2015

Hari Bharadwaj, Ph.D.

Hari Bharadwaj, Ph.D.

Massachusetts General Hospital
A systems approach to characterization of subcortical and cortical contributions to temporal processing deficits in central auditory processing disorders

Increasingly in the clinic, children report difficulty in understanding speech in the presence of other competing sounds. When these children are able to detect faint tones normally and show no classic signs of other neurological disorders, they are labeled as having Central Auditory Processing Disorder (CAPD). Understanding speech in a noisy setting is complex and relies both on the representation of subtle sound features by the auditory system, and the brain’s ability to make use of this information. Thus, difficulty can arise for a variety of reasons. Indeed, difficulty communicating in noisy settings is reported in a wide range of diagnostic categories such as Language Delays, Autism Spectrum Disorders, and Dyslexia among others. Yet, robust diagnostics that characterize CAPD – an auditory-specific disorder – as distinct from these other disorders are lacking. Here, we will use otoacoustic emissions and non-invasive brain imaging techniques (Electro/Magnetoencephalography) to passively measure how children’s inner ear, brainstem and cortex capture sound information. By examining the relationship between these measures and listening behavior, we aim to obtain a detailed objective test battery for the assessment of auditory function that would lead to novel clinical diagnostics for CAPD and provide clues for targeted intervention.

Brad Buran, Ph.D.

Brad Buran, Ph.D.

Oregon Health & Science University
Neural mechanisms of hyperacusis in the inferior colliculus and cortex of ferrets with noise-induced auditory neurodegeneration

The development of effective treatments for hyperacusis (the diminished tolerance of loud sounds) and tinnitus (a persistent ringing in the ears) is limited by existing animal models. Current animal models are generated by high-intensity noise exposure or by the administration of salicylate, the active ingredient in aspirin. In addition to producing symptoms of hyperacusis and tinnitus, both of these manipulations lead to elevated hearing thresholds by damaging inner ear sensory cells. Damage to inner ear sensory cells leads to altered auditory processing, which makes it difficult to identify the specific changes that produce hyperacusis and tinnitus. While hearing loss is the primary risk factor for these disorders, they cannot be explained by damage to sensory cells alone. In fact, hyperacusis, tinnitus, and difficulty understanding speech in noise have been reported even in individuals with normal auditory thresholds. Therefore, in order to tease out the specific changes to the auditory system that result in tinnitus and hyperacusis, the ideal animal model should not have sensory cell damage.

Recent evidence from studies in mice suggests that moderate noise exposure can cause damage to the auditory nerve without altering hearing thresholds. Mice with this type of auditory nerve damage show symptoms of hyperacusis and humans who report tinnitus, but have normal auditory thresholds, also show signs of similar damage. It has also been hypothesized that auditory nerve damage will lead to increased difficulty understanding speech in the presence of background noise. Thus, moderate noise exposure provides a potential animal model for patients who have normal hearing thresholds, yet still experience hyperacusis, tinnitus, or difficulty hearing in noise. We will assess the perceptual effects of this auditory nerve damage by training noise-exposed ferrets to perform behavioral tests designed to parallel tests of hyperacusis, tinnitus, and difficulty hearing in noise that are conventionally used in human listeners. We will also assess how auditory responses in the central auditory system are altered by this type of auditory deficit to determine whether the changes in neural responses may explain the perceptual effects of hyperacusis, tinnitus, and difficulty hearing in noise.

Andrew Dimitrijevic, Ph.D.

Andrew Dimitrijevic, Ph.D.

Cincinnati Children's Hospital Medical Center
Sensory and Cognitive Processing in Children with Auditory Processing Disorders: Behavior and Electrophysiology

Central Auditory Processing Disorder (CAPD) can be defined as having a listening difficulty despite having normal hearing. One theory of CAPD is that this bottom-up processing isn’t working properly, a bit like listening to a de-tuned radio or TV. However, when the sound code reaches the cortex, it is mixed with a variety of signals from other systems, including vision, memory and attention. A second theory of CAPD is that the problem occurs at this level of mixing. In this ‘top-down’ theory, inappropriate control signals from high-level thinking systems, especially memory and attention, are thought to lead to misunderstanding of the code produced in the auditory system. Unfortunately, these two theories are difficult to tease apart. For example, a typical statement by a parent of a child with CAPD is that (s)he seems unaware when being spoken to. This could indicate poor listening due to inattention, or due to an inability to process speech sounds in the auditory system. Understanding which theory is correct may be important for treatment of CAPD. This research aims to tease apart these two theories by examining how the brain processes sound. One aspect of this research will examine how the brain encodes pitch and level fluctuations in sound. Both of these sound qualities are the “building blocks” of speech. If there are deficits at this level of neural processing then perhaps a “bottom up” or sound encoding problem exists. Another aspect of this research will examine a more cognitive approach and examine how the brain deals with speech in noise. This will be indexed by use of brain oscillations which are thought to reflect neural networks across different parts of the brain. Therefore by approaching CAPD from these two directions, it may be possible to show whether their listening difficulties are due to bottom-up or top-down processing problems.

Noah R. Druckenbrod , Ph.D.

Noah R. Druckenbrod , Ph.D.

Harvard University
Identifying roles for contact-dependent signaling between neurons and glia during axon guidance and synaptic targeting

The mature cochlea is a spiraled hollow chamber of bone that contains all the necessary components to transmit sound information to the brain. This feat is accomplished by the precise arrangement of hair cells and spiral ganglion neurons (SGNs). This arrangement requires SGNs extend peripheral projections and establish precise synaptic connections with hair cells. What signals guide these axons through the three-dimensional terrain of the cochlea? Most studies focus on the roles of classically described axon guidance cues, which act over long distances to attract or repel axons. However, mounting evidence from recent studies and our own preliminary data lead us to hypothesize that contact-dependent signaling between SGNs and Schwann cells (SCs) are required for normal development of inner ear neural architecture and hearing. The precise role of contact-dependent interactions between SGN axons and SCs on auditory circuit formation remains unknown. This is due in part to the obstacles towards gathering high-resolution, time-lapsed information on the spatial relationships between SGNs and SCs in situ. Therefore, we will genetically label and characterize live cellular interactions between these cells in their normal, and then abnormal, physiological environment. We will measure the extent to which each of these cell types rely on each other for normal migration, differentiation, proliferation and survival. Because we have identified a mutant in which SGN-Schwann cell interaction appears disrupted, these studies will also provide insight to our understanding of Schwannoma formation. Schwannomas are Schwann cell tumors commonly found in the inner-ear and are thought to arise from a disruption in reciprocal signaling between spiral ganglion neurons (SGNs) and Schwann cells. As these tumors grow they compress afferent vestibular and auditory nerves, usually causing hearing loss, tinnitus, and dizziness. Therefore, these studies will not only contribute to our understanding of auditory circuit formation but also provide insight into what can go wrong when SGN-Schwann cell interaction is disrupted.

Wafaa Kaf, M.D., MS.c., Ph.D.

Wafaa Kaf, M.D., MS.c., Ph.D.

Missouri State University
Novel Ménière’s disease diagnosis: extratympanic simultaneous recording of ECochG and ABR to fast click rates using CLAD technique

Ménière’s disease is mainly diagnosed clinically with no available sensitive objective measures to confirm clinical diagnosis. Current auditory electrophysiologic measures such as standard electrocochleography (ECochG) to a slow click rate has low sensitivity that limits its clinical use. Also, standard ECochG to slow rate cannot measure neural adaptation phenomenon (decrease in the neural firing between the inner hair cells and auditory nerve) that occurs in response to continuous presentation of a fast acoustic stimulus. Although other technique modifications of ECochG such as maximum length sequence to fast rate seem to be promising, several limitations in extracting responses to very fast rates exist with this measure that hinder their clinical use for detection of Ménière’s disease. The new continuous loop averaging deconvolution (CLAD) algorithm is a promising technique to extract overlapping auditory evoked responses to very fast rates, providing valuable information about cochlear and neural function of clinical populations. Thus, the use of CLAD with fast rate ECochG and auditory brainstem response (ABR) has the potential to detect early Ménière’s disease by studying the neural adaptation phenomenon. It is hypothesized that Ménière’s disease may show abnormally fast neural adaptation that may manifest as fast degradation of AP and ABR response amplitudes and prolongation of latency as a function of click rate. The current objectives and the long-term goals of this project are to establish and advance ECochG and ABR measures using CLAD technique to identify the critical rate at which neural adaptation starts as a marker for early diagnosis, differential diagnosis and classification of Ménière’s disease.

Beula Magimairaj, Ph.D.

Beula Magimairaj, Ph.D.

University of Central Arkansas
Moving the science forward through interdisciplinary collaborative research integrating Hearing, Language, and Cognitive Science

Clinicians and researchers lack a consensual theoretical and clinical framework for conceptualizing Central Auditory Processing Disorder (CAPD) because professionals in different disciplines characterize it differently. Children diagnosed with CAPD may have deficits in attention, language, and memory, which often go unrecognized. There is a lack of a valid and reliable assessment tool that can characterize auditory processing, attention, language, and memory on the front-end. This project is an interdisciplinary effort to lay the foundation for such an assessment. Our goal is to develop an assessment that includes sensitive measures that can help build an initial profile of a child’s source(s) of difficulties that may be manifested as auditory processing deficits. During this 1-year project, computer-based behavioral tasks that integrate theoretical and methodological advances from the CAPD literature, and hearing, language, and cognitive science, will be developed. Tasks will be piloted on sixty typically developing children (7-11 years) who have no history of auditory processing/cognitive disorders for feasibility testing. Developing an assessment that will validly characterize the abilities of affected children is a multi-stage enterprise and this project is a critical first step.

Frances Meredith, Ph.D.

Frances Meredith, Ph.D.

University of Colorado Denver
The role of K+ conductances in coding vestibular afferent responses

Approximately 615,000 people in the United States suffer from Meniere’s disease, a disorder of the inner ear that causes episodic vertigo, tinnitus and progressive hearing loss. The underlying etiology of the disease is not known but may include defects in ion channels and alterations in inner ear fluid potassium (K+) ion concentration. Specialized hair cells inside the ear detect head movement in the vestibular system and sound signals in the cochlea. A rich variety of channels is found on the membranes of hair cells as well as on the afferent nerve endings that form connections (synapses) with hair cells. Many of these channels selectively allow the passage of K+ ions and are thought to be important for maintaining the appropriate balance of K+ ions in inner ear fluids. I study an unusual type of nerve ending called a calyx, found at the ends of afferent nerves that form synapses with type I hair cells of the vestibular system. These nerves send electrical signals to the brain about head movements. My goal is to use immunocytochemistry and electrophysiology to identity K+ channels on the calyx membrane and to explore their role in regulating electrical activity and K+ levels in inner ear fluid. I will identify potential routes for K+ entry that could influence calyx properties. I will investigate whether altered ionic concentrations in inner ear fluid change the buffering capacity of K+ channels and whether this affects the signals that travel along the afferent vestibular nerve to the brain. Meniere’s disease is a disorder of the entire membranous labyrinth of the inner ear and thus affects both the vestibular sensory organs and the cochlea. Similar K+ ion channels are expressed in vestibular and auditory afferent neurons. Studying ion channels present in both auditory and vestibular systems will reveal properties common to both systems and will increase our understanding of the importance of ion channels in Meniere’s disease.

Kelly Radziwon, Ph.D.

Kelly Radziwon, Ph.D.

State University of New York at Buffalo
Noise-induced hyperacusis in rats with and without hearing loss

Hyperacusis is an auditory perceptual disorder in which everyday sounds are perceived as uncomfortably or excruciatingly loud. Researchers and audiologists assess hyperacusis in the clinic by asking patients to rate sounds based on their perceived loudness, resulting in a measure known as a loudness discomfort level (LDL). Loudness discomfort ratings are a useful clinical tool, but in the lab we cannot ask animals to “rate” sounds. Instead, to measure loudness perception in animals, our lab trains rats to detect a variety of sounds of varying intensity. By measuring how quickly the animals respond to each sound—faster in reaction to higher intensity sounds and more slowly to lower intensity sounds—we can obtain an accurate picture of perceived loudness in animals. By comparing electrophysiological recordings with behavioral performances of the individual animals, this project aims to characterize the relationship between changes in neural activity and loudness perception in animals with and without noise-induced hearing loss.

The relationship between pain-associated proteins in the auditory pathway and hyperacusis

Hyperacusis is a condition in which sounds of moderate intensity are perceived as intolerably loud or even painful. Despite the apparent link between pain and hyperacusis in humans, little research has been conducted directly comparing the presence of inflammation along the auditory pathway and the occurrence of hyperacusis. One of the major factors limiting this research has been the lack of a reliable animal behavioral model of hyperacusis. However, using reaction time measurements as a marker for loudness perception, I have successfully assessed rats for drug-induced hyperacusis and, more recently, noise-induced hyperacusis. Briefly, the animals will be trained to detect noise bursts of varying intensity. As in humans, the rats will respond faster with increasing sound intensity. Following drug administration or noise exposure, rats will be deemed to have hyperacusis if they have faster-than-normal reaction times to moderate and high-level sounds. Therefore, the goal of the proposed research is to correlate the presence of pain-related molecules along the auditory pathway with reliable behavioral measures of drug and noise-induced hyperacusis.

Kenneth Vaden, Ph.D.

Kenneth Vaden, Ph.D.

Medical University of South Carolina
Adaptive control of auditory representations in listeners with central auditory processing disorder

Central Auditory Processing Disorder (CAPD) is typically defined as impairment in the ability to listen and use auditory information because of atypical function within the central auditory system. The current study uses neuroimaging to characterize CAPD in older adults whose impaired auditory processing abilities could be driven by cognitive and hearing-related declines, in addition to differences in central auditory nervous system function. Functional neuroimaging experiments will be used to test the hypothesis that older adults with CAPD fail to benefit from top-down enhancement of auditory cortex representations for speech. In particular, activation of the adaptive control system in cingulo-opercular cortex is predicted to enhance speech representations in auditory cortex for normal listeners, but not to the same extent for older adults with CAPD. This project aims to develop methods to assess the quality of speech representations based on brain activity and characterize top-down control systems that interact with auditory cortex. The results of this study will improve our understanding of a specific top-down control mechanism, and examine when and how adaptive control enhances speech recognition for people with CAPD.

Xiping Zhan, Ph.D.

Xiping Zhan, Ph.D.

Howard University
Dopaminergic activity in modulation of noise-induced tinnitus

Tinnitus is a major challenge for public health because it is a condition that is associated with hearing loss and can contribute to debilitating emotional stress, anxiety, and mental fatigue. Dr. Zhan’s interest is focused on the mechanisms that generate tinnitus and modulate tinnitus associated anxiety and depression using an animal model. His studies focus on dopaminergic activity in the limbic midbrain. Dopamine and its receptors play an important role in human mood behavior. Recently, dopamine has been suggested to be involved in tinnitus. Dr. Zhan’s research is designed to find out how dopamine neurons are communicating with other neurons to contribute to tinnitus generation. In addition, he also investigates how the functions of dopamine cells are modified during the development of tinnitus following noise exposures. These studies will shed light on the cellular mechanisms of tinnitus and offer a novel avenue for drug therapy.

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