Functional connectivity across the human subcortical auditory system using a Gaussian copula graphical model approach with partial correlations

Abstract

Abstract/SummaryThe central auditory system is comprised of multiple subcortical brain structures that hierarchically process and refine incoming acoustic signals along the primary auditory pathway. Due to the technical limitations of imaging small structures deep inside the brain, most of our knowledge of the subcortical auditory system is based on research in animal models using invasive methodologies. Advances in ultra-high field functional magnetic resonance imaging (fMRI) acquisition have enabled novel non-invasive investigations of the human auditory subcortex, including fundamental features of auditory representation such as tonotopy and periodotopy. However, functional connectivity across subcortical networks is still underexplored, with ongoing development of functional connectivity methods. Traditionally, functional connectivity using fMRI data is estimated with simple correlation matrices. Partial correlations however reveal the connectivity between two regions after removing the effects of all other regions and hence are often more meaningful. Partial correlation analysis is particularly promising in the subcortical auditory system, where sensory information is passed serially, in an obligatory manner, from nucleus to nucleus up the primary auditory pathway, providing redundant but also increasingly abstract representations of auditory stimuli (Chechik and Nelken, 2012). In this project, we adapted a Gaussian copula graphical model (GCGM) approach to estimate the partial correlations and thereby infer the functional connectivity patterns within the auditory system. Given the paucity of non-invasive methods for human subcortical investigations, we aim to provide novel insights regarding the hierarchy and direct connections throughout the human subcortical auditory system. Our results show strong positive partial correlations between contralateral structures throughout the auditory system, particularly in the auditory midbrain and thalamus. We also found positive partial correlations between successive structures in the auditory pathway on each side (left and right), including between auditory midbrain and thalamus, and between primary and associative auditory cortex. Further, we confirmed that these connectivity estimates were unique to the auditory system, as non-auditory regions included as controls—namely, visual cortex and superior frontal cortex—were strongly connected to their contralateral homologues but only minimally connected with auditory brain regions. Additionally, these results were highly stable when splitting the data in half according to the acquisition schemes and computing partial correlations separately for each half of the data, as well as across cross-validation folds. Overall, these results demonstrate that unique functional connectivity patterns along the auditory pathway are recoverable using novel connectivity approaches and that our connectivity methods are reliable across multiple acquisitions.FundingThis work was supported by the National Science Foundation grant NSF DMS-1953712 (to AS and BC) and the National Institutes of Health/National Institute on Deafness and Other Communication Disorders (K01DC019421 to KRS and R01DC01550 to BC).