Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Allman, Brian L.

Abstract

How the auditory cortex and higher-order cortical regions, e.g., the prefrontal cortex, interact for accurate auditory processing and perception is not fully understood. Furthermore, although hearing loss is correlated with cognitive impairment, and animal studies have shown that loud noise exposure causes hippocampal neuropathology, the effects of noise-induced hearing loss on the medial prefrontal cortex (mPFC) and higher-level cognitive functions have not been well studied. Using electrophysiological and cognitive-behavioural testing in rats, Chapter 2 provides the first evidence of noise-induced plasticity in the mPFC (e.g., loss of functional connectivity with the auditory cortex) and deficits in stimulus-response habit learning. Although the behavioural consequences of this plasticity remain unknown, past studies have suggested that functional connectivity between the auditory cortex and mPFC is crucial for sound detection in background noise. That said, the effect of permanent noise-induced hearing loss on sound detection in noisy environments has been studied comprehensively in rodent models. In Chapter 3 I first designed an operant conditioning-based behavioural task that required rats to detect a target sound in quiet or noisy backgrounds. Using this novel task, it was found that the same noise exposure that led to a decreased functional connectivity between the auditory cortex and mPFC did not necessarily lead to impaired sound detection. Finally, because the role of the mPFC in auditory processing and perception has not been fully elucidated, in Chapter 4 I used a battery of electrophysiological and behavioural experiments in rats to assess the effects of the mPFC (via pharmacological inactivation) on auditory functions. mPFC inactivation had limited effects on basic auditory processing; however, it significantly affected higher-order activity in the auditory cortex (e.g., diminished deviant effect, decreased mismatch response, and decreased spontaneous gamma oscillations) and worsened the rats' ability to detect sound in noise. Collectively, the novel findings in this thesis provide (1) further evidence of the complex and detrimental effects of noise exposure on higher-order cortical regions and cognitive functions, and (2) report exciting discoveries regarding the role of mPFC in sound detection and processing, thereby opening possible new research paths into the field of auditory perception.

Summary for Lay Audience

The sense of hearing allows us to chat with friends, listen to Freddy Mercury while taking a morning shower, or notice an upcoming emergency vehicle. Our brains are capable of processing sounds and making sense of them, including when we need to detect sounds that are important to us while ignoring background noise. Despite extensive research, the mechanisms giving rise to these common experiences are not fully known. Although we might be tempted to listen to our favourite song on maximum volume, we know it could lead to hearing loss. Beyond just damaging our hearing, studies report that noise exposure can also have detrimental effects on cognition. That said, which cognitive functions are most affected and the mechanisms linking hearing loss to those consequences remain unknown. Using a rat model, my first study found that noise exposure impaired the ability to learn a specific motor response following a visual stimulus (i.e., stimulus-response habit learning), and altered the way that sound information was processed across brain regions (i.e., functional connectivity between the auditory and prefrontal cortices). To further investigate how noise-induced hearing loss affects the brain, in my second study, I developed a task for rats to assess their ability to detect sounds in background noise. The results indicated that, although the severity of the rats’ hearing loss was correlated with their performance, those rats with a mild hearing impairment did not exhibit a performance deficit. In my final study, I investigated how the prefrontal cortex—a higher-order brain region involved in cognitive processes such as attention—influences behaviours involving sound processing as well as the neural activity within the auditory system. By suppressing the activity of the prefrontal cortex using a drug manipulation, the rats had an impaired ability to detect sounds in a noisy background, and their brains were unable to effectively notice when a novel sound was presented. Taken together, the results of this thesis help to improve our understanding of how noise exposure can affect the brain, and the interactions between areas of the brain that ultimately contribute to the accurate processing of sounds within our environment.

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