$m Bipolar CMOS DMOS (BCD) process.

Figure 6

(a) Layout illustration (bottom and top side) of the designed neuromodulation system prototype; (b) Physical photograph (bottom and top side) of the designed neuromodulation system prototype.

Figure 7

Nerve activity recording from a guinea pig’s sciatic nerve, where a two-channel fully differential nerve recording is performanced on the same nerve with current stimulation in a bipolar configuration. (a) Physical photograph and (b) illustration of experimental setup for simultaneous stimulation and recording.

Figure 8

Compound action potentials (CAPs) recordings from a guinea pig’s sciatic nerve, where the stimulation current is presented to the guinea pig’s left foot and a one-channel fully differential nerve recording is performed on the sciatic nerve. (a) Illustration of experimental setup; (b) Recorded compound action potentials in response to foot stimulation with 2 mA, biphasic, 500 $\mathsf{\mu }$s pulse duration current. In total, 30 trials are plotted, where each colored curve represents a single trial.

Figure 9

Measurement results of nerve recording and stimulating on the same sciatic nerve. (a) Ten trials of the recorded nerve activity showing the recorded waveforms in response to electrical stimulation of the sciatic nerve; (b–d) Zoom-in of the recorded stimulation artifacts, nerve activity, and motion artifacts/electromyography (EMG), respectively.

Figure 10

Measured nerve activity with a commercial system (Tucker–Davis Technologies (TDT), Alachua, FL, USA; PZ2-64 (Amplifier) and RZ2 (BioAmp Processor)) when the stimulation electrode is connected to the foot and the recording electrode is interfaced with the left sciatic nerve of a guinea pig. (a) Ten trials of the measured nerve activity when the stimulation electrode does not deliver current. (b) Ten trials of the measured nerve activity when the stimulation electrode delivers 2.82 mA, biphasic, 205 $\mathsf{\mu }$s current pulses.

Figure 11

Measured nerve activity with the TDT system when both the stimulation electrode and recording electrode are connected to the left sciatic nerve of a guinea pig. (a) Ten trials of the measured nerve activity when the stimulation electrode does not deliver current; (b) Ten trials of the measured nerve activity when the stimulation electrode delivers 14.13 $\mathsf{\mu }$A, biphasic, 205 $\mathsf{\mu }$s current pulses. Note the drastic change in signal amplitudes and ordinate scale bars in (b) compared to (a).