PROJECT SUMMARY / ABSTRACT
Only 17% of the 466 million people worldwide who might bene¿t from hearing aids actually use one,
imparting a large national and indeed worldwide cost on hearing and cognitive health. One reason for
such low hearing-aid adoption rates is the unclear bene¿t they provide when listening in noisy
environments. Di¿culty hearing in noise typically begins in mid-life, often well before the onset of
age-related hearing loss as measured by audiometry and is the primary hearing rehabilitation goal of
individuals visiting audiology clinics. The contributions of dysfunctional central auditory processing
towards the inability to hear in noise have received little attention compared to contributions of
peripheral dysfunction. One likely contributor to the reduced ability to hear in noise as we age is loss of
neuronal inhibition in the central auditory pathway, particularly auditory cortex (AC). Work in
experimental animals has shown that both hearing loss and age, per se, are associated with reduced
levels of the inhibitory neural transmitter GABA (gamma aminobutyric acid) in AC and other nuclei of the
ascending auditory pathway. Such loss of neuronal inhibition likely has severe consequences for the
ability to hear in noise via hyperexcitability of AC neurons. Hyperexcitability, de¿ned as increased
spontaneous or evoked ¿ring rates, is hypothesized behaviorally to reduce the listener’s ability to
suppress distracting acoustic input and focus on behaviorally relevant sounds. However, despite
extensive animal work showing reduced GABA levels in AC, very few studies have directly examined this
in humans. Even fewer have examined the role such reduced AC GABA levels might play in decreased
hearing-in-noise ability. Here, we directly examine the relationship between age-related loss of inhibition
in AC, AC hyperexcitability, and the ability to hear in noise. In Aim 1, we establish that age is indeed
associated with reduced levels of GABA in human AC, while controlling for age-related hearing loss (Exps.
1A-1C). In Aim 2, we determine how reduced AC GABA levels manifest behaviorally for speech-in-noise
perception (Exp. 2A) and behaviorally and neurophysiologically for detecting non-speech target sounds in
noise (Exp. 2B). In Aim 3, we examine whether age-related changes in markers of AC hyperexcitability can
be accounted for by loss of GABA at the circuit level through the use of biophysical modeling capable of
identifying candidate circuit-level mechanisms. The results of this study will establish a combined
imaging, physiological, and modeling framework for understanding the behavioral and
neurophysiological consequences of loss of neuronal inhibition in human AC. Planned R01 work will
solidify the link between AC GABA loss and di¿culty hearing noise and identify candidate circuit-level
mechanisms that can be further explored with animal models.