Enhancing selectivity of minimally invasive peripheral nerve interfaces using combined stimulation and high frequency block: from design to application

Abstract

The discovery of the excitable property of nerves was a fundamental step forward in our knowledge of the nervous system and our ability to interact with it. As the injection of charge into tissue can drive its artificial activation, devices have been conceived that can serve healthcare by substituting the input or output of the peripheral nervous system when damage or disease has rendered it inaccessible or its action pathological. Applications are far-ranging and transformational as can be attested by the success of neuroprosthetics such as the cochlear implant. However, the body’s immune response to invasive implants have prevented the use of more selective interfaces, leading to therapy side-effects and off-target activation. The inherent tradeoff between the selectivity and invasiveness of neural interfaces, and the consequences thereof, is still a defining problem for the field. More recently, continued research into how nervous tissue responds to stimulation has led to the discovery of High Frequency Alternating Current (HFAC) block as a stimulation method with inhibitory effects for nerve conduction. While leveraging the structure of the peripheral nervous system, this neuromodulation technique could be a key component in efforts to improve the selectivity-invasiveness tradeoff and provide more effective neuroprosthetic therapy while retaining the safety and reliability of minimally invasive neural interfaces. This thesis describes work investigating the use of HFAC block to improve the selectivity of peripheral nerve interfaces, towards applications such as bladder control or vagus nerve stimulation where selective peripheral nerve interfaces cannot be used, and yet there is an unmet need for more selectivity from stimulation-based therapy. An overview of the underlying neuroanatomy and electrophysiology of the peripheral nervous system combined with a review of existing electrode interfaces and electrochemistry will serve to inform the problem space. Original contributions are the design of a custom multi-channel stimulator able to combine conventional and high frequency stimulation, establishing a suitable experimental platform for ex-vivo electrophysiology of the rat sciatic nerve model for HFAC block, and exploratory experiments to determine the feasibility of using HFAC block in combination with conventional stimulation to enhance the selectivity of minimally-invasive peripheral nerve interfaces.