Andrej Nedic

In vivo characterization of regenerative peripheral nerve interface function.

OBJECTIVE Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. APPROACH Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. MAIN RESULTS Raw RPNI signals were active during walking, with amplitudes of 1 mVPP, and quiet during standing, with amplitudes less than 0.1 mVPP. RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. SIGNIFICANCE In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the transduced signals were generated via central nervous system control.

Abstract 60: Signal Strength, Reliability, and Validity of Active Regenerative Peripheral Nerve Interface Device Operation during Voluntary Movement

PurPose: Regenerative Peripheral Nerve Interface (RPNI) devices successfully transduce peripheral nerve action potentials to electrical signals suitable for prosthesis control. Voltage changes are the controlling mechanism and can be observed during electromyography (EMG). However, RPNI device signaling has not been characterized during voluntary movements. This study: a) characterizes active RPNI signal strength compared to background activity and b) defines the reliability and validity of RPNI signal function during purposeful movements.

Von Frey monofilament testing successfully discriminates between sensory function of mixed nerve and sensory nerve regenerative peripheral nerve interfaces

Regenerative peripheral nerve interfaces (RPNIs) transfer motor and sensory signals between amputee and prosthesis. Von Frey (VF) monofilaments are used clinically to evaluate sensory feedback but have not been validated at locations used in our rodent studies. Our purposes were to determine VF sensory test reliability at the ankle and thigh, and to evaluate sensory function of Mixed Nerve (MN) and Sensory Nerve (SN) RPNIs. For reliability testing, VF monofilaments were applied to Normal rats at the ankle and thigh in an up-down pattern. Paw Withdraw Thresholds were determined by alternately exceeding and reducing filament pressure. VF tests were then administered to experimental MN-RPNIs or SN-RPNIs. Reliability results at the ankle showed sensation did not vary over six weeks. At the thigh, reliability was similar during week 0 and 1, but with further testing sensation increased. Comparison between location found at weeks 0 and 1, the ankle was significantly more sensitive than the thigh (p<;0.05). VF administration to experimental animals revealed that the MN-PRNI group was significantly less sensitive than both the SN-RPNI and Normal groups (p<;0.05); while the SN-RPNI and Normal groups did not differ. VF monofilament testing was reliable and successful at distinguishing between sensations of normal skin with dense sensory endings (ankle) and disperse sensory endings (thigh). VF testing successfully discriminated between mixed and sensory nerve RPNI groups.

Adjacent regenerative peripheral nerve interfaces produce phase-antagonist signals during voluntary walking in rats

BackgroundRegenerative Peripheral Nerve Interfaces (RPNIs) are neurotized muscle grafts intended to produce electromyographic signals suitable for motorized prosthesis control. Two RPNIs producing independent agonist/antagonist signals are required for each control axis; however, it is unknown whether signals from adjacent RPNIs are independent. The purpose of this work was to determine signaling characteristics from two adjacent RPNIs, the first neurotized by a foot dorsi-flexor nerve and the second neurotized by a foot plantar-flexor nerve in a rodent model.MethodsTwo Control group rats had electrodes implanted onto the soleus (tibial nerve) and extensor digitorum longus (peroneal nerve) muscles in the left hind limb. Two Dual-RPNI group rats had two separate muscles grafted to the left thigh and each implanted with electrodes: the extensor digitorum longus was neurotized with a transected fascicle from the tibial nerve, and the tibialis anterior was implanted with a transected peroneal nerve. Four months post-surgery, rats walked on a treadmill, were videographed, and electromyographic signals were recorded. Amplitude and periodicity of all signals relative to gait period were quantified. To facilitate comparisons across groups, electromyographic signals were expressed as a percent of total stepping cycle activity for each stance and swing gait phase. Independence between peroneal and tibial nerve activations were assessed by statistical comparisons between groups during stance and swing.ResultsElectromyographic activity for Control and Dual-RPNI rats displayed alternating activation patterns coinciding with stance and swing. Significant signal amplitude differences between the peroneal and tibial nerves were found in both the Control and Dual-RPNI groups. Non-inferiority tests performed on Dual-RPNI group signal confidence intervals showed that activation was equivalent to the Control group in all but the peroneal RPNI construct during stance. The similar electromyographic activity obtained for Control and RPNI suggests the latter constructs activate independently during both stance and swing, and contain minimal crosstalk.ConclusionsIn-vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Adjacent RPNIs neurotized with agonist/antagonist nerves display activity amplitudes similar to Control during voluntary walking. The distinct and expected activation patterns indicate the RPNI may provide independent signaling in humans, suitable for motorized prosthesis control.

Abstract 49: Neuroprosthetic Hand Real-Time Proportional Control by Rodent Regenerative Peripheral Nerve Interfaces

patients experiencing DSWI requiring flap stayed significantly longer in the hospital (28.4 versus 13.3 days, p < 0.001), more often experienced subsequent unplanned readmission (46.5% versus 6.5%, p < 0.001), were more likely to experience 90-day mortality (18.2% versus 5.0%, p < 0.001), and accrued significantly greater healthcare costs (

Abstract 18: real-time proportional control of a neuroprosthetic hand by a rodent regenerative peripheral nerve interface.

180,330 versus

Abstract P18: Validating Regenerative Peripheral Nerve Interface Function in Relationship to Hind Limb Kinematics during Treadmill Locomotion

66,256, p < 0.001). As such, the risk stratification tool appropriately demonstrated that higher risk patients experienced increased length of primary hospital stay (p < 0.001), more readmissions (p < 0.001). higher rates of mortality (p < 0.001), and accrued greater cost (p < 0.001)

LOP31: Reliability and Validity of RPNI Signaling of Gait Phases during Voluntary Walking

27 Volume 133, Number 3 (Supplement) • PSRC Abstract Supplement F ray, M arch 7, 2014 ConClusion: Comparisons of electrophysiological responses, muscle mass, and histology indicated that sRPNI muscle and nerve fiber recovery approached equivalence. These findings demonstrate that freely transferred muscle becomes reinnervated and viable when neurotized by a transected sensory nerve. Furthermore, electrophysiological signal is successfully transmitted between the sRPNI and residual nerve. Through electrical stimulation of this functional sRPNI, there is enormous potential for enhancing the recovery and quality of life of thousands of amputees by restoring the sense of touch.

Abstract 16: Adjacent Antagonistic RPNIs Produce Independent Signaling for Prosthesis Control

PurPose: Regenerative Peripheral Nerve Interfaces (RPNI) are neurotized autologous free muscle grafts equipped with electrodes to record myoelectric signals for prosthetic control. RPNI devices implanted into rats have been shown, using evoked responses, to be stable and viable for up to 2 years. In vivo characterization of RPNI signaling is critical for assessing their utility as a control modality for prosthetic devices. This work quantifies RPNI signal activation and relates it to gait; its ultimate purpose is to define signaling relationships between RPNI and native muscle during volitional control.

Abstract P27: Signals from Adjacent RPNIs Are Independent during Voluntary Walking

Introduction: Regenerative Peripheral Nerve Interfaces (RPNIs) are neurotized muscle grafts that control prostheses through electromyography (EMG). RPNI signals have not been quantified during phases of voluntary movements. This study: a) characterizes active RPNI signaling compared to background activity and b) defines the reliability and validity of RPNI function during gait phases of rat walking. Material and Methods: Rat groups were: Control (n=3), RPNI (n=3), Denervated (n=3). Bipolar electrodes were implanted onto the soleus muscles in each group. The Control group was left intact. The Denervated group had the tibial nerve transected. For RPNIs, the soleus muscle was freely grafted to the ipsilateral thigh and neurotized by the transected tibial nerve. While walking on a treadmill, rats were videographed and raw EMG signals were simultaneously recorded. Outcome measurements were integrated EMG (iEMG) and iEMG normalized (NiEMG) to stance, swing, or sit gait phase. Results: Majority of EMG activity was observed within the stance phase—70% for Control and 79% for RPNI—as expected for active soleus postural muscles. Stance NiEMG signals were greater than swing NiEMG averages for Control and RPNI groups (Fig 1). The Denervated group stance and swing NiEMG signals were not different without peripheral nerve control. Fidelity of RPNI stance activity (NiEMG signal to background signal) was 5.6 to 1, or double the Control signal fidelity. Correlations between iEMG and stance time for the Control (r=0.74) and RPNI (r=0.76) indicate strong signal reliability (Fig. 2). Conclusion: Measurements of fidelity, reliability, and validity for RPNI signal detection all exceeded normal probability (p<0.05) during voluntary movement.