Selective Nerve Stimulation Research Articles

Functional outcome of tongue motions with selective hypoglossal nerve stimulation in patients with obstructive sleep apnea.

Selective upper airway stimulation of the hypoglossal nerve is a novel therapy option for obstructive sleep apnea. Different tongue motions were observed after surgery during active therapy. We examined tongue motions in 14 patients (mean age 51±10years) who received an implantation of an upper airway stimulation system (Inspire Medical Systems) from September 2013 to February 2014 in three different implantation centers in Germany after surgery. Sleep recording was performed preoperatively: 2months (M02) and 6months (M06) after surgery. There were three different tongue motions observed after surgery at 1month (M01), M02, and M06 after surgery: bilateral protrusion (BP), right protrusion (RP), and mixed activation (MA). At M01: 10 BP, 2 RP, and 2 MA; at M02: 12 BP, 0 RP, and 2 MA; and at M06: 12 BP, 0 RP, and 2 MA could be detected. The average apnea-hypopnea index (AHI) was reduced from 32.5±14.2/h before surgery to 17.9±23.3/h at M02 and 14.1±19.8/h at M06. An increased reduction in AHI was found in BP and RP group (Baseline: 29.6±12.6/h; M02: 12.06±14.1/h; M06: 9.7±12.6/h) compared to the MA group (Baseline 49.6±13.8/h; M02: 49.7±5.1/h; M06: 40.5±4.1/h). These findings suggest that the postoperative tongue motions in upper airway stimulation are associated with the therapy outcome. The stimulation electrode placement on the hypoglossal nerve for selective muscle recruitment may play a role in the mechanism of action.

Effects of aging on evoked retrusive tongue actions

ObjectiveTongue strength, timing, and coordination deficits may underlie age-related swallowing function. Retrusive tongue actions are likely important in retrograde bolus transport. However, age-related changes in retrusive tongue muscle contractile properties have not been identified in animal studies. Because previous studies employed whole hypoglossal nerve stimulation that activated both protrusive and retrusive tongue muscles, co-contraction may have masked retrusive muscle force decrements. The hypotheses of this study were: (1) retrusive tongue muscle contraction forces would be diminished and temporal characteristics prolonged in old rats when lateral nerves were selectively activated, and (2) greater muscle contractile forces with selective lateral branch stimulation would be found relative to whole hypoglossal nerve stimulation. DesignNineteen Fischer 344/Brown Norway rats (9 old, 10 young adult) underwent tongue muscle contractile property recording elicited by: (1) bilateral whole hypoglossal nerve stimulation, and (2) selective lateral branch stimulation. Twitch contraction time (CT), half-decay time, maximal twitch and tetanic forces, and a fatigue index were measured. ResultsFor whole nerve stimulation, CT was significantly longer in the old group. No significant age group differences were found with selective lateral nerve stimulation. Significantly reduced twitch forces (old group only), increased tetanic forces and significantly less fatigue were found with selective lateral nerve stimulation than with whole hypoglossal stimulation. ConclusionsRetrusive tongue forces are not impaired in old rats. Deficits observed in swallowing with aging may be due to other factors such as inadequate bolus propulsive forces, mediated by protrusive tongue muscles, or timing/coordination of muscle actions.

Electrochemical performance of platinum electrodes within the multi-electrode spiral nerve cuff.

In this study, the electrochemical performance of platinum electrodes within a multi-electrode spiral cuff to be used for selective nerve stimulation was investigated. The original cuff, simplified into a half-cuff, contained a single row of nine electrodes (0.5×2mm) at a distance of 2mm from its inner surface. Cyclic voltammetry was used to investigate the electrochemical reactions at the electrode-electrolyte interface, to define a potential window within which the electrode could be safely used in selective nerve stimulation, to calculate the charge injection capacity and cathodal charge storage capacity. Voltage transients retrieved during excitation with quasitrapezoidal biphasic current pulses, tested by selective nerve stimulation of the isolated porcine left cervical vagus nerve segment, were used to determine the maximum polarization across the electrode-electrolyte interface and to calculate cathodic charge injection capacity of the electrode. The results show that the most negative and most positive potentials across the electrode-electrolyte interface reached -0.54 and 0.59V; these did not exceed the safe potential limits for water electrolysis. Furthermore, the time integral of the cathodic current by cyclic voltammetry measured over the potential range of water electrolysis, actually representing the cathodal charge storage capacity, was approximately -4mCcm(-2). The charge injection capacity, representing the maximum charge density injected in a current stimulation pulse, using only reversible processes, however, was around 75µCcm(-2). In conclusion, both, the tested stimulation pulse and electrode are suitable for efficient and safe selective nerve stimulation.

Alternative Paradigm of Selective Vagus Nerve Stimulation Tested on an Isolated Porcine Vagus Nerve

Alternative paradigm for spatial and fibre-type selective vagus nerve stimulation (VNS) was developed using realistic structural topography and tested in an isolated segment of a porcine cervical left vagus nerve (LVN). A spiral cuff (cuff) containing a matrix of ninety-nine electrodes was developed for selective VNS. A quasitrapezoidal stimulating pulse (stimulus) was applied to the LVN via an appointed group of three electrodes (triplet). The triplet and stimulus were configured to predominantly stimulate the B-fibres, minimizing stimulation of the A-fibres and by-passing the stimulation of the C-fibres. To assess which fibres made the most probable contribution to the neural response (NR) during selective VNS, the distribution of conduction velocity (CV) within the LVN was considered. Experimental testing of the paradigm showed the existence of certain parameters and waveforms of the stimulus, for which the contribution of the A-fibres to the NR was slightly reduced and that of the B-fibres was slightly enlarged. The cuff provided satisfactory fascicle discrimination in selective VNS as well as satisfactory fascicle discrimination during NR recording. However, in the present stage of development, fibre-type VNS remained rather limited.

Dual-Channel neuromodulation of pudendal nerve with closed-loop control strategy to improve bladder functions

Although sacral anterior root neuromodulation (SARN) has proven to be effective in patients with neurogenic bladder, it is not widely accepted due to the need to conduct a dorsal rhizotomy, and commercially available SARN devices are not usually equipped with a closed-loop controller for the automatic regulation of bladder functions. Therefore, there is still a need for a more effective electrical neuromodulation scheme to restore bladder function. Intravesical pressure (IVP) is the major biosignal that reflects the state of bladder conditions. The present study develops a closed-loop control strategy for improving bladder emptying and verifies its performance using animal experiments. Two channel outputs of electrical currents triggered by IVP-feedback signals were set to automatically regulate a rat's pudendal nerve for selective nerve stimulation and blocking. Under this experimental design, a series of in vivo animal experiments were conducted on anesthetized rats, including the computational characterization of biosignals, the development of an intermittent high-frequency blocking current waveform for blocking the nerve, and verification of the control strategy. Results show that the IVP-feedback control strategy for dual-channel pudendal neuromodulation performed well in animal experiments and could be utilized to selectively stimulate and block the pudendal nerve to augment bladder contraction and restore external urethral sphincter bursting activity to improve bladder emptying. This study demonstrates the feasibility of the IVP-based feedback-control strategy with animal experiments. The results could provide a basis for developing a sophisticated neural prosthesis for restoring bladder function in clinical use or for neurophysiological study.

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

α-Conotoxin AuIB is a selective α3β4 nicotinic acetylcholine receptor (nAChR) subtype inhibitor. Its analgesic properties are believed to result from it activating GABAB receptors and subsequently inhibiting CaV2.2 voltage-gated calcium channels. The structural determinants that mediate diverging AuIB activity at these targets are unknown. We performed alanine scanning mutagenesis of AuIB and α3β4 nAChR, homology modeling, and molecular dynamics simulations to identify the structural determinants of the AuIB·α3β4 nAChR interaction. Two alanine-substituted AuIB analogues, [P6A]AuIB and [F9A]AuIB, did not inhibit the α3β4 nAChR. NMR and CD spectroscopy studies demonstrated that [F9A]AuIB retains its native globular structure, so its activity loss is probably due to loss of specific toxin-receptor residue pairwise contacts. Compared with AuIB, the concentration-response curve for inhibition of α3β4 by [F9A]AuIB shifted rightward more than 10-fold, and its subtype selectivity profile changed. Homology modeling and molecular dynamics simulations suggest that Phe-9 of AuIB interacts with a two-residue binding pocket on the β4 nAChR subunit. This hypothesis was confirmed by site-directed mutagenesis of the β4-Trp-59 and β4-Lys-61 residues of loop D, which form a putative binding pocket. AuIB analogues with Phe-9 substitutions corroborated the finding of a binding pocket on the β4 subunit and gave further insight into how AuIB Phe-9 interacts with the β4 subunit. In summary, we identified critical residues that mediate interactions between AuIB and its cognate nAChR subtype. These findings might help improve the design of analgesic conopeptides that selectively "avoid" nAChR receptors while targeting receptors involved with nociception.

Selective stimulation of human tooth-pulp with a new stable method: Responses and validation

The aims of this study were to establish a safe technique for selective stimulation of nerves in human tooth-pulp during long experiments and to validate its use even with stimuli of high intensities. A custom-made veneer containing 2 silver wire-conductive cream electrodes was attached with cement to the labial surface of an upper central incisor tooth. A variety of stimulus intensities were applied, and sensory and reflex responses from jaw-closing muscles were recorded. In 15 participants, the stimuli evoked predominantly sharp or painful sensations and reflex inhibitions of activity in the jaw muscles. Stimulation of 3 non-vital teeth evoked no sensations or reflexes, even at intensities that evoked maximal reflexes in vital teeth. The electrodes had reasonably stable resistances throughout experiments lasting up to 90 min. The method described enables responses to low- or high-intensity stimulation of human pulpal nerves to be investigated in long experiments.

Experimental Validation of a Hybrid Computational Model for Selective Stimulation Using Transverse Intrafascicular Multichannel Electrodes

Recently a hybrid model based on the finite element method and on a compartmental biophysical representation of peripheral nerve fibers and intraneural electrodes was developed founded on experimental physiological and histological data. The model appeared to be robust when dealing with uncertainties in parameter selection. However, an experimental validation of the findings provided by the model is required to fully characterize the potential of this approach. The recruitment properties of selective nerve stimulation using transverse intrafascicular multichannel electrodes (TIME) were investigated in this work in experiments with rats and were compared to model predictions. Animal experiments were performed using the same stimulation protocol as in the computer simulations in order to rigorously validate the model predictions and understand its limitations. Two different selectivity indexes were used, and new indexes for measuring electrode performance are proposed. The model predictions are in decent agreement with experimental results both in terms of recruitment curves and selectivity values. Results show that these models can be used for extensive studies targeting electrode shape design, active sites shape, and multipolar stimulation paradigms. From a neurophysiological point of view, the topographic organization of the rat sciatic nerve, on which the model was based, has been confirmed.

Frequency dependent effect of selective biphasic left vagus nerve stimulation on heart rate and arterial pressure

Activation of the parasympathetic pathway leads to negative chronotropic, dromotropic, and inotropic changes of heart function. The ability to selectively stimulate certain superficial compartments of peripheral nerves has been demonstrated previously. The aim of the present study was to find a clinically acceptable selective biphasic vagus nerve stimulation technique, which could allow gradual regulation of heart rate and systemic arterial pressure. In two patients, the left vagus nerve was stimulated with a combination of quasi-trapezoidal cathodic and rectangular anodic current pulses with different stimulation frequencies (10Hz, 20Hz, 30Hz) and increasing current. The heart rate and systemic arterial pressure decreased with increasing current at all different stimulation frequencies (p<0.05). The heart rate and arterial pressure response was more gradual with 10Hz compared to 20Hz/30Hz vagus nerve stimulation (p<0.05). In conclusion, selective vagus nerve stimulation, with a combination of quasi-trapezoidal cathodic and rectangular anodic current pulses at 10Hz, offers gradual heart rate and systolic arterial pressure control.

An inverse technique for excitation design in nerve fascicle activation: a theoretical study

Position selective stimulation of nerves is an important problem in FES systems, but no systematic method exists to determine the spatio-temporal excitation current profile. In this paper, we provide a theoretical background towards solving this problem. The efficacy of the technique is investigated through Monte Carlo experiments based on simplified computer models of a nerve.

Laparoscopic implantation of neural electrodes on pelvic nerves: an experimental study on the obturator nerve in a chronic minipig model

Laparoscopic exposure of pelvic nerves has opened a new area in the field of neuromodulation. However, electrode design and material deterioration remain issues that limit clinical application. The objective of this study was to evaluate experimentally the laparoscopic implantation of different types of neural electrodes in order to achieve functional and selective electrical stimulation of pelvic nerves. This was a prospective comparative study of the laparoscopic implantation and tolerance and efficacy of three monopolar cuff electrodes implanted on the obturator nerve in ten Göttingen minipigs (18-20 months old; 14.5-24 kg body weight). Animals were allocated to two groups. A 3-mm-diameter laparoscopic instrument was used during dissection of paravesical fossa and obturator nerve on both sides in order to minimize nerve damage. In all animals, a "split-cylinder" cuff electrode was implanted around the left obturator nerve. On the right side, a "lasso" cuff electrode was implanted in the first group and a "closed-cylinder" cuff was implanted in the second group. Electrical stimulation (0-5 V, 20 Hz) was performed for implanted electrodes on days 0, 7, 15, 30, 45, 60, and 90. Current intensity thresholds were identified by palpation of muscle contraction. Strength developed according to stimulation level and was measured using weight transducers. All procedures were performed by laparoscopy. Mean operative times differed significantly among groups, the shortest being for split-cylinder electrodes (P = 0.0002). No electrical spread phenomena were observed. Initial thresholds were below 1.5 V (range = 0.5-1.3); however, a significant rise was observed, with time to a maximum of 2.7 V (P < 0.0001). Only split-cylinder electrodes remained functional after 3 months. The mean value of maximum strength remained stable during the study period (P = 0.21, NS). The laparoscopic approach to implanting neuroprostheses seems to be very attractive. Furthermore, this approach could allow highly selective nerve stimulation to be achieved using simpler devices such as split-cylinder monopolar electrodes.

Comparative analysis of transverse intrafascicular multichannel, longitudinal intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles

The selection of a suitable nerve electrode for neuroprosthetic applications implies a trade-off between invasiveness and selectivity, wherein the ultimate goal is achieving the highest selectivity for a high number of nerve fascicles by the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME) is intended to be transversally inserted into the peripheral nerve and to be useful to selectively activate subsets of axons in different fascicles within the same nerve. We present a comparative study of TIME, LIFE and multipolar cuff electrodes for the selective stimulation of small nerves. The electrodes were implanted on the rat sciatic nerve, and the activation of gastrocnemius, plantar and tibialis anterior muscles was recorded by EMG signals. Thus, the study allowed us to ascertain the selectivity of stimulation at the interfascicular and also at the intrafascicular level. The results of this study indicate that (1) intrafascicular electrodes (LIFE and TIME) provide excitation circumscribed to the implanted fascicle, whereas extraneural electrodes (cuffs) predominantly excite nerve fascicles located superficially; (2) the minimum threshold for muscle activation with TIME and LIFE was significantly lower than with cuff electrodes; (3) TIME allowed us to selectively activate the three tested muscles when stimulating through different active sites of one device, both at inter- and intrafascicular levels, whereas selective activation using multipolar cuff (with a longitudinal tripolar stimulation configuration) was only possible for two muscles, at the interfascicular level, and LIFE did not activate selectively more than one muscle in the implanted nerve fascicle.

Somatic innervation of the feline lower urinary tract

Electrical stimulation of pudendal nerve sensory pathways can evoke excitatory bladder reflexes. However, the precise peripheral innervation pattern of these somatic fibers remains unclear. In adult male cats, we investigated pudendal nerve innervation of the lower urinary tract (LUT) by employing anatomical (Sihler's stain) and electrophysiological (selective electrical nerve stimulation) techniques. The stained specimens revealed differential innervation of the proximal and distal urethrae by fibers derived from the sensory branch of the pudendal nerve. Cranial sensory branch fibers penetrated the prostate to terminate along the intraluminal surface of the urethra, whereas the dorsal nerve of the penis primarily innervated the glans penis. Further examination of the proximal urethra showed a separate pathway (deep perineal nerve) that inserted directly into the external urethral sphincter. These observations were confirmed electrophysiologically by the measured urethral sphincter activity evoked in response to selective nerve stimulation. Electrical activation of the sensory pathway evoked only reflex (latency = 8.9 ± 1.1 ms) contractions of the urethral muscle, whereas stimulation of the perineal pathway elicited direct (latency = 1.3 ± 0.1 ms) responses. Our findings identify specific pudendal nerve sensory pathways that can be used potentially to restore bladder function in persons with spinal cord injury and also treat LUT symptoms such as urinary retention.

Selective Stimulation of Autonomic Nerves and Recording of Electroneurograms in a Canine Model

The article presents the results of modeling, design, and experimental testing of a multielectrode spiral cuff (CUFF) to determine to what extent a CUFF could be used for selective stimulation of different types of nerve fibers within particular compartments and for selective recording of electoneurograms (ENGs) from particular compartments of the peripheral autonomic nerve. The CUFF was implanted on the left cervical vagus nerve (LVN) of a dog. The relative positions of the particular nerve regions that innervated the cardiovascular (CV) and respiratory system (RS) were identified by delivering the stimuli to the particular group of three electrodes (GTE). The stimuli caused both selective stimulation of mainly B fibers within the particular compartments, and differential block of A fibers by membrane hyperpolarization. It was shown that when the stimuli were delivered to GTE9, the heart rate began to fall and when the stimuli were delivered to GTE4, the rate of breathing decreased. The defined and randomly chosen GTEs were used also as recording GTEs while CV or RS were stimulated by carotid artery massage, epinephrine injection, and noninvasive positive end-expiratory pressure ventilation (NIPEEPV). Results demonstrate that the function of a particular internal organ can be modulated via the selective stimulation of the innervating compartment of the peripheral nerve. Results also showed that stimulations elicited site-specific changes in ENG power spectra recorded from the particular compartments of the LVN.

Pulsed laser versus electrical energy for peripheral nerve stimulation

Transient optical neural stimulation has previously been shown to elicit highly controlled, artifact-free potentials within the nervous system in a non-contact fashion without resulting in damage to tissue. This paper presents the physiologic validity of elicited nerve and muscle potentials from pulsed laser induced stimulation of the peripheral nerve in a comparative study with the standard method of electrically evoked potentials. Herein, the fundamental physical properties underlying the two techniques are contrasted. Key laser parameters for efficient optical stimulation of the peripheral nerve are detailed. Strength response curves are shown to be linear for each stimulation modality, although fewer axons can be recruited with optically evoked potentials. Results compare the relative transient energy requirements for stimulation using each technique and demonstrate that optical methods result in highly selective functional nerve stimulation. Adjacent stimulation and recording of compound nerve potentials in their entirety from optical and electrical stimulation are presented, with optical responses shown to be free of any stimulation artifact. Thus, use of a pulsed laser exhibits distinct advantages when compared to standard electrical means for excitation of muscle potentials in the peripheral nerve in the research domain and possibly for clinical diagnostics in the future.

Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor

Pain therapeutics discovered by molecular mining of the expressed genome of Australian predatory cone snails are providing lead compounds for the treatment of neurological diseases such as multiple sclerosis, shingles, diabetic neuropathy and other painful neurological conditions. The high specificity exhibited by these novel compounds for neuronal receptors and ion channels in the brain and nervous system indicates the high degree of selectivity that this class of neuropeptides can be expected to show when used therapeutically in humans. A lead compound, ACV1 (conotoxin Vc1.1 from Conus victoriae), has entered Phase II clinical trials and is being developed for the treatment for neuropathic pain. ACV1 will be targeted initially for the treatment of sciatica, shingles and diabetic neuropathy. The compound is a 16 amino acid peptide [Sandall et al., 2003. A novel α-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo. Biochemistry 42, 6904–6911], an antagonist of neuronal nicotinic acetylcholine receptors. It has potent analgesic activity following subcutaneous or intramuscular administration in several preclinical animal models of human neuropathic pain [Satkunanathan et al., 2005. Alpha conotoxin Vc1.1 alleviates neuropathic pain and accelerates functional recovery of injured neurons. Brain. Res. 1059, 149–158]. ACV1 may act as an analgesic by decreasing ectopic excitation in sensory nerves. In addition ACV1 appears to accelerate the recovery of injured nerves and tissues.

Polymer-Based Implantable Electrodes: State of the Art and Future Prospects

ABSTRACTElectrical interfaces between technical system and the biological system differs with respect to material and shape depending on their intended application. Although there are different approaches using silicon as basic material for sieve or needle like electrodes interfacing the nerve tissue. This abstract will focus on polymer-based flexible implantable electrodes.Mechanical interaction between the electrode and tender nerve tissues can induce adverse body reaction such as fibrous tissue encapsulation. Using flexible materials to design the electro-biological interface might reduce this effect. Different designs of such flexible electrodes were proposed for contacting the nerve or as platform for sensors. For example, Cuff like electrodes can be elastically wrapped around the nerve for recording or stimulation of neural signals. Using microtechnology for the structuring of polymer substrates new fiber like electrodes with multiple electrode sites were developed that can be sewed into the nerve. Thereby the possibility of selective nerve recording and stimulation was improved. One major problem of these tiny and flexible electrodes is the connection to recording and stimulation system. Incorporating electronics such as multiplexer or amplifier directly on the flexible substrate could reduce the number of connection lines or improve the sensor capabilities. Further, the integration of flexible organic electronics on the implant allows the design of more flexible and intelligent electrodes. Additionally the electrodes and sensors can be designed using conductive polymers to create a new generation of “All Polymer” active implants. Not only the chemical and mechanical properties of the materials employed can influence the biocompatibility of an implant but also the surface topography in the nanometer range plays a key role such as the growth of cells on the implants. Selective adhesion of different type of cells to different parts of the implant is a challenge for the interdisciplinary research. Finally the combination of surface nanostructuring, for example the interference laser beam structuring, and organic electronics with microstructured polymer implants offers interesting potentials for new active implants of the next decades

Fascicular anatomy and surgical access of the human pudendal nerve

The ability to access selectively distal nerve branches at the level of the compound pudendal nerve (PN) would allow control of multiple neural pathways and genitourinary functions at a single location. Nerve cuff electrodes can selectively stimulate individual fascicles; however the PN fascicular anatomy is unknown. The fascicular representation of distal branches was identified and traced proximally to create fascicle maps of 12 compound PNs in seven cadavers. Distal nerves were represented as groups of individual fascicles in the PN. Fascicle maps were consistent between specimens and along the PN within specimens. PN branch free length was 26+/-7.7 mm. PN cross-sections were relatively flat with major and minor diameters of 4.3+/-0.90 and 1.7+/-0.45 mm, respectively. Placing a nerve cuff on the PN is anatomically and surgically feasible. The PN fascicular anatomy, branch free length, and cross-section geometry are conducive to selective stimulation of distal nerves with a single nerve cuff electrode.

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° and 60°), 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.

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.