Lycke, RoyKim, RobinZolotavin, PavloMontes, JonSun, YingchuKoszeghy, AronAltun, EsraNoble, BrianYin, RongkangHe, FeiTotah, NelsonXie, ChongLuan, Lan2023-07-212023-07-212023Lycke, Roy, Kim, Robin, Zolotavin, Pavlo, et al.. "Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes." <i>Cell Reports,</i> 42, no. 6 (2023) Cell Press: https://doi.org/10.1016/j.celrep.2023.112554.https://hdl.handle.net/1911/114963Intracortical 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.engExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of Fair Use or other exemptions to copyright law must be obtained from the copyright holder.Journal article1-s2-0-S221112472300565X-mainhttps://doi.org/10.1016/j.celrep.2023.112554