Announcing 2020 Capita Foundation Auditory Research (CFAR) grant award recipients

Alessia Paglialonga, Ph.D.

National Research Council of Italy (CNR); Institute of Electronics, Information Engineering and Telecommunications (IEIIT), Milan, Italy

Project Title: “Widespread Hearing Impairment Screening and Prevention of Risk (WHISPER)”

Project WHISPER will develop and evaluate a novel, web-based system to support widespread screening and prevention of hearing impairment. It will be the first system to combine: (1) remote speech recognition testing using an automated, language-independent speech-in-noise test, (2) assessment of the risk factors for developing hearing impairment via a language-independent, icon-based interface, and (3) modeling of the individual risk for developing hearing impairment and the associated cognitive decline using explainable artificial intelligence (AI). The project will help answer the need to increase access to screening and prevention (for older adults, for individuals in underserved areas, for minorities, and for those with low socioeconomic status). It will develop tools that are language-independent and natively designed to be delivered at a distance, e.g. via web or mobile app, and natively integrated with explainable AI to extract actionable knowledge from the measured data.

Daniel Q. Sun, M.D.

Johns Hopkins University School of Medicine

Project Title:  "Treatment of hearing loss using a novel magnetic nanoparticle gene delivery platform"

Currently gene therapy using adeno-associated viral vectors (AAV) has been successful in small mammals, but nearly 80% of all genes that are affected in genetic forms of hearing loss are too large to fit into AAV vectors found in humans. Thus, there is an unmet need for the development of alternative gene-delivery tools in the translational development of gene therapy for congenital hearing loss.  Successful completion of the aims in this proposal will provide a foundational understanding of Magnetic Nanoparticle (MNP) behavior in small animal models and accrue preclinical data to support the translational development of MNP technology for inner ear gene delivery. Leveraging this team’s experience in successfully bringing other inner ear therapeutics from the bench top to the bedside, we intend to similarly advance the translational development of MNPs into nonhuman primates and ultimately human clinical trials.

Mridula Sharma, Ph.D.

Macquarie University - Sydney, Australia 

Project Title:  "Effect of age and background noise on cortical EEG entrainment to natural conversation:  a preliminary study in adults with hearing loss"

This project addresses fundamental clinical and research needs in understanding how natural speech in a conversation is processed and perceived in complex listening situations and how this is affected by age in adults with hearing loss.  Therefore, the aims of this project are:
1. To assess and understand the mechanisms underlying speech perception in an innovative and more ecologically valid manner by using EEG and novel signal processing methods.
2. To delineate the effects of age on processing and understanding natural speech in noise.
3. To identify neural indices that could be used, in future clinical studies, as clinical measure of an individual’s ability to understand speech in the real world.
The outcomes will significantly advance knowledge in our understanding of the auditory processes that are required for older adults to understand natural speech. By including a clinical test population, the proposed project will provide the knowledge required for future development of clinical management protocols and strategies using speech tracking, thereby ensuring future clinical translation of the project outcomes.

The figure shows  EEG as recorded to the continuous speech and the continuous speech signal which is routed into the EEG amplifier. After the filtering and processing of the EEG and speech amplitude envelope, Temporal response function (TRF) is determined across all channels for the condition. Topographical maps of TRF at 100-150ms are also shown for the condition. 

The figure that shows the analysis from our pilot data

Soroush Sadeghi, M.D., Ph.D.

Center for Hearing and Deafness, State University of New York (SUNY) at Buffalo

Project Title: "Improving the vestibular nerve function by pharmacological manipulation of the inner ear"

The general aim of my research is to reach a better understanding of vestibular signaling and its modulation following compensation or adaptation and to find practical ways for enhancing vestibular compensation in humans.  This can be specifically useful for patients (e.g., after therapeutic vestibular neurectomy) or in conditions where unusual adaptation is required (e.g., space travel). 

Figure 1

Figure 1. Intra-labyrinthine injection and VsEP recordings.  (A) Method of injection through the oval window. Note the exit point made on the anterior canal.  (B) Mouse’s head is attached to a linear shaker for VsEP recordings. 

In recent years, the traditional notion that peripheral end organs (i.e., hair cells and afferent terminals) in the inner ear are mere sensors has been challenged due to the presence of feedback (via an efferent pathway) from central areas. It has been shown that efferent inputs can modulate the activity of hair cells and afferents in vitro. The funding from Capita Foundation will be used to study the effect of the GABAergic and cholinergic efferent pathways on the response properties of the vestibular pathway.  Using an in vivo mouse model, we will use a method developed in our lab for intralabyrinthine injection (Fig. 1A) of different agonists and antagonists of relevant receptors and ionic channels and evaluate their effect on the vestibular nerve response by measuring the vestibular sensory evoked potentials (VsEP) (Fig. 1B). To find the behavioral correlate of the observed neuronal changes, we will measure the effect of intralabyrinthine injections of these drugs on the vestibulo-ocular reflex (VOR) – a reflex that functions to stabilize the eyes during head movements (Fig. 2).

Figure 2

Figure 2. Recording the VOR response in mice.   Eye movements will be recorded with an infrared camera in a head-restrained mouse. The mouse is rotated in the horizontal plane at different frequencies and velocities in the dark.  Right panel traces shows example eye movements during VOR response to head rotation.  

Results of the above studies could provide the means for designing new therapeutic approaches through local application of drugs in the inner ear, which could result in fewer adverse effects compared to the current systemic (e.g., oral) use of similar drugs in patients.