Our goal is to improve the treatment and prevention of voice, speech and swallowing disorders. For this purpose, the Section conducts both research on the neural control of the larynx for voice, speech and swallowing as well as studies of the pathogenesis and pathophysiology of neurogenic idiopathic disorders. Clinical trials are being conducted to develop new treatments for spasmodic dysphonia and chronic pharyngeal dysphagia. Significant advances have been made during the last year in several areas. The laryngeal adductor response is a selective thyroarytenoid muscle spasm that occurs in response to stimulation of mechanoreceptors in the larynx. Previously we have found that when this reflex is elicited by electrical stimulation of afferents in the superior laryngeal nerve, responses are not normally suppressed in patients with spasmodic dysphonia, an idiopathic chronic focal dystonia affecting voice production. We have used an animal model to determine the brain stem regions that may be involved in eliciting this reflex. Fos immunohistochemistry was used to determine which neurons in the medulla fired when this reflex was elicited. With unilateral electrical stimulation of the internal branch of the superior laryngeal nerve, significant increases (p <0.003) occurred in the interstitial subnucleus, the ventrolateral subnucleus, the commissural subnucleus of the nucleus tractus solitarius, the lateral tegmental field of the reticular formation, the area postrema and the nucleus ambiguus. This pathway involved a subset of the same structures as those involved in cough and swallow. Neither the dorsal motor nucleus of the vagus, usually active for swallow, nor the nucleus retroambiguus, retrofacial nucleus, or the lateral reticular nucleus, usually active for cough, were active with elicitation of the laryngeal adductor response alone. Because many voice disorders have their onset with laryngitis, we have been investigating possible changes in brain stem function as a result of acute and chronic laryngeal inflammation. We have been using lipopolysaccharide injection into one vocal to induce an inflammatory reaction and examining c fos expression and cytokine expression (IL1 beta and TNF alpha) in the same regions previously identified with electrical stimulation of the laryngeal afferents (see above). Collaboration with another group is addressing whether these findings can be replicated using in situ hybridization. Because of the hypothesized role of sensory feedback in the generation of involuntary muscles spasms during speech in spasmodic dysphonia, we have been investigating normal human responses to air pressure indentation of the laryngeal mucosa using air puffs in humans. In the first study we presented 100 ms air puff stimuli to the laryngeal mucosa overlying the arytenoid cartilages on one side while recording from the thyroarytenoid and cricothyroid muscles. The earliest laryngeal muscle responses occurred between 80 and 125 ms after the air pressure onset in the thyroarytenoid muscles on both sides. Further in a second study, we recently determined that with repeated air puffs, muscles responses are normally suppressed when stimuli are presented at intervals of less than 1 second. Similar studies are planned in spasmodic dysphonia to determine if muscle responses to laryngeal stimulation are abnormal in these patients. For rehabilitation of laryngeal motor control disorders, improved understanding of the biomechanical actions of each of the laryngeal muscles is needed. We combined laryngeal imaging, to quantify vocal fold movement, with synchronized recordings of laryngeal muscles in normal speakers during different laryngeal tasks; sniff, cough and repetition of syllables involving a glottal fricative /h/ and a vowel. Cross-correlations between vocal fold position and level of muscle activity distinguished whether a muscle was active for vocal fold closing or opening. Only the posterior cricoarytenoid muscle related well with vocal fold motion; it had a high relationship with vocal fold opening during all three tasks. The cricothyroid muscle had an opening action only for sniff while the adductor muscles only related with closing during cough. Different combinations of muscles were used by different subjects on various tasks to accomplish vocal fold opening and closing. This motor equivalence across individuals and tasks in the use of the laryngeal muscles for vocal fold movement was most evident during speech. Dysphagia, a significant health problem, usually stems from central nervous system injury, leaving peripheral muscles intact and functional but without appropriate control. Last year, we used intra-muscular hooked wires to stimulate muscles in normal volunteers at rest and used videofluoroscopy to measure the extent of hyo-laryngeal anterior and superior movement when single muscles and different combinations were stimulated. Recently, a study of patients with chronic pharyngeal dysphagia was initiated to compare the effects of intra-muscular stimulation and surface stimulation on the frequency of aspiration during swallowing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002980-06
Application #
6990714
Study Section
(MNB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2004
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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