Juan Gabriel Hincapie

Excitation properties of the right cervical vagus nerve in adult dogs.

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and depression, and it is currently under investigation for applications in Alzheimers disease, anxiety, heart failure, and obesity. However, the mechanism(s) by which VNS has its effects are not clear, and the stimulation parameters for obtaining therapeutic outcomes appear highly variable. The purpose of this study was to quantify the excitation properties of the right cervical vagus nerve in adult dogs anesthetized with propofol and fentanyl. Input-output curves of the right cervical vagus nerve compound action potential and laryngeal muscle electromyogram were measured in response to VNS across a range of stimulation parameters: amplitudes of 0.02-50mA, pulsewidths of 10, 50, 100, 200, 300, 500, and 1,000μs, frequencies of 1-2Hz, and train lengths of 20 pulses with 3 different electrode configurations: monopolar cathode, proximal anode/distal cathode, and proximal cathode/distal anode. Electrode configuration and stimulation waveform (monophasic vs. asymmetric charge-balanced biphasic) did not affect the threshold or recruitment of the vagal nerve fibers that were activated. The rheobase currents of A- and B-fibers were 0.4mA and 0.7mA, respectively, and the chronaxie of both components was 180μs. Pulsewidth had little effect on the normalized threshold difference between activation of A- and B-fibers. The results provide insight into the complement of nerve fibers activated by VNS and guidance to clinicians for the selection of optimal stimulation parameters.

High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog

OBJECTIVE Not fully understanding the type of axons activated during vagus nerve stimulation (VNS) is one of several factors that limit the clinical efficacy of VNS therapies. The main goal of this study was to characterize the electrical recruitment of both myelinated and unmyelinated fibers within the cervical vagus nerve. APPROACH In anesthetized dogs, recording nerve cuff electrodes were implanted on the vagus nerve following surgical excision of the epineurium. Both the vagal electroneurogram (ENG) and laryngeal muscle activity were recorded in response to stimulation of the right vagus nerve. MAIN RESULTS Desheathing the nerve significantly increased the signal-to-noise ratio of the ENG by 1.2 to 9.9 dB, depending on the nerve fiber type. Repeated VNS following nerve transection or neuromuscular block (1) enabled the characterization of A-fibers, two sub-types of B-fibers, and unmyelinated C-fibers, (2) confirmed the absence of stimulation-evoked reflex compound nerve action potentials in both the ipsilateral and contralateral vagus nerves, and (3) provided evidence of stimulus spillover into muscle tissue surrounding the stimulating electrode. SIGNIFICANCE Given the anatomical similarities between the canine and human vagus nerves, the results of this study provide a template for better understanding the nerve fiber recruitment patterns associated with VNS therapies.

A musculoskeletal model of the upper extremity for use in the development of neuroprosthetic systems

Upper extremity neuroprostheses use functional electrical stimulation (FES) to restore arm motor function to individuals with cervical level spinal cord injury. For the design and testing of these systems, a biomechanical model of the shoulder and elbow has been developed, to be used as a substitute for the human arm. It can be used to design and evaluate specific implementations of FES systems, as well as FES controllers. The model can be customized to simulate a variety of pathological conditions. For example, by adjusting the maximum force the muscles can produce, the model can be used to simulate an individual with tetraplegia and to explore the effects of FES of different muscle sets. The model comprises six bones, five joints, nine degrees of freedom, and 29 shoulder and arm muscles. It was developed using commercial, graphics-based modeling and simulation packages that are easily accessible to other researchers and can be readily interfaced to other analysis packages. It can be used for both forward-dynamic (inputs: muscle activation and external load; outputs: motions) and inverse-dynamic (inputs: motions and external load; outputs: muscle activation) simulations. Our model was verified by comparing the model calculated muscle activations to electromyographic signals recorded from shoulder and arm muscles of five subjects. As an example of its application to neuroprosthesis design, the model was used to demonstrate the importance of rotator cuff muscle stimulation when aiming to restore humeral elevation. It is concluded that this model is a useful tool in the development and implementation of upper extremity neuroprosthetic systems.

Feasibility of EMG-Based Neural Network Controller for an Upper Extremity Neuroprosthesis

The overarching goal of this project is to provide shoulder and elbow function to individuals with C5/C6 spinal cord injury (SCI) using functional electrical stimulation (FES), increasing the functional outcomes currently provided by a hand neuroprosthesis. The specific goal of this study was to design a controller based on an artificial neural network (ANN) that extracts information from the activity of muscles that remain under voluntary control sufficient to predict appropriate stimulation levels for several paralyzed muscles in the upper extremity. The ANN was trained with activation data obtained from simulations using a musculoskeletal model of the arm that was modified to reflect C5 SCI and FES capabilities. Several arm movements were recorded from able-bodied subjects and these kinematics served as the inputs to inverse dynamic simulations that predicted muscle activation patterns corresponding to the movements recorded. A system identification procedure was used to identify an optimal reduced set of voluntary input muscles from the larger set that are typically under voluntary control in C5 SCI. These voluntary activations were used as the inputs to the ANN and muscles that are typically paralyzed in C5 SCI were the outputs to be predicted. The neural network controller was able to predict the needed FES paralyzed muscle activations from ldquovoluntaryrdquo activations with less than a 3.6% RMS prediction error.

Selective control of physiological responses by temporally-patterned electrical stimulation of the canine vagus nerve

Vagus nerve stimulation (VNS) is effective for treating epilepsy and depression, and has emerging indications for anxiety and heart failure. However, stimulation-evoked side effects remain a challenge for long-term compliance. We investigated the feasibility of reducing VNS side effects by using a temporally-modified stimulation pattern. In 4 anesthetized canines, we measured changes in both the heart rate and evoked laryngeal muscle activity. Compared to baseline, we found that a 5% duty cycle (measured by the number of pulses per second of stimulation) could still evoke a 21% reduction in heart rate; whereas compared to continuous stimulation (3 mA, 300 μs pulsewidth, 20 Hz) the same 5% duty cycle reduced the evoked laryngeal muscle activity by 90%. The results of this study indicate that temporally-patterned stimulation may provide an effective tool for optimizing VNS therapy.

Musculoskeletal Model-Guided, Customizable Selection of Shoulder and Elbow Muscles for a C5 SCI Neuroprosthesis

Individuals with C5/C6 spinal cord injury (SCI) have a number of paralyzed muscles in their upper extremities that can be electrically activated in a coordinated manner to restore function. The selection of a practical subset of paralyzed muscles for stimulation depends on the specific condition of the individual, the functions targeted for restoration, and surgical considerations. This paper presents a musculoskeletal model-based approach for optimizing the muscle set used for functional electrical stimulation (FES) of the shoulder and elbow in this population. Experimentally recorded kinematics from able-bodied subjects served as inputs to a musculoskeletal model of the shoulder and elbow, which was modified to reflect the reduced muscle force capacities of an individual with C5 SCI but also the potential of using FES to activate paralyzed muscles. A large number of inverse dynamic simulations mimicking typical activities of daily living were performed that included (1) muscles with retained voluntary control and (2) many different combinations of stimulated paralyzed muscles. These results indicate that a muscle set consisting of the serratus anterior, infraspinatus and triceps would enable the greatest range of relevant movements. This set will become the initial target in a C5SCI neuroprosthesis to restore shoulder and elbow function.

EMG-based Control for a C5/C6 Spinal Cord Injury Upper Extremity Neuroprosthesis

The goal of this project is to enhance the benefits of functional electrical stimulation (FES) for individuals with cervical mid-level spinal cord injury (C5-C6 SCI) by providing upper arm function that complements the hand function provided by current FES systems. As a result of stimulation to selected shoulder and elbow muscles, individuals are able to increase their range of motion, their reaching ability, and improve their overall shoulder stability. An approach that provides a natural way of controlling arm stimulation is proposed. The controller extracts information from recorded EMG activity of muscles under retained voluntary control and processes these signals to generate the appropriate stimulation levels for the stimulated paralyzed muscles. One subject with complete C5 paralysis has been implemented with this advanced neuroprosthesis which includes four implanted EMG electrodes and 24 channels of stimulation. Eight of these channels were used for hand grasp and six were used for trunk stimulation to provide posture control, trunk stability and weight relief. The shoulder and elbow implanted stimulation channels include the suprascapular, thoracodorsal and radial nerves (via nerve-cuff electrodes) and the pectoralis major, rhomboids and pronator quadratus muscles (via muscle-based electrodes). The thoracic portion of the pectoralis major was transferred to the scapula to restore the actions of the denervated serratus anterior muscle, essential for reaching tasks and shoulder stability. The four EMG channels implanted include the trapezius, biceps, deltoids and extensor carpi radialis longus. Currently, the EMG control strategy is being refined and tested with the subject including evaluation of the functional benefits of the intervention.

Adaptive neural network controller for an upper extremity neuroprosthesis

The long term goal of this project is to develop an adaptive neural network controller for an upper extremity neuroprosthesis targeted for people with C5/C6 spinal cord injury (SCI). The challenge is to determine how to simultaneously stimulate different paralyzed muscles based on the EMG activity of muscles under retained voluntary control. The controller extracts the movement intention from the recorded EMG signals and generates the appropriate stimulation levels to activate the paralyzed muscles. To test the feasibility of this controller, different arm movements were recorded from able bodied subjects. Using a musculoskeletal model of the arm, inverse simulations provided muscle activation patterns corresponding to these movements. The model was modified to reflect C5/C6 SCI and the optimization criteria were varied to reflect different nervous system motor control strategies. Activation patterns were then used to train a time-delayed neural network to predict paralyzed muscle activations from voluntary muscle activations. Forward simulations were performed to obtain predicted movements and use the kinematic errors to design an adaptive strategy to account for disturbances and changes in the system.

Modulation of heart rate by temporally patterned vagus nerve stimulation in the anesthetized dog

Despite current knowledge of the myriad physiological effects of vagus nerve stimulation (VNS) in various mammalian species (including humans), the impact of varying stimulation parameters on nerve recruitment and physiological responses is not well understood. We investigated nerve recruitment, cardiovascular responses, and skeletal muscle responses to different temporal patterns of VNS across 39 combinations of stimulation amplitude, frequency, and number of pulses per burst. Anesthetized dogs were implanted with stimulating and recording cuff electrodes around the cervical vagus nerve, whereas laryngeal electromyogram (EMG) and heart rate were recorded. In seven of eight dogs, VNS‐evoked bradycardia (defined as ≥10% decrease in heart rate) was achieved by applying stimuli at amplitudes equal to or greater than the threshold for activating slow B‐fibers. Temporally patterned VNS (minimum 5 pulses per burst) was sufficient to elicit bradycardia while reducing the concomitant activation of laryngeal muscles by more than 50%. Temporal patterns of VNS can be used to modulate heart rate while minimizing laryngeal motor fiber activation, and this is a novel approach to reduce the side effects produced by VNS.

Selection of Muscle and Nerve-Cuff Electrodes for Neuroprostheses Using Customizable Musculoskeletal Model

Neuroprosthetic systems based on functional electrical stimulation aim to restore motor function to individuals with paralysis following spinal cord injury. Identifying the optimal electrode set for the neuroprosthesis is complicated because it depends on the characteristics of the individual (such as injury level), the force capacities of the muscles, the movements the system aims to restore, and the hardware limitations (number and type of electrodes available). An electrode-selection method has been developed that uses a customized musculoskeletal model. Candidate electrode sets are created based on desired functional outcomes and the hard ware limitations of the proposed system. Inverse-dynamic simulations are performed to determine the proportion of target movements that can be accomplished with each set; the set that allows the most movements to be performed is chosen as the optimal set. The technique is demonstrated here for a system recently developed by our research group to restore whole-arm movement to individuals with high-level tetraplegia. The optimal set included selective nerve-cuff electrodes for the radial and musculocutaneous nerves; single-channel cuffs for the axillary, suprascapular, upper subscapular, and long-thoracic nerves; and muscle-based electrodes for the remaining channels. The importance of functional goals, hardware limitations, muscle and nerve anatomy, and surgical feasibility are highlighted.