Term Paper Proposal ixk51

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Background


A stable interface between a man-made device and the nervous system is a way to monitor and control the information flow of the body. In particular, neural interfaces are used for Functional Electrical Stimulation (FES) as a way to restore bodily functions such as bladder voiding, deglutition (swallowing), provide pain relief, and restore limb control in upper and lower extremities after neurological impairment [1]. Closed-loop control systems of FES devices are able to recruit proper muscles in a way that is most similar to the central nervous system (CNS) by recording neural information from the body and using it as a control signal [2]. Neural recording is also crucial for developing advanced prosthetic limbs which sense the amputee’s natural command signals and activate the prosthetic device in a fashion corresponding to his or her desires [3]. Two main types of electrodes have been developed in various labs to address the need for recording neural signals: extra-neural cuff electrodes that are wrapped around the nerve and intra-fascicular electrodes that are threaded inside nerve bundles, or fascicles. An example of the former is the Flat Interface Nerve Electrode (FINE) which is relatively non-invasive, yet, being outside the nerve, provides only average recording selectivity (defined as the ability to discern between signals originating from different fascicles) [4]. On the other hand, intra-fascicular multielectrode arrays and longitudinal intra-fascicular electrodes provide excellent selectivity; [5, 6], yet their chronic performance is ultimately questionable due to their highly invasive nature. The need is evident for an electrode that does not invade the fascicle (in order to prevent neuronal damage) and is still able to selectively record neural signals to be useful as feedback in FES and prosthetic systems. I propose that an inter-fascicular electrode (one that is inside the nerve but outside the fascicle) will be able to selectively record from different nerve fascicles, a hypothesis that will be validated separately by a mathematical and animal model.


Specific Aims


Aim 1: To validate the claim that inter-fascicular electrodes can selectively record signals from separate fascicles using a mathematical model

This aim will be addressed by creating a Finite Element Model (FEM) of generic nerves with various degrees of fasciculation. Interfascicular electrodes will be placed into the model in the epineurium (outside the fascicle but inside the nerve). Standard action potentials will propagate along the nerve fibers in the simulation and the signal captured by the electrodes will be recorded and processed. A selectivity index (SI), as defined in [4], will be computed for various degrees of fasciculation, types of contacts, electrode spacing, and location. Several modeling studies have been performed to quantify the recording capabilities of cuff electrodes [4, 7] and stimulation properties of both extraneural and intrafascicular electrodes [8]; however, the recording properties of interfascicular electrodes in the epineurim have not been reported in literature. The current aim will address this apparent gap in knowledge. I hypothesize that the results of the model will yield high selectivity values, driving the need for validating the model with animal experiments.


Aim 2: To quantify the recording selectivity of interfascicular electrodes in animal models

This aim will experimentally address the recording capabilities of interfascicular wire electrodes. Acute experiments will be performed on anesthetized rabbits. The sciatic nerve will be exposed bilaterally and stimulation as well as recording FINEs will be implanted approximately 1 cm distal to the bifurcation of the sciatic nerve into the tibial and peroneal branches. Up to 5 inter-fascicular recording electrodes will be implanted per side, making sure they do not penetrate the fascicles. An accurate method of inserting the electrodes into the epineurium will need to be developed, probably utilizing a micro-stepper motor. The selectivity index of various wire electrodes will be computed as in [4]. The electrodes will be kept in the nerve, such that after the experiment, it will be possible to perform histology to ensure that they were in fact in the epineurium. The selectivity index computed in-vivo will be compared to the one obtained using the FEM.


Aim 3: To determine the viability of using interfascicular electrodes in chronic animal models

In this aim, I will determine the long-term performance of the interfascicular electrodes in vivo. This is particularly important if the technology is eventually meant to be used as a feedback system for neural prostheses for human patients. To address this need, chronic animal experiments will be performed. Interfascicular electrodes will be implanted into the sciatic nerve in an antiseptic surgical procedure. Animals will be given time to recover from the surgery. After this period of time, the recording capabilities of the interfascicular electrode will be tested on a weekly basis. During each test, the signal-to-noise ratio (SNR) of the recording electrode will be computed by recording neural signals at rest and during physical perturbation of the leg with a motorized lever system as in [9]. I propose that since the electrode does not invade the fascicle, there should be no long-term neurological damage to the nerve. Chronic recording experiments involving nerve cuffs [10] and intrafascicular electrodes [11, 12] have been performed; however, this aim will address the lack in experimental data about the biocompatibility of interfascicular electrodes in vivo.


References

1. Peckham, P.H. and J.S. Knutson, Functional electrical stimulation for neuromuscular applications. Annu Rev Biomed Eng, 2005. 7: p. 327-60.

2. Popovic, D.B., et al., Sensory nerve recording for closed-loop control to restore motor functions. IEEE Trans Biomed Eng, 1993. 40(10): p. 1024-31.

3. Dhillon, G.S. and K.W. Horch, Direct neural sensory feedback and control of a prosthetic arm. IEEE Trans Neural Syst Rehabil Eng, 2005. 13(4): p. 468-72.

4. Yoo, P.B. and D.M. Durand, Selective recording of the canine hypoglossal nerve using a multicontact flat interface nerve electrode. IEEE Trans Biomed Eng, 2005. 52(8): p. 1461-9. 5. McDonnall, D., G.A. Clark, and R.A. Normann, Selective motor unit recruitment via intrafascicular multielectrode stimulation. Can J Physiol Pharmacol, 2004. 82(8-9): p. 599-609.

6. Yoshida, K., K. Hennings, and S. Kammer. Acute Performance of the Thin-Film Longitudinal Intra-Fascicular Electrode. in Biomedical Robotics and Biomechatronics, 2006. BioRob 2006. The First IEEE/RAS-EMBS International Conference on. 2006.

7. Perez-Orive, J. and D.M. Durand, Modeling study of peripheral nerve recording selectivity. IEEE Trans Rehabil Eng, 2000. 8(3): p. 320-9. 8. Veltink, P.H., J.A. van Alste, and H.B. Boom, Simulation of intrafascicular and extraneural nerve stimulation. IEEE Trans Biomed Eng, 1988. 35(1): p. 69-75.

9. Djilas, M., et al., Spike sorting of muscle spindle afferent nerve activity recorded with thin-film intrafascicular electrodes. Comput Intell Neurosci, 2010: p. 836346.

10. Sahin, M., D.M. Durand, and M.A. Haxhiu, Chronic recordings of hypoglossal nerve activity in a dog model of upper airway obstruction. J Appl Physiol, 1999. 87(6): p. 2197-206.

11. Lago, N., et al., Assessment of biocompatibility of chronically implanted polyimide and platinum intrafascicular electrodes. IEEE Trans Biomed Eng, 2007. 54(2): p. 281-90.

12. Badia, J., et al., Biocompatibility of Chronically Implanted Transverse Intrafascicular Multichannel Electrode (Time) in the Rat Sciatic Nerve. IEEE Trans Biomed Eng, 2011.