Functional magnetic resonance imaging investigation of cross-modal interactions in auditory central nervous system

Abstract

Being one of the five basic senses for human, hearing works closely with other sensory and non-sensory systems to form a collective representation of environment and facilitate behavioral responses. Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a noninvasive technique that can provide assessments of hemodynamic responses in auditory system with large field of view. The objectives of this doctoral work were to develop and apply state-of-the-art fMRI techniques, for in vivo investigation of the cross-modal interactions in the auditory central nervous system in rodent models. Firstly, fMRI combined with auditory and visual stimulation paradigms was applied to explore the influence of visual stimulation on auditory responses in auditory midbrain, inferior colliculus (IC). Auditory-evoked IC responses were suppressed by the low-frequency (1-Hz) suprathreshold visual stimulus, and such stimulus was able to induce the BOLD activation in non-visual regions, such as auditory cortex (AC). However, high-frequency (10-Hz) or subthreshold visual stimulus failed to alter the IC auditory responses or evoke BOLD activation in non-visual regions. The results suggested that such cross-modal processing in IC depends on frequency and intensity of visual stimulation. It probably originates from the top-down feedback from the cortical regions. Secondly, auditory fMRI combined with novel optogenetic techniques was developed to investigate the visual cortical descending influences on auditory midbrain responses. The optogenetic stimulation of visual cortex (VC) did not directly evoke BOLD responses in IC, but enhanced the auditory midbrain responses to broadband noise. The results indicated that VC facilitates auditory midbrain processing of basic sound features, which is likely driven by excitatory neurons in VC. Such combined optogenetic and auditory fMRI approach not only shed light on the large-scale modulatory effects of corticofugal pathways but also guide detailed electrophysiological studies in the future. Thirdly, auditory fMRI combined with pharmacology and optogenetics on hippocampus (HP) was applied for investigating the hippocampal-auditory interactions in auditory midbrain. Pharmacologically inactivating the dorsal hippocampus (dHP) induced an enhancement effect on IC responses to broadband noise initially. Then, such enhancement gradually decreased and an adaptation effect was observed. Meanwhile, low-frequency (1-Hz) optogenetic stimulation of dHP only enhanced the responses to vocalization in IC, but not broadband noise. These findings indicated that dHP dynamically shapes the IC auditory responses and plays a sound-specific role in midbrain auditory processing. Lastly, BOLD auditory fMRI combined with optogenetics on ventral posteromedial thalamus (VPM) was applied to study the somatosensory influence on auditory processing to noise in the whole auditory central pathway. Low-frequency (1-Hz) optogenetic stimulation of VPM enhanced the auditory responses in AC, medial geniculate body (MGB), IC and lateral lemniscus (LL), rather than the lower regions, superior olivary complex (SOC) or cochlear nucleus (CN). Moreover, different IC subdivisions exhibited different patterns affected by optogenetically-evoked somatosensory inputs. These findings indicated the complexity of such somatosensory-auditory interactions and implied the above interactions might be due to the top-down feedback controls from the cortical region(s). Future studies will use this method in combination with other biomedical technologies to expose the mechanism(s) of the interactions observed in fMRI.