Vocal and tongue exercise in early to mid-stage Parkinson disease using the Pink1-/- rat.

Vocal and swallowing deficits are common in Parkinson disease (PD). Because these impairments are resistant to dopamine replacement therapies, vocal and lingual exercise are the primary treatment, but not all individuals respond to exercise and neural mechanisms of treatment response are unclear. To explore putative mechanisms, we used the progressive Pink1-/- rat model of early to mid-stage PD and employed vocal and lingual exercises at 6- and 10-months of age in male Pink1-/- and wild type (WT) rats. We hypothesized that vocal and lingual exercise would improve vocal and tongue use dynamics and increase serotonin (5HT) immunoreactivity in related brainstem nuclei. Rats were tested at baseline and after 8 weeks of exercise or sham exercise. At early-stage PD (6 months), vocal exercise resulted in increased call complexity, but did not change intensity, while at mid-stage (10 months), vocal exercise no longer influenced vocalization complexity. Lingual exercise increased tongue force generation and reduced relative optical density of 5HT in the hypoglossal nucleus at both time points. The effects of vocal and lingual exercise at these time points are less robust than in prodromal stages observed in previous work, suggesting that early exercise interventions may yield greater benefit. Future work targeting optimization of exercise at later time points may facilitate clinical translation.

Evaluation of poly-L-lactic acid and polyglycolic acid resorbable stents for repair of tracheomalacia in a porcine model.

Poly-L-lactic acid and polyglycolic acid (PLPG) resorbable stents may offer a potential solution to the problem of tracheomalacia. Advantages of this material include its strength, its versatile shaping characteristics, and its resorbability, which would preclude surgical removal and allow for airway growth. The purpose of this pilot study was to examine the usefulness of PLPG stents for temporary external airway stenting of tracheomalacia in a porcine model. A severe tracheomalacia was created in 6 pigs by submucosal resection of segments of tracheal cartilage from 6 consecutive rings. The PLPG stent was then shaped to recreate the tracheal contour and sutured to the underlying airway. Endoscopic photodocumentation during spontaneous ventilation was obtained before and after reconstruction. After creation of the malacic tracheal segment, all animals developed stridor, retractions, and cyanosis during spontaneous ventilation. After repair, all animals were extubated without complication. All animals survived the follow-up period of 9 to 12 weeks without evidence of respiratory distress and with rapid weight gain. Repeat bronchoscopy showed no evidence of airway collapse during spontaneous ventilation. Tracheal measurements revealed growth of the stented segment with a mild narrowing within the repaired region. Histologic examination showed preservation of respiratory epithelium. These preliminary findings suggest that PLPG stents may serve a useful role in the surgical management of tracheomalacia.

Muscle fiber-type changes induced by botulinum toxin injection in the rat larynx.

This study examined muscle fiber-type alterations after single or multiple botulinum toxin (BT) injections to better understand possible morphologic changes induced by therapeutic BT injections in patients with spasmodic dysphonia. Muscle fiber staining was accomplished in rat intrinsic laryngeal muscles with antibodies to specific myosin heavy chains. Results indicated that the typical baseline distributions of type II muscle fibers (ie, types IIa, IIb, IIx, and IIL) were altered by BT injection, while no change was observed in type I fibers. Embryonic fibers were observed only along the needle insertion site at 7 days post BT injection. Although inferences from these animal data to human neuromuscular function must be made with caution, our findings provide insight into the possible cellular and molecular changes characterizing BT-injected muscles.

Movement-related skin strain associated with goal-oriented lip actions.

It is generally accepted that sensory input contributes to the generation of natural movements. In most motor systems, muscle spindles, tendon organs, joint receptors, and cutaneous mechanoreceptors may provide proprioceptive information. However, the perioral area of the human face lacks muscle spindles, tendon organs, and joint receptors and is therefore a model system for the study of cutaneous afferent contributions to proprioception. This investigation examined a series of skin strains associated with lower-lip movements in human subjects to determine if such strains, which serve as stimuli for cutaneous mechanoreceptors, may underlie proprioception in the face. The results suggested that strains associated with lower-lip movements were of sufficient magnitude to elicit cutaneous mechanoreceptor discharge, as shown in recent human microneurographic studies. Further, the magnitude of multiple strains was predictive of lower-lip movement endpoints. These results highlight the potential importance of cutaneous mechanoreceptors as putative proprioceptors.

Physiologic assessment of botulinum toxin effects in the rat larynx.

OBJECTIVE: Botulinum toxin (BT) is a currently used treatment for spasmodic dysphonia (SD) and other related focal dystonias. The goal of this study is to provide a basis for using the rat larynx to objectively assess physiological and histological effects of BT. STUDY DESIGN: Dosages and volumes of BT injection were varied and three physiological parameters were measured. These measures included: optical density of PAS-stained laryngeal muscle after electrical stimulation, which is an indirect measure of denervation, spontaneous laryngeal muscle activity, and laryngeal movement. METHODS: A new microlaryngoscopic technique was developed, which made it possible to observe and manipulate the rat larynx endoscopically. Laryngeal movement and electromyographic (EMG) measures were made prior to injection and 3 days following BT injections of various dosages and volumes. Optical density measures were made 3 days after injection. RESULTS: Significant reductions in vocal fold motion and spontaneous laryngeal muscle activity as a function of increased BT dosage were observed. In addition, the optical density of PAS-stained laryngeal muscle after electrical stimulation was increased following BT injection. Significant volume effects in optical density were observed in the lateral thyroarytenoid and lateral cricoarytenoid muscles on the contralateral side. CONCLUSIONS: The rat laryngeal model is suitable for assessing BT effects. In addition, the three physiological variables provided useful and reliable measures of laryngeal function. It is the authors' intention to use the rat laryngeal model to further examine the physiological and histological effects of BT with the goal of developing new methods for the treatment of patients with SD and other focal dystonias.

Increased acute and chronic mitotic activity in rat laryngeal muscles after botulinum toxin injection.

OBJECTIVES: To characterize the acute and chronic cellular effects of botulinum toxin (BT) injection into rat laryngeal muscles. A complete characterization of these effects is important because patients with focal dystonias of the head and neck are commonly treated with BT injection. Further, potential muscular changes in the larynx must be carefully delineated owing to the critical phonatory and airway protective functions of these muscles. STUDY DESIGN: The acute and chronic cellular effects of BT injection were studied using 5'-bromo 2'-deoxyuridine (BrdU) following single and repeated BT injection into rat laryngeal muscles. BrdU is incorporated into mitotically active nuclei such that changes in cell proliferative behavior following BT injection can be monitored. RESULTS: Increased mitotic activity was detected in the tissue samples studied following BT injection. Differences in the times of the peak distribution of BrdU-labeled cells in each laryngeal muscle were observed. This may be related to the diffusion effects of BT. Prolonged muscle fiber changes, including splitting, were also observed as the result of repeated BT injection. CONCLUSIONS: The results of this study suggest that BT may induce a proliferative response in muscle tissue.

Task-dependent variations in parkinsonian motor impairments.

Studies of visually-guided arm movements in patients with Parkinson's disease (PD) have suggested a relationship between slowness of movement and a reduction in the ratio of movement amplitude and peak velocity. Recent studies indicate, however, that PD impairments may be different for well-learned, natural movements performed without visual guidance, or movements associated with sequential motor behaviours such as speech. To address this issue, PD subjects and age/sex-matched controls were compared on the performance of three tasks, all of which required lowering the jaw: (1) single, rapid, visually-guided movements; (2) equivalent movements associated with a single speech syllable (inherently without visual guidance), and (3) well-learned speech movements produced in a natural sequence. PD subjects manifested similar deficits for visually-guided jaw lowering as those previously reported for arm movements, namely reduced velocity/amplitude ratios and increased movement durations. By contrast, analogous jaw movements during the sequential speech tasks were unimpaired on these measures. These results suggest that PD motor impairments are influenced by a variety of factors, including the degree to which tasks are familiar and natural, and the availability of visual information.

Sensorimotor contributions of the basal ganglia: recent advances.

In the last decade, a great deal of research has been aimed at ascertaining the manner in which the basal ganglia (BG) contribute to the control of movement. The formation of workable hypotheses, however, has been limited by the great variety of putative roles reported in the literature. Reported functions have often been in direct conflict. Recent developments, however, provide new perspectives from which to view seemingly discordant functions. Data reviewed in this article suggest a distinct anatomical topography within the BG, allowing for highly specialized subfunctions. In parallel, BG cellular activity has been found primarily in association with specific sensory and task-related dimensions relevant to particular movements. The multiple sensorimotor contributions of the BG therefore are not contradictory, but represent BG contributions within different functional contexts. These multiple roles of the BG offer particular clinical insights.

Parkinsonian deficits in serial multiarticulate movements for speech.

Unlike the single joint arm movements so commonly the focus of Parkinson's disease (PD) studies, orofacial movements for speech are well-learned, complex motor sequences generated without visual guidance. The present study of upper lip, lower lip, and jaw movements during speech in PD was thus aimed at determining whether (1) PD speech kinematic deficits are comparable to those often observed in simpler limb movements; (2) coordination for multimovement actions such as speech is aberrant in PD, as recently claimed; and (3) the component muscle groups involved in this behaviour manifest uniform deficits. Results indicated that despite reduced amplitudes of jaw and upper lip displacement in PD subjects, all three of these oral movements were of normal duration. Secondly, PD lower lip movements manifested no deficits and bradykinesia (reduced velocity) was only found in movements of the jaw. Finally, there was an indication of movement coordination aberrations in these parkinsonian subjects. Overall, these results not only suggest a difference between orofacial and limb movement impairments in PD, but also document the need to broaden our perspectives on this movement disorder by examining a wider range of functional motor tasks.

Comparisons of perceptual and acoustic characteristics of tracheoesophageal and excellent esophageal speech.

The results of recent studies have established significant acoustic differences between tracheoesophageal (TE) and conventional esophageal speech. Listener preferences and acoustic differences between TE and excellent esophageal speech were examined in the present investigation. Although, as a group, TE speech was characterized by longer extended phonation, more syllables per breath, and increased intensity, there were no significant differences in listener preference between the groups.

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.

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.

Dynamic aspects of phonatory control in spasmodic dysphonia.

To understand the voluntary laryngeal movement disorder in spasmodic dysphonia (SD), SD patients were compared with normal controls on speech tasks with different laryngeal motor-control demands. Nine patients with idiopathic chronic SD and no other speech, otolaryngologic, neurologic, or psychiatric disorders were compared with 15 control subjects who were free of such disorders. Speech production tasks required different degrees of dynamic and precise control of vocal fold movement. Phonatory off times were increased in the SD patients, while maximum phonation time, phonatory on time, frequency and intensity control, and reaction times for CV syllables were not affected. On a reaction-time task, the onset of laryngeal movement was not delayed in the SD patients, however, the time between the onset of laryngeal movement and phonatory onset was significantly increased in the SD patients in comparison with the controls. Therefore, SD patients had no difficulty with the onset of laryngeal movement but were slow to achieve phonation, indicating a movement-control disorder affecting vocal fold adduction for phonation onset.

Acoustic and physiologic correlates of the voicing distinction in esophageal speech.

This study was designed to compare high- and low-intelligibility productions of /t/ and /d/ in esophageal speakers by using a combination of acoustic, perceptual, and physiologic measurements. Observations from these comparisons were incorporated into clinical strategies for modifying a single subject's low-intelligibility utterances. Acoustic comparison indicated that esophageal speakers used voice onset and phonation off-times but not vowel durations to differentiate /t/ and /d/ in high-intelligibility productions. Intraoral pressure measures during /t/ and /d/ production demonstrated excessively high intraoral pressures in both consonants for a low-intelligibility speaker and did not suggest systematic differences in intraoral pressure between /t/ versus /d/. Two weeks of biofeedback treatment with a low-intelligibility speaker were associated with a reduction in intraoral pressures for /t/ and /d/ productions, improved intelligibility, and changes in acoustic characteristics for /t/.