Johns Hopkins University

Modulation of neuro-glial cortical networks during tinnitus

My long term goals are to understand the complexity and temporal sequencing of tinnitus effectors with an integrative perspective, considering the interplay of the diverse cell types that might promote the development and maintenance of tinnitus to provide an updated interpretation of this disorder. Additionally, to use glial cells as a key therapeutic target to treat tinnitus.

Generously funded by the Les Paul Foundation

Johns Hopkins University School of Medicine

Emergence of tonotopically organized spontaneous activity in the brain after genetic disruption of MET channel

Secondary disorders develop alongside hearing loss, such as the perception of phantom sounds (tinnitus) and a hypersensitivity to sound (hyperacusis). These disorders have no curative treatment, in part due to our poor understanding of the underlying neurobiology. Using experimental models of hearing loss, I recently discovered that sound-independent (SI) patterns of neural activity emerge in the brain’s auditory centers that resemble those elicited by sound in hearing mice. This finding indicates that the brain can self- generate neural patterns that resemble sound processing, independent of the inner ear. To understand the relevance of SI activity to human disorders like tinnitus, I’ll expand these findings to more translationally relevant models of hearing loss (loud noise exposure and age-related hearing loss), as well as determine the area of the brain that generates these patterns. The results of these studies may help to develop new approaches to treat tinnitus, hyperacusis, and related disorders.

University of Pittsburgh
Characterizing tinnitus-induced changes in auditory corticofugal networks

The irrepressible perception of sounds without an external sound source is a symptom that is present in a number of different auditory dysfunctions. It is the primary complaint of tinnitus sufferers, who report significant “ringing” in the ears, and it is one of the primary sensory symptoms present in schizophrenia sufferers who “hear voices.” Tinnitus is thought to reflect a disorder in gain: A loss of input at the periphery shifts the balance of excitation and inhibition throughout the auditory hierarchy leading to excess hyperexcitability, which then leads to the perception of phantom sounds. This project aims to quantify how such “phantom sound” signals are routed and broadcast across the entire brain, and to understand how these signals impact our ability to perceive sound. Identifying improper regulation of brain-wide neural circuits in this way will provide a foundation for the development of new treatments for tinnitus and other hearing disorders.

University of Michigan
Development and transmission of the tinnitus neural code

Noise overexposure is a common risk factor of tinnitus, and is thus used as a common tinnitus inducer in animal research. However, noise exposure does not always cause tinnitus, and researchers would rely on behavioral testing to infer an animal’s subjective pathology. However, behavioral tests only work under the assumption that tinnitus is unchanging during the long testing period, which does not reflect the dynamic nature of tinnitus as well as ignoring variability. This inability to measure tinnitus within a short time window impedes our understanding of its emergence and progression. The project addresses these limitations through bypassing behavioral testing and directly identifying and locating an objective code for tinnitus in real-time spiking neurons. Using a novel data-driven approach, we can pinpoint exactly when/where tinnitus emerges and examine how noise trauma triggers and transmits the tinnitus signal throughout the auditory pathway.