John A. Russell

Targeted exercise therapy for voice and swallow in persons with Parkinson's disease

Sensorimotor deficits affecting voice and swallowing ability can have a devastating impact on the quality of life of people with Parkinson disease (PD). Recent scientific findings in animal models of PD pinpoint targeted exercise therapy as a potential treatment to reduce neurochemical loss and decrease parkinsonian symptoms. Although there may be beneficial effects, targeted exercise therapy is not a standard component of therapy for the cranial sensiromotor deficits seen in PD. In this paper, we review the scientific evidence for targeted training for voice and swallowing deficits. The literature search revealed 19 publications that included targeted training for voice and only one publication that included targeted training for swallowing. We summarize 3 main findings: (1) targeted training may be associated with lasting changes in voice behavior; (2) targeted training of sensorimotor actions with anatomical or functional overlap with voice and swallowing may improve voice and swallowing to some degree, but it is unknown whether these effects endure over time; and (3) evidence regarding cranial sensorimotor interventions for Parkinson disease is sparse. We concluded that targeted training for voice and swallow is a promising but understudied intervention for cranial sensorimotor deficits associated with PD and posit that animal models can be useful in designing empirically based studies that further the science on targeted training.

Ultrasonic output from the excised rat larynx.

The source of ultrasonic vocalizations (USVs) produced by rats is thought to be within the larynx. The purpose of this investigation was to determine if the rat larynx is capable of producing ultrasounds with the full range of frequencies reported in vivo. Acoustic output of excised rat larynges with and without vocal fold constriction was measured. At biologically-reasonable airflow rates and pressures, only larynges with a constriction produced the full range of ultrasounds reported in vivo, providing support for the hypothesis that a constriction within the larynx is likely the source of rat USVs.

Tongue force and timing deficits in a rat model of Parkinson disease

Deficits in tongue function in conjunction with airway compromise can contribute to dysphagia associated with Parkinson disease (PD). However, it is unknown if these deficits are related to the primary disease pathology in PD, nigrostriatal dopamine depletion. To directly study the impact of striatal dopamine depletion on tongue function, we used unilateral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle and measured tongue force and timing parameters during a complex tongue protrusion task for a water reward. Maximal and average forces were significantly diminished and average press time was significantly longer after neurotoxin administration, reflecting aspects of bradykinesia and hypokinesia associated with PD. Our findings suggest that even unilateral deficits to the nigrostriatal dopamine system may be contributing to some of the lingual sensorimotor deficits seen in PD. Because previous research in rat models of PD has shown that targeted training of the limb can rescue behavioral deficits and spare striatal dopamine neurons, early intervention for cranial sensorimotor deficits may also be indicated.

Videofluorographic assessment of deglutitive behaviors in a rat model of aging and Parkinson disease

Dysphagia is commonly associated with aging and Parkinson disease and can have a significant impact on a person’s quality of life. In some cases, dysphagia may be life-threatening. Animal models may be used to study underlying mechanisms of dysphagia, but paradigms that allow adequate imaging of the swallow in combination with measurement of physiological variables have not been forthcoming. To begin development of methods that allow this, we used videofluorography to record the deglutition behaviors of 22 Fisher 344/Brown Norway rats in young adult (9xa0months old), old (32xa0months old), and parkinsonian (unilateral lesion to the medial forebrain bundle) groups. We hypothesized that the old and parkinsonian rats would manifest deficits in deglutition behaviors analogous to those found in human clinical populations. Our results supported our hypothesis in that the old group demonstrated reductions in bolus transport speeds and mastication rate while the parkinsonian rats showed impairments in oral processing. Interpretation of these results should consider the particular animal model, lesion type, and videofluorographic protocol used in this work. Future studies will link swallow imaging data of this kind with physiological and anatomical data in a manner not possible with human participants.

Assessing the role of dopamine in limb and cranial-oromotor control in a rat model of Parkinson's disease

UNLABELLEDnParkinsons disease (PD) is a neurodegenerative disorder primarily characterized by sensorimotor dysfunction. The neuropathology of PD includes a loss of dopamine (DA) neurons of the nigrostriatal pathway. Classic signs of the disease include rigidity, bradykinesia, and postural instability. However, as many as 90% of patients also experience significant deficits in speech, swallowing (including mastication), and respiratory control. Oromotor deficits such as these are underappreciated, frequently emerging during the early, often hemi-Parkinson, stage of the disease. In this paper, we review tests commonly used in our labs to model early and hemi-Parkinson deficits in rodents. We have recently expanded our tests to include sensitive models of oromotor deficits. This paper discusses the most commonly used tests in our lab to model both limb and oromotor deficits, including tests of forelimb-use asymmetry, postural instability, vibrissae-evoked forelimb placing, single limb akinesia, dry pasta handling, sunflower seed shelling, and acoustic analyses of ultrasonic vocalizations and pasta biting strength. In particular, we lay new groundwork for developing methods for measuring abnormalities in the acoustic patterns during eating that indicate decreased biting strength and irregular intervals between bites in the hemi-Parkinson rat. Similar to limb motor deficits, oromotor deficits, at least to some degree, appear to be modulated by nigrostriatal DA. Finally, we briefly review the literature on targeted motor rehabilitation effects in PD models.nnnLEARNING OUTCOMESnReaders will: (a) understand how a unilateral lesion to the nigrostriatal pathway affects limb use, (b) understand how a unilateral lesion to the nigrostriatal pathway affects oromotor function, and (c) gain an understanding of how limb motor deficits and oromotor deficits appear to involve dopamine and are modulated by training.

Effect of aging on tongue protrusion forces in rats.

The purpose of this study was to ascertain the effect of aging on muscle contractile properties associated with tongue protrusion in a rat model. Fischer 344/Brown Norway hybrid rats, ten young (9 months old) and ten old (32 months old), were used to measure protrusive contractile properties. Results showed a significant reduction in tetanic forces in the old animals. The following measures of muscle contraction were not different between age groups: mean twitch contraction force, twitch contraction time, twitch contraction half-decay time, and a calculated measure of fatigability. In conclusion, aging influenced protrusive tongue muscle contractions in a rat model such that tetanic forces were reduced. The reduction of tetanus force may parallel findings in human subjects relative to isometric tongue force generation and may be associated with age-related disorders of swallowing.

Differential effects of targeted tongue exercise and treadmill running on aging tongue muscle structure and contractile properties.

Age-associated changes in tongue muscle structure and strength may contribute to dysphagia in elderly people. Tongue exercise is a current treatment option. We hypothesized that targeted tongue exercise and nontargeted exercise that activates tongue muscles as a consequence of increased respiratory drive, such as treadmill running, are associated with different patterns of tongue muscle contraction and genioglossus (GG) muscle biochemistry. Thirty-one young adult, 34 middle-aged, and 37 old Fischer 344/Brown Norway rats received either targeted tongue exercise, treadmill running, or no exercise (5 days/wk for 8 wk). Protrusive tongue muscle contractile properties and myosin heavy chain (MHC) composition in the GG were examined at the end of 8 wk across groups. Significant age effects were found for maximal twitch and tetanic tension (greatest in young adult rats), MHCIIb (highest proportion in young adult rats), MHCIIx (highest proportion in middle-aged and old rats), and MHCI (highest proportion in old rats). The targeted tongue exercise group had the greatest maximal twitch tension and the highest proportion of MHCI. The treadmill running group had the shortest half-decay time, the lowest proportion of MHCIIa, and the highest proportion of MHCIIb. Fatigue was significantly less in the young adult treadmill running group and the old targeted tongue exercise group than in other groups. Thus, tongue muscle structure and contractile properties were affected by both targeted tongue exercise and treadmill running, but in different ways. Studies geared toward optimizing dose and manner of providing targeted and generalized tongue exercise may lead to alternative tongue exercise delivery strategies.

Cutaneous tissue flap viability following partial venous obstruction.

Background: Venous outflow obstruction is the most common cause of tissue failure after microvascular reconstructive surgery. If it is not recognized early, there is an increased risk of tissue damage and loss. Currently, however, there are no adequate models for the study of this clinical problem. The purpose of this study was to develop a partial congestion model for the study of skin flap physiology in response to varying levels of occluded venous outflow. Methods: Nine mixed-breed pigs were equally divided into three experimental groups (0 percent, 20 percent, and 50 percent venous outflow) to determine the effects of varying venous outflow on cutaneous flap color, oxygen tension, and edema. A cutaneous pedicle flap model and a partial congestion system were used to observe changes in variable venous obstruction. Results: Only 0 percent venous outflow resulted in progressive color change across time. In addition, 0 percent venous outflow demonstrated significantly different oxygen tension levels relative to the other groups. Twenty percent venous outflow resulted in significant edema formation relative to the other groups. The 50 percent group showed an increase in oxygen tension from the second hour of venous obstruction to the end of the experiment. Conclusions: Tissue flap color is the clinical standard on which flap health is measured. After 8 hours, only complete venous occlusion resulted in significant color change. However, physiological changes that could affect tissue flap health were noted with only partial venous occlusion, including the development of edema formation. Accordingly, subtle color change could indicate partial venous congestion and may warrant intervention by the surgeon.

Biochemistry of anterior, medial, and posterior genioglossus muscle in the rat.

The tongue plays a vital role in swallowing actions. However, tongue muscles have been understudied, and it is unclear if tongue muscles are homogeneous with respect to muscle fiber-type distribution. We examined myosin heavy chain (MHC) composition of anterior, medial, and posterior sections of the genioglossus muscle (GG) using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in ten adult (9 months old) male Fischer 344/Brown Norway hybrid rats. We found that Type IIx MHC predominated in the anterior, medial, and posterior regions of the GG muscle (pxa0=xa00.002), followed by IIa, then IIb. The anterior GG contained a significantly greater (pxa0=xa00.004) proportion of Type IIa than did the medial or posterior regions, while the posterior GG contained a significantly greater (pxa0=xa00.002) proportion of Type IIb MHC than did the medial or anterior GG. Accordingly, we found variable expression of MHC isoforms across anterior, medial, and posterior portions of the GG muscle, with more fast-contracting isoforms found posteriorly. Because motor control of the tongue requires precise and rapid movements for bolus manipulation and airway protection, variable expression of MHC isoforms along the anteroposterior axis of the GG muscle may be required to efficiently achieve deglutition and maintenance of airway patency.

Effect of Aging on Blood Flow in Rat Larynx

Objective/Hypothesis: Age‐associated muscular changes and fatigue have been shown to affect phonatory function. Reductions in blood flow with aging could translate to reductions in oxidative capacity within laryngeal muscles and increased fatigability. We tested the hypothesis that there would be increased capillary red blood cell (RBC) velocity and a reduction of capillary density in the thyroarytenoid (TA) muscle of senescent rats.