Laryngeal afferent stimulation enhances Fos immunoreactivity in periaqueductal gray in the cat.

The main functions of the larynx are protection of the airways, respiration, and vocalization. Previous studies have suggested a link between the mechanisms controlling vocalization and afferent feedback from the larynx. We inquired whether stimulation of the laryngeal afferents that run in the internal branch of the superior laryngeal nerve (ISLN) activates neurons of the periaqueductal gray (PAG), a midbrain region implicated in vocalization. We counted the number of neurons expressing Fos, the protein product of the immediate early gene c-fos, in the PAG. The counts were done both in experimental cats after electrical stimulation of the ISLN and nonstimulated controls. We also investigated the possible presence of nitric oxide synthase, an enzyme that synthesizes nitric oxide, in PAG neurons that respond to laryngeal afferent stimulation by double labeling for reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and Fos. Fos expression was significantly greater (P < or = 0.00714) in the lateral and dorsolateral regions of the PAG in the experimental group than in the controls. The Fos-immunoreactive neurons did not contain NADPH-diaphorase, a marker for nitric oxide synthase. Our study suggests that laryngeal afferent stimulation activates neurons in discrete longitudinal columns of the PAG including the regions that have previously been shown to be involved in vocalization, and that these neurons do not contain nitric oxide synthase.

Glutamate receptor subunits in the nucleus of the tractus solitarius and other regions of the medulla oblongata in the cat.

The nucleus of the tractus solitarius (NTS) is a primary termination zone for laryngeal, gustatory, cardiovascular, respiratory, gastrointestinal, and other visceral afferents. Although considerable information is available on the neurochemical aspects of the NTS in general, very little is known about glutamate receptors that may underlie many of the different functions mediated by the NTS. In addition, most previous glutamate receptor distribution studies were performed in the rat, whereas the cat, the subject of many physiological experiments involving the NTS, has received little attention. In the present study, the immunohistochemical distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-selective glutamate receptor subunits (GluR1, GluR2/3, GluR4) and the N-methyl-D-aspartate (NMDA) receptor subunit NR1 in the cat caudal brainstem was investigated by using subunit-specific antibodies. In the NTS, statistically significant differences were seen in the distribution of each antibody. Highest labeling was seen for GluR2/3 in most subnuclei, whereas GluR1-immunoreactive neurons were found more frequently than were NR1- or GluR4-immunoreactive neurons. GluR1 immunolabeling was particularly high in the interstitial subnucleus, whereas GluR2/3 immunolabeling was particularly high in the intermediate subnucleus. Qualitatively, labeling for GluR4 was most common in glia. The present results indicate that glutamate receptors show different subunit distributions in the subnuclei of the NTS and in other adjacent structures. This finding suggests that neurons in these structures are designed to respond differently to excitatory input.

Effects of botulinum toxin injections on speech in adductor spasmodic dysphonia.

Adductor spasmodic dysphonia involves an overadduction of the vocal folds during speech causing uncontrolled voice and pitch breaks and slow, effortful speech. The disorder is resistant to speech therapy and often recurs following initial benefit from unilateral recurrent laryngeal nerve resection. Botulinum toxin injections into multiple sites of the thyroarytenoid muscle on one side were performed in 16 patients. Speech was recorded prior to injection and three times post-injection. Symptoms were measured by two examiners from speech spectrograms without knowledge of speaker identity or recording session. Significant (p less than or equal to 0.03) reductions in pitch and voice breaks, phonatory aperiodicity, and sentence time occurred only when injections resulted in unilateral vocal fold paralysis. Symptoms returned with the restoration of vocal fold movement, 3 months later. Reduction in speed of swallowing without aspiration was reported in 80% of cases. Although speech volume was reduced, there were no instances of aphonia.

Blink reflex excitability recovery curves in patients with spasmodic dysphonia.

We studied 12 patients with spasmodic dysphonia (SD) and 12 healthy control subjects. The patients, who had no symptomatic involvement of the eyes, were evaluated for increased excitability of blink reflexes, which is characteristic of blepharospasm and generalized dystonia. We measured symptom severity from sound spectrograms of five sentences, including sentence production time, number of pitch phonatory breaks, and percentage of aperiodic phonation. We evoked blink reflexes by electrical and mechanical stimulation, and assessed excitability by obtaining excitability recovery curves and responses to trains of stimuli. Patients and controls differed from each other in test R2 amplitude attenuation across all intervals from 150 to 1,000 msec to electrical and mechanical stimulation. Our results indicate that patients with SD have increased excitability of blink reflexes, which suggests that the dystonia involves not only the larynx but also other anatomical structures.

Stop consonant production in isolated and repeated syllables in Parkinson's disease.

To determine if Parkinson's disease (PD) patients have increasing difficulty as speech tasks become longer or more complex, the timing and accuracy of isolated syllables and repeated sequences of syllables were studied. Acoustic measures of PD patient's syllables were similarly impaired relative to normal controls for both isolated and repeated syllable sequences. Listeners' identification scores were equally high for both types of productions. Unlike previous studies of other types of movements in PD, speech accuracy and timing does not deteriorate as items become longer or more complex.

Lesion locations associated with speech perception deficits following penetrating head injury.

Speech discrimination and identification tasks assessing voicing and place distinctions were given to 16 unilaterally brain injured subjects free of aphasic or dysarthric symptoms 12-15 yr post head injury. Seven subjects did not demonstrate any difficulty with these speech tasks, while five left- and four right-brain-injured subjects showed moderate difficulties. These difficulties were more pronounced on the discrimination than on the identification tasks. Analysis of CT scans demonstrated that the lesion locations most clearly associated with the speech discrimination deficits were upper levels of the white matter subjacent to cortical regions in either hemisphere.

A double-blind comparison of clomipramine and desipramine in the treatment of developmental stuttering.

BACKGROUND: Clomipramine, a serotonin reuptake blocker that has been shown to be effective in treating obsessive-compulsive disorder and other unwanted repetitive, ritualized behaviors, was hypothesized to be superior to desipramine, a tricyclic antidepressant with selective noradrenergic effects, for developmental stuttering. METHOD: Seventeen psychiatrically normal subjects, aged 14-61 years, with developmental stuttering completed a 10-week double-blind crossover trial of clomipramine and desipramine after a 2-week single-blind placebo phase. RESULTS: Clomipramine was superior to desipramine (two-tailed, p < .05) for 5 of 10 self-report ratings including stuttering severity on two scales, degree of preoccupation with stuttering and resistance to stuttering on a visual analog scale, and "expectancy" of stuttering on the Perceptions of Stuttering Inventory. CONCLUSION: Clomipramine may be clinically useful for some patients with developmental stuttering. Biological links between developmental stuttering and other repetitive motor patterns that are selectively responsive to serotonergic agents should be explored.

Qualitative analysis of scopolamine-induced amnesia.

The neurochemistry of memory remains to be determined. Acetylcholine may be one of the neuotransmitters which mediates memory function, since the anticholinergic drug scopolamine produces amnesia in man. This study of scopolamine-induced memory deficits further defines those cognitive processes which are disrupted. The drug does not diminish attention, as assessed with an auditory vigilance task, or initial signal detection. More complex auditory decoding is affected, however. Scopolamine impairs aspects of initial memory acquisition (e. g., encoding and consolidation) and spontaneous memory retrieval. Retention is unaffected. Precise delineation of the neurochemistry of human memory will require comparative studies of amnesia-producing compounds, systematically examining the neuropsychological processes impaired by each.

Cerebral activation during speech discrimination in temporal lobe epilepsy.

Eight patients with uncontrolled complex partial seizures underwent positron emission tomography with 18-fluoro-2-deoxyglucose both at rest and during an auditory order discrimination task using speech syllables. Eight age-matched controls were scanned under identical conditions; an additional 18 normal subjects were scanned only at rest. No consistent task-related changes were seen in control subjects. For the 3 patients with left temporal epileptogenic foci, left inferior temporal lobe hypometabolism was more evident during the activated than during the resting scan. Activation procedures may augment the diagnostic yield of metabolic scanning in epilepsy.

The swallowing side effects of botulinum toxin type A injection in spasmodic dysphonia.

Botulinum toxin type A (BOTOX) injection of the thyroarytenoid muscle is used to control speech symptoms in patients with adductor spasmodic dysphonia. Transient difficulty in swallowing liquids is a common treatment side effect. Laryngeal movement durations were measured during swallowing in 13 adductor spasmodic dysphonia patients undergoing treatment and in 6 normal control subjects in order to determine the following: 1. whether, prior to the injection, laryngeal movement durations were longer in the spasmodic dysphonia patients than in the control subjects; 2. whether movement durations increased following the injections; 3. whether preinjection swallowing difficulties related to postinjection swallowing measurements and postinjection patient reports of swallowing problems. A piezoelectric movement transducer was shown to be accurate for noninvasive measurement of laryngeal movement duration in relation to muscle onset and offset for hyoid elevation and relaxation. Before botulinum toxin type A injection, no significant differences in swallowing duration were found between the patient and control groups. Four patients with swallowing complaints prior to injection had longer laryngeal movement durations than the other spasmodic dysphonia patients and the control subjects. Following injection, laryngeal movement durations increased in the patients with spasmodic dysphonia, and eight patients reported dysphagia for an average of 2 weeks. Relationships were found between the patients' initial reports of swallowing problems and increased laryngeal movement durations before and after botulinum toxin type A injection. Those patients initially reporting swallowing difficulties had severe dysphagia for 2 weeks after the injection. Patient reports of dysphagia prior to injection may indicate a greater likelihood of significant dysphagia following thyroarytenoid injection with botulinum toxin type A.

Laryngeal muscle activity during speech breaks in adductor spasmodic dysphonia.

To determine the laryngeal muscle activation abnormalities that are associated with speech symptoms in adductor spasmodic dysphonia (ADSD), electromyographic measures of extrinsic and intrinsic laryngeal muscles during speech compared 1) muscle activity when ADSD patients had breaks in words with when they produced the same words without breaks; and 2) muscle activity in ADSD patients during speech without voice breaks with normal control producing phonetically similar words. Simultaneous electromyographic recordings were made from the thyroarytenoid (TA), cricothyroid (CT), sternothyroid (ST), thyrohyoid (TH) and the posterior cricoarytenoid (PCA) muscles during speech testing in 11 ADSD patients and 10 control subjects. Speech breaks were identified and mean muscle activity measured starting 100 ms preceding a voice break and for the remainder of the word. Mean muscle activity level was significantly greater on break than non break words in ADSD patients only for the thyroarytenoid muscle (p<.001). No significant differences were found between the ADSD and control subjects during non break words for any of the laryngeal muscles studied. The results demonstrated that 1) only the thyroarytenoid, of the muscles tested, was affected in ADSD, 2) that muscle activation abnormalities were spasmodic, only appearing when symptoms occurred and 3) no imbalances of muscle tone were evident when speech disruptions did not appear.

Aging effects on motor units in the human thyroarytenoid muscle.

OBJECTIVES: To determine whether age differences are present in the human laryngeal thyroarytenoid muscle that would indicate that different normative values would be needed for identifying motor unit abnormalities. STUDY DESIGN: Twenty-six consecutively recruited healthy subjects between the ages of 21 and 72 years participated in a laryngeal electromyography study. METHODS: Bipolar needle electrodes were used to record motor unit action potentials from several locations in the right and left thyroarytenoid muscles of each subject. The duration of a motor unit was measured when at least 10 firings of the same motor unit could be identified. On the average, four units were measured per muscle. RESULTS: In the subjects less than 60 years of age, motor unit duration did not increase significantly with age. However, motor units from subjects greater than 60 years of age had longer durations than those from subjects less than 60 years of age (P < .00005), and 25% of the units measured in subjects greater than 60 years of age had longer durations than any of the units measured in subjects less than 60 years of age. Further, the older subjects differed from each other in their mean unit durations (P < .0001). In subjects less than 60 years of age, significantly longer durations were found for units innervated by the longer, left-side recurrent laryngeal nerve in comparison with the right-side nerve (P = .005). CONCLUSIONS: Different mean and SD values should be used for patients less than and greater than 60 years of age and for the right and left sides, when evaluating motor units in the thyroarytenoid muscles.

Effects of adductor muscle stimulation on speech in abductor spasmodic dysphonia.

OBJECTIVE: To determine whether adductor laryngeal muscle stimulation might be a beneficial treatment alternative for abductor spasmodic dysphonia (ABSD). STUDY DESIGN: Baseline comparisons were made on measures of voiceless consonant and syllable duration between patients with ABSD and normal control subjects, and speech and voice production with and without muscle stimulation were compared within 10 patients with ABSD. METHODS: Baseline group comparisons were conducted on measures of syllable and voiceless consonant duration between the patients and the control subjects. Neuromuscular stimulation was applied to the thyroarytenoid or lateral cricoarytenoid muscles in the patients during extended phonation, and measures were made of fundamental frequency and sound pressure level in the stimulated and nonstimulated conditions. Voiceless consonant duration was compared with and without adductor laryngeal muscle stimulation during syllable repetitions and sentences in the patients. RESULTS: Before stimulation, the patients had increased syllable durations in comparison with control subjects (P = .003). Repeated within-patient comparisons with and without stimulation demonstrated significant (P < .008) reductions in voiceless consonant durations during syllable repetition. The more severely affected patients had the greatest reductions in voiceless consonant duration during sentence production. CONCLUSIONS: Adductor muscle stimulation improved speech production in patients with ABSD, and the improvement was greatest in the most severely affected patients. Therefore adductor muscle stimulation has potential for benefiting patients with ABSD.

A new surface electrode for recording from the posterior cricoarytenoid muscle.

A new pharyngeal surface electrode for recording posterior cricoarytenoid muscle activity through the hypopharyngeal mucosa has been evaluated. The electrode was passed through one nasal passage into the hypopharynx. Correct electrode location was verified by increased activity during inhalation, with decreased activity during phonation. The procedure was evaluated in 45 subjects, 10 normal speakers and 35 patients with dysphonia. Accurate recordings were obtained in 25 subjects (56%). Problems encountered were lack of pharyngeal descent, electrode dysfunction, and signal interference due to phonatory vibration or interarytenoid activity. Signal validity was evaluated in four normal speakers with accurate electrode placement. Significant (p less than or equal to 0.001) increases in PCA activity occurred during tasks requiring vocal fold abduction. The electrode proved to be a useful, noninvasive clinical tool for recording PCA activity in some patients.

Speech timing in Parkinson's and Huntington's disease.

The purpose was to determine the effects of two different basal ganglia diseases on speech planning, initiation, and production. Patients with Parkinson's Disease (PD) and Huntington's Disease (HD) were compared with normal subjects on speech timing tasks. Speech reaction time was unimpaired, while changes in duration at different speech rates were affected differently in the two patient groups. In HD, changes in the duration of syllables, of pauses between phrases, and of sentences were all reduced, while in PD only the control of sentence duration was impaired. The HD patients had reduced syllable repetition rates, but both patient groups maintained their repetition rates over 5 sec. The ratios of word to phrase time, and of phrase to sentence time, remained constant across regular and fast speaking rates and did not differ from normal in either patient group. The results suggest that PD and HD patients are not impaired in speech planning or initiation, but have poor control over the duration of speech events.

An evaluation of laryngeal muscle activation in patients with voice tremor.

Eight patients with voice tremor were studied to characterize laryngeal muscle involvement. Electromyographic (EMG) recordings were made from intrinsic laryngeal muscles, simultaneously with some extrinsic laryngeal muscles, respiratory movement, and voice recordings during respiration, whisper, and phonation. Spectral measures were used to determine the tremor frequency and the prominence of spectral peaks in the EMG, respiratory and acoustic signals, while correlation coefficients were computed between pairs of tremulous EMG signals to measure the synchrony of tremor between muscles. The intrinsic laryngeal muscles were tremulous during respiration and speech, with the thyroarytenoid most often involved. Tremor was also detected in some of the extrinsic muscle recordings and the percentage of muscles with tremor was higher during phonation than during whisper or respiration. Time delays were found between tremor oscillations in laryngeal muscles. Because the thyroarytenoid was affected in all the patients studied, botulinum toxin injections may be beneficial in treatment of this voice disorder.

Technique for injection of botulinum toxin through the flexible nasolaryngoscope.

A new endoscopic method of injecting botulinum toxin into the thyroarytenoid muscles for treatment of adductor spasmodic dysphonia was evaluated. Twelve patients with adductor spasmodic dysphonia were given injections in the thyroarytenoid muscle under video visualization with a flexible catheter needle that was passed through the working channel of a flexible nasolaryngoscope. Six patients received unilateral injections, and six received bilateral injections. Preinjection and postinjection speech samples were compared by use of spectrographic analysis. Significant decreases in voice breaks and sentence duration were found after treatment with both unilateral and bilateral injections. Patient interviews and diaries documented the reported degree and duration of symptom reduction. All 12 patients reported that the injections were of significant benefit and that the endoscopic procedure was tolerable. We concluded that this is a safe and effective technique for injecting botulinium toxin into laryngeal muscles for treatment of spasmodic dysphonia.

Successful treatment of selected cases of abductor spasmodic dysphonia using botulinum toxin injection.

Ten patients with abductor spasmodic dysphonia, who exhibited spasmodic bursts and heightened activity of the cricothyroid muscle during speech, were selected for participation. Between 5 and 20 U of botulinum toxin type A were injected into both right and left cricothyroid muscles. Six patients benefited substantially, whereas four did not. Acoustic analyses of voice patterns showed similar changes to the clinical impressions. Significant group improvements were found in sentence duration while selected patients improved in the proportion of their speech that was voiced and the duration of their voiceless consonants. Those patients with abductor spasmodic dysphonia and other muscle abnormalities in addition to the cricothyroid and with constant breathiness did not benefit.

Effects of stimulus intensity on laryngeal long latency responses in awake humans.

Percutaneous electrical stimulation applied to the internal branch of the superior laryngeal nerve (ISLN) results in two long latency laryngeal adductor responses in awake humans: an ipsilateral thyroarytenoid (TA) R1 muscle response at 16 ms, and later bilateral TA R2 muscle responses at 60 ms. The purpose of this study was to determine whether a functional relationship existed between the R1 and R2 responses by gradually increasing the level of electrical stimulation from threshold to supramaximal levels. R1 amplitude increased linearly with stimulation intensity in 9 of the 11 subjects, whereas R2 only had a positive linear relationship in 3 subjects and a negative relationship with stimulation intensity in 1 subject. Significant negative relationships were found between response latency and stimulation intensity in 3 subjects for the R1 responses and 3 other subjects for the R2 responses. Overall, R1 amplitudes increased systematically, whereas R2 responses varied in latency and amplitude with increasing stimulus intensity. Neither the latencies nor the amplitudes of the two responses were related after adjusting for stimulation intensity within subjects by using partial correlation coefficients. The R1 and R2 responses were functionally unrelated and most likely have different neural components.

Procedures for the selection of spastic dysphonia patients for recurrent laryngeal nerve section.

Patients with spastic dysphonia were studied to identify the characteristics of patients benefiting from recurrent laryngeal nerve (RLN) surgery. Studies included laryngeal video recordings made during speech, measures of frequency and amplitude variations during extended phonation, the effects of altered auditory feedback on dysfluencies, and temporary unilateral RLN block. Two patients had vocal fold adductor spasms during connected speech, had increased acoustic phonatory tremor in frequency, were not benefited by altered auditory feedback, and responded favorably to nerve block. Subsequent RLN section improved the speech of both patients. Other patients had speech blocks, repetitions and prolongations, vocal fold tremors during phonation, reduced dysfluencies during altered auditory feedback, and were not benefited by temporary nerve block. Two subtypes of spastic dysphonic patients are proposed.