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Decoding and modulation of spiking activity of the sciatic nerve in an awake and moving rodent
Katharina S Fischer, MD1,2; Eric T Zhao, MA3; Zeshaan N Maan, MD MSc4; Janos A Barrera, MD3; Kellen Chen, PhD3,5; Dominic Henn, MD3; Chikage Noishiki, MD PhD6; Dharshan Sivaraj, BS3; Gurtner Geoffrey, MD3,5; Nicholas T Melosh, PhD3
1University of Arizona, Tucson, AZ; 2Stanford University, Stanford, AZ; 3Stanford University, Stanford, CA; 4Stanford University, PALO ALTO, CA; 5University of Arizona, Tucson, CA; 6Stanford University School of Medicine, Stanford, CA

Introduction: Conventional prostheses do not interface directly with neural signals but use either body motion or muscle activity as a proxy. Consequently, these prostheses are difficult to use, tiring, have limited function, and provide no sensory feedback. For the development of an advanced anthropomorphic prosthetic arm that can recapitulate the degrees of freedom and sensory feedback of the human hand, it is critical to design a low damage, high fidelity, and stable peripheral nerve interface (PNI). The key innovation of our microfabricated device, is that our electrodes are orders of magnitudes more compliant than existing PNIs, approximately 1500 and 40,000,000 times more compliant than the Transverse Intrafascicular Multichannel Electrode (TIME) and Utah Slanted Electrode Array (USEA) respectively.
Methods: The device consists arrays of individual 1 ?m thick, and 4 ?m wide electrodes, each with a 15 ?m diameter recording/stimulation pad, mimicking the dimensions, compliance, and spatial distribution of axon bundles in the peripheral nerve. An electrochemically etched, 80 ?m tungsten microwire was threaded through a hole on the device and drawn through the sciatic nerve of a C57BL/6J mouse. A custom designed circuit board was mounted on a 3D-printed backpack to facilitate chronic recording and stimulation.
Results: Mice ran voluntarily on a cylindrical treadmill in a head strained condition, while we recorded the neural activity with our device. Spiking activity was readily observed in our electrodes, where we isolated 6 single units across our 16 electrodes. Using markerless pose estimation, we extracted the joint angles innervated by the sciatic nerve and found a robust correlation between spiking activity and gait. The ultra-small size of the electrodes and their proximity to individual axons permitted extremely local stimulation down to eliciting movement in a single toe.
Discussion: To our knowledge, we are the first to record single neuron spiking activity in the peripheral nervous system of an awake and moving rodent. This represents a substantial advance, in that we overcame a series of challenges involving: (1) Microfabrication of ultra-thin electrodes to mirror the surrounding biomechanical environment to minimize the foreign body response, (2) Device robustness under substantial movement and strain, (3) Microsurgical device implantation to minimize acute insertion damage. Future work will involve electrical modulation to augment movement in peripheral nerve neuropathies and translation into larger animal models with increased channel counts for movement decoding


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