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    Neural Engineering

    (L-445) Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes

    Friday, October 13, 2023
    3:30 PM – 4:30 PM PDT
    Location: Exhibit Hall - Row L - Poster # 445
    Introduction::

    Intracortical microstimulation (ICMS) neural implants are used to treat a range of neurological disorders by targeted stimulation of the nervous system, and while many disorders have been addressed with current electrode designs, the stimulation resolution, efficacy, and chronic stability of conventional ICMS neural implants are limited due to the chronic immune response to indwelling electrodes. The chronic implantation of conventional rigid electrodes produces a strong immune response theorized to be due to the mechanical mismatch between the stiff electrode and the soft brain tissue inducing chronic mechanical stress. To address the low-selectivity of classical intracortical microstimulation (ICMS), we propose using ultraflexible nanoelectronic thread (NET) neural implants to minimize adverse immune responses, establish a stable tight tissue-electrode interface, and selectively stimulate neural populations with sufficient resolution to activate neural ensembles encoding complex neural network patterns to treat neurological disorders.



    Materials and Methods:: In this study, GCaMP6s mice were implanted with 32-channel StimNET implants into the primary somatosensory cortex with an optical window over the implantation site. The volumetric neural activation induced by chronic low-amplitude stimulation via the StimNET was quantified by two-photon calcium imaging synchronized with constant neural stimulation, ranging from 2 μA to 10 μA, to electrode sites at varying depths within the cortex of awake animals. The perceptibility of chronic stimulation was evaluated utilizing a Go/No-Go behavioral task quantifying the threshold of sensory perception to stimulation along the depth of the StimNET for up to 8 months post-implantation. The tissue compatibility of the StimNET was assessed utilizing in vivo two-photon imaging of the tissue-electrode interface and device in situ histological quantification of the immune response to the chronically indwelling implant.

    Results, Conclusions, and Discussions::

    Results. StimNETs demonstrated 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 mA. Stimulating neighboring electrode sites revealed significant selective activation of neural populations at low stimulation currents with increased coactivation of neural populations and reduced selectivity as current amplitudes increased and distance between stimulation sites decreased. StimNETs evoke longitudinally stable behavioral responses for over eight months at markedly low charge injection of 0.25 nC/phase. Quantified histological analysis showed that chronic ICMS via StimNETs induced no significant neuronal degeneration or glial scarring. 


    Conclusion. These results suggest that tissue-integrated electrodes, here the StimNET, provide robust, long-lasting, spatially-selective neuromodulation at low currents, which lessens risks of tissue damage or exacerbation of off-target side effects, crucial for effective chronic neural recording and neuromodulation. This seamless interface allows for the selective activation of neural populations providing precise, stable ICMS avoiding the confounding chronic immune response, which has limited the resolution, efficacy, and chronic stability of conventional ICMS neural implants. As such, NET electrodes can improve the efficacy and precisely probe the mechanics of the brain without disrupting local tissue and serve as a platform from which high-fidelity bidirectional medical neural stimulation systems aiming to deliver complex neuromodulation can be developed.


    Discussion. Neural electrode technology focusing on flexibility and miniaturization has made high-density, long-lasting, tissue-compatible neural recordings possible. However, it remained challenging to make these electrodes structurally and functionally robust for long-term stimulation. Here, we engineered the currently thinnest, most flexible penetrating microelectrode array for robust ICMS. Leveraging in vivo imaging, behavioral, and histological techniques, we showed low thresholds of 1–2 μA both by imaging and behavioral detection, longitudinal stability in the neuronal activation and high level of spatial selectivity months post-implantation, and robust and stable behavioral detectability chronically up to 226 days at a record low current of 1.5 μA. This tight tissue integration of StimNETs is pivotal to superior stability and low threshold activation.

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