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.