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Focal stimulation of the sheep motor cortex with a chronically implanted minimally invasive electrode array mounted on an endovascular stent

Abstract

Direct electrical stimulation of the brain can alleviate symptoms associated with Parkinson’s disease, depression, epilepsy and other neurological disorders. However, access to the brain requires invasive procedures, such as the removal of a portion of the skull or the drilling of a burr hole. Also, electrode implantation into tissue can cause inflammatory tissue responses and brain trauma, and lead to device failure. Here, we report the development and application of a chronically implanted platinum electrode array mounted on a nitinol endovascular stent for the localized stimulation of cortical tissue from within a blood vessel. Following percutaneous angiographic implantation of the device in sheep, we observed stimulation-induced responses of the facial muscles and limbs of the animals, similar to those evoked by electrodes implanted via invasive surgery. Proximity of the electrode to the motor cortex, yet not its orientation, was integral to achieving reliable responses from discrete neuronal populations. The minimally invasive endovascular surgical approach offered by the stent-mounted electrode array might enable safe and efficacious stimulation of focal regions in the brain.

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Fig. 1: Delivery of the Stentrode to the motor cortex.
Fig. 2: Effect of electrode placement on the stimulation-induced response.
Fig. 3: Somatotopy of endovascular, subdural and penetrating cortical stimulation.
Fig. 4: Effect of orientation on electrode efficacy.

Data availability

The datasets generated and analysed during the study are available from the corresponding author upon reasonable request.

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Acknowledgements

This research was supported by the following grants: US Defense Advanced Research Projects Agency (DARPA) Microsystems Technology Office contract N66001-12-1-4045; Office of Naval Research (ONR) Global N62909-14-1-N020; National Health and Medical Research Council of Australia (NHMRC) Project Grant APP1062532. N.L.O. acknowledges the support of Westpac for the Bicentennial Research Fellowship.

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N.L.O., S.E.J., D.B.G., T.J.H.L., C.N.M., T.J.O'Brien and T.J.Oxley designed the research. N.L.O., S.E.J., G.S.R., S.M.R., Y.T.W., G.G., C.N.M., P.E.Y., A.D., S.L.W., T.C.M.S., T.J.H.L., T.V. and T.J.Oxley performed the experiments. N.L.O., S.M.R. and G.G. fabricated the devices, and N.L.O., S.E.J., Y.T.W., S.L.W., T.C.M.S., D.B.G. and G.G. analysed the data, N.L.O. wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Nicholas L. Opie.

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N.L.O., G.S.R., S.M.R., S.E.J. and T.J.Oxley. have a financial interest in Synchron Inc. All other authors have no competing interests.

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Supplementary Video 1

Minimally invasive angiographic delivery and deployment of a stent electrode array to the motor cortex in sheep

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Opie, N.L., John, S.E., Rind, G.S. et al. Focal stimulation of the sheep motor cortex with a chronically implanted minimally invasive electrode array mounted on an endovascular stent. Nat Biomed Eng 2, 907–914 (2018). https://doi.org/10.1038/s41551-018-0321-z

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