Project Grant R01DC021990

CENTRAL MODULATION-PAIRED MOTOR REHABILITATION FOR RECURRENT LARYNGEAL NERVE INJURY - PROJECT SUMMARY/ABSTRACT RECURRENT LARYNGEAL NERVE (RLN) INJURY CAUSES VOCAL FOLD MOTION IMPAIRMENTS (E.G., VOCAL FOLD PARALYSIS). THE INABILITY TO ADDUCT (CLOSE) THE VOCAL FOLDS HAS CONSEQUENCES FOR AIRWAY PROTECTION DURING SWALLOWING (DEGLUTITION) AND VOCAL COMMUNICATION. THESE LARYNGEAL MOTOR DEFICITS RESULT IN INCREASED RISK OF ASPIRATION PNEUMONIA AND HAVE PROFOUND EFFECTS ON VOCAL COMMUNICATION REQUIRED FOR VOCATION, SAFETY, AND SOCIAL ENCOUNTERS. THE RESULT IS ALSO SIGNIFICANT ECONOMIC BURDEN, PSYCHOSOCIAL CONSEQUENCES, AND REDUCED QUALITY OF LIFE. CURRENT SURGICAL APPROACHES FOCUS ON MEDIALIZING THE VOCAL FOLDS TO IMPROVE GLOTTIC CLOSURE, BUT THEY DO LITTLE TO RESTORE FUNCTIONAL MOBILITY TO THE VOCAL FOLD MUSCLES WITHIN THE LARYNX. THE KEY ISSUE IS THAT CURRENT TREATMENTS RARELY RECOVER VOCAL FOLD MOVEMENT AFTER RLN INJURIES DUE TO NERVE SYNKINESIS AT THE PERIPHERY AND UPSTREAM CORTICOBULBAR SOMATO- TOPIC DISORGANIZATION AFTER SPONTANEOUS REINNERVATION. ONE SOLUTION IS TO REORGANIZE UPSTREAM MOTOR PATHWAYS IN THE CENTRAL NERVOUS SYSTEM TO IMPROVE DOWNSTREAM RESTORATION OF LARYNGEAL MUSCLE FUNCTION AFTER RLN INJURY. ELECTRICAL STIMULATION TO THE VAGUS NERVE HAS PREVIOUSLY BEEN SHOWN TO RELEASE NEUROMODULATORS IN THE BRAIN THAT EXCITE TASK-SPECIFIC NEURAL CIRCUITS AND DOWN-REGULATE LESS IMPORTANT CIRCUITS TO IMPROVE MOTOR INPUT TO THE FORELIMB AFTER MEDIAN-ULNAR NERVE INJURY IN A RAT FORELIMB INJURY MODEL. SIMILARLY, OUR PRELIMINARY DATA IN A RAT MODEL OF RIGHT RLN INJURY HAS SHOWN THAT TEMPORAL PAIRING OF ENHANCED CENTRAL NEUROMODULATION IN THE BRAIN WITH A MOTOR-SPECIFIC LARYNGEAL BEHAVIOR, LIKE DEGLUTITION, MAY ALSO RESTORE LARYNGEAL MOTOR FUNCTION. THE OBJECTIVE OF THIS PROPOSAL IS TO DETERMINE THE EFFECTS OF NEUROMODULATION-PAIRED DEGLUTITION ON RECOVERY OF LARYNGEAL MOTOR FUNCTION AND CENTRAL NEUROPLASTICITY IN A RAT MODEL OF RLN INJURY. CAPITALIZING ON OUR PROMISING PRELIMINARY DATA, ANIMALS WILL BE DIVIDED INTO ONE OF THREE GROUPS: ENHANCED NEUROMODULATION PAIRED WITH DEGLU- TITION, DEGLUTITION TRAINING ONLY, AND NEUROMODULATION ONLY. ENHANCED NEUROMODULATION OUTCOMES ACROSS ACUTE AND CHRONIC RLN INJURY WILL BE DETERMINED IN AIM 1 AND ACROSS IPSILATERAL AND CONTRALATERAL INJURY IN AIM 2. FUNC- TIONAL EFFECTS OF NEUROMODULATION/DEGLUTITION COMBINATIONS WILL BE EVALUATED USING LARYNGOSCOPY TO QUANTIFY VOCAL FOLD MOVEMENT ESSENTIAL FOR AIRWAY PROTECTION AND VOCALIZATION. WE WILL ALSO RECORD ULTRASONIC VOCALIZATIONS TO CHARACTERIZE CHANGES IN VOCAL INTENSITY AND TONALITY ACROSS THE GROUPS. CENTRAL NEUROPLASTIC EFFECTS WILL BE ELUCI- DATED WITH RETROGRADE TRACING AND SOMATOTOPIC CORTICOBULBAR MAPPING. EFFECTS OF IPSILATERAL SIMULATION ON THE RLN WILL ALSO BE ELUCIDATED IN AIM 2 USING LARYNGEAL MUSCLE NEUROMUSCULAR JUNCTION COUNT AND MORPHOLOGY ANALYSIS. EXPECTED OUTCOMES WILL BE KNOWN FUNCTIONAL AND MECHANISTIC EFFECTS OF NEUROMODULATION-PAIRED DEGLUTITION. RE- SULTS WILL PROVIDE A SPRINGBOARD FOR NOVEL TREATMENT APPROACHES FOR PATIENTS WITH RLN INJURY-INDUCED LARYNGEAL MOTOR IMPAIRMENTS (E.G., VOCAL FOLD PARALYSIS).