The long-term objective of our research is to better understand the neural control of swallowing and airway protection, to analyze the mechanisms of neurogenic dysphagia and aspiration in a controlled and systematic way, and to develop novel therapies based on pathogenesis. Our specific thesis is that laryngeal afferent feedback during swallowing facilitates the swallowing pattern generator's output to laryngeal and pharyngeal muscles. The internal branch of the superior laryngeal nerve (ISLN) is the principal sensory nerve of the larynx in humans. We propose to study how the ISLN regulates swallowing using nerve blocking and stimulating techniques in healthy subjects. Then, we plan to use what we learn about the ISLN to devise a method for improving glottic closure and pharyngeal contraction during swallowing in patients with dysphagia and aspiration due to cerebral lesions.
Specific aims are: 1) To determine the physiological mechanism of aspiration in healthy subjects with ISLN blockade. Our preliminary studies show that the bolus usually penetrates the laryngeal inlet during the pharyngeal phase of swallowing. We will use electromygraphic, fluoroscopic and manometric techniques to analyze whether laryngeal penetration is due to reduced activation of laryngeal adductors, excessive intrapharyngeal pressure, or excessive inspiratory effort. 2) To test for extrafusal motor fibers in the ISLN. We will test the widely held view that the ISLN functions purely as an afferent by applying supramaximal current pulses to the isolated ISLN in patients undergoing laryngeal surgery. The presence of efferent fibers would be supported by a short latency (<5msec) laryngeal or pharyngeal motor response that is abolished following ISLN transection. 3) To optimize the activation of laryngeal adductors and pharyngeal constrictors evoked by ISLN stimulation. In awake healthy subjects with blocked ISLNs, we will attempt to reverse dysphagia and aspiration by electrically stimulating the ISLN central to the block, and the optimum stimuli that potentiate swallowing without causing discomfort will be determined. 4) To test the feasibility of ISLN stimulation for treatment of neurogenic dysphagia and aspiration in patients with cerebral lesions. We will stimulate the ISLN (using optimum parameters from Aim 3) in patients with neurogenic dysphagia caused by focal cerebral damage, and we will test for improvement in swallowing and decrease in aspiration.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071884-03
Application #
6917108
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Twery, Michael
Project Start
2003-07-17
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$278,250
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Neurology
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Indic, Premananda; Paydarfar, David; Barbieri, Riccardo (2013) Point process modeling of interbreath interval: a new approach for the assessment of instability of breathing in neonates. IEEE Trans Biomed Eng 60:2858-66
Indic, Premananda; Paydarfar, David; Barbieri, Riccardo (2011) A point process model of respiratory dynamics in early physiological development. Conf Proc IEEE Eng Med Biol Soc 2011:3804-7
Indic, Premananda; Bloch-Salisbury, Elisabeth; Bednarek, Frank et al. (2011) Assessment of cardio-respiratory interactions in preterm infants by bivariate autoregressive modeling and surrogate data analysis. Early Hum Dev 87:477-87
Indic, Premananda; Schwartz, William J; Paydarfar, David (2008) Design principles for phase-splitting behaviour of coupled cellular oscillators: clues from hamsters with 'split'circadian rhythms. J R Soc Interface 5:873-83