Stability of flexible thin-film metallization stimulation electrodes: analysis of explants after first-in-human study and improvement of in vivo performance.

OBJECTIVE: Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. APPROACH: This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A failure mode analysis on the explanted devices was performed after a first-in-human study limited to 30 d. MAIN RESULTS: About 90% of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5% of the stimulation contacts showed signs of delamination at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions within a rodent animal trial. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. SIGNIFICANCE: Failure mode analysis guided implant stability optimization. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications. (Document number of Ethical Committee: P/905/CE/2012; Date of approval: 2012-10-04).

Comparison of the efficiency of chopped and non-rectangular electrical stimulus waveforms in activating small vagus nerve fibers.

BACKGROUND: In the context of morbid obesity, vagus nerve stimulation could be used to control gastric function targeting the small afferent B-fibers and C-fibers. Compared to large A-fibers, activation thresholds of these small efferent fibers are 10 to 100 times greater, inducing technical constraints and possible nerve damages. Although rectangular waveform is commonly used in nerve stimulation, recent modeling and experimental studies suggest that non-rectangular waveforms could reduced the charge injected by the stimulator. NEW METHOD: The objective of the present study is to evaluate the charge injection of complex waveforms such as the ramp, quarter sine and chopped pulses in the context of vagus nerve stimulation. We performed in-vivo study on the porcine abdominal vagus nerves and evaluated charge injection at activation thresholds. A modeling study was performed to further extent the results obtained in-vivo. COMPARISON WITH EXISTING METHOD: Compared to the rectangular pulse, the ramp and quarter sine waveforms activated gastric fibers with the lowest charge injection: -23.2% and -30.1% respectively. The efficacy of chopped pulses is questioned through the consideration of the strength-duration curve. CONCLUSION: Continuous ramp and quarter sine waveforms effectively activate small diameter fibers. These pulse shapes may be considered for long-term vagus nerve stimulation. The results predicted by computational models were qualitatively consistent with experiments. This suggested the relevance of using modeling in the context of complex waveforms prior to future in-vivo tests.

Investigation of the efficiency of the shape of chopped pulses using earthworm model.

In neural electrical stimulation, limiting the charge delivered during a stimulus pulse is essential to avoid nerve tissue damage and to save power. Previous experimental and modeling studies indicated that waveforms such as non-rectangular continuous pulses or rectangular chopped pulse were able to improve stimulation efficiency. The goal of this study is to evaluate if non-rectangular chopped pulses such as quarter sine and ramp are more charge efficient than rectangular chopped pulse. We performed in vivo study on 17 lumbricus terrestris and compared the charge per stimulating phase needed to activate lateral giant fibers (LGF) and medial giant fiber (MGF) using chopped non-rectangular pulses and rectangular pulse, varying stimulation duration parameters. Results indicated that non rectangular chopped pulses activated MGF and LGF with less charge than rectangular chopped pulses. For MGF (respectively LGF), the gain of charge was up to 33.9\% (resp. 17.8\%) using chopped ramp, and up to 22.8\% (resp. 18.1\%) using chopped quarter sine.

Exploring Selective Neural Electrical Stimulation for Upper Limb Function Restoration.

This article introduces a new approach of selective neural electrical stimulation of the upper limb nerves. Median and radial nerves of individuals with tetraplegia are stimulated via a multipolar cuff electrode to elicit movements of wrist and hand in acute conditions during a surgical intervention. Various configurations corresponding to various combinations of a 12-poles cuff electrode contacts are tested. Video recording and electromyographic (EMG) signals recorded via sterile surface electrodes are used to evaluate the selectivity of each stimulation configuration in terms of activated muscles. In this abstract we introduce the protocol and preliminary results will be presented during the conference.

Vagus nerve stimulation: state of the art of stimulation and recording strategies to address autonomic function neuromodulation.

OBJECTIVE: Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. APPROACH: This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. MAIN RESULTS: We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans.

Delaying discharge after the stimulus significantly decreases muscle activation thresholds with small impact on the selectivity: an in vivo study using TIME.

The number of devices for electrical stimulation of nerve fibres implanted worldwide for medical applications is constantly increasing. Stimulation charge is one of the most important parameters of stimulation. High stimulation charge may cause tissue and electrode damage and also compromise the battery life of the electrical stimulators. Therefore, the objective of minimizing stimulation charge is an important issue. Delaying the second phase of biphasic stimulation waveform may decrease the charge required for fibre activation, but its impact on stimulation selectivity is not known. This information is particularly relevant when transverse intrafascicular multichannel electrode (TIME) is used, since it has been designed to provide for high selectivity. In this in vivo study, the rat sciatic nerve was electrically stimulated using monopolar and bipolar configurations with TIME. The results demonstrated that the inclusion of a 100-µs delay between the cathodic and the anodic phase of the stimulus allows to reduce charge requirements by around 30 %, while only slightly affecting stimulation selectivity. This study shows that adding a delay to the typical stimulation waveform significantly ([Formula: see text]) reduces the charge required for nerve fibres activation. Therefore, waveforms with the delayed discharge phase are more suitable for electrical stimulation of nerve fibres.

A survey on robotic devices for upper limb rehabilitation.

The existing shortage of therapists and caregivers assisting physically disabled individuals at home is expected to increase and become serious problem in the near future. The patient population needing physical rehabilitation of the upper extremity is also constantly increasing. Robotic devices have the potential to address this problem as noted by the results of recent research studies. However, the availability of these devices in clinical settings is limited, leaving plenty of room for improvement. The purpose of this paper is to document a review of robotic devices for upper limb rehabilitation including those in developing phase in order to provide a comprehensive reference about existing solutions and facilitate the development of new and improved devices. In particular the following issues are discussed: application field, target group, type of assistance, mechanical design, control strategy and clinical evaluation. This paper also includes a comprehensive, tabulated comparison of technical solutions implemented in various systems.

Automated determination of peripheral nerve stimulation parameters to achieve desired effector response - a procedural routine, preliminary studies and proposal of improvements.

BACKGROUND: The feasibility of selectively stimulating fascicles and fibers within peripheral nerves has been demonstrated by a number of groups. Although various multi-contact electrodes have been developed for this purpose, the lack of procedures for fast determination of stimulation parameters to produce the desired effector activity hampers the clinical application of these techniques.In this paper, we propose an automated search routine that may facilitate the determination of stimulation parameters. To verify the routine's performance, we also developed an another routine that performs systematic stimulus-response mapping (the mapping routine). METHOD: The mapping routine performs systematic mapping of all possible combinations of the allowed stimulation parameters (i.e. combinations of electrode contacts used to provide the stimulus and sets of stimulus parameters values) and the observed displacements. The proposed automated search routine, similarly to the mapping routine, maps stimulation parameters to muscle responses, but it first investigates stimuli of the low charge and during the mapping process it compares the recorded responses with the desired one. Depending on the result of that comparison, it decides whether the use of a particular combination of electrode contacts should be further investigated or skipped.Both approaches were implemented on a custom-made closed-loop FES platform and preliminary experiments were performed on a rat model. The rat's sciatic nerve was stimulated with a 12-contact cuff electrode and the resulting displacement of the rat's paw was determined using a MEMS accelerometer. RESULTS: The automated search routine was faster than the mapping routine; however, it failed to find correct stimulation parameters in one out of three searches. This could be due to unexpectedly high variability in the responses to a constant stimulus. CONCLUSION: Our initial tests have proven that the proposed method determines the desired stimulation parameters much more quickly than systematic stimulus-response mapping. However, the factors influencing the variability of responses to constant stimuli should be identified, and their influence diminished; the remaining essential variability can then be identified. Thereafter, the criteria influencing the search process should be investigated and refined.Further improvements to the search routine are also proposed.

An improved kinematic model of the spine for three-dimensional motion analysis in the Vicon system.

The mechanism of creation and pathomechanics of lateral spinal deformation is still not fully explained. Modern medical imaging techniques give scientists possibility to understand some aspects, but vast majority of those techniques is based on static trials. A motion capture system belongs to techniques which enable visualization of a spine during dynamic trials; however, due to lack of appropriate computational model, it is unsuitable for scoliosis imaging. A few years ago our group has proposed a kinematic model of the spine to be used with Vicon Motion Capture System, which was based on Bézier curves. That model allowed for much more precise investigation of spinal kinematics during dynamic trials as compared with other computational models. However, it did not allowed to restrict only selected movements for particular segments of the spine (e.g. axial rotation for lumbar spine). The aim of the current work is to improve the proposed model in order to be able to restrict selected movements according to the knowledge concerning spinal anatomy and spinal range of motion. The new kinematic model of the spine was written in BodyBuilder for Biomechanics Language. For the purpose of visualization also an accurate graphical representation of each vertebra (polygon mesh) was computed and adapted to be compatible with the kinematic model. Using a new version of the model it is possible to perform precise analysis of movement of all vertebrae during such dynamic activities as e.g. gait and forward or lateral bending, as well as to present the results not only on the charts, but also as a 3D animation of movements of a realistically looking spine. The paper describes the new kinematic model and the process of creating graphical representation of the vertebrae. Also sample results obtained using that model are presented.

Restrainer of pelvis and lower limbs in thoracic and lumbar range of motion measurement--preliminary report.

BACKGROUND: Range of motion (ROM) is a parameter of prime importance for clinical assessment of spinal function. Many spinal ROM assessment techniques of varying reliability are currently in use. Immobilization of the pelvis and lower extremities improves control of the neutral position and decreases the error resulting from compensatory hip motion during measurement. To present a prototypic station for active 3-dimensional spinal ROM assessment; to analyze repeatability of measurements and reproducibility of the neutral position. METHODS: A quintuple 3-dimensional measurement of the lumbar and thoracic active range of motion in 12 healthy volunteers. RESULTS: The series of results obtained for each subject fulfilled the criteria of a normal distribution. The mean values of thoracic ROM were as follows: sagittal 40.1 degrees (SD=5.56 degrees; mean coefficient of variation CV=13.88%); horizontal 75.2 degrees (SD=6.01 degrees; CV=7.99%); frontal 34.0 degrees (SD=3.01 degrees; CV=8.84%). The mean values of lumbar ROM were as follows: sagittal 112.0 degrees (SD=4.13; CV=3.68%); horizontal 14.8 degrees (SD=3.77 degrees; CV=25.45%); frontal 67.6 degrees (SD=2.72 degrees; CV=4.03%). Inter-class correlation coefficients for particular subjects ranged between 0.95 and 0.99 (p<0.0001). Mean reproducibility of the neutral position was 1.08 degrees-2.63 degrees in thoracic spine and 1.23 degrees-2.31 degrees in lumbar spine. Comparison of the results with literature data revealed good neutral position reproducibility and high values of inter-class correlation coefficients in the present study. Potential reasons for assessment errors are discussed. Recommendations for the construction of an improved immobilizer for diagnostic purposes are presented. CONCLUSIONS: Validated spinal ROM measurements are useful in monitoring patients with musculoskeletal disorders. Immobilization of the pelvis and lower limbs improves repeatability of thoracic and lumbar ROM assessment and reproducibility of a neutral position. The prototype enables highly repeatable measurements, but requires technical improvements.