Four grants were awarded for research that will increase our understanding of the causes, diagnosis, and treatment of CAPD, an umbrella term for a variety of disorders that affect the way the brain processes auditory information. All four of our CAPD grantees are General Grand Chapter Royal Arch Masons International award recipients.
+ Richard A. Felix II, Ph.D.
Washington State University Vancouver
Neural mechanisms underlying deficits encoding temporal sound features associated with central auditory processing disorder
A critical function of the auditory system is to extract meaning from complex sounds. When this basic function is impaired, quality of life can be greatly affected. This is particularly true for speech processing, where degrading temporal information significantly alters the ability to listen. Difficulty encoding temporal cues is a hallmark central auditory processing disorder (CAPD), which is also marked by problems understanding complex sounds despite normal function of the peripheral auditory system. The origin of deficits associated with CAPD has been localized to the brain, but the neural mechanisms underlying the encoding of temporal sound cues remain poorly understood.
The goal of this research is to examine the contributions of inhibitory connections to the midbrain, the first known site in the auditory pathway that exhibits abnormal function in those with CAPD. These midbrain inputs signal temporal sound features important in the emergence of CAP and might therefore play an important role in the generation of listening problems. The results of this project will be a key step in advancing our understanding of how the processing of temporal information at the level of brain circuits relate to deficits associated with CAPD.
Research area: CAPD
Long-term goal: To gain a thorough understanding of the neural mechanisms that govern the temporal processing of speech. This work has the potential to impact those with hearing loss by providing vital information needed for treatments designed to ameliorate listening problems associated with CAPD.
Felix received his Ph.D. in neuroscience from West Virginia University working on temporal aspects of auditory processing with Albert Berrebi, Ph.D. He completed a postdoctoral fellowship at Karolinska Institutet in Stockholm with Anna Magnusson, Ph.D., examining brain circuits suited for encoding natural sounds. His is currently at Washington State University Vancouver with the lab of Christine Portfors, Ph.D.
+ ELIZABETH MCCULLAGH, PH.D.
University of Colorado
The role of the MNTB in sound localization impairments in autism spectrum disorder
The processing of sound location and the establishment of spatial channels to separate several simultaneous sounds is critical for social interaction, such as carrying on a conversation in a noisy room or focusing on a person speaking. Impairments in sound localization can often result in central auditory processing disorders (CAPD). A form of CAPD is also observed clinically in all autism spectrum disorders, and is a significant to quality-of-life issues in autistic patients.
The circuit in charge of initially localizing sound sources and establishing spatial channels is located in the auditory brain stem and functions with precisely integrated neural excitation and inhibition. A recent theory posits that autism may be caused by an imbalance of excitatory and inhibitory synapses, particularly in sensory systems. An imbalance of excitation and inhibition would lead to a decreased ability to separate competing sound sources. While the current excitation to inhibition model of autism assumes that most inhibition in the brain is GABAergic, the sound localization pathway in the brainstem functions primarily with temporally faster and more precise glycinergic inhibition.
The role of glycinergic inhibition has never been studied in autism disorders, and could be a crucial component of altered synaptic processing in autism. The brainstem is a good model to address this question since the primary form of inhibition is through glycine, and the ratio of excitation to inhibition is crucial for normal processing.
Research areas: CAPD, Fragile X syndrome, glycinergic inhibition, excitation/inhibition ratio, sound localization
Long-term goal: To determine how the auditory brainstem functions in autism in order to lead us to greater insights to the disorder in general, as well as specifically in auditory dysfunction, and ultimately to provide a medical intervention to restore the balance of excitation and inhibition in autistic patients.
McCullagh received her Ph.D. at the University of Illinois at Chicago where, under the mentorship of David Featherstone, Ph.D., she studied molecular and behavioral neuroscience to understand the link between genetics and resulting behaviors. She is currently a postdoctoral researcher at the University of Colorado, Anschutz Medical Campus, in the lab of Achim Klug, Ph.D.
+ NATHAN HIGGINS, PH.D.
Biomarkers of spatial processing in auditory cortex measured with functional near-infrared spectroscopy
Central auditory processing disorders (CAPD) comprise a number of functional deficits, such as impairments in the ability to process complex information used for localizing, fusing, and discriminating acoustic objects or streams. Binaural hearing (integrating information from the two ears) represents a fundamental aspect of central auditory processing and can be objectively measured in the brain using biomarkers such as the blood oxygenation level-dependent (BOLD) signal in the auditory cortex.
Functional near-infrared spectroscopy (fNIRS) is an emerging technique for measuring the BOLD signal, and is well suited for study of CAPD clinically due to its low noise, portability, and cost effectiveness. As a clinical tool for objective measures of central auditory processing, fNIRS has a bright future. This project will measure fNIRS sensitivity to binaural tuning of BOLD responses, testing the hypothesis of broad contralateral tuning as seen with fMRI. Attention will be manipulated by tasks requiring feature detection in different modalities (location, pitch, visual). Also to be measured is the effect of task engagement on the BOLD signal, compared with passive listening, in order to yield an objective biomarker of cortical processing for task-related attention. This is an important tool when examining clinical populations (e.g. young children) who are unable to provide reliable feedback.
Research areas: CAPD, functional near-infrared spectroscopy, binaural hearing, task-related attention
Long-term goal: To establish consistent biomarkers for central auditory processing, and determine the utility of fNIRS for a variety of patient populations by quantifying the influence of task-related attention on cortical activity. This will aid the development of neuroimaging-based assessments of central auditory function that can then be used by clinicians to help diagnose and focus treatment for individuals with CAPD. In addition, since fNIRS is still gaining acceptance within research and clinical fields, and is in many ways largely untapped, this project may help establish fNIRS as a research and clinical tool.
Higgins received his Ph.D. at the University of Connecticut, where he was mentored by Heather Read, Ph.D., and studied neural responses to interaural level difference cues in rat auditory cortex. He is now a postdoctoral research fellow with Christopher Stecker, Ph.D., at Vanderbilt University.
+ Nirmal Kumar Srinivasan, Ph.D.
Understanding and decoding CAPD in adults
Understanding speech in complex listening environments involves both on top-down and bottom-up processes. Central auditory processing disorder (CAPD) refers to a reduction in the efficiency and effectiveness of how the central nervous system utilizes the presented auditory information. It is characterized by a diminished perception of speech and non-speech sounds that is not attributable to peripheral hearing loss or intellectual impairment. Hearing loss and CAPD can adversely affect everyday communication, learning, and physical well-being.
A substantial number of adults evaluated for CAPD complain about difficulties in resolving auditory events that are similar to that of individuals with hearing impairment. These individuals have audiograms that are similar to those of age-matched individuals. Since the audiogram is the primary tool used in the clinic to distinguish people with hearing loss, it is imperative to understand the fundamental differences observed in behavioral experiments for individuals with CAPD and individuals with hearing loss.
Research areas: CAPD, aging, hearing loss, speech perception, reverberation
Long-term goal: To better understand the difficulties encountered by listeners with CAPD in complex listening environment. Findings from this project will lead to a series of studies to identify relevant tests that would separate listeners with hearing loss and CAPD; identify test variables that captures most of the underlying variance in the difference in performance with aging and hearing loss; develop tests that could be used in clinical settings to quickly estimate the extent of processing deficits; and develop effective rehabilitation and intervention for listeners with CAPD.
Nirmal Kumar Srinivasan, Ph.D. is currently an Assistant Professor in the Department of Audiology, Speech-Language Pathology and Deaf Studies at Towson University, Maryland. Dr. Srinivasan received his Ph.D. in Speech Language Pathology and Audiology from University of Nebraska-Lincoln. Prior to that, he received his M.S. in Electrical Engineering and B.E. in Electronics and Communication Engineering from University of Nebraska-Lincoln and University of Madras, respectively. He subsequently completed post-doctoral training at University of Louisville with Dr. Pavel Zahorik, University of Texas at Dallas with Dr. Emily Tobey and at the National Center for Rehabilitative Auditory Research with Dr. Frederick Gallun and Dr. Michelle Molis.
One grant was awarded that is focused on research (e.g., animal models, brain imaging, biomarkers, electrophysiology) that will increase our understanding of the mechanisms, causes, diagnosis, and treatments of hyperacusis and severe forms of loudness intolerance. Research that explores distinctions between hyperacusis and tinnitus is of special interest. This grant was funded by Hyperacusis Research.
+ Xiying Guan, Ph.D.
Massachusetts Eye and Ear, Harvard Medical School
Hyperacusis caused by abnormalities in auditory mechanics
Many hyperacusis patients have what is called “conductive hyperacusis,” due to mechanical abnormalities of the ear that result in a hypersensitivity to sounds/vibrations transmitted through their bodies. These include the sensation of one’s own voice (autophony), pulse, and body movements such as eye motion and footsteps, as well as sensing the vibrations of items such as vehicles. These symptoms are common among patients who have an opening in the bone encapsulating the inner ear (termed a superior canal dehiscence, a type of pathological third-window lesion).
Compared with hyperacusis stemming from neurosensory issues, conductive hyperacusis has the potential for treatment. Recently, surgical treatment for hyperacusis by changing the mechanics of surrounding structures of the inner ear show mixed results, with some patients experiencing worse symptoms after surgery.
Although these “experimental” surgical treatments in patients are increasing, the mechanisms of conductive hyperacusis are not well understood, and scientific research targeting this problem is lacking. This study aims to understand how mechanical changes in fresh cadaveric specimens with similar gross mechanics as the living can influence the cochlear input drive (an estimate of hearing), resulting in hyperacusis. Our novel intracochlear pressure measurement technique will allow the monitoring of the cochlear input drive as we manipulate the mechanics surrounding the inner ear.
Research areas: middle and inner ear mechanics, bone conduction, hearing loss, conductive hyperacusis
Long-term goal: To understand how hyperacusis can occur due to mechanical disturbances of the middle and inner ear, and to provide the necessary scientific understanding to enable treatment.
Guan received his Ph.D. in bioengineering from University of Oklahoma. He is currently a postdoctoral research fellow of Eaton-Peabody Laboratories at Massachusetts Eye and Ear and in the Department of Otolaryngology at Harvard Medical School.
One grant was awarded for innovative research that will increase our understanding of the inner ear and balance disorder Ménière’s disease. This grant was generously supported by The Estate of Howard F. Schum.
+ Gail Ishiyama, M.D.
David Geffen School of Medicine at UCLA
The molecular and ultrastructural biology of the human blood-labyrinthine barrier in Ménière’s disease
Ménière’s disease is characterized by hearing loss, vertigo, tinnitus, and the sensation of ear fullness. This study proposes that it may be due to the alteration and degeneration of the inner ear blood vessels (vasculature). Understanding the molecular mechanisms that regulate the vascular integrity of the inner ear is critical for understanding the pathology of Ménière’s disease and how it affects hearing and balance, as the excessive leakage of fluid and proteins from blood vessels to the interstitial space that occurs in Ménière’s disease is likely associated with its symptoms.
This research will investigate degenerative changes in the cellular components of the vasculature of the inner ear balance organ, the utricle. Immunohistochemistry will be used to identify the endothelial cells, pericytes, and the surrounding cellular matrix, and electron microscopy will be used to identify subcellular changes associated with hyperpermeability and degenerative changes of the vasculature in Ménière’s disease.
Research area: Ménière’s disease
Long-term goal: To characterize the cellular components of the human blood-labyrinthine barrier, and the delineation of cellular and molecular changes in Ménière’s disease. It is hoped that these findings will translate into the development of new therapeutic interventions (e.g. pharmacologic agents designed to diminish vascular damage) aimed at preventing the progression of this disabling disease.
Ishiyama received her medical degree from the David Geffen School of Medicine at UCLA where she is now a clinician-scientist in the department of neurology, and after completing a two-year postdoctoral research fellowship in neurotology to understand the neurochemistry of the auditory and vestibular system.
One grant was awarded for innovative research tthat will increase our understanding of strial atrophy and/or development of the stria. This grant was funded by a generous family foundation with an interest in funding Strial Atrophy research.
+ Rahul Mittal, Ph.D.
University of Miami Miller School of Medicine
Deciphering the role of Slc22a4 in the development of stria vascularis, and to determine the effect of supplementation of its antioxidant substrate ergothioneine, on age-related hearing loss
Since mutations in the SLC22 gene family have been implicated in various pathological conditions, there has been a renewed interest in understanding their role in the maintenance of normal physiological functions of cells. SLC22A4 is ubiquitously expressed in the body and transports across the cellular plasma membrane various compounds, including acetylcholine and carnitine as well as the naturally occurring antioxidant ergothioneine (ERGO). In addition, SLC22A4 is abundantly expressed in the stria vascularis (SV), but its role in SV biology is not known.
This project will help in understanding how SLC22A4 contributes to SV development, atrophy, and dysfunction of the cochlea, leading to hearing loss. The project also aims to determine whether ERGO supplementation can prevent SV atrophy and ameliorate age-related hearing loss (presbycusis) in a mouse model.
Research areas: stria vascularis (SV), SV atrophy, presbycusis
Long-term goal: To better understand the biological processes leading to presbycusis, which may lead to the development of drugs to prevent and/or treat hearing loss in old age. Specifically, the goal is to understand the development of auditory organs including stria vascularis (SV) and how gene mutations trigger SV atrophy that can affect cochlear function, leading to hearing loss.
Mittal received his Ph.D. from Panjab University, India. After completing his postdoctoral fellowship from Children’s Hospital Los Angeles, he joined the department of otolaryngology as a research scientist at University of Miami Miller School of Medicine.
Two grants were awarded for innovative research that will increase our understanding of the mechanisms, causes, diagnosis, and treatment of tinnitus.
+ Julia Campbell, Au.D., Ph.D.
University of Texas at Austin
Auditory gating in tinnitus
Tinnitus is the perception of sound, such as ringing or buzzing, without an external source. Though tinnitus likely arises, in part, from hearing loss in the inner ear, research has determined that the ongoing perception of tinnitus occurs in the brain. It has been suggested that auditory gating, a function carried out by the brain in filtering out unimportant auditory information, may be abnormal in individuals with tinnitus and contribute to the conscious perception of the phantom sound.
Auditory gating can be measured noninvasively through the brain’s cortical response to sound during recording of brainwave activity, known as EEG (electroencephalography). In typical auditory gating function, cortical auditory evoked potentials (CAEPs) recorded during EEG show a decrease in amplitude when sounds (e.g., tone pairs) are presented close together in time. This decrease in amplitude reflects the brain’s ability to filter out repetitive auditory input. In atypical gating function, CAEP amplitude remains the same across sound presentation or shows little change, again suggestive of the brain’s inability to filter out irrelevant input.
This study aims to evaluate auditory gating processes in tinnitus, including cortical sources of active gating networks as observed through source localization analyses. These results will be correlated with subject reports of tinnitus severity.
Research areas: high-density electroencephalography, cortical plasticity, hearing loss, tinnitus, sensory processing, source localization, auditory gating, perception, cognitive neuroscience
Long-term goal: To identify a possible biomarker of tinnitus that may be a viable clinical tool for assessment purposes as well as inform future treatment options.
Campbell received an Au.D. from the University of Colorado at Boulder, later received a combined triple Ph.D. in speech, language, and hearing sciences; behavioral neuroscience; and cognitive neuroscience while studying cortical plasticity in hearing loss under Anu Sharma, Ph.D. She is an assistant professor at the University of Texas at Austin in the department of communication sciences and disorders.
+ Harrison W. Lin, M.D.
University of California, Irvine
Objective and subjective suprathreshold measures of auditory neurodegenerationObjective and subjective suprathreshold measures of auditory neurodegeneration
Recent research on animals convincingly demonstrates that degeneration of the auditory nerve, called auditory neurodegeneration, will result from a brief, moderate noise exposure. These animals suffered from severe, permanent deterioration of the function and microscopic appearance of the auditory nerve from a seemingly short, innocuous noise exposure. Interestingly, the animal’s ability to recognize the presence of sound fully recovered to normal threshold levels following the trauma.
However, when presented with sound levels above their ability to hear (“suprathreshold” levels), the strength of the electric signals from the auditory nerve was reduced by as much as 50 percent in some frequencies. Because standard hearing tests (audiograms) of these noise-exposed animals were indistinguishable from unexposed animals, the phenomenon of auditory neurodegeneration may result in a “hidden hearing loss,” and moreover, play a key role in the development of tinnitus, hyperacusis, and other auditory processing abnormalities.
Many military personnel who are subject to severe noise trauma and blast injuries subsequently develop chronic, oftentimes debilitating, tinnitus, and it is thought that this auditory neurodegeneration phenomenon is at least partially responsible for these symptoms. But auditory neurodegeneration in humans has not been established, and its perceptual consequences, including tinnitus, remain unknown. This project aims to establish the missing link between animal and human studies on auditory neurodegeneration and to provide quantitative and qualitative assessment of perceptual consequences of neurodegeneration.
Research areas: tinnitus, auditory neurodegeneration
Long-term goal: To determine and thoroughly evaluate the objective differences in the characteristics of a specialized but broadly available hearing test among patients with and without chronic tinnitus. This will provide clinicians and scientists with a standardized, objective method to document the extent of auditory neurodegeneration that can be correlated to tinnitus characteristics and also monitored over time to evaluate treatment options that promote the survival and health of auditory nerve cells.
Lin received his medical degree from the University of Southern California, after which he completed surgical training as a resident at Harvard Medical School and as a neurotology and skull base surgery fellow at UC San Diego. He then joined the faculty at UC Irvine, where he is an attending otolaryngologist, neurotologic surgeon, and an assistant professor in the department of otolaryngology–head and neck surgery.
Dr. Lin's grant was generously funded by The Barbara Epstein Foundation, Inc.