Review Article
Tongue Anatomy and Physiology, the Scientific Basis for a Novel Targeted Neurostimulation System Designed for the Treatment of Obstructive Sleep Apnea

https://doi.org/10.1111/j.1525-1403.2012.00514.xGet rights and content

Introduction

Obstructive sleep apnea (OSA) is a chronic condition that affects millions adults. The effective standard treatment is positive airway pressure (PAP). However, approximately half of the patients that are prescribed PAP are unable or unwilling to comply with this therapy. Untreated OSA ultimately leads to very serious comorbidities. An alternative therapy for this patient population, therefore, is desirable. Hypoglossal nerve (HGN) stimulation is under investigation by multiple groups as a possible alternative therapy for OSA.

Objective

To understand the underlying mechanisms of actions related to HGN stimulation, and the implication of this knowledge for specifying and designing a neurostimulation system for the treatment of OSA.

Results

Loss of lingual and pharyngeal tone within a narrow airway is the primary mechanism for OSA. Posterior and anterior tongues are different in their anatomy and physiology. Muscle fibers in the posterior tongue are predominantly fatigue resistant that are responsible for the long sustained tonic activities required for maintaining the tongue’s position and preventing its mass from falling into the retroglossal airway. The human tongue is a muscular hydrostat and hence would benefit from a sophisticated HGN stimulation system that is capable of achieving a concerted spatio-temporal interplay of multiple lingual muscles, including retrusors.

Conclusion

Targeted neurostimulation of the proximal HGN presents as a viable system approach that is far more versatile and physiologic and quite different than prior systems.

Section snippets

INTRODUCTION

Obstructive sleep apnea (OSA) is a common disorder that affects over 6% adults (1) with very serious consequences (comorbidities) (2). It is characterized by repetitive episodes of obstructions of the upper airway, causing decline in blood oxygen, and subsequent arousal from sleep (3). Progressive loss of lingual and pharyngeal tone in the upper airway is the primary cause of OSA (4). Airway blockage is associated with a reduction of lingual muscle tone and is presumably attributed to

A TALE OF TWO TONGUES

The human tongue assists in a variety of functions, from speech and mastication to maintenance of the pharyngeal stability. In particular, the anterior tongue plays a prominent role in speaking and mastication, while the posterior tongue performs a critical role in upper airway maintenance. Speaking and mastication require fine motor movement, while upper airway maintenance requires sustained muscle tone. It is not surprising then, that as discussed later, the anterior and posterior portions of

THE POSTERIOR AND ANTERIOR TONGUES ARE DIFFERENT IN THEIR ANATOMY AND PHYSIOLOGY

The tongue is a unique motor organ that is comprised almost entirely of muscles with very little skeletal support (13). The human tongue consists of eight pairs of skeletal muscles—four extrinsic muscles (attached to bony attachment): the genioglossus, styloglossus, hyoglossus, and palatoglossus, and four intrinsic muscles (without any bony support): the transversalis, verticalis, inferior longitudinalis, and superior longitudinalis [(14); Fig. 1]. Extrinsic muscle fibers originate from

FATIGUE RESISTANT PROPERTIES OF THE MAMMALIAN TONGUE: THE POSTERIOR TONGUE MUSCLES ARE MORE FATIGUE RESISTANT THAN THE ANTERIOR TONGUE MUSCLES

While the fatigue resistance properties of cardiac and diaphragmatic muscle have been recognized for some time, it is only recently emphasized in the posterior tongue (24., 25., 26.). The ability of the muscles to resist fatigue is related to the type and the metabolic properties of muscle fibers. The oxidative capacity of muscle fibers, as measured by the activity of mitochondrial enzyme NADH-TR, is known to be associated with the fatigability of muscle (27). The human tongue muscles, like

THE HUMAN HYPOGLOSSAL NERVE IS HISTOLOGICALLY MONOFASCICULAR IN THE PROXIMAL SUBMANDIBULAR REGION: IMPLICATIONS ON THE DESIGN OF THE STIMULATION ELECTRODE

The human HGN, or XII cranial nerve, is the primary motor nerve that innervates seven of the eight muscles of the hemi-tongue. The palatoglossus, an extrinsic tongue muscle, is innervated by the vagus (X cranial) nerve. Nerve axons forming the HGN exit the hypoglossal nucleus as a row of small fascicles (inferior to the fourth ventricle in the medulla) ventrally between the inferior olive and the pyramid via the hypoglossal canal in the skull (40). Upon emerging from the hypoglossal foramen,

MUSCULAR HYDROSTAT MODEL EFFECTS TONGUE MOTIONS

The human tongue is unique in the sense that some of its muscles are attached to only one static support (mandible or styloid process, e.g., the genioglossus or styloglossus), or to a floating support (hyoid bone, e.g., the hyoglossus), while other muscles are not attached to any bone and instead are attached to each other (e.g., intrinsic muscles and the free ends of the extrinsic muscles). The implication is that because the muscles cannot contract to a bony support, as in the arm or leg, the

CO-STIMULATION OF AGONIST AND ANTAGONIST MUSCLES IN OPTIMAL PROPORTIONS IMPROVES THE AIRWAY PATENCY

Extrinsic tongue muscles change the position of the tongue, whereas the intrinsic tongue muscles alter its shape (59,60). Among the extrinsics the genioglossus muscle is considered to be the tongue protrusor while styloglossus and hyoglossus muscles are considered retrusors. Geniohyoid, a non-lingual muscle, innervated by HGN, provides the muscular floor for the tongue, also affects the tongue by altering the position of the hyoid complex (51,52,61). However, its precise function is unknown.

TONGUE STIMULATION STIFFENS PHARYNGEAL WALL AND IMPROVES AIRWAY PATENCY—MECHANICAL DRAG VIA THE SUPERIOR PHARYNGEAL CONSTRICTOR AND THE PALATOGLOSSUS MUSCLES

Reduced muscle tone and increased compliance is the major cause of the pharyngeal collapse in patients with obstructive sleep apnea (64,65). The anterior wall of the oropharynx (roughly one-third) is formed by the posterior surface of the tongue. The pliant hypo-pharyngeal wall is anchored not only by its own muscles, i.e., the overlapping superior and middle pharyngeal constrictor muscles, but also by lingual muscles. Niimi et al. (48,49) demonstrated that tongue muscles interact anatomically

TONIC STIMULATION STRENGTHENS THE LINGUAL AND THE PHARYNGEAL MUSCLES

Neuromuscular electrical stimulation of the skeletal muscle has been long used for increasing muscle strength, mass, and functional performance in sports and regenerative medicine (73,74). Changes reported include changes in the myofibrillar proteins expression—fatigue prone-to-fatigue resistance phenotype shift that results in a strengthening of the cytoskeleton; in energy production—a glycolytic-to-oxidative shift in the metabolic profile; in antioxidant mediated defense—an increased

ROLE OF THE CYCLIC TONIC ELECTRICAL STIMULATION IN FATIGUE MITIGATION

The application of a current pulse to a peripheral nerve bundle such as the HGN, causing depolarization of the nerve membranes and action potentials, occurring first in axons that lie closest to the activating electrode contact (87). An action potential, whether caused by normal neural activity or by external electrical stimulation appears to the end organ to be indistinguishable by origin (88). The amplitude of current and duration of application at the cathodal contact of a stimulator

IMPLICATIONS OF HYPOGLOSSAL NERVE STIMULATION FOR THE TREATMENT OF OSA

Attempts to stimulate lingual muscles with intramuscular electrodes to increase tone (93., 94., 95.) or to stimulate the HGN (9,10,96., 97., 98., 99., 100., 101.) have produced variable results. In particular, attempts to stimulate the entire HGN lacked selectivity in stimulating those portion(s) of the HGN that would reliably enlarge the airway. Previous neurostimulation efforts have activated the entire HGN (en masse), or its distal branch necessitating a synchronized system to avoid the

TARGETED HYPOGLOSSAL NERVE (THN) SLEEP THERAPY—A NEW APPROACH

An alternative approach to genioglossus-based electrical stimulation would be to selectively activate or target muscle groups that result in restoration of tongue tone and position. It would require simultaneous activation of appropriate muscle groups to obtain a coordinated opening of the oropharyngeal airway. This would be accomplished by activating the proximal HGN in the neck to allow sub-populations to be activated by regional nerve cuff contacts and still activate several motor units

SUMMARY

We review the neurobiology of the human tongue and its implications for the specification and design of a novel platform device, an electrical neurostimulation system for the treatment of the OSA.

Recognizing the anatomical design, contractile patterns of the tongue and its neural supply are key to understanding how the tongue functions and what is required to artificially activate it with electrical stimulation. Simple Platform stimulators designed for another physiological system may not work

Authorship Statements

Faisal Zaidi and Paul Meadows wrote the manuscript. Ofer Jacobowitz and Terence Davidson reviewed it. All authors approved the submitted version of the manuscript.

How to Cite this Article:

Zaidi F. N., Meadows P., Jacobowitz O., Davidson T. M. 2012. Tongue Anatomy and Physiology, the Scientific Basis for a Novel Targeted Neurostimulation System Designed for the Treatment of Obstructive Sleep Apnea. Neuromodulation 2012; e-pub ahead of print. DOI: 10.1111/j.1525-1403.2012.00514.x

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    Financial Support: Imthera Medical provided all financial support for this study.

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