ATA-Funded Research

The following six grants were selected by ATA's Scientific Advisory Committee in March 2011 and approved for funding by the ATA Board of Directors in April 2011.

 

Berthold Langguth, M.D., Ph.D., University of Regensburg, Bezirksklinikum, Germany
Research Project: rTMS for the Treatment of Tinnitus: Optimization by Stimulation of the Cortical Tinnitus Network
Roadmap to a Cure Paths: A,B,C,D
Funded: 1 Year, $45,000

"It is well known that tinnitus is related to increased activity in central auditory pathways. Repetitive transcranial magnetic stimulation (rTMS) is an innovative method for locally modulating brain activity. With the idea to down-regulate increased activity in the auditory cortex, rTMS has been introduced as a new treatment for tinnitus. Reduction of tinnitus by rTMS has been demonstrated in many studies, however unfortunately the over-all benefits from this treatment are only relatively small. In the last years additional brain areas have been identified, which are strongly connected with the auditory cortex in tinnitus patients. These so-called neuronal networks reflect conscious perception of tinnitus and the emotional reaction to it. With the aim to attack tinnitus more efficiently we propose a new multi-site stimulation protocol perturbing these tinnitus networks at several nodes. We expect that this new rTMS procedure will reduce tinnitus better and in more patients than the existing procedure and will thus provide an efficient new treatment option for the many patients suffering from tinnitus. The presented study is motivated by the concept that tinnitus generation and maintenance is related to a cortical tinnitus network. Within this study these very recent advances in the understanding of the neurobiological mechanisms underlying tinnitus are translated in a hypothesis-driven new treatment approach. Modulation of network activity by rTMS stimulation at multiple sites can be considered either as a new treatment approach or as refinement of rTMS treatment to the auditory cortex and thus applied to path C and D of the ATA roadmap to a cue. In addition effects of this treatment on cortical structure and function will be assessed by EEG, MRI and fMRI. Comparison of clinical and neurobiological findings will provide an unique opportunity to confirm and refine the knowledge about tinnitus related cortical networks, contributing to path A and B of the Roadmap."

 

Jay Piccirillo, M.D., FACS, Washington University in St. Louis, School of Medicine
Research Project: Exploration of Cortical Neural Network in Patients with Bothersome Tinnitus
Roadmap to a Cure Paths: A,B,C,D
Funded: 1 Year, $12,900

 

"Tinnitus is the perceived sensation of sound without actual acoustic stimulation that affects 50 million Americans, with 15 million being significantly bothered. Using functional connectivity MRI (fcMRI), we have found distinct differences in the cortical attention networks between patients with bothersome tinnitus and age‐matched controls. These novel findings suggest that some of the classic and most disturbing characteristics of tinnitus result from derangements in cortical pathways. Using a validated task‐based functional MRI (fMRI) paradigm developed at Washington University, we will explore the ventral and dorsal frontoparietal cortical attention networks in patients with bothersome tinnitus and non‐tinnitus controls. This will be an experimental task‐based fMRI pilot study involving the neuroimaging assessment of patients with severely bothersome tinnitus, defined by a global bothersome scale. We plan to enroll a total of 12 participants (6 severely bothered tinnitus and 6 age‐matched non‐tinnitus controls) over the course of six months to undergo task‐based imaging. The selected paradigm will allow us to advance knowledge about the role of the attention, control, and other cortical networks in the development and maintenance of bothersome tinnitus."

 

Susan Shore, Ph.D., The Regents of the University of Michigan
Research Project: Somatosensory Influence on Physiological and Behavioral Correlates of Tinnitus - Towards an Effective Technique for Alleviating Tinnitus
Roadmap to a Cure Paths: A,B,C

Funded: 1 Year, $45,000

"Tinnitus can be modulated by manipulations of the face, neck or head, such as jaw clenching or pushing on the face or neck. It can also appear after insults to these regions, such as tooth abscess, implicating a somatosensory role in the mechanisms underlying tinnitus. Somatosensory-based treatments of tinnitus in people show promise but there is currently no standard treatment based on rigorous knowledge of underlying mechanisms. Our laboratory team proposes to undertake a detailed evaluation of the acoustic-somatosensory mechanisms involved in tinnitus, preparatory to the development of an implantable electrode to be tested in an animal model (guinea pigs). Our research suggests that combined auditory-somatosenory stimulation may prove to be a viable therapy for the alleviation of tinnitus- and these experiments will provide the crucial groundwork needed before human trials can be recommended. This research encompasses three categories of the Roadmap. A, where tinnitus starts, B how tinnitus starts, and C developing therapies to suppress tinnitus. The main focus of this proposal is to use our previous findings that somatosensory regions projects to the auditory system (A) and cause changes in firing rates and synchrony of auditory brainstem neurons (correlates of tinnitus) (B). Using these findings to develop an optimal electrical stimulation paradigm based on these factors to reduce tinnitus addresses the third goal of the Roadmap (C)."

 

Lucien Thompson, Ph.D., University of Texas at Dallas
Research Project: Developing and Treating Tinnitus by Modulating Neuroplasticity in Hippocampus and Amygdala
Roadmap to a Cure Paths: A,B,C
Funded: 1 Year, $45,000

"Treatments reducing or eliminating tinnitus are critically needed. Surprising changes have been seen in the brains of rats exposed for 30 minutes to loud noise – our experimental tinnitus model. Excitatory neurons in the hippocampus, a limbic region not typically considered an auditory processing region of the brain, lose normal spatial mapping functions minutes after intense noise exposure and acquire a new pattern of activity that lasts at least a day after. We will record and compare changes in these same excitatory and also in inhibitory hippocampal neurons with changes in the amygdala, a limbic region recent fMRI studies suggest is involved in the development and maintenance of tinnitus. We will then test treatments with D-cycloserine, which modulates excitatory glutamate receptors in these and related brain regions and may be beneficial to reduce or prevent both the induction of tinnitus and to reduce or eliminate well established tinnitus, necessitating our planned series of both short- and long-term studies of plasticity. Although tinnitus induces plasticity in the central nervous system, most research has focused upon classical auditory structures. Considerable neural plasticity occurs in limbic regions, supporting both beneficial functions like learning and memory but also significantly contributing to pathologies like epilepsy and tinnitus. Goble et al. (2009) demonstrated novel, robust and rapidly developing altered firing patterns of excitatory neurons in the hippocampus that persisted for 24 hr after high intensity sound exposure in our rat model of tinnitus. The aims of the current proposal are: 1.) to more fully characterize the nature and time course of this plasticity, comparing excitatory and inhibitory neuron firing of both hippocampus and amygdala (another limbic region outside classic auditory pathways but important both for plasticity and for attending to auditory signal relevance) in behaving rats. Tinnitus-induced psychophysical (perceptual) and neural plasticity of hippocampal and amygdala excitatory and inhibitory neurons will be assessed early (immediately after noise exposure), persistently (hours to days later) and long-term (days to months later) to give a quantitative timecourse of tinnitus’s development and maintenance. 2.) test dose- and schedule-dependent effects of D-cycloserine, a drug that modulates limbic plasticity, to eliminate neural and perceptual plasticity early after tinnitus induction, and, also to reduce or eliminate this abnormal plasticity at longer time intervals, after stable tinnitus has been well established. Beneficial treatment effects on limbic neural plasticity and on perceptual changes in tinnitus will be directly compared."

 

Pim Van Dijk, Ph.D., University Medical Center Groningen, Netherlands
Research Project: Response of the Central Auditory System in Tinnitus and Hearing Loss, an fMRI study
Roadmap to a Cure Path: A

Funded: Year 3, $45,000; Grant renewal; 3rd year of 3-year project; (Year 1: $88,006; Year 2: $50,000; Total: $183,006)

"Every sound we hear, including tinnitus, is related to some pattern of activity in the brain. Tinnitus is unusual in that it is not related to an acoustic sound from outside the body. It is believed that tinnitus is caused by pathological neural activity in the brain. The proposed project will investigate brain activity using function magnetic resonance imaging (fMRI). The study compares hearing impaired patients with and without tinnitus. The data that were acquired during the first two years of the project suggest very similar function of the auditory areas in both subject  groups. Possibly, the difference between the groups is not in the auditory areas but in other, non-auditory areas. Specifically, the limbic system in the brain has been suggested to play a role in tinnitus. In the next two years we will try to see whether the interaction between the auditory and non-auditory brain areas might be special in tinnitus subjects. This may explain why some people with hearing loss get tinnitus, while others don't. The third year of this project will include three areas: 1. Subject inclusion and scanning will be completed. This will provide a comprehensive dataset of well-characterized subjects, with and without tinnitus, all with moderate hearing loss. 2. We will analyze interactions between the auditory and limbic brain areas by correlation analysis and independent component analysis (ICA). 3. We will apply voxel-based morphometry (VBM) to identify possible anatomic differences between the subject. Together, these analyses approaches are to identify structural and functional differences between the subject groups."

 

Na Zhu, Ph.D. student; Wayne State University
Research Project: Development of an Innovative, 3D Computer Aided Diagnostic System for Tinnitus
Roadmap to a Cure Path: A

Funded: Student grant, 1 year, $10,000

"This student research project aims at developing an innovative 3D computer aided diagnostic (CAD) system to pinpoint the exact locations of the tinnitus-related neural network activities inside the brain auditory structure. This CAD system will be utilized to monitor changes in tinnitus-related neural network activities at the identified locations after noise exposure and neuromodulation using auditory cortex electrical stimulations (ACES). These procedures will be used to assess tinnitus percepts in animal subjects to observe if there is any causality correlations in the locations where tinnitus-related neural network activities are found most active. The specific aims of this project are to: 1) Examine the effectiveness and robustness of using advanced signal processing technologies, for example, fast wavelet transform (FWT) to suppress uncorrelated interfering and background noise; 2) Examine the accuracy of using the time reversal (TR) algorithm to pinpoint the locations of tinnitus-related neural network activities in the brain auditory pathway, which includes the dorsal cochlear nucleus (DCN), inferior colliculus (IC), and auditory cortex (AC) based on the sanitized data; 3) Monitor the changes in neural network activities at the locations identified in the Specific Aim 2) before and after noise exposure, and utilize the existing metrics to assess the tinnitus percepts in animal subjects; and 4) Establish a causality relationship between hyperactivities at the location identified in the Specific Aim 2 and the tinnitus percepts defined in the Specific Aim. 3). The project will have a significant impact on providing an in-depth understanding of the fundamental neural mechanisms underlying tinnitus, and results will ultimately lead to an effective treatment for a tinnitus patient. This project will address the issues identified in the Roadmap Path A: Determine sites in the brain where tinnitus-producing signals arise. In particular, it will focus on using a novel 3D CAD system to identify the exact locations in the auditory system that exhibits tinnitus-related activities, measure and monitor the changes in these identified locations, assess tinnitus percepts based on the existing metric, and observe and establish any causality relationship between tinnitus percepts and tinnitus activities."