Dysphagia in Parkinson Disease: Part I - Pathophysiology and Diagnostic Practices.

Purpose of Review: Dysphagia affects the majority of individuals with Parkinson disease (PD) and is not typically diagnosed until later in disease progression. This review will cover the current understanding of PD pathophysiology, and provides an overview of dysphagia in PD including diagnostic practices, gaps in knowledge, and future directions. Recent Findings: Many non-motor and other motor signs of PD appear in the prodrome prior to the manifestation of hall- mark signs and diagnosis. While dysphagia often presents already in the prodrome, it is not routinely addressed in standard neurology examinations. Summary: Dysphagia in PD can result in compromised efficiency and safety of swallowing, which significantly contributes to malnutrition and dehydration, decrease quality of life, and increase mortality. The heterogeneous clinical presentation of PD complicates diagnostic procedures which often leads to delayed treatment. Research has advanced our knowledge of mechanisms underlying PD, but dysphagia is still largely understudied, especially in the prodromal stage.

Early ultrasonic vocalization deficits and related thyroarytenoid muscle pathology in the transgenic TgF344-AD rat model of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurologic disease and the most common cause of dementia. Classic pathology in AD is characterized by inflammation, abnormal presence of tau protein, and aggregation of ß-amyloid that disrupt normal neuronal function and lead to cell death. Deficits in communication also occur during disease progression and significantly reduce health, well-being, and quality of life. Because clinical diagnosis occurs in the mid-stage of the disease, characterizing the prodrome and early stages in humans is currently challenging. To overcome these challenges, we use the validated TgF344-AD (F344-Tg(Prp-APP, Prp-PS1)19/Rrrc) transgenic rat model that manifests cognitive, behavioral, and neuropathological dysfunction akin to AD in humans. Objectives: The overarching goal of our work is to test the central hypothesis that pathology and related behavioral deficits such as communication dysfunction in part manifest in the peripheral nervous system and corresponding target tissues already in the early stages. The primary aims of this study are to test the hypotheses that: (1) changes in ultrasonic vocalizations (USV) occur in the prodromal stage at 6 months of age and worsen at 9 months of age, (2) inflammation as well as AD-related pathology can be found in the thyroarytenoid muscle (TA) at 12 months of age (experimental endpoint tissue harvest), and to (3) demonstrate that the TgF344-AD rat model is an appropriate model for preclinical investigations of early AD-related vocal deficits. Methods: USVs were collected from male TgF344-AD (N = 19) and wildtype (WT) Fischer-344 rats (N = 19) at 6 months (N = 38; WT: n = 19; TgF344-AD: n = 19) and 9 months of age (N = 18; WT: n = 10; TgF344-AD: n = 8) and acoustically analyzed for duration, mean power, principal frequency, low frequency, high frequency, peak frequency, and call type. RT-qPCR was used to assay peripheral inflammation and AD-related pathology via gene expressions in the TA muscle of male TgF344-AD rats (n = 6) and WT rats (n = 6) at 12 months of age. Results: This study revealed a significant reduction in mean power of ultrasonic calls from 6 to 9 months of age and increased peak frequency levels over time in TgF344-AD rats compared to WT controls. Additionally, significant downregulation of AD-related genes Uqcrc2, Bace2, Serpina3n, and Igf2, as well as downregulation of pro-inflammatory gene Myd88 was found in the TA muscle of TgF344-AD rats at 12 months of age. Discussion: Our findings demonstrate early and progressive vocal deficits in the TgF344-AD rat model. We further provide evidence of dysregulation of AD-pathology-related genes as well as inflammatory genes in the TA muscles of TgF344-AD rats in the early stage of the disease, confirming this rat model for early-stage investigations of voice deficits and related pathology.

Assays of tongue force, timing, and dynamics in rat and mouse models.

Communication and swallowing are highly complex sensorimotor events that are tightly linked to respiration and vital to health and well-being. The tongue is a complex organ, often described as a muscular hydrostat, that is crucial for maintaining airway patency, preparing and safely transporting food/liquid, and rapidly changing position and shape for speech. As with any complex behavior, tongue function can be compromised with aging, diseases/conditions, trauma, or as a pharmacologic side effect. As such, modeling lingual function and dysfunction for basic and translational research is paramount; understanding how the nervous system controls tongue function for complex behavior is foundational to this work. Non-invasive access to tongue tissues and kinematics during awake behavior has been historically challenging, creating a critical need to measure tongue function in model systems. Germane to this field of study are the instruments and assays of licking/lapping and drinking, including tongue force and timing measures, many of which were designed or modified by Dr. Stephen C. Fowler. The focus of this paper is to review some of the important contributions of measuring tongue behaviors in awake rats and mice and how these have been modified by other researchers to advance translational science.

Semi-Automated Training of Rat Ultrasonic Vocalizations.

Rats produce ultrasonic vocalizations (USVs) for conspecific communication. These USVs are valuable biomarkers for studying behavioral and mechanistic changes in a variety of diseases and disorders. Previous work has demonstrated operant conditioning can progressively increase the number of USVs produced by rats over multiple weeks. This operant conditioning paradigm is a useful model for investigating the effects of increased laryngeal muscle use on USV acoustic characteristics and underlying central and peripheral laryngeal sensorimotor mechanisms. Previous USV operant conditioning studies relied on manual training to elicit USV productions, which is both time and labor intensive and can introduce human variability. This manuscript introduces a semi-automated method for training rats to increase their rate of USV production by pairing commercially available operant conditioning equipment with an ultrasonic detection system. USV training requires three basic components: elicitation cue, detection of the behavior, and a reward to reinforce the desired behavior. With the semi-automated training paradigm, indirect exposure to the opposite sex or an olfactory cue can be used to elicit USV production. The elicited USV is then automatically detected by the ultrasonic acoustic system, which consequently triggers the release of a sucrose pellet reward. Our results demonstrate this semi-automated procedure produces a similar increase in USV production as the manual training method. Through automation of USV detection and reward administration, staffing requirements, human error, and subject behavioral variability may be minimized while scalability and reproducibility are increased. This automation may also result in greater experimental flexibility, allowing USV training paradigms to become more customizable for a wider array of applications. This semi-automated USV behavioral training paradigm improves upon manual training techniques by increasing the ease, speed, and quality of data collection.