When a mouse hears a predictable sound pattern and a single tone is unexpectedly skipped, its auditory cortex neurons fire as if the missing sound had actually occurred — a neural prediction that the brain uses to fill in gaps. This matters because age-related hearing loss often leaves people unable to follow conversation in noisy rooms, even when their audiograms look normal. The problem is not simply that sounds are too quiet; the brain struggles to compensate for degraded or masked signals. This project tests the hypothesis that predictive neural activity — the brain's ability to anticipate upcoming sounds — becomes more important when the acoustic signal is weak, and that this mechanism may break down with age. If successful, this fundamental science will reveal how the hippocampus and auditory cortex work together to generate predictions that support hearing in low signal-to-noise conditions. Understanding these neural circuits could eventually inform more targeted interventions for age-related hearing difficulties — for example, hearing aids or training programmes that boost the brain's predictive abilities rather than simply amplifying sound. The work is curiosity-driven, but similar discoveries about predictive coding in the brain have already reshaped how researchers approach sensory disorders.
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Age-related hearing loss often manifests as impaired speech comprehension in a noisy background. Effective hearing in such environments relies on acoustic signals and other predictive cues, such as context. These predictive signals play a crucial, however little understood, role in hearing. To elucidate their role, I propose to examine how predictions about upcoming sounds can enhance auditory responses and whether such predictions are affected by age-related hearing loss. The proposal builds on my results in mice showing predictive activity in auditory cortex neurons. When mice listen to a predictable sound sequence, an unexpected omission of one of the sounds elicits a well-timed and predictive of that sound response. I hypothesise that such predictive signals are amplified when predictions need to compensate for obscured or diminished auditory signals. Such a mechanism could support hearing in low signal-to-ratio conditions. To test this, I propose experiments that isolate the effect that predictive signals have on the sound-evoked and omission responses. To address how these auditory predictions are generated, I plan to optogenetically test the role of the hippocampus, which follows up on my preliminary results showing the hippocampal neurons activate in a sequence that unfolds over the duration of the sound sequence. Together, these investigations explore how neuronal predictions contribute to sound detection to compensate for auditory inputs obscured by noise or peripheral damage. Understanding the mechanism of such predictive neuronal activity could help develop more effective interventions addressing age-related hearing difficulties. This project is being funded with the support of the Vivensa Foundation.
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