Reversing Pathological Plasticity of Tinnitus in a Rat Model Using Paired Vagus Nerve Stimulation

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Reversing Pathological Plasticity of Tinnitus in
a Rat Model Using Paired Vagus Nerve Stimulation
Navzer Engineer MicroTransponder, Inc.
Disclosure Navzer Engineer, MD, PhD, is a
full-time employee of MicroTransponder, Inc.
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Vagus Nerve Stimulation (VNS)
Auditory Cortex
Lower Auditory Stations
Cochlea

Tones
Vagus Nerve Stimulation
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VNS directs powerful and highly specific neural
plasticity
Normal Auditory Cortex Map
Auditory Cortex Map after pairing a 9 kHz tone
with VNS
Engineer et al., (Accepted, Nature)
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Sensory Input

Neuromodulator Release
Neural Plasticity
VNS Pairing is Key for Generating Plasticity
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Can VNS-directed plasticity be used to treat
tinnitus?
Tones
VNS
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Tinnitus Pathophysiology
Tinnitus
Pathological Plasticity
Hearing Loss or Noise Exposure
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Normal Auditory Cortex Tonotopic Map
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Experimental Design
Control group 1 (300 tones x 20 days)
Experimental group (300 pairings/day x 20 days)
Control group 2 (300 stims x 20 days)
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Behavioral model of the tinnitus percept in rats
VNS TONE PAIRING
Gap detection model (Turner et al., 2006)
SHAM CONTROLS
Engineer et al., (Accepted, Nature)
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Multi-unit Recordings from Auditory Cortex Neurons
Data Acquisition
Auditory Cortex Map
Extracellular Recordings
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VNS tone pairing
Map Distortion
Receptive field size
Excitability
Cortical Synchrony
Engineer et al., (Accepted, Nature)
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Results Summary
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• Proposed Clinical Delivery of VNS-Tone Therapy
• Preclinical optimization is ongoing
• Planning pilot clinical study
• Pursuing other clinical applications
• (PTSD, stroke, phantom limb pain)

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• Acknowledgements
• Michael Kilgard, PhD
• Jonathan Riley
• Jonathan Seale
• Jai Shetake
• Will Vrana
• Mike Borland
• Sindhu Sudanagunta

University of Texas at Dallas