Model-based analysis of implanted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea.

STUDY OBJECTIVES: Individuals with obstructive sleep apnea (OSA), characterized by frequent sleep disruptions from tongue muscle relaxation and airway blockage, are known to benefit from on-demand electrical stimulation of the hypoglossal nerve. Hypoglossal nerve stimulation (HNS) therapy, which activates the protrusor muscles of the tongue during inspiration, has been established in multiple clinical studies as safe and effective, but the mechanistic understanding for why some stimulation parameters work better than others has not been thoroughly investigated. METHODS: In this study, we developed a detailed biophysical model that can predict the spatial recruitment of hypoglossal nerve fascicles and axons within these fascicles during stimulation through nerve cuff electrodes. Using this model, three HNS programming scenarios were investigated including grouped cathode (---), single cathode (o-o), and guarded cathode bipolar (+-+) electrode configurations. RESULTS: Regardless of electrode configuration, nearly all hypoglossal nerve axons circumscribed by the nerve cuff were recruited for stimulation amplitudes <3 V. Within this range, monopolar configurations required lower stimulation amplitudes than the guarded bipolar configuration to elicit action potentials within hypoglossal nerve axons. Further, the spatial distribution of the activated axons was more uniform for monopolar versus guarded bipolar configurations. CONCLUSIONS: The computational models predicted that monopolar HNS provided the lowest threshold and the least sensitivity to rotational angle of the nerve cuff around the hypoglossal nerve; however, this setting also increased the likelihood for current leakage outside the nerve cuff, which could potentially activate axons in unintended branches of the hypoglossal nerve. CLINICAL TRIAL REGISTRATION: NCT01161420.

Corpus callosum low-frequency stimulation suppresses seizures in an acute rat model of focal cortical seizures.

OBJECTIVE: Low-frequency fiber-tract stimulation has been shown to be effective in treating mesial temporal lobe epilepsies through activation of the hippocampal commissure in rodents and human patients. The corpus callosum is a major pathway connecting the two hemispheres of the brain; however, few experiments have documented corpus callosum stimulation. The objective is to determine the efficacy of corpus callosum stimulation at low frequencies to suppress cortical seizures. METHODS: 4-Aminopyridine was injected in the primary motor cortex of 24 rats under anesthesia. Recording electrodes were placed in the contralateral motor cortex and hippocampus. Three pairs of stimulating electrodes were inserted into the corpus callosum along its longitudinal axis. Local field potentials were recorded 1 hour before, during, and after stimulation to determine the effect of stimulation on seizure duration. Stimulation was delivered from each pair of electrodes independently in separate experiments. Furthermore, electrical stimulation was applied to the region of the corpus callosum with the highest degree of innervation of the seizure focus to compare the efficacy of different stimulation frequencies (1-30 Hz) on seizure suppression. RESULTS: Corpus callosum stimulation was effective at suppressing seizures at 10 Hz by 76% (P < 0.05, n = 5) and at 20 Hz by 95% (P < 0.0001, n = 14). Stimulation at frequencies of 1 and 30 Hz did not have a significant effect on reducing the total time spent seizing (P > 0.9999, n = 5). Furthermore, stimulation was only effective at suppressing seizures when the pair of electrodes was placed within the section of corpus callosum containing fibers innervating the seizure focus. Secondarily generalized seizures in the hippocampus were eliminated when seizures in the cortical focus were suppressed. SIGNIFICANCE: Low-frequency fiber-tract stimulation of the corpus callosum suppresses both cortical and cortically induced hippocampal seizures in an acute model of focal cortical seizures. The stimulation paradigm is selective, as it is only effective when targeted to specific regions of the corpus callosum that project maximally to cortical regions generating the seizure activity. Selective placement of stimulation electrodes along the corpus callosum could be used as a patient-specific treatment for cortical epilepsies.

Long-lasting hyperpolarization underlies seizure reduction by low frequency deep brain electrical stimulation.

Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease. Deep brain electrical stimulation (DBS) of grey matter has been used for MTLE with limited success. However, stimulation of a white matter tract connecting the hippocampi, the ventral hippocampal commissure (VHC), with low frequencies that simulate interictal discharges has shown promising results, with seizure reduction greater than 98% in bilateral hippocampi during stimulation and greater than 50% seizure reduction in bilateral hippocampi after treatment. A major hurdle to the implementation and optimization of this treatment is that the mechanisms of seizure reduction by low frequency electrical stimulation (LFS) are not known. The goal of this study is to understand how commissural fibre tract stimulation reduces bilateral hippocampal epileptic activity in an in vitro slice preparation containing bilateral hippocampi connected by the VHC. It is our hypothesis that electrical stimuli induce hyperpolarization lasting hundreds of milliseconds following each pulse which reduces spontaneous epileptic activity during each inter-stimulus interval (ISI). Stimulus-induced long-lasting-hyperpolarization (LLH) can be mediated by GABA(B) inhibitory post-synaptic potentials (IPSPs) or slow after-hyperpolarization (sAHP). To test the role of LLH in effective bilateral seizure reduction by fibre tract stimulation, we measured stimulus-induced hyperpolarization during LFS of the VHC using electrophysiology techniques. Antagonism of the GABA(B) IPSP and/or sAHP diminished stimulus-induced hyperpolarization concurrently with LFS efficacy (greater than 50% reduction). Blocking both the GABA(B) IPSP and sAHP simultaneously eliminated the effect of electrical stimulation on seizure reduction entirely. These data show that LFS of the VHC is an effective protocol for bilateral hippocampal seizure reduction and that its efficacy relies on the induction of long-lasting hyperpolarization mediated through GABA(B) IPSPs and sAHP. Based on this study, optimization of the timing of LFS and LFS-induced-LLH may lead to improved outcomes from DBS treatments for human epilepsy.

High density mapping of atrial fibrillation during vagal nerve stimulation in the canine heart: restudying the Moe hypothesis.

INTRODUCTION: Moe et al. hypothesized that multiple wavelets (random reentry) were the mechanism of atrial fibrillation (AF) based on studies in a vagal nerve stimulation (VNS) canine model and a computer model of AF, but atrial mapping during AF in this model has not been done. We restudied this model using high density, simultaneous site mapping to test the hypothesis that AF was due to multiple wavelets. METHODS AND RESULTS: During pacing induced AF during VNS in 10 dogs, 512 unipolar atrial electrograms were recorded simultaneously from both atria. AF activation maps were produced including through AF termination after VNS cessation. During sustained AF, multiple foci (persistent and transient) of different cycle lengths (CLs) were present in both atria. Persistent foci of short (mean 112 ± 25 milliseconds), regular (standard deviation 5.3 ± 3 milliseconds) CLs were predominantly found in the left atria, near the pulmonary veins and coronary sinus. Both types of foci acted as drivers, and each produced wave fronts that largely resulted in collision or merging with each other at variable sites. No random reentry (multiple wavelets) was demonstrated. Ordered reentry (circus movement with head-tail interaction) was infrequently seen. With cessation of VNS, focal firing slowed and disappeared, followed by resumption of sinus rhythm after a prolonged pause. CONCLUSIONS: In contrast to the prediction of the multiple wavelet hypothesis, during AF in the Moe model, multiple foci drove the atria, producing and maintaining AF. Reentry played little, if any, role.

Fiber tract stimulation can reduce epileptiform activity in an in-vitro bilateral hippocampal slice preparation.

Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease that has been treated with electrical stimulation of gray matter with limited success. However, stimulation of a white matter tract connecting the hippocampi could maximize treatment efficacy and extent. We tested low-frequency stimulation (LFS) of a novel target that enables simultaneous targeting of bilateral hippocampi: the ventral hippocampal commissure (VHC) with a novel in-vitro slice preparation containing bilateral hippocampi connected by the VHC. The goal of this study is to understand the role of hippocampal interplay in seizure propagation and reduction by commissural fiber tract stimulation. LFS is applied to the VHC as extracellular and intracellular recording techniques are combined with signal processing to estimate several metrics of epilepsy including: (1) total time occupied by seizure activity (%); (2) seizure duration (s); (3) seizures per minute (#); and (4) power in the ictal (V(2)Hz(-1)); as well as (5) interictal spectra (V(2)Hz(-1)). Bilateral epileptiform activity in this preparation is highly correlated between hippocampi. Application of LFS to the VHC reduces all metrics of epilepsy during treatment in an amplitude and frequency dependent manner. This study lends several insights into the mechanisms of bilateral seizure reduction by LFS of the VHC, including that depolarization blocking, LTD/LTP and GABA(A) are not involved. Importantly, enhanced post-stimulation 1-Hz spiking correlates with long-lasting seizure reduction and both are heightened by targeting bilateral hippocampi via the VHC. Therefore, stimulating bilateral hippocampi via a single electrode in the VHC may provide an effective MTLE treatment.

Low frequency stimulation of ventral hippocampal commissures reduces seizures in a rat model of chronic temporal lobe epilepsy.

PURPOSE: To investigate the effects of low frequency stimulation (LFS) of a fiber tract for the suppression of spontaneous seizures in a rat model of human temporal lobe epilepsy. METHODS: Stimulation electrodes were implanted into the ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model of human temporal lobe epilepsy (n = 7). Two recording electrodes were placed in the CA3 regions bilaterally and neural data were recorded for a minimum of 6 weeks. LFS (60 min train of 1 Hz biphasic square wave pulses, each 0.1 ms in duration and 200 µA in amplitude, followed by 15 min of rest) was applied to the VHC for 2 weeks, 24 h a day. KEY FINDINGS: The baseline mean seizure frequency of the study animals was 3.7 seizures per day. The seizures were significantly reduced by the application of LFS in every animal (n = 7). By the end of the 2-week period of stimulation, there was a significant, 90% (<1 seizure/day) reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period following LFS (p < 0.05) when compared to baseline. LFS also resulted in a significant reduction of hippocampal interictal spike frequency (71%, p < 0.05), during 2 weeks of LFS session. The hippocampal histologic analysis showed no significant difference between rats that received LFS and SE induction and those that had received only SE-induction. None of the animals showed any symptomatic hemorrhage, infection, or complication. SIGNIFICANCE: Low frequency stimulation applied at a frequency of 1 Hz significantly reduced both the excitability of the neural tissue as well as the seizure frequency in a rat model of human temporal lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be an effective method for the suppression of spontaneous seizures in a temporal lobe model of epilepsy in rats and could lead to the development of a new therapeutic modality for human patients with temporal lobe epilepsy.

Control of seizure activity by electrical stimulation: effect of frequency.

Epilepsy is a devastating disease of the central nervous system, affecting approximately 1% of the world's population. Drug therapy is effective in many patients, but 25% of the patients do not respond to anticonvulsants. Surgical resection can be an effective treatment but is associated with serious complications that can remove it as an option. Electrical stimulation has been successful to control abnormal activity such as motor disorders and current research is aimed at determining the efficacy of this method for seizure control. Several electrical stimulation frequencies and waveforms have been developed to control seizure activity. The purpose of this presentation is to review these various approaches, and to discuss their underlying mechanisms and their potential for clinical implementation.

High frequency stimulation can block axonal conduction.

High frequency stimulation (HFS) is used to control abnormal neuronal activity associated with movement, seizure, and psychiatric disorders. Yet, the mechanisms of its therapeutic action are not known. Although experimental results have shown that HFS suppresses somatic activity, other data has suggested that HFS could generate excitation of axons. Moreover it is unclear what effect the stimulation has on tissue surrounding the stimulation electrode. Electrophysiological and computational modeling literature suggests that HFS can drive axons at the stimulus frequency. Therefore, we tested the hypothesis that unlike cell bodies, axons are driven by pulse train HFS. This hypothesis was tested in fibers of the hippocampus both in-vivo and in-vitro. Our results indicate that although electrical stimulation could activate and drive axons at low frequencies (0.5-25 Hz), as the stimulus frequency increased, electrical stimulation failed to continuously excite axonal activity. Fiber tracts were unable to follow extracellular pulse trains above 50 Hz in-vitro and above 125 Hz in-vivo. The number of cycles required for failure was frequency dependent but independent of stimulus amplitude. A novel in-vitro preparation was developed, in which, the alveus was isolated from the remainder of the hippocampus slice. The isolated fiber tract was unable to follow pulse trains above 75 Hz. Reversible conduction block occurred at much higher stimulus amplitudes, with pulse train HFS (>150 Hz) preventing propagation through the site of stimulation. This study shows that pulse train HFS affects axonal activity by: (1) disrupting HFS evoked excitation leading to partial conduction block of activity through the site of HFS; and (2) generating complete conduction block of secondary evoked activity, as HFS amplitude is increased. These results are relevant for the interpretation of the effects of HFS for the control of abnormal neural activity such as epilepsy and Parkinson's disease.

A flat interface nerve electrode with integrated multiplexer.

One of the goals of peripheral nerve cuff electrode development is the design of an electrode capable of selectively activating a specific population of axons in a common nerve trunk. Several designs such as the round spiral electrode or the flat interface nerve electrode (FINE) have shown such ability. However, multiple contact electrodes require many leads, making the implantation difficult and potentially damaging to the nerve. Taking advantage of the flat geometry of the FINE, multiplexers were embedded within the cuff electrode to reduce the number of leads needed to control 32 channels. The circuit was implemented on a polyimide film using off-the-shelf electronic components. The electronic module was surface-mounted directly onto the electrode's flat substrate. Two circuit designs were designed, built, and tested: 1) a single supply design with only two wires but limited to cathodic-first pulse and 2) a dual-supply design requiring three lead wires but an arbitrary stimulation waveform. The electrode design includes 32 contacts in a 1 mm x 8 mm opening. The contact size is 300 microm x 400 microm with access resistance less than 1 k ohm. This electrode is not intended for long-term use, but developed as a feasibility study for future development using low-water-absorption materials such as liquid crystal polymer and an application specific integrated circuit.

Flexible nerve stimulation electrode with iridium oxide sputtered on liquid crystal polymer.

Current electrode designs require flexible substrates that absorb little moisture and provide large charge injection capability. Sputtered iridium oxide films have superior charge injection capabilities versus noble metals and can adhere to various substrates. Liquid crystal polymers (LCPs) have very little water absorption compared to other flexible substrates. Therefore, the combination of sputtered iridium oxide film on LCP substrate was studied using 50 Hz, 100 micros duration, and 10 mA biphasic current waveforms for 700 h at 67 degrees C in bicarbonate buffer saline. Scanning electron micrograph analysis showed no delamination and approximately 1% of electrode material was lost to the bicarbonate buffer. The charge injection limit and the cathodic charge storage capacity within the water window were 4.6 +/- 1.0 and 31.5 +/-6.6 mC/cm2, respectively. Additional electrochemical analysis revealed significant charge imbalance attributed to oxygen reduction within the water window. These results, along with the flexible, chemically inert, and biocompatible substrate, indicate that sputtered iridium oxide films on LCP could become the method of choice for flexible substrate nerve electrodes.

Motion control of musculoskeletal systems with redundancy.

Motion control of musculoskeletal systems for functional electrical stimulation (FES) is a challenging problem due to the inherent complexity of the systems. These include being highly nonlinear, strongly coupled, time-varying, time-delayed, and redundant. The redundancy in particular makes it difficult to find an inverse model of the system for control purposes. We have developed a control system for multiple input multiple output (MIMO) redundant musculoskeletal systems with little prior information. The proposed method separates the steady-state properties from the dynamic properties. The dynamic control uses a steady-state inverse model and is implemented with both a PID controller for disturbance rejection and an artificial neural network (ANN) feedforward controller for fast trajectory tracking. A mechanism to control the sum of the muscle excitation levels is also included. To test the performance of the proposed control system, a two degree of freedom ankle-subtalar joint model with eight muscles was used. The simulation results show that separation of steady-state and dynamic control allow small output tracking errors for different reference trajectories such as pseudo-step, sinusoidal and filtered random signals. The proposed control method also demonstrated robustness against system parameter and controller parameter variations. A possible application of this control algorithm is FES control using multiple contact cuff electrodes where mathematical modeling is not feasible and the redundancy makes the control of dynamic movement difficult.

Pharmacodynamic effects of cinacalcet after kidney transplantation: once- versus twice-daily dose.

BACKGROUND: In the setting of kidney transplantation, cinacalcet has been given, mainly, once daily, but also twice daily. The aims of this prospective study were to assess the acute pharmacodynamic effect of cinacalcet administrated once or twice daily to kidney transplant patients with normal renal function and persisting hypercalcaemia due to hyperparathyroidism and to evaluate 1-year efficacy and tolerance of cinacalcet given at a dose of 30 mg b.i.d. METHODS: Eleven patients, who received a transplant 6 (6-59) months previously, were included in the study. A first kinetic was done after administration of 60 mg of cinacalcet at 8 a.m. After a washout period of 1 week, the second kinetic was performed with cinacalcet given at 30 mg b.i.d within a 12-h period. RESULTS: During both kinetics, serum calcium (sCa), ionized calcium (sCa(2+)), albumin-corrected Ca and parathyroid hormone (PTH) levels decreased significantly. At 24 h after the second kinetic, sCa(2+) was significantly lower. After 1 year of cinacalcet treatment, given at the dose of 30 mg b.i.d., there was a significant decrease in sCa, sCa(2+), PTH levels and calcium x phosphorus (Ph) product. In contrast, Ph levels increased significantly. There was no significant change in renal function. CONCLUSION: Once- or twice-daily acute administration of cinacalcet to kidney-transplant patients has similar efficacy. One-year administration of cinacalcet, given as two daily doses, is safe and efficient.

Structure and phase diagram of nucleosome core particles aggregated by multivalent cations.

The degree of compaction of the eukaryotic chromatin in vivo and in vitro is highly sensitive to the ionic environment. We address the question of the effect of multivalent ions on the interactions and mutual organization of the chromatin structural units, the nucleosome core particles (NCPs). Conditions of precipitation of NCPs in the presence of 10 mM Tris buffer and various amounts of either magnesium (Mg(2+)) or spermidine (Spd(3+)) are explored, compared, and discussed in relation to theoretical models. In addition, the structure of the aggregates is analyzed by complementary techniques: freeze-fracture electron microscopy, cryoelectron microscopy, and x-ray diffraction. In Mg(2+)-NCP aggregates, NCPs tend to stack on top of one another to form columns that are not long-range organized. In the presence of Spd(3+), NCPs precipitate to form a dense isotropic phase, a disordered phase of columns, a two-dimensional columnar hexagonal phase, or a three-dimensional crystal. The more ordered phases (two-dimensional or three-dimensional hexagonal) are found close to the precipitation line, where the number of positive charges carried by cations is slightly larger than the number of available negative charges of the NCPs. All ordered phases coexist with the dense isotropic phases. Formation of hexagonal and columnar phases is prevented by an excess of polycations.

Dilation of the oropharynx via selective stimulation of the hypoglossal nerve.

The functional effects of selective hypoglossal nerve (HG) stimulation with a multi-contact peripheral nerve electrode were assessed using images of the upper airways and the tongue in anesthetized beagles. A biphasic pulse train of 50 Hz frequency and 2 s duration was applied through each one of the tripolar contact sets of the nerve electrode while the pharyngeal images were acquired into a computer. The stimulation current was limited to 20% above the activation threshold for maximum selectivity. The images showed that various contact sets could generate several different activation patterns of the tongue muscles resulting in medial and/or lateral dilation and closing of the airways at the tongue root. Some of these patterns translated into an increase in the oropharyngeal size while others did not have any effect. The pharyngeal sizes were not statistically different during stimulation either between the two different positions of the head (30 degrees and 60 degrees), or when the lateral contacts were compared with the medial ones. The contacts that had the least effect generated an average of 53 +/- 15% pharyngeal dilation relative to the best contacts, indicating that the results are marginally sensitive to the contact position around the HG nerve trunk. These results suggest that selective HG nerve stimulation can be a useful technique to produce multiple tongue activation patterns that can dilate the pharynx. This may in turn increase the size of the patient population who can benefit from HG nerve stimulation as a treatment method for obstructive sleep apnea.

Influence of chain length and polymer concentration on the gelation of (amidated) low-methoxyl pectin induced by calcium.

The gelation of low-methoxyl pectin (LMP) induced by addition of Ca2+ was studied by measuring the storage modulus as a function of temperature during cooling. Samples with different molar masses were prepared by mechanical degradation. The effect of the molar mass and the pectin concentration on the gelation properties was investigated. The effect of partial amidation was studied by comparing LMP and partially amidated LMP with the same molar mass and degree of methylation. The results are compared to those from a model developed for Ca2+-induced pectin gelation, and good agreement is found except at low concentrations and low molar masses where the gels are weaker than predicted. At low concentrations intrachain bonding weakens the gel, while the presence of small pectin chains weakens the gel because it neutralizes binding sites on larger chains.

Effects of selective hypoglossal nerve stimulation on canine upper airway mechanics.

Electrical stimulation of the hypoglossal (XII) nerve has been demonstrated as an effective approach to treating obstructive sleep apnea. The physiological effects of conventional modes of stimulation (i.e., genioglossus activation or whole XII nerve stimulation), however, have yielded inconsistent and only partial alleviations of hypopneic or apneic events. Although selective stimulation of the multifasciculated XII nerve offers many stimulus options, it is not clear how these will functionally affect the upper airway (UAW). To study these effects, animal experiments in eight beagles were performed to investigate changes in the UAW resistance and critical pressure during simulated expiration (n = 4) and inspiration (n = 4). During expiration, nonselective XII nerve stimulation yielded the greatest improvement in UAW resistance (-0.66 +/- 0.11 cm H2O x l(-1) x min(-1)), compared with that for selective activation of the geniohyoid (-0.29 +/- 0.09 cm H2O x l(-1) x min(-1)), genioglossus (-0.31 +/- 0.12 cm H2O x l(-1) x min(-1)), and hyoglossus/styloglossus (0.37 +/- 0.06 cm H2O x l(-1) x min(-1)) muscles. For simulated inspiration, on the other hand, only whole XII nerve stimulation (-0.9 +/- 0.4 cm H2O) and coactivation of the genioglossus + hyoglossus/styloglossus muscles (-1.18 +/- 0.6 cm H2O) produced significant (P < 0.05) improvements in UAW stability (i.e., lowered critical pressure), compared with baseline (-0.52 +/- 0.32 cm H2O). The results of this study suggest that a multicontact nerve electrode can be used to achieve both UAW dilation and patency, comparable to that obtained with nonselective stimulation, by selectively activating the various branches of the XII nerve.

Chronic measurement of the stimulation selectivity of the flat interface nerve electrode.

The flat interface nerve electrode (FINE) is an attempt to improve the stimulation selectivity of extraneural electrodes. By reshaping peripheral nerves into elliptical cylinders, central fibers are moved closer to the nerve-electrode interface, and additional surface area is created for contact placement. The goals of this study were to test the hypothesis that greater nerve reshaping leads to improved selectivity and to examine the chronic recruitment properties of the FINE. Three FINEs were developed to reshape peripheral nerves to different degrees. Four electrodes of each type were implanted on the sciatic nerves of 12 cats and tested for selectivity over at least three months. There was physiologic evidence of nerve injury in two cats with the tightest cuffs, but the other animals behaved normally. All cuff types were capable of selectively activating branches of the sciatic nerve, as well as groups of fibers within branches. The electrodes that moderately reshaped the nerves demonstrated the most selectivity. Both the selectivity measurements and the recruitment curve characteristics were stable throughout the implant period. From an electrophysiological standpoint, the FINE is a viable alternative for neuroprosthetic devices. A histological analysis of the nerves is under way to evaluate the safety of the FINE.

A novel electrode array for diameter-dependent control of axonal excitability: a simulation study.

Electrical extracellular stimulation of peripheral nerve activates the large-diameter motor fibers before the small ones, a recruitment order opposite the physiological recruitment of myelinated motor fibers during voluntary muscle contraction. Current methods to solve this problem require a long-duration stimulus pulse which could lead to electrode corrosion and nerve damage. The hypothesis that the excitability of specific diameter fibers can be suppressed by reshaping the profile of extracellular potential along the axon using multiple electrodes is tested using computer simulations in two different volume conductors. Simulations in a homogenous medium with a nine-contact electrode array show that the current excitation threshold (Ith) of large diameter axons (13-17 microm) (0.6-3.0 mA) is higher than that of small-diameter axons (2-7 microm) (0.4-0.7 mA) with 200-microm axon-electrode distance and 10-micros stimulus pulse. The electrode array is also tested in a three-dimensional finite-element model of the sacral root model of dog (ventral root of S3). A single cathode activates large-diameter axons before activating small axons. However, a nine-electrode array activates 50% of small axons while recruiting only 10% of large ones and activates 90% of small axons while recruiting only 50% of large ones. The simulations suggest that the near-physiological recruitment order can be achieved with an electrode array. The diameter selectivity of the electrode array can be controlled by the electrode separation and the method is independent of pulse width.

Selective stimulation of the canine hypoglossal nerve using a multi-contact cuff electrode.

Electrical activation of the tongue protrusor muscle has been demonstrated as an effective technique for alleviating upper airway (UAW) obstructions and is considered a potential treatment for obstructive sleep apnea (OSA). Recent studies, however, have shown marked improvements in UAW patency by coactivating the tongue protrudor and retractor muscles. As such, selective stimulation of the hypoglossal nerve (XII) using a single implantable device presents an attractive approach for treating OSA. In order to demonstrate the feasibility of such a device, the maximum achievable stimulation selectivity of the Flat Interface Nerve Electrode (FINE) was investigated. The XII nerve of beagles was stimulated with an acutely implanted FINE, while the corresponding neural and muscular responses were recorded and analyzed. The overall performance of the FINE, as depicted by the average of the maximum target-specific selectivity values, S(i), confirmed that high degrees of selectivity can be achieved at both the fascicular and muscular levels: 0.93 +/- 0.03 (n = 5) and 0.88 +/- 0.03 (n = 4), respectively. The results of this study demonstrate the feasibility of the FINE for selective stimulation of the XII nerve branches and the innervated tongue muscles.

Analysis of efficiency of magnetic stimulation.

Magnetic stimulation can activate excitable tissues noninvasively. However, this method requires high energy to operate and can produce equipment heat that leads to inefficient stimulation. In this study, a comprehensive optimization of efficiency for magnetic stimulation has been conducted. A total of 16 781 coil designs were tested in order to determine the optimal coil geometry and inductance for neural excitation. Induced electric fields were calculated to find the optimal stimulation site (OSS) of a given coil. The threshold energy of a magnetic pulse for neural excitation was then calculated based on the transmembrane responses of a nerve model. Simulation results show that there exists an optimal inductance, as a consequence of an optimal pulse duration, corresponding to a minimum threshold energy. A longer pulse width is required to obtain the maximum efficiency for axons with slower membrane dynamics, a longer coil-to-fiber distance, and greater values of resistance (R) and capacitance (C) of the resistance-inductance-capacitance circuit. The optimal geometry features a minimum coil height, suggesting a flat coil design for optimal efficiency. The dimension of the optimal coil design increases with the coil-to-fiber distance. Moreover, the cloverleaf design achieves the highest efficiency for infinitely long fibers whereas the butterfly design is optimal for terminating or bending fibers.