Regenerative Peripheral Nerve Interfacing Of Sensory Modalities

Abstract

Peripheral neural interfaces (PNI) has proved potential to record motor commands for the control of these prosthetic limbs, together with stimulation of specific sensory axons, so as to transmit specific sensory sub-modalities. Although PNI is hypothesized to provide adequate sensory feedback, realizing this degree of specificity is not fully established. Recently, a regenerative multi-electrode interface (REMI) was reported to be capable of recording peripheral nerve activity from a transected nerve. This study is aimed at interfacing neural activity specific to sensory sub-modalities, such as thermal pain, mechanoception and limb stretching using the REMI, in a freely moving animal. In the experiment, a floating multi-electrode array comprising 18 Platinum/Iridium electrodes encased within a collagen-filled hollow polyurethane tube was implanted in female adult Lewis rats. Surgery involved transection of the mixed sciatic nerve followed by suturing of nerve stumps to the conduit. Neural activity was recorded every week using Omniplex data acquisition system (Plexon Inc. USA) equipped with live Cineplex video tracking, during various sensory tests like Plantar Von Frey stimulation (mechanoception), Plantar thermal (nociception) and wake/resting (Control). Extracellular spikes (single/multi-unit) were recorded weekly, from regenerating axons beginning from 7 days to 42 days post implantation, with high signal to noise ratio (up to 7.98:1). The neural activity was evaluated in terms of different parameters, such as: firing rate, amplitude and wave-shape, known to encode the stimulus properties in the sensory system. Results demonstrate that single unit spikes recorded at early time points of 7-21 days were possibly from unmyelinated fibers with incomplete re-innervation accounting for spontaneous discharge, on the other hand neural activity at 28 days through 42 days were more correlated to the evoked sensory response during stimulation and the motor response due to paw withdrawal. However, average recorded channels per animal decreased in number from 35% at 14days to 12.5% at 42 days (i.e. approx. 5% reduction every week) due to mechanical device failures, causing statistically insignificant number of samples by 42 days. Neural activity was first categorized by the discharge pattern observed during sensory behavioral tests into spontaneous, random and burst pattern. Further evaluation was done by the wave shape into monophasic, biphasic and triphasic units. However, recording at these early time points from a mixed regenerating nerve lead to inconclusive results as the stimulation causes successive activation of numerous nerve fibers. Similar assessment, based on the wave shape parameters and firing pattern was used to evaluate the immediate effect of cyclic stretching of the interfaced limb resulted in insignificant change (<20%) with reference to the recorded neural activity prior to stretching.