Integrating brainstem and cortical functional architectures

Brisbane Convention & Exhibition Centre 

The brainstem is a fundamental component of the central nervous system, yet it is typically excluded from in vivo human brain mapping efforts, precluding a complete understanding of how the brainstem influences cortical function. Here we study how functional activity throughout the brainstem aligns with cortical function. We use high-resolution 7 Tesla resting-state fMRI, via a novel brainstem-optimized acquisition protocol and processing pipeline, to image the whole-brainstem across 58 anatomically defined nuclei spanning midbrain, pons and medulla. First, we identify hubs of brainstem-cortex functional connectivity (FC) and link brainstem-cortex FC with cytoarchitectonic classes, laminar differentiation, and electrophysiological signatures of neural oscillations. Next, we cluster brainstem nuclei with respect to their cortical FC. We identify five modules of brainstem nuclei with distinct patterns of cortical FC related to memory, cognitive control, multisensory coordination, perception and movement, and emotion. Furthermore, we use PET-estimated brain maps for 18 neurotransmitter receptors and transporters to determine whether neurotransmitter systems are mediating the link between neuromodulatory brainstem nuclei and cortical functional activation patterns. Finally, we find that cortical regions are functionally connected with the brainstem along a unimodal-transmodal hierarchy, indicating that the putative cortical functional gradient can be traced back to the brainstem. To ensure all findings are robust, we replicate the analyses using 3 Tesla data acquired in the same individuals, using an alternative parcellation resolution, and in the subcortex. Altogether, using simultaneous in vivo human imaging of brainstem and cortical functional activity, this study extends our perspective of cortical function---including dynamics, cognitive function, and the unimodal-transmodal cortical functional gradient---to the brainstem, demonstrating how cortical functional architecture consistently reflects the brainstem.