Daniel J. Lee, M.D., F.A.C.S.
Assistant Professor of Otology and Laryngology, Harvard Medical School
Efferent auditory brainstem circuits
Our laboratory has focused on auditory brainstem circuits that control the middle ear muscle reflexes, one of two major descending systems that provide feedback to the auditory periphery. Collaborating with M. Christian Brown, Ph.D., we are characterizing the anatomy and physiology of the middle ear muscle reflexes in a rat model using retrograde labeling studies as well as lesioning experiments of the cochlear nucleus. We also perform transneuronal tracing of these auditory brainstem pathways using pseudorabies virus (PRV), a powerful neurotropic viral tracer. Our group is using PRV to identify synaptically linked neurons in the CNS that are involved in both the medial olivocochlear and middle ear muscle reflex pathways.
Auditory brainstem implants
My clinical research interests in pediatric and adult cochlear implants have extended to work in the central auditory system as the principal investigator and director of the Helene and Grant Wilson Auditory Brainstem Implant (ABI) Program, a multidisciplinary research and clinical effort with collaborators at MEEI and the Massachusetts General Hospital. Our goals are to 1) provide ABIs to patients who are deaf and are not candidates for cochlear implants due to injured or absent auditory nerves (patients with Neurofibromatosis Type 2, cochlear ossification / labyrinthitis ossificans, severe cochlear hypoplasia, or traumatic bilateral auditory nerve injury and 2) conduct basic and clinical research on how to improve the performance of ABIs.
Optical stimulation of the auditory system
Our recent work in the ABI lab has included the first efforts to use optical stimulation using to stimulate neurons in the central auditory system. In neural prostheses, optical stimulation may offer more selectivity than electrical stimulation due to reduced spread of the stimulus. Results of peripheral auditory neural stimulation using low power infrared lasers have been previously described by Izzo et al. (2006, Lasers Surg Med 38: 745-53) and Richter et al. (2008, Hear Res 242: 42-51). Our work is the first description of optical stimulation of the CNS and we have shown that mid-wavelength infrared lasers are capable of acutely stimulating neurons of the cochlear nucleus without tissue damage. These findings may provide the basis for novel auditory implant stimulation paradigms in the future.
Figure 1. Optical stimulation of the cochlear nucleus. A: Photo showing exposure of the brainstem following suboccipital craniotomy and cerebellar aspiration (left cochlear nucleus and 4th ventricle are indicated) in a rat model. An optical fiber, mounted on a micromanipulator, contacts the caudal surface of the lateral aspect of the dorsal cochlear nucleus. B: Optically evoked auditory brainstem responses (oABRs) in the anesthetized animal measured during baseline optical stimulation of the cochlear nucleus (black) and with laser output blocked (gray) demonstrate that observed oABRs are not an artifact produced by the laser source. C: oABRs measured immediately before administration of lethal anesthetic dose (black), and 30 minutes later, soon after death of the animal (gray).
Vestibular prosthesis development
My secondary basic research interests have included a collaboration with Daniel Merfeld, Ph.D., and Richard Lewis, M.D., of the Jenks Vestibular Laboratory, MEEI. The focus of our joint project has been to develop a vestibular prosthesis in a rhesus monkey model. Future work will include optical stimulation approaches to stimulate the vestibular periphery using a low power infrared laser.
1. Lee, D. J., H. B. Cahill, et al. (2003). "Effects of congenital deafness in the cochlear nuclei of Shaker-2 mice: an ultrastructural analysis of synapse morphology in the endbulbs of Held." J Neurocytol 32: 229-243.
2. Lee, D. J. and M. Driver (2005). "Cochlear implant fixation using titanium screws." Laryngoscope 115(5): 910-1.
3. Lee, D. J., L. Lustig, et al. (2005). "Effects of cytomegalovirus (CMV) related deafness on pediatric cochlear implant outcomes." Otolaryngol Head Neck Surg 133(6): 900-5.
4. Lee, D. J., R. K. de Venecia, et al. (2006). "Central auditory pathways mediating the rat middle ear muscle reflexes." Anat Rec 288(4): 358-69.
5. Lee, D. J., B. Maseyesva, et al. (2006). "Microsatellite analysis of recurrent vestibular schwannoma (acoustic neuroma) following stereotactic radiosurgery." Otol Neurotol 27(2): 213-9.
6. Lewis, R., C. Haburcakova, et al. (2006). "Effects of semicircular canal activation on perceived head orientation " Abstr Assoc Res Otolaryngol 29.
7. Watters, K. F., J. J. Rosowski, et al. (2006). "Superior semicircular canal dehiscence presenting as postpartum vertigo." Otol Neurotol 27(6): 756-68.
8. Lewis, R. F., C. Haburcakova, et al. (2007). "Vestibular influences on tilt perception and postural control in rhesus monkey." Neuroscience Abstracts 2007.
9. Merchant, S. M., H. H. Nakajima, et al. (2007). "Clinical investigation and mechanism of air-bone gap in large vestibular aqueduct syndrome." Ann Otol Rhinol Laryngol 116(7): 532-541.
10. Poissant, S. F., F. Beaudoin, et al. (2007). "The impact of cochlear implantation on speech understanding, depression, and loneliness in the elderly." Am J Otolaryngol 37(4): in press.
11. Roditi, R., S. F. Poissant, et al. (2008). "A predictive model of cochlear implant performance in postlingually deafened adults." Otol Neurotol: in press.
12. Lee, D. J., T. E. Benson, et al. (2008). "Diverse synaptic terminals on rat stapedius motoneurons." J Assoc Res Otolaryngol 9(3): 321-33.
13. Lee, D. J., K. E. Hancock, et al. (2009). "Optical stimulation of the central auditory system." Abstr Assoc Res Otolaryngol 32