Recruitment characteristics of nerve fascicles stimulated by a multi-groove electrode

The recruitment characteristics of fascicle-selective nerve stimulation by a multigroove electrode have been investigated both theoretically and in acute experiments. A three-dimensional (3-D) volume conductor model of fascicles in a multigroove device and a model of myelinated nerve fiber stimulation were used to calculate threshold stimuli of nerve fibers in these fascicles. After their exposition, fascicles from rat sciatic nerve were positioned in different grooves of appropriate sizes and stimulated separately. The device appeared to be suitable for fascicle-selective stimulation, because both computer simulations and acute animal experiments showed that crosstalk between neighboring fascicles is not a problem, even when monopolar stimulation was used. The threshold stimulus was lower for a small fascicle than for a large one. When the amount of (conducting) medium between contact and perineurium or its conductivity was reduced, threshold stimuli were lower. Moreover, simulations predict that the slopes of recruitment curves are smaller and inverse recruitment order is less pronounced. Simulations also showed that a small contact is preferable to a large one, because a small contact gives a slightly smaller slope of the recruitment curve. Both experimentally and theoretically a significantly smaller slope of recruitment curves was obtained by stimulation with a cathode and an anode at opposite sides of the fascicle, driven by two current sources giving simultaneous pulses with different, but linearly dependent amplitude

Endoneural selective stimulating using wire-microelectrode arrays

In acute experiments eight 5- to 24-wire-microelectrode arrays were inserted into the common peroneal nerve of the rat, to investigate whether the electrodes could selectively stimulate motor units of the extensor digitorum longus (EDL) muscle. Twitch-force-recruitment curves were measured from the EDL for each array electrode. The curves were plotted on a double-logarithmic scale and parameterized by the low-force slope (which represents the power p in the power-law relationship of force F versus stimulus current I, or F~Ip) and the threshold current. The slopes and threshold currents measured with array electrodes did not differ significantly from those obtained with randomly inserted single wire-microelectrodes. This indicates that, although involving a more invasive insertion procedure, electrode arrays provide neural contacts with low-force recruitment properties similar to those of single wires. Array results revealed partial blocking of neural conduction, similar to that reported with microneurographic insertion with single needles. The efficiency of the array was defined as the fraction of array electrodes selectively contacting a motor unit and evoking the corresponding threshold force. Efficiency thus expresses the practical value of the used electrode array in terms of the total number of distinct threshold forces that can be stimulated by selecting the appropriate electrodes. The eight arrays were capable of evoking threshold forces selectively with an average efficiency of 0.81 (or 81%

3D Neuro-electronic interface devices for neuromuscular control: Design studies and realisation steps

In order to design the shape and dimensions of new 3D multi-microelectrode information transducers properly, i. e. adapted to the scale of information delivery to and from peripheral nerve fibres, a number of studies were, and still are, being performed on modelling and simulation of electrical volume conduction inside and outside nerves, on animal experiments on stimulation and recording with single wires and linear arrays, and on new technologies for 3D micro-fabrication. This paper presents a selection of the results of these `Neurotechnology¿ studies at the University of Twente. The experimental and simulation results apply primarily to the peripheral motor nerves of the rat, but are also of interest for neural interfacing with myelinated nerves in man, as fascicles in man are about the same size as in the rat

Perspectives on new electrode technology for stimulating peripheral nerves with implantable motor prostheses

Journal ArticleAbstract-The limits of present electrode technology are being reached in current motor prostheses for restoring functional movement in paralyzed people. Improved devices require electrodes and stimulation methods that will activate muscles selectively and independently with less implanted hardware. A practical functional neuromuscular stimulation (FNS) system may need to employ extraneural, intraneural, epimysial, or intramuscular electrodes or a combination of these types. The limitations of current muscle electrodes and the anatomy of peripheral nerve innervation of muscle have pointed to stimulation of peripheral nerve trunks as a promising area for investigation. Attempts to use conventional (extraneural) peripheral nerve electrodes for selective activation of muscles in chronic applications have met with only limited success. Intraneural (intrafascicular) electrodes offer the advantages of greater selectivity and lower power requirements, but these may be offset by the difficulty of inserting delicate electrodes through the collagenous epineurium and perineurium while avoiding unacceptable amounts of trauma. Cuff electrodes require more power than intrafascicular ones but may provide more stable recruitment patterns over time, and the opportunity for retrieval and replacement

Dilation of the oropharynx via selective stimulation of the hypoglossal nerve

Obstructive sleep apnea (OSA) is caused by the retraction of the tongue to occlude the upper airway (UAW). Electrical stimulation of the tongue protrudor and retractor muscle has been demonstrated as an effective technique to alleviate UAW obstructions and is considered to be a potential treatment for OSA. Recent studies have shown that selective stimulation of the hypoglossal nerve (HG) to activate tongue muscles using a single implantable device presents an attractive approach for treating OSA. In this study, the functional outcome of selective hypoglossal nerve stimulation with a multi-contact peripheral nerve electrode was studied by imaging the airway in anesthetized beagles. A pulse train of varying amplitude was applied through each one of the tripolar contact sets of the nerve electrode while the pharyngeal images were acquired via a video grabber into a computer. For the open mouth positions, the tongue activation patterns were also viewed and videotaped with a digital camcorder through the mouth. The percent dilation of the pharyngeal opening for each contact was calculated. The images show that stimulations delivered through the electrode contacts placed around the HG nerve trunk can generate several different activation patterns of the tongue muscles. Some of these patterns translate into a substantial increase in the oropharyngeal size, while others do not have any effect on the pharynx. The activation patterns vary as a function of the head position and the lower jaw. These results suggest that selective nerve stimulation can be a useful technique to maximize the effects of HG nerve stimulation in removing the obstructions in sleep apnea patients

Organotopic organization of the porcine mid-cervical vagus nerve

Introduction: Despite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function. / Methods and results: We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization. / Discussion: Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N = 4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fiber-containing fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders, and more

Imaging fascicular organisation in mammalian vagus nerve for selective VNS

Nerves contain a large number of nerve fibres, or axons, organised into bundles known as fascicles. Despite the somatic nervous system being well understood, the organisation of the fascicles within the nerves of the autonomic nervous system remains almost completely unknown. The new field of bioelectronics medicine, Electroceuticals, involves the electrical stimulation of nerves to treat diseases instead of administering drugs or performing complex surgical procedures. Of particular interest is the vagus nerve, a prime target for intervention due to its afferent and efferent innervation to the heart, lungs and majority of the visceral organs. Vagus nerve stimulation (VNS) is a promising therapy for treatment of various conditions resistant to standard therapeutics. However, due to the unknown anatomy, the whole nerve is stimulated which leads to unwanted off-target effects. Electrical Impedance Tomography (EIT) is a non-invasive medical imaging technique in which the impedance of a part of the body is inferred from electrode measurements and used to form a tomographic image of that part. Micro-computed tomography (microCT) is an ex vivo method that has the potential to allow for imaging and tracing of fascicles within experimental models and facilitate the development of a fascicular map. Additionally, it could validate the in vivo technique of EIT. The aim of this thesis was to develop and optimise the microCT imaging method for imaging the fascicles within the nerve and to determine the fascicular organisation of the vagus nerve, ultimately allowing for selective VNS. Understanding and imaging the fascicular anatomy of nerves will not only allow for selective VNS and the improvement of its therapeutic efficacy but could also be integrated into the study on all peripheral nerves for peripheral nerve repair, microsurgery and improving the implementation of nerve guidance conduits. Chapter 1 provides an introduction to vagus nerve anatomy and the principles of microCT, neuronal tracing and EIT. Chapter 2 describes the optimisation of microCT for imaging the fascicular anatomy of peripheral nerves in the experimental rat sciatic and pig vagus nerve models, including the development of pre-processing methods and scanning parameters. Cross-validation of this optimised microCT method, neuronal tracing and EIT in the rat sciatic nerve was detailed in Chapter 3. Chapter 4 describes the study with microCT with tracing, EIT and selective stimulation in pigs, a model for human nerves. The microCT tracing approach was then extended into the subdiaphragmatic branches of the vagus nerves, detailed in Chapter 5. The ultimate goal of human vagus nerve tracing was preliminarily performed and described in Chapter 6. Chapter 7 concludes the work and describes future work. Lastly, Appendix 1 (Chapter 8) is a mini review on the application of selective vagus nerve stimulation to treat acute respiratory distress syndrome and Appendix 2 is morphological data corresponding to Chapter 4

New stimulation device to drive multiple transverse intrafascicular electrodes and achieve highly selective and rich neural responses

Peripheral Nerve Stimulation (PNS) is a promising approach in functional restoration following neural impairments. Although it proves to be advantageous in the number of implantation sites provided compared with intramuscular or epimysial stimulation and the fact that it does not require daily placement, as is the case with surface electrodes, the further advancement of PNS paradigms is hampered by the limitation of spatial selectivity due to the current spread and variations of nerve physiology. New electrode designs such as the Transverse Intrafascicular Multichannel Electrode (TIME) were proposed to resolve this issue, but their use was limited by a lack of innovative multichannel stimulation devices. In this study, we introduce a new portable multichannel stimulator-called STIMEP-and implement different stimulation protocols in rats to test its versatility and unveil the potential of its combined use with TIME electrodes in rehabilitation protocols. We developed and tested various stimulation paradigms in a single fascicle and thereafter implanted two TIMEs. We also tested its stimulation using two different waveforms. The results highlighted the versatility of this new stimulation device and advocated for the parameterizing of a hyperpolarizing phase before depolarization as well as the use of small pulse widths when stimulating with multiple electrodes

A combined cuff electrode array for organ-specific selective stimulation of vagus nerve enabled by Electrical Impedance Tomography

Previously developed spatially-selective Vagus Nerve Stimulation (sVNS) allows the targeting of specific nerve fascicles through current steering in a multi-electrode nerve cuff but relies on a trial-and-error strategy to identify the relative orientation between electrodes and fascicles. Fast Neural Electrical Impedance Tomography (FN-EIT) has been recently used for imaging neural traffic in the vagus nerves of pigs in a cross-correlation study with sVNS and MicroCT fascicle tracking. FN-EIT has the potential for allowing targeted sVNS; however, up to now, stimulation and imaging have been performed with separate electrode arrays. In this study, different options were evaluated in-silico to integrate EIT and stimulation into a single electrode array without affecting spatial selectivity. The original pig vagus EIT electrode array geometry was compared with a geometry integrating sVNS and EIT electrodes, and with direct use of sVNS electrodes for EIT imaging. Modelling results indicated that both new designs could achieve image quality similar to the original electrode geometry in all tested markers (e.g., co-localisation error <100 µm). The sVNS array was considered to be the simplest due to the lower number of electrodes. Experimental results from testing evoked EIT imaging of recurrent laryngeal activity using electrodes from the sVNS cuff returned a signal-to-noise ratio similar to our previous study (3.9 ± 2.4 vs. 4.1 ± 1.5, N = 4 nerves from 3 pigs) and a lower co-localisation error (≈14% nerve diameter vs. ≈25%, N = 2 nerves from 2 pigs). Performing FN-EIT and sVNS on the same nerve cuff will facilitate translation to humans, simplify surgery and enable targeted neuromodulation strategies