ATA-Funded Research in 2013-2014
In June, ATA named the recipients of our 2013-2014 advanced tinnitus research grants. This year, the ATA Board of Directors approved $110,000 of total funding to support 3 unique and particularly-promising tinnitus research projects. A synopsis of each proposal is included below, so you can read more about these projects and their potential impact for tinnitus patients.
Role of the Cholinergic System in Modulation of Tinnitus
James Kaltenbach, Ph.D., Cleveland Clinic, Cleveland, OH
Roadmap to a Cure: Pathway C
Tinnitus is often attributed to hyperactivity of the brain’s auditory neurons. (Neurons are special cells that process sound information through electrical and chemical signals.) When a person is exposed to a loud sound or other tinnitus-inducing trauma, the brain circuits get altered and neurons start firing excessively. The result is the perception of sound when no external noise is present. In this model of tinnitus, the perception of sound (ringing) could be eliminated by reducing or compensating for the hyperactivity of these neurons.
Dr. Kaltenbach’s laboratory at the Cleveland Clinic has been studying the brain’s cholinergic system—how neurons transmit information using chemical neurotransmitters—and has identified a specific neurotransmitter, acetylcholine, that modulates the hyperactivity that underlies tinnitus. His previous research has already shown that the chemical compound Carbachol successfully activates the acetylcholine receptor, reducing neural hyperactivity and effectively eliminating tinnitus. Unfortunately, this compound is not useful as a therapy due to its extreme side effects, which include significant damage to the heart and gastrointestinal system.
However, Dr. Kaltenbach believes it is possible to identify a related compound that only targets neural activity related to tinnitus. (Each neuron has many receptor subtypes, each controlling a different neural reaction; the key to this study is finding a chemical compound that will stimulate only those receptors related to auditory activity.) Dr. Kaltenbach will use funding from ATA to explore three particularly promising compounds that target specific receptors in animals, to see which one best and most safely suppresses neuron hyperactivity and the perception of tinnitus. He is especially optimistic about work related to the muscarinic receptors, as there is already a strong consensus that drug interactions with these receptors are safe for humans.
The potential impact of this research is huge. If Dr. Kaltenbach can show that activating one or more receptor subtypes results in suppression of tinnitus, it would implicate these specific neural areas as useful drug targets. If successful, this research would accelerate the development of commercially-available prescription medications to silence tinnitus.
Tinnitus and Tonotopic Remapping of the Auditory Cortex
Pim van Dijk, Ph.D., Emile de Kleine, Ph.D. and D.R.M. Langers, Ph.D., University Medical Center Groningen, Groningen, The Netherlands
Roadmap to a Cure: Pathways A, B & C
Tinnitus is believed to be related to changes in the brain, specifically a process referred to as tonotopic reorganization. (Tonotopy is the organization of how particular sound frequencies are processed in different areas of the brain.) Reorganizaiton may lead to an overrepresentation of particular sound frequencies in the brain, which leads to the perception tinnitus. Several therapies have been proposed to restore normal tonotopy, and thereby possibly cure tinnitus.
However, the underlying assumption that tinnitus is caused by tonotopic reorganization has never been fully tested in humans. Dr. Van Dijk’s project addresses this gap in the research. For the first time, researchers will used a new state-of-the-art functional magnetic resonance imaging (fMRI) to robustly measure detailed tonotopic maps in subjects with and without tinnitus will be tested. By a comparison of these two groups, it will become clear to what extent tinnitus is associated with the manifest tonotopic reorganization.
If it is affirmed that tinnitus is related to tonotopic reorganization in the human brain, it will strongly stimulate the development of therapies (such a new sound therapies) that aim to restore normal tonotopic representation and thereby cure tinnitus.
Dissociating Mechanisms of Tinnitus & Hyperacusis:
A Survey & Behavioral Study
Jenise Imani Chappell (Student) and Fatima Husain, Ph.D. (Mentor), University of Illinois at Urbana, Urbana, IL
Roadmap to a Cure: Pathways A & D
Tinnitus and hyperacusis are often co-morbid conditions; past research has estimated that 40-79% of tinnitus patients also report increased sensitivity to sound. This study will explore whether the two conditions share a common physiological pathway, by comparing otoacoustic emissions in patients with just tinnitus, patients with just hyperacusis, patients with both tinnitus and hyperacusis and a control group.
Otoacoustic emissions are sounds that are generated by the hair cells in the inner ear, which are part of healthy, normal hearing. These emissions diminish after inner ear damage, so measuring these sounds is a clinically useful way of assessing inner ear health. Otoacoustic emissions are NOT the cause of tinnitus; these sounds are imperceptible to the human brain and can only be measured by very sensitive microphones.
Through an online survey and in-person patient testing, the researcher will determine whether tinnitus and hyperacusis share similar otoacoustic emission correlates. If both conditions show similar physiological dynamics, it would indicate that they both could be treated through similar means.
By focusing on patients with both tinnitus and hyperacusis, this study will also highlight the particular treatment needs for this population, with a particular emphasis on how to best use and fit hearing aids. While often used for tinnitus management, current clinical practices around hearing aids do not adequately account for the noise-sensitivity of hyperacusis patients. A better understanding the internal mechanisms of hyperacusis would account for the variable efficacy of hearing aids for these patients and point towards clinical practices for improving outcomes.