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A wireless and artefact-free 128-channel neuromodulation device for closed-loop stimulation and recording in non-human primates

Abstract

Closed-loop neuromodulation systems aim to treat a variety of neurological conditions by delivering and adjusting therapeutic electrical stimulation in response to a patient’s neural state, recorded in real time. Existing systems are limited by low channel counts, lack of algorithmic flexibility, and the distortion of recorded signals by large and persistent stimulation artefacts. Here, we describe an artefact-free wireless neuromodulation device that enables research applications requiring high-throughput data streaming, low-latency biosignal processing, and simultaneous sensing and stimulation. The device is a miniaturized neural interface capable of closed-loop recording and stimulation on 128 channels, with on-board processing to fully cancel stimulation artefacts. In addition, it can detect neural biomarkers and automatically adjust stimulation parameters in closed-loop mode. In a behaving non-human primate, the device enabled long-term recordings of local field potentials and the real-time cancellation of stimulation artefacts, as well as closed-loop stimulation to disrupt movement preparatory activity during a delayed-reach task. The neuromodulation device may help advance neuroscientific discovery and preclinical investigations of stimulation-based therapeutic interventions.

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Fig. 1: WAND system architecture.
Fig. 2: Wireless, multi-channel recording.
Fig. 3: LFP recordings during the joystick task.
Fig. 4: Overnight, untethered recording of brain signals from an NHP during sleep.
Fig. 5: Residual artefact analysis and cancellation.
Fig. 6: In vivo closed-loop experiment to disrupt movement preparatory activity during a delayed-reach task.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported in part by the Defense Advanced Research Projects Agency (W911NF-14–2–0043 to R.M., J.M.R. and J.M.C.) and National Science Foundation Graduate Research Fellowship Program (grant number 1106400 to A.Z.). The authors thank the Wagner Foundation and the sponsors of the Berkeley Wireless Research Center. They also thank E. Alon, S. Gambini and I. Izyumin for technical discussion.

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J.M.R., J.M.C and R.M. are co-principal investigators. A.Z., B.C.J., G.A., A.M., F.L.B., J.M.R. and R.M. designed and tested the system. B.C.J. and R.M. designed and tested the integrated circuits. S.R.S. and J.M.C. designed the in vivo experiments. A.Z., S.R.S., B.C.J., G.A. and A.M. performed the experiments and analysis. J.M.R., J.M.C. and R.M. oversaw the project. A.Z., S.R.S., B.C.J., G.A., A.M., J.M.R., J.M.C. and R.M. wrote and edited the paper.

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Correspondence to Rikky Muller.

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B.C.J., J.M.R., J.M.C. and R.M. have financial interests in Cortera Neurotechnologies, which has filed a patent application on the integrated circuit used in this work.

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Zhou, A., Santacruz, S.R., Johnson, B.C. et al. A wireless and artefact-free 128-channel neuromodulation device for closed-loop stimulation and recording in non-human primates. Nat Biomed Eng 3, 15–26 (2019). https://doi.org/10.1038/s41551-018-0323-x

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