Structural Connectivity of Human Inferior Colliculus Subdivisions Using in vivo and post mortem Diffusion MRI Tractography

Inferior colliculus (IC) is an obligatory station along the ascending auditory pathway that also has a high degree of top-down convergence via efferent pathways, making it a major computational hub. Animal models have attributed critical roles for the IC in in mediating auditory plasticity, egocentric selection, and noise exclusion. IC contains multiple functionally distinct subdivisions. These include a central nucleus that predominantly receives ascending inputs and external and dorsal nuclei that receive more heterogeneous inputs, including descending and multisensory connections. Subdivisions of human IC have been challenging to identify and quantify using standard brain imaging techniques such as MRI, and the connectivity of each of these subnuclei has not been identified in the human brain. In this study, we estimated the connectivity of human IC subdivisions with diffusion MRI (dMRI) tractography, using both anatomical-based seed analysis as well as unsupervised k-means clustering. We demonstrate sensitivity of tractography to overall IC connections in both high resolution post mortem and in vivo datasets. k-Means clustering of the IC streamlines in both the post mortem and in vivo datasets generally segregated streamlines based on their terminus beyond IC, such as brainstem, thalamus, or contralateral IC. Using fine-grained anatomical segmentations of the major IC subdivisions, the post mortem dataset exhibited unique connectivity patterns from each subdivision, including commissural connections through dorsal IC and lateral lemniscal connections to central and external IC. The subdivisions were less distinct in the context of in vivo connectivity, although lateral lemniscal connections were again highest to central and external IC. Overall, the unsupervised and anatomically driven methods provide converging evidence for distinct connectivity profiles for each of the IC subdivisions in both post mortem and in vivo datasets, suggesting that dMRI tractography with high quality data is sensitive to neural pathways involved in auditory processing as well as top-down control of incoming auditory information.