Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes

Roy Lycke; Robin Kim; Pavlo Zolotavin; Jon Montes; Yingchu Sun; Aron Koszeghy; Esra Altun; Brian Noble; Rongkang Yin; Fei He; Nelson Totah; Chong Xie; Lan Luan

doi:10.1016/j.celrep.2023.112554

Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes

Cell Rep. 2023 Jun 27;42(6):112554. doi: 10.1016/j.celrep.2023.112554. Epub 2023 May 24.

Authors

Roy Lycke¹, Robin Kim¹, Pavlo Zolotavin¹, Jon Montes², Yingchu Sun¹, Aron Koszeghy³, Esra Altun⁴, Brian Noble⁵, Rongkang Yin¹, Fei He¹, Nelson Totah⁶, Chong Xie⁷, Lan Luan⁸

Affiliations

¹ Department of Electrical and Computer Engineering, Rice University, Houston, TX 77005, USA; Rice Neuroengineering Initiative, Rice University, Houston, TX 77005, USA.
² Rice Neuroengineering Initiative, Rice University, Houston, TX 77005, USA; Department of Bioengineering, Rice University, Houston, TX 77005, USA.
³ Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00790 Helsinki, Finland.
⁴ Rice Neuroengineering Initiative, Rice University, Houston, TX 77005, USA; Material Science and NanoEngineering, Rice University, Houston, TX 77005, USA.
⁵ Rice Neuroengineering Initiative, Rice University, Houston, TX 77005, USA; Applied Physics Program, Rice University, Houston, TX 77005, USA.
⁶ Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00790 Helsinki, Finland; Faculty of Pharmacy, University of Helsinki, 00790 Helsinki, Finland.
⁷ Department of Electrical and Computer Engineering, Rice University, Houston, TX 77005, USA; Rice Neuroengineering Initiative, Rice University, Houston, TX 77005, USA; Department of Bioengineering, Rice University, Houston, TX 77005, USA. Electronic address: chongxie@rice.edu.
⁸ Department of Electrical and Computer Engineering, Rice University, Houston, TX 77005, USA; Rice Neuroengineering Initiative, Rice University, Houston, TX 77005, USA; Department of Bioengineering, Rice University, Houston, TX 77005, USA. Electronic address: lan.luan@rice.edu.

Abstract

Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation are often compromised by adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-nanoelectronic threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stable ICMS in awake, behaving mouse models. In vivo two-photon imaging reveals that StimNETs remain seamlessly integrated with the nervous tissue throughout chronic stimulation periods and elicit stable, focal neuronal activation at low currents of 2 μA. Importantly, StimNETs evoke longitudinally stable behavioral responses for over 8 months at a markedly low charge injection of 0.25 nC/phase. Quantified histological analyses show that chronic ICMS by StimNETs induces no neuronal degeneration or glial scarring. These results suggest that tissue-integrated electrodes provide a path for robust, long-lasting, spatially selective neuromodulation at low currents, which lessens risk of tissue damage or exacerbation of off-target side effects.

Keywords: CP: Neuroscience; behavioral detection; brain-machine interface; chronic stability; electrical stimulation; flexible electrodes; intracortical microstimulation; neural implants; neuromoduation; two-photon imaging.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Electric Stimulation / methods
Electrodes
Electrodes, Implanted
Mice
Somatosensory Cortex* / physiology

Abstract

Publication types

MeSH terms

Grants and funding