Functional magnetic resonance imaging investigation of central auditory processing in animal models

Abstract

Hearing is one of the five basic senses of humans. The auditory system works closely with other sensory and non-sensory modalities to sense the acoustic environment, thus facilitate sound detection and perception. Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a non-invasive technique that can measure hemodynamic responses throughout the auditory system with relatively high spatial and temporal resolutions. The objectives of this doctoral work were to develop and apply novel fMRI techniques, for in vivo investigation of the central auditory processing in rodent models. Firstly, auditory fMRI was combined with optogenetics to investigate the role of hippocampus in central auditory processing in a cell-type and spatiotemporally specific manner. Optogenetic stimulation at the ventral hippocampus (vHP) evoked brain-wide BOLD responses in multiple brain regions, including auditory cortex (AC). Interestingly, optogenetically activating vHP enhanced the auditory responses to vocalizations with a negative or positive valence in a similar manner, but not to their temporally reversed counterparts or broadband noise. These findings demonstrated a top-down modulatory role of hippocampus in processing of behaviorally relevant sounds. The results expand our present understandings of large-scale central auditory processing beyond the traditional pathways. Secondly, auditory fMRI was employed to examine the impact of chronic intermittent hypoxia (CIH) on central auditory processing. CIH treatment was performed on rodents and significantly reduced their arterial oxygen partial pressure and oxygen saturation. Sound-evoked BOLD responses were observed in major auditory structures, including the auditory midbrain and cortex. BOLD responses in bilateral AC were significantly increased after CIH treatment, while the responses in contralateral lateral lemniscus (LL) were significantly reduced. Meanwhile, BOLD responses in the neighboring inferior colliculus (IC) were relatively unaffected. These findings revealed the multi-level impacts of chronic intermittent hypoxia on auditory processing, which are likely related to hearing disorders associated with sleep apnea. Thirdly, to identify the neural correlates of hyperacusis in an animal model, we employed auditory fMRI with tonal stimuli to evaluate the impact of hyperacusis, induced with an ototoxic drug, on auditory processing. After drug administration, fMRI revealed significantly enhanced sound-evoked BOLD responses in AC. Meanwhile, auditory responses in IC were also enhanced, but to a less extent. These results indicated the enhanced central auditory gain in hyperacusis. This study demonstrated the feasibility of using fMRI to identify regions of hyperactivity throughout the auditory pathways in an animal model of hyperacusis. Lastly, to characterize the longitudinal impact of noise-induced sensorineural hearing loss, auditory fMRI was performed before, as well as 7 and 14 days after acute noise exposure. fMRI with monoaural tonal stimulations was applied to evaluate the central auditory functions across time points. Specifically, reduced BOLD responses in LL and IC were observed on the seventh day after noise exposure. By fourteen days after, partial recovery of BOLD responses was detected in the auditory midbrain. These findings indicated that acute noise exposure leads to functional changes in central auditory structures with a timescale of weeks. Overall, these imaging findings in animal models will provide critical insights and implications for future auditory research.