Statistical mapping of sound-evoked activity in the mouse auditory midbrain using Mn-enhanced MRI

Manganese-enhanced MRI (MEMRI) has been developed to image brain activity in small animals, including normal and genetically modified mice. Here, we report the use of a MEMRI-based statistical parametric mapping method to analyze sound-evoked activity in the mouse auditory midbrain, the inferior colliculus (IC). Acoustic stimuli with defined frequency and amplitude components were shown to activate and enhance neuronal ensembles in the IC. These IC activity patterns were analyzed quantitatively using voxel-based statistical comparisons between groups of mice with or without sound stimulation. Repetitive 40-kHz pure tone stimulation significantly enhanced ventral IC regions, which was confirmed in the statistical maps showing active regions whose volumes increased in direct proportion to the amplitude of the sound stimuli (65 dB, 77 dB, and 89 dB peak sound pressure level). The peak values of the activity-dependent MEMRI signal enhancement also increased from 7% to 20% for the sound amplitudes employed. These results demonstrate that MEMRI statistical mapping can be used to analyze both the 3D spatial patterns and the magnitude of activity evoked by sound stimuli carrying different energy. This represents a significant advance in the development of MEMRI for quantitative and unbiased analysis of brain function in the deep brain nuclei of mice.