[New therapy for sleep apnea at CHUV: hypoglossal nerve stimulation]. / Nouvelle thérapie de l'apnée du sommeil au CHUV: le neurostimulateur du nerf hypoglosse.

Neurostimulation of the hypoglossal nerve is a new alternative treatment to CPAP (Continuous Positive Airway Pressure) for patients with moderate-to-severe OSAS (Obstructive Sleep Apnea Syndrome) with anteroposterior pharyngeal obstruction visualized during a Drug Induced Sleep Endoscopy (DISE). Implantation and follow-up are performed at the CHUV with the collaboration between the SAOS-ronchopathie unit, the maxillofacial and dental surgery division and the center for investigation and research on sleep (CIRS). In this article, we present the technique, its indication and the outcomes through a recent review of the literature. This new device has been used for five years, mainly in the United States and Europe.

La neurostimulation du nerf hypoglosse est un nouveau traitement alternatif à la CPAP (Continuous Positive Airway Pressure: ventilation en pression positive continue) pour les patients présentant un SAOS (syndrome d'apnées obstructives du sommeil) de stade modéré à sévère avec une obstruction pharyngée antéro-postérieure, objectivée lors d'un examen endoscopique en sommeil induit (DISE). L'implantation du dispositif et le suivi sont réalisés au CHUV grâce à une étroite collaboration entre l'Unité SAOS-ronchopathie, la division de chirurgie maxillo-faciale et dentaire et le Centre d'investigation et de recherche sur le sommeil (CIRS). Dans cet article, nous présentons la technique, ses indications ainsi que les résultats à travers une revue de la littérature récente sur cette technologie qui est pratiquée depuis maintenant cinq ans, principalement aux Etats-Unis et en Europe.

Microsurgical Anatomy of the Terminal Hypoglossal Nerve Relevant for Neurostimulation in Obstructive Sleep Apnea.

BACKGROUND: Neurostimulation of the hypoglossal nerve has shown promising results in the treatment of obstructive sleep apnea. This anatomic study describes the detailed topography of the hypoglossal nerve's motor points as a premise for super-selective neurostimulation in order to optimize results and minimize the risk of complications related to main nerve trunk manipulation. METHODS: Thirty cadaveric hypoglossal nerves were dissected and characterized by number of branches, arborization pattern, and terminal branch motor point location. For each motor point, the distance to cervical midline (x axis), distance to posterior aspect of the symphysis (y axis), and depth from the plane formed by the inferior border of symphysis and anterior border of hyoid (z axis) were recorded. RESULTS: The average number of distal branches for each hypoglossal nerve was found to be 9.95 ± 2.28. The average number of branches per muscle was found to be 3.3 ± 1.5 for the hyoglossus muscle, 1.8 ± 0.9 for the geniohyoid muscle, and 5.0 ± 1.6 for the genioglossus muscle. It was found that branches to the genioglossus and geniohyoid muscles were located closer to midline (relative lengths of 0.19 ± 0.07 and 0.19 ± 0.05, respectively) while hyoglossus branches were located more laterally (0.38 ± 0.10 relative length). On the y-axis, the branches to the genioglossus were the most anterior and therefore closest to the posterior symphysis of the mandible (relative length of 0.48 ± 0.11), followed by the geniohyoid (0.66 ± 0.09), and the hyoglossus (0.76 ± 0.16). The branches to the geniohyoid were the most superficial (relative length of 0.26 ± 0.06), followed by the genioglossus (0.36 ± 0.09), and finally, the hyoglossus branches (0.47 ± 0.11), which were located deeply. CONCLUSION: A topographical map of the hypoglossal nerve terminal motor points was successfully created and could provide a framework for the optimization of the neurostimulation techniques.

Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation.

STUDY OBJECTIVES: The major goal of the study was to determine whether changes in tongue morphology under selective hypoglossal nerve therapy for obstructive sleep apnea were associated with alterations in airway patency during sleep when specific portions of the hypoglossal nerve were stimulated. METHODS: This case series was conducted at the Johns Hopkins Sleep Disorders Center at Johns Hopkins Bayview Medical Center. Twelve patients with apnea implanted with a multichannel targeted hypoglossal nerve-stimulating system underwent midsagittal ultrasound tongue imaging during wakefulness. Changes in tongue shape were characterized by measuring the vertical height and polar dimensions between tongue surface and genioglossi origin in the mandible. Changes in patency were characterized by comparing airflow responses between stimulated and adjacent unstimulated breaths during non-rapid eye movement sleep. RESULTS: Two distinct morphologic responses were observed. Anterior tongue base and hyoid-bone movement (5.4 [0.4] to 4.1 [1.0] cm (median and [interquartile range]) with concomitant increases in tongue height (5.0 [0.9] to 5.6 [0.7] cm) were associated with decreases in airflow during stimulation. In contrast, comparable anterior hyoid movement (tongue protrusion from 5.8 [0.5] to 4.5 [0.9] cm) without significant increases in height (5.2 [1.6] to 4.6 [0.8] cm) were associated with marked increases in airflow during sleep. CONCLUSIONS: Tongue protrusion with preservation of tongue shape predicted increases in patency, whereas anterior movement with concomitant increases in height were associated with decreased pharyngeal patency. These findings suggest that pharyngeal patency can be best stabilized by stimulating lingual muscles that maintain tongue shape while protruding the tongue, thereby preventing it from prolapsing posteriorly during sleep. CITATION: Fleury Curado T, Pham L, Otvos T, et al. Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation. J Clin Sleep Med. 2023;19(5):947-955.

Personalized multimodal management for severe obstructive sleep apnea in a patient intolerant of positive airway pressure with hypoglossal nerve stimulator and mandibular advancement device.

Treatment of moderate to severe obstructive sleep apnea poses clinical challenges in persons with intolerance or inadequate response to traditional treatment modalities, including positive airway pressure and mandibular advancement devices. Hypoglossal nerve stimulation is a new treatment option, but few management guidelines exist when it is intolerable or ineffective. Combining several treatment modalities has been an effective strategy for improving symptoms, tolerance, and efficacy. We describe a patient intolerant to positive airway pressure therapy who had continued sleepiness, morning headaches, and snoring with a mandibular advancement device. He underwent hypoglossal nerve stimulation implantation but was intolerant of the voltages required to adequately control his obstructive sleep apnea. Multimodal management with hypoglossal nerve stimulation, mandibular advancement device, and positional therapy was successfully implemented to improve sleepiness, nocturnal symptoms, and the apnea-hypopnea index. This case highlights the personalization and adaptability of combination therapy to suit patient needs while effectively controlling obstructive sleep apnea. CITATION: Lowery MM, Rundo JV, Walia HK, Shah V. Personalized multimodal management for severe obstructive sleep apnea in a patient intolerant of positive airway pressure with hypoglossal nerve stimulator and mandibular advancement device. J Clin Sleep Med. 2023;19(2):403-408.

Obstructive Sleep Apnea: Non-positive Airway Pressure Treatments.

Undiagnosed and untreated obstructive sleep apnea (OSA) is associated with health comorbidities and negatively affects quality of life. Alternative treatments should be considered in patients who are unable to tolerate or benefit from positive airway pressure treatment. When properly indicated, positional devices, oral appliances, airway surgery, and hypoglossal nerve stimulation have been shown to be effective in treating OSA. Hypoglossal nerve stimulation is a successful second-line treatment with low associated morbidity and complication rate.

Responses evoked by electrical stimulation of the brainstem reticular formation in the jaw-opening and hypoglossal motor nerves of an arterially perfused rat preparation.

The interneuronal system in the brainstem reticular formation plays an important role in elaborate muscle coordination during various orofacial motor behaviors. In this study, we examined the distribution in the brainstem reticular formation of the sites that induce monosynaptic motor activity in the mylohyoid (jaw-opening) and hypoglossal nerves using an arterially perfused rat preparation. Electrical stimulation applied to 286 and 247 of the 309 sites in the brainstem evoked neural activity in the mylohyoid and hypoglossal nerves, respectively. The mean latency of the first component in the mylohyoid nerve response was significantly shorter than that in the hypoglossal nerve response. Moreover, the latency histogram of the first component in the hypoglossal nerve responses was bimodal, which was separated by 4.0 ms. The sites that induced short-latency (<4.0 ms) motor activity in the mylohyoid nerve and the hypoglossal nerve were frequently distributed in the rostral portion and the caudal portion of the brainstem reticular formation, respectively. Such difference in distributions of short-latency sites for mylohyoid and hypoglossal nerve responses likely corresponds to the distribution of excitatory premotor neurons targeting mylohyoid and hypoglossal motoneurons.

Interacting effects of genioglossus stimulation and mandibular advancement in sleep apnea.

Both mandibular advancement (MA) and stimulation of the genioglossus (GG) have been shown to improve upper airway patency, but neither one achieves the effect of continuous positive airway pressure (CPAP) treatment. In the present study we assessed the combined effect of MA and GG stimulation on the relaxed pharynx in patients with obstructive sleep apnea (OSA). We evaluated responses of upper airway pressure-flow relationships and endoscopically determined pharyngeal cross-sectional area to MA and electrical stimulation of the GG in 14 propofol-anesthetized OSA patients. Measurements were undertaken at multiple levels of CPAP, enabling calculation of the critical closing pressure (Pcrit), upstream resistance (Rus), and pharyngeal compliance. GG stimulation, MA, and the combination of both shifted the pressure:flow relationships toward higher flow levels, resulting in progressively lower Pcrit (from baseline of 2.9 +/- 2.2 to 0.9 +/- 2.5, -1.4 +/- 2.9, and -4.2 +/- 3.3 cmH(2)O, respectively), without significant change in Rus. DeltaPcrit during GG stimulation was significantly larger during MA than under baseline conditions (-2.8 +/- 1.4 vs. -2.0 +/- 1.4 cmH(2)O, P = 0.011). Combining the effect of GG stimulation with MA lowered Pcrit below 0 in all patients and restored pharyngeal patency to a level that enabled flow above the hypopnea level in 10/14 of the patients. Velopharyngeal compliance was not affected by either manipulation. We conclude that the combined effect of MA and GG stimulation is additive and may act in synergy, preventing substantial flow limitation of the relaxed pharynx in most OSA patients.

Cortical control of appropriate tongue protrusion during licking in cats--increase in regional cerebral blood flow (rCBF) of the contralateral area P and in tongue protrusion after the unilateral area P lesion.

Adequate tongue protrusion may be regulated by cat bilateral area P (the motor cortex for jaw and tongue movements) (Hiraba and Sato, Somatosens Mot Res 2005b;22:183-192). The ICMS (intracortical microstimulation) in the unilateral area P evoked motor effects of tongue protrusion without deviation (Hiraba and Sato, Somatosens Mot Res 2004;23:1-12), and cats with the unilateral lesion of area P showed abnormal tongue protrusion without deviation during licking (Hiraba and Sato, Somatosens Mot Res 2005b;22:183-192). Further, the measurements of the regional cerebral blood flow (rCBF) in the bilateral jaw and tongue motor cortical areas were shown to have the same activity rate during the lateral licking (Hiraba and Sato, Somatosens Mot Res 2005c;22:307-317). We assumed from these results that cortical control for tongue protrusion was executed by networks between the bilateral area P including inhibitory interneurons. We prepared the measurable cats of the rCBF in the contralateral side after the unilateral area P lesion. Changes in the rates of rCBF and tongue protrusion during licking were examined over a long time course of about 1-2 months after the unilateral area P lesion. All cats after the unilateral area P lesion showed increased rate (double or triple in comparison with the normal ones) of rCBF of the contralateral area P in the early (0-20 days) phase. On the other hand, increased rates of tongue protrusion were about 120% in the early phase, and about 180% in the middle (21-35 days) and late (36-last days) phases. The results support the organization of networks between bilateral area P including the inhibitory interneurons.

Carbon fiber on polyimide ultra-microelectrodes.

OBJECTIVE: Most preparations for making neural recordings degrade over time and eventually fail due to insertion trauma and reactive tissue response. The magnitudes of these responses are thought to be related to the electrode size (specifically, the cross-sectional area), the relative stiffness of the electrode, and the degree of tissue tolerance for the material. Flexible carbon fiber ultra-microelectrodes have a much smaller cross-section than traditional electrodes and low tissue reactivity, and thus may enable improved longevity of neural recordings in the central and peripheral nervous systems. Only two carbon fiber array designs have been described previously, each with limited channel densities due to limitations of the fabrication processes or interconnect strategies. Here, we describe a method for assembling carbon fiber electrodes on a flexible polyimide substrate that is expected to facilitate the construction of high-density recording and stimulating arrays. APPROACH: Individual carbon fibers were aligned using an alignment tool that was 3D-printed with sub-micron resolution using direct laser writing. Indium deposition on the carbon fibers, followed by low-temperature microsoldering, provided a robust and reliable method of electrical connection to the polyimide interconnect. MAIN RESULTS: Spontaneous multiunit activity and stimulation-evoked compound responses with SNR >10 and >120, respectively, were recorded from a small (125 µm) peripheral nerve. We also improved the typically poor charge injection capacity of small diameter carbon fibers by electrodepositing 100 nm-thick iridium oxide films, making the carbon fiber arrays usable for electrical stimulation as well as recording. SIGNIFICANCE: Our innovations in fabrication technique pave the way for further miniaturization of carbon fiber ultra-microelectrode arrays. We believe these advances to be key steps to enable a shift from labor intensive, manual assembly to a more automated manufacturing process.

Anatomic predictors of response and mechanism of action of upper airway stimulation therapy in patients with obstructive sleep apnea.

Study Objectives: Upper airway stimulation has been shown to be an effective treatment for some patients with obstructive sleep apnea. However, the mechanism by which hypoglossal nerve stimulation increases upper airway caliber is not clear. Therefore, the objective of this study was to identify the mechanism of action of upper airway stimulation. We hypothesized that, with upper airway stimulation, responders would show greater airway opening in the retroglossal (base of the tongue) region, greater hyoid movement toward the mandible, and greater anterior motion in the posterior, inferior region of the tongue compared with nonresponders. Methods: Seven participants with obstructive sleep apnea who had been successfully treated with upper airway stimulation (responders) and six participants who were not successfully treated (nonresponders) underwent computed tomography imaging during wakefulness with and without hypoglossal nerve stimulation. Responders reduced their apnea-hypopnea index (AHI) by 22.63 ± 6.54 events per hour, whereas nonresponders had no change in their AHI (0.17 ± 14.04 events per hour). We examined differences in upper airway caliber, the volume of the upper airway soft tissue structures, craniofacial relationships, and centroid tongue and soft palate movement between responders and nonresponders with and without hypoglossal nerve stimulation. Results: Our data indicate that compared with nonresponders, responders had a smaller baseline soft palate volume and, with stimulation, had (1) a greater increase in retroglossal airway size; (2) increased shortening of the mandible-hyoid distance; and (3) greater anterior displacement of the tongue. Conclusions: These results suggest that smaller soft palate volumes at baseline and greater tongue movement anteriorly with stimulation improve the response to upper airway stimulation.

Effect of galanin on substance P- and vasoactive intestinal polypeptide-induced nociceptive trigemino-hypoglossal reflex in rats.

Substance P (SP), vasoactive intestinal polypeptide (VIP) and galanin (GAL), present in primary sensory neurons, are involved in transmission of nociceptive signaling from the peripheral to central nervous system. In this study we investigated the effect of GAL on SP-induced or VIP-induced evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during perfusion of the cerebral ventricles with SP or VIP solutions. The experiments were carried out on rats under chloralose anesthesia. It was shown that both, SP and VIP, perfused through the cerebral ventricles enhanced the ETJ amplitude as compared with control, but the effect produced by SP was stronger. The intracerebroventricular perfusion of GAL 5 minutes before SP caused a dose-dependent inhibition of SP-induced ETJ, whereas GAL perfused through the cerebral ventricles 5 minutes before VIP did not reduce the excitatory effect of VIP on ETJ. These results indicate that the antinociceptive effect of GAL perfused through the cerebral ventricles, tested on the trigemino-hypoglossal reflex in rats, is specifically mediated by the SP-ergic system.

In Vivo Evaluation of the Mechanical and Viscoelastic Properties of the Rat Tongue.

The tongue is a highly innervated and vascularized muscle hydrostat on the floor of the mouth of most vertebrates. Its primary functions include supporting mastication and deglutition, as well as taste-sensing and phonetics. Accordingly, the strength and volume of the tongue can impact the ability of vertebrates to accomplish basic activities such as feeding, communicating, and breathing. Human patients with sleep apnea have enlarged tongues, characterized by reduced muscle tone and increased intramuscular fat that can be visualized and quantified by magnetic resonance imaging (MRI). The abilities to measure force generation and viscoelastic properties of the tongue constitute important tools for obtaining functional information to correlate with imaging data. Here, we present techniques for measuring tongue force production in anesthetized Zucker rats via electrical stimulation of the hypoglossal nerves and for determining the viscoelastic properties of the tongue by applying passive Lissajous force/deformation curves.

Coordinated control of the tongue during suckling-like activity and respiration.

The tongue can move freely and is important in oral motor functions. Tongue movement must be coordinated with movement of the hyoid, mandible, and pharyngeal wall, to which it is attached. Our previous study using isolated brainstem-spinal cord preparations showed that application of N-methyl-D-aspartate induces rhythmic activity in the hypoglossal nerve that is coincident with rhythmic activity in the ipsilateral trigeminal motor nerve. Partial or complete midline transection of the preparation only abolishes activity in the trigeminal motor nerve; therefore, the neuronal network contributing to coordinated activity of the jaw/tongue muscles is located on both sides of the preparation and sends motor commands to contralateral trigeminal motoneurons. Arterially perfused decerebrate rat preparations exhibit stable inspiratory activity in the phrenic nerve, with efferent nerves innervating the upper airway muscles (the hypoglossal nerve, a branch of the cervical spinal nerve, the external branch of the superior laryngeal nerve, and the recurrent laryngeal nerve) under normocapnic conditions (5% CO2). During hypercapnia (8% CO2), pre-inspiratory discharges appear in all nerves innervating upper airway muscles. Such coordinated activity in the pre-inspiratory phase contributes to dilation of the upper airway and improves hypercapnia.

Nerve cuff electrode using embedded magnets and its application to hypoglossal nerve stimulation.

OBJECTIVE: A novel nerve cuff electrode with embedded magnets was fabricated and developed. In this study, a pair of magnets was fully embedded and encapsulated in a liquid crystal polymer (LCP) substrate to utilize magnetic force in order to replace the conventional installing techniques of cuff electrodes. In vitro and in vivo experiments were conducted to evaluate the feasibility of the magnet-embedded nerve cuff electrode (MENCE). Lastly, several issues pertaining to the MENCE such as the cuff-to-nerve diameter ratio, the force of the magnets, and possible concerns were discussed in the discussion section. APPROACH: Electrochemical impedance spectrum and cyclic voltammetry assessments were conducted to measure the impedance and charge storage capacity of the cathodal phase (CSCc). The MENCE was installed onto the hypoglossal nerve (HN) of a rabbit and the movement of the genioglossus was recorded through C-arm fluoroscopy while the HN was stimulated by a pulsed current. MAIN RESULTS: The measured impedance was 0.638 âˆ  -67.8° kΩ at 1 kHz and 5.27 âˆ  -82.1° kΩ at 100 Hz. The average values of access resistance and cut-off frequency were 0.145 kΩ and 3.98 kHz, respectively. The CSCc of the electrode was measured as 1.69 mC cm-2 at the scan rate of 1 mV s-1. The movement of the genioglossus contraction was observed under a pulsed current with an amplitude level of 0.106 mA, a rate of 0.635 kHz, and a duration of 0.375 ms applied through the MENCE. SIGNIFICANCE: A few methods to close and secure cuff electrodes have been researched, but they are associated with several drawbacks. To overcome these, we used magnetic force as a closing method of the cuff electrode. The MENCE can be precisely installed on a target nerve without any surgical techniques such as suturing or molding. Furthermore, it is convenient to remove the installed MENCE because it requires little force to detach one magnet from the other, enabling repeatable installation and removal. We anticipate that the MENCE will become a very useful tool given its unique properties as a cuff electrode for neural engineering.

Zirconia to Ti-6Al-4V braze joint for implantable biomedical device.

A strong, hermetic, reliable, and biocompatible ceramic-to-metal seal is essential for many implantable medical devices. Yttria-stabilized tetragonal zirconia polycrystals (Y-TZPs) and a titanium alloy Ti-6Al-4V were selected as the ceramic and metal components of the seal because both materials have excellent mechanical properties and favorable biocompatibility. A brazing method using titanium nickel (TiNi)-clad braze filler material is presented to bond the components together forming a seal. Laboratory tests show that the ceramic-to-metal seal is hermetic, strong, and resistant to electrochemical corrosion. Twenty-eight microstimulators utilizing the ceramic-to-metal seals were implanted in seven sheep to stimulate the hypoglossal nerve. When the tissue was evaluated by gross inspection at necropsy and examined histologically by a pathologist, there were no signs of local hemorrhage, infection, or hypoglossal nerve tissue damage.

Excitation of hypoglossal motoneurons responsible for tongue protrusions is associated with palatally induced jaw-closing reflex.

The excitation of hypoglossal motoneurons innervating the genioglossus and geniohyoid muscles during transient jaw closing, the so-called jaw-closing reflex, was studied in cats. The application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex, and it was found that mechanosensory inputs from the posterior palatal mucosa sent excitatory synaptic inputs to both genioglossus and geniohyoid motoneurons. We demonstrated that, during the palatally induced jaw-closing reflex, the tongue extended at jaw closure and was still extended forward in the initial part of the opening phase. In five of 27 genioglossus motoneurons and nine of 23 geniohyoid motoneurons, the onset of burst was elicited before the onset of jaw closure. The remaining cells produced the onset of burst in the closing phase and in the initial part of the occlusal phase. However, the onset of excitatory postsynaptic potentials was 75-180 ms (n=20), earlier than that of jaw closure. During the jaw-closing reflex, the genioglossus and geniohyoid motoneurons were excited during the same phase of jaw movements and there was no difference in the onset of firing between the genioglossus and geniohyoid motoneurons. It is concluded that the excitation of the genioglossus and geniohyoid motoneurons may be associated with tongue protrusions during the palatally induced jaw-closing reflex.

Inhibition of styloglossus motoneurons during the palatally induced jaw-closing reflex.

The inhibition of hypoglossal motoneurons innervating the styloglossus muscle during transient jaw closing, the so-called jaw-closing reflex, was studied in cats. The application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex and inhibitory postsynaptic potentials in the styloglossus motoneurons, indicating that mechanosensory inputs from the posterior palatal mucosa sent inhibitory synaptic inputs to styloglossus motoneurons. We also demonstrated that, during the palatally induced jaw-closing reflex, the tongue extended at jaw closure and was still extended forward in the initial part of the opening phase. In all of 22 styloglossus motoneurons studied, the depression of firing was elicited after the onset of jaw closure. In 14 of 22 styloglossus motoneurons, the depression of firing was elicited in the closing phase, and in the remaining cells it was elicited in the occlusal phase. By increasing the intracellular concentration of chloride ions, the inhibitory postsynaptic potential elicited in the styloglossus motoneuron converted to a depolarizing potential. It is concluded that the inhibition of styloglossus motoneurons may be involved in the maintenance of tongue protrusions during the palatally induced jaw-closing reflex, and that inhibitory postsynaptic potentials evoked in the styloglossus motoneurons are partly due to a chloride-dependent inhibitory postsynaptic potential.

Trigeminal orosensation and ingestive behavior in the rat.

A deafferentation procedure was used to examine the contributions of trigeminal orosensation to the control of ingestive behavior in the rat. The procedure removed somatosensory input from the mouth, sparing olfaction, lingual taste, and vibrissae inputs as well as proprioceptive afferents from and efferents to the jaw muscles. Rats with sections of tongue or jaw muscle efferents served as oromotor controls. Bilateral trigeminal orosensory deafferentation was followed by an array of effects on ingestive behavior whose magnitudes were proportional to the extent of the deafferentation. The "trigeminal syndrome" includes a disruption of food and water intake (aphagia, adipsia), impairments in the sensorimotor control of eating and drinking, decreased responsiveness to food and water, and a reduction in the level of body weight regulation. Trigeminal deafferentation spared elementary ingestive movement patterns (biting, licking, chewing) but disrupted their control by the perioral stimuli, which normally elicit them, so that eating and drinking sequences were either aborted or inefficient. Deficits in food intake varied with the sensory properties of the diet. Recovery of intake took place along a palatability gradient, and recovery of water intake paralleled that of dry food. The chronically reduced body weight was caused by a persistent hypophagia and reflects reduced responsiveness to food. These findings suggest a considerable degree of overlap in the neural mechanisms mediating the sensorimotor and motivational control of intake in the rat.

MRI study of pharyngeal airway changes during stimulation of the hypoglossal nerve branches in rats.

The medial branch (Med) of the hypoglossal nerve innervates the tongue protrudor muscles, whereas the lateral branch (Lat) innervates tongue retractor muscles. Our previous finding that pharyngeal airflow increased during either selective Med stimulation or whole hypoglossal nerve (WHL) stimulation (coactivation of protrudor and retractor muscles) led us to examine how WHL, Med, or Lat stimulation affected tongue movements and nasopharyngeal (NP) and oropharyngeal (OP) airway volume. Electrical stimulation of either WHL, Med, or Lat nerves was performed in anesthetized, tracheotomized rats while magnetic resonance images of the NP and OP were acquired (slice thickness 0.5 mm, in-plane resolution 0.25 mm). NP and OP volume was greater during WHL and Med stimulation vs. no stimulation (P < 0.05). Ventral tongue depression (measured in the midsagittal images) and OP volume were greater during Med stimulation than during WHL stimulation (P < 0.05). Lat stimulation did not alter NP volume (P = 0.39). Our finding that either WHL or Med stimulation dilates the NP and OP airways sheds new light on the control of pharyngeal airway caliber by extrinsic tongue muscles and may lead to new treatments for patients with obstructive sleep apnea.

Synaptic bases of cortically-induced rhythmical hypoglossal motoneuronal activity in the cat.

Intracellular recordings were made from hypoglossal motoneurons during cortically-induced fictive mastication in paralyzed encéphale isolé cats. Repetitive stimulation of the masticatory area of the cerebral cortex induced rhythmical tongue movements coordinated with jaw movements. After the animal was immobilized, the cortical stimulation still induced rhythmical burst activity in the hypoglossal nerve and the digastric nerve. The burst activities in the medial and lateral branches of the hypoglossal nerve alternated rhythmically, and were in and out of phase with the burst activities of the digastric nerve, respectively. All hypoglossal motoneurons showed rhythmical intracellular potentials during repetitive cortical stimulation. The rhythmical depolarizing potentials superimposed by spike bursts appeared in phase with rhythmical bursts in either the lateral or medial branch of the hypoglossal nerve. No hyperpolarization was present between consecutive depolarizing potentials. Synaptic activation noise increased coincidentally with the depolarizing potential, indicating that EPSPs were involved in the generation of the depolarizing potential. No evidence was obtained for the existence of IPSPs during the inter-depolarizing phase by intracellular current injection. It was concluded that rhythmical bombardment of excitatory impulses to hypoglossal motoneurons was responsible for the rhythmical activity induced by repetitive stimulation of the cortical masticatory area.