Uncovering Deficits in Auditory Processing and Cognition Following Hearing Loss and Prefrontal Cortex Dysfunction

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\u27 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