Functional Magnetic Resonance Imaging Investigation of Auditory Processing in the Midbrain

Author: Peng Gao

ISBN/ASIN: 1361031077

This dissertation, "Functional Magnetic Resonance Imaging Investigation of Auditory Processing in the Midbrain" by Peng, Gao, 高鵬, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: The inferior colliculus (IC) is the major auditory nucleus in the midbrain. It integrates all ascending auditory projections from multiple brainstem nuclei and receives massive descending projections from the cortices. Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a noninvasive technique that can measure the hemodynamic responses as neural correlates throughout a nucleus with high spatial and temporal resolution. The objectives of this doctoral work were to develop and apply novel fMRI methods, for in vivo assessment of the auditory midbrain functions in rodent models. Firstly, fMRI combined with an oddball auditory stimulation paradigm was applied to investigate the role of the IC in detecting deviant sound. For two different sound tokens, BOLD responses to the deviant (with lower occurrence probability) were significantly higher than to the standard (with higher occurrence probability). The results demonstrated the involvement of the IC in deviance detection and revealed the highly adaptive nature of a substantial population of neurons in medial IC, where the strongest responses to the deviant were observed. Secondly, fMRI combined with two-tone stimulation paradigm was applied to investigate the IC responses to ultrahigh frequency (UHF) sounds. UHF vocalizations, but not pure tones at similar UHFs, evoked robust IC BOLD responses. Furthermore, IC BOLD responses were detected when a pair of UHF pure tones was presented simultaneously. For four different pairs, a cluster of voxels in ventromedial IC always showed the strongest responses, displaying combination sensitivity. Meanwhile, voxels in dorsolateral IC responded to each pair of UHFs in a similar way to a pure tone at their quadratic distortion frequency, suggesting that they are sensitive to cochlear distortion. The results indicated that different neural mechanisms are employed by large and spatially distinctive IC neuron populations to represent UHFs. Thirdly, to investigate the functional influences of cortical descending projections on auditory midbrain processing, fMRI paradigms were devised to measure the IC BOLD responses after bilateral ablation of either auditory or visual cortices. Auditory cortex (AC) ablation increased the gain of midbrain responses to noise stimuli, and decreased response selectivity to species-specific vocalizations. In contrast, visual cortex (VC) ablation decreased the gain, but caused much smaller effect on response selectivity. Direct and indirect projections from the AC to the midbrain appeared to play different roles in producing the auditory cortical modulation effects. These results revealed the large-scale influences of cortical descending projections, both within and across sensory modalities. Lastly, auditory fMRI combined with the optogenetics technique were explored for investigating the corticofugal modulation of auditory midbrain processing in a cell-type and spatiotemporally specific manner. Optogenetic activation of the AC or the VC induced extensive BOLD responses in multiple brain areas, but not in the IC. Furthermore, optogenetically activating the VC enhanced the IC BOLD responses to noise stimulation. These results demonstrated that combining auditory and optogenetic fMRI can be a powerful method for studying the large-scale corticofugal influences on auditory midbrain processing. Future studies will apply

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