Michelle R. Ciucci

High-Resolution Manometry of Pharyngeal Swallow Pressure Events Associated with Head Turn and Chin Tuck:

Objectives We quantified the effect of swallowing maneuvers on pharyngeal pressure events using high-resolution manometry. Methods Seven subjects swallowed multiple 5-mL water boluses in 3 different postural conditions: neutral, head turn, and chin tuck. Pressure and timing events were recorded with a 36-sensor high-resolution manometry catheter. We analyzed the regions of the velopharynx and the base of the tongue for maximum pressure, rate of pressure increase, pressure gradient, and duration of pressure above baseline. In the region of the upper esophageal sphincter (UES), we analyzed the duration of pressure declination, minimum pressure during UES opening, and maximum pressures before and after UES opening. Results The maneuvers did not have a significant effect on maximum pressure, rate of pressure increase, or pressure gradients in the velopharyngeal or tongue base regions. The duration of pressure above baseline was significantly longer in the velopharynx for head turn. The preswallow maximum UES pressure was significantly greater for neutral swallows than for head turn, and the postswallow maximum pressure was significantly lower for chin tuck. Both maneuvers appeared to prolong UES pressure declination duration, but neither prolongation reached significance. Conclusions High-resolution manometry allows for optimal spatial and temporal resolution during recording of pressure events along the length of the pharynx, and revealed previously undetected task-dependent pressure and timing differences during chin tuck and head turn in healthy adults. These maneuvers appear to influence the UES to a greater degree than the velopharynx or the tongue base. Further studies designed to quantify the effect of other maneuvers and bolus consistencies on the generation of pharyngeal pressure events both in normal and in disordered subjects may lead to hypothesis-driven, optimal, individualized swallowing therapies.

Pharyngeal swallow adaptations to bolus volume measured with high resolution manometry

To determine the effect of bolus volume on pharyngeal swallowing using high‐resolution manometry (HRM).

Subthalamic Nucleus Deep Brain Stimulation Improves Deglutition in Parkinson's Disease

Relatively little is known about the role of the basal ganglia in human deglutition. Deep brain stimulation (DBS) affords us a model for examining deglutition in humans with known impairment of the basal ganglia. The purpose of this study was to examine the effects of subthalamic nuclei (STN) DBS on the oral and pharyngeal stages of deglutition in individuals with Parkinsons Disease (PD). It was hypothesized that DBS would be associated with improved deglutition. Within participant, comparisons were made between DBS in the ON and OFF conditions using the dependent variables: pharyngeal transit time, maximal hyoid bone excursion, oral total composite score, and pharyngeal total composite score. Significant improvement occurred for the pharyngeal composite score and pharyngeal transit time in the DBS ON condition compared with DBS OFF. Stimulation of the STN may excite thalamocortical or brainstem targets to sufficiently overcome the bradykinesia/hypokinesia associated with PD and return some pharyngeal stage motor patterns to performance levels approximating those of “normal” deglutition. However, the degree of hyoid bone excursion and oral stage measures did not improve, suggesting that these motor acts may be under the control of different sensorimotor pathways within the basal ganglia.

High-resolution manometry of pharyngeal swallow pressure events associated with effortful swallow and the Mendelsohn maneuver.

Effortful swallow and the Mendelsohn maneuver are two common strategies to improve disordered swallowing. We used high-resolution manometry (HRM) to quantify the effects of these maneuvers on pressure and timing characteristics. Fourteen normal subjects swallowed multiple, 5-ml water boluses using three techniques: normal swallow, effortful swallow, and the Mendelsohn maneuver. Maximum pressure, rate, duration, area integral, and line integral were determined for the velopharynx and tongue base. Minimum pressure, duration of pressure-related change, duration of nadir pressure, maximum preopening and postclosure pressure, area integral, and line integral were recorded for the upper esophageal sphincter (UES). Area and line integrals of the velopharyngeal pressure curve significantly increased with the Mendelsohn maneuver; the line integral increased with the effortful swallow. Preopening UES pressure decreased significantly for the Mendelsohn, while postclosure pressure tended to increase insignificantly for both maneuvers. UES area and line integrals as well as nadir UES pressure duration increased with both maneuvers. Maneuver-dependent changes were observed primarily at the velopharynx and UES. These regions are critical to safe swallowing, as the velopharynx provides positive pressure at the bolus tail while the UES allows a bolus to enter the esophagus without risk of regurgitation. Integrals were more responsive than maximum pressure or duration and should be investigated further.

Automated Analysis of Pharyngeal Pressure Data Obtained with High-Resolution Manometry

We present an algorithm developed in MATLAB that can be applied to both normal and disordered swallowing to automatically extract a wide array of measurements from the spatiotemporal plots produced by high-resolution manometry (HRM) of the pharyngeal swallow. The algorithm was developed from data from 12 normal and 3 disordered subjects swallowing 5-ml water boluses. Automated extraction was compared to manual extraction for a subset of seven normal and the three disordered subjects to evaluate algorithm accuracy. Area and line integrals, pressure wave velocity, and pressure gradients during upper esophageal sphincter opening were also measured. Automated extraction showed strong correlations with manual extraction, producing high correlation coefficients in both normal and disordered subjects for maximum velopharyngeal pressure and maximum tongue base pressure. Timing data were also strongly correlated for all variables, including velopharyngeal pressure duration, tongue base pressure duration, and total swallow duration. Preliminary descriptive data on area and line integrals are presented. Our results indicate that the algorithm can effectively extract data automatically from HRM spatiotemporal plots. The efficiency of the algorithm makes it a valuable tool to supplement clinical and research use of HRM.

Morphological and behavioral impact of AAV2/5-mediated overexpression of human wildtype alpha-synuclein in the rat nigrostriatal system.

The discovery of the involvement of alpha-synuclein (α-syn) in Parkinson’s disease (PD) pathogenesis has resulted in the development and use of viral vector-mediated α-syn overexpression rodent models. The goal of these series of experiments was to characterize the neurodegeneration and functional deficits resulting from injection of recombinant adeno-associated virus (rAAV) serotype 2/5-expressing human wildtype α-syn in the rat substantia nigra (SN). Rats were unilaterally injected into two sites in the SN with either rAAV2/5-expressing green fluorescent protein (GFP, 1.2 x 1013) or varying titers (2.2 x 1012, 1.0 x 1013, 5.9 x 1013, or 1.0 x 1014) of rAAV2/5-α-syn. Cohorts of rats were euthanized 4, 8, or 12 weeks following vector injection. The severity of tyrosine hydroxylase immunoreactive (THir) neuron death in the SN pars compacta (SNpc) was dependent on vector titer. An identical magnitude of nigrostriatal degeneration (60-70% SNpc THir neuron degeneration and 40-50% loss of striatal TH expression) was observed four weeks following 1.0 x 1014 titer rAAV2/5-α-syn injection and 8 weeks following 1.0 x 1013 titer rAAV2/5-α-syn injection. THir neuron degeneration was relatively uniform throughout the rostral-caudal axis of the SNpc. Despite equivalent nigrostriatal degeneration between the 1.0 x 1013 and 1.0 x 1014 rAAV2/5-α-syn groups, functional impairment in the cylinder test and the adjusting steps task was only observed in rats with the longer 8 week duration of α-syn expression. Motor impairment in the cylinder task was highly correlated to striatal TH loss. Further, 8 weeks following 5.9 x 1013 rAAV2/5-α-syn injection deficits in ultrasonic vocalizations were observed. In conclusion, our rAAV2/5-α-syn overexpression model demonstrates robust nigrostriatal α-syn overexpression, induces significant nigrostriatal degeneration that is both vector and duration dependent and under specific parameters can result in motor impairment that directly relates to the level of striatal TH denervation.

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.

Dopaminergic influence on rat tongue function and limb movement initiation

Altering dopamine synaptic transmission can affect both cranial and limb sensorimotor function, but often to a different degree of severity. We hypothesized that haloperidol has dose-dependent but differential effects on lingual forces, lingual movement rates, and limb movement initiation. We measured average and maximal lingual force, tongue press rate and cataleptic descent time in nine Fischer 344/Brown Norway rats in varied doses of haloperidol. Decreases in lingual force and temporal parameters and increases in cataleptic descent time were related to haloperidol dose. However, they were related to a different degree as the relationships were strong between average force and tongue press rate, moderate between maximal force and tongue press rate, moderate between average force and cataleptic descent time, and weak between maximal force and cataleptic descent time. Elucidating the relationships between the cranial and limb sensorimotor systems in the context of altered dopamine synaptic transmission may assist in developing therapies for conditions such as Parkinson’s disease.