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Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

Abstract

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.

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Figure 1: Principle and experimental set-up of functional electrochemical stimulation with in situ ion concentration modulation through ISMs.
Figure 2: Operation modes of electrochemical stimulation with modulation of the local ion concentration adjacent to a nerve.
Figure 3: Comparison of excitability without and with modulating Ca2+ ion concentration.
Figure 4: Characterization of the electrochemical stimulation device under various parametric conditions.
Figure 5: Nerve-conduction-block experiment with a microfabricated ISM device.

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Acknowledgements

This work was conducted with support from a Massachusetts Institute of Technology faculty discretionary research fund, a Harvard Catalyst Grant from the Harvard Clinical and Translational Science Center (National Institutes of Health Award UL1 RR 025758) and financial contributions from Harvard University and its affiliated academic health-care centres.

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Contributions

Y-A.S. carried out fabrication of ion-selective electrodes and membranes, experimental work and confocal imaging. R.M., A.N.R., A.M.S.I., D.M. and A.T. conducted experimental work and data analysis. J.H. and S.J.L. carried out project planning. A.N.R., Y-A.S., S.J.L. and J.H. wrote the manuscript.

Corresponding authors

Correspondence to Jongyoon Han or Samuel J. Lin.

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The authors have applied for a patent based on the technique described in this paper.

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Song, YA., Melik, R., Rabie, A. et al. Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes. Nature Mater 10, 980–986 (2011). https://doi.org/10.1038/nmat3146

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  • DOI: https://doi.org/10.1038/nmat3146

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