Integrating brainstem and cortical functional architectures

1714 

Abstract Submission 

Justine Hansen¹, Simone Cauzzo², Kavita Singh², Maria Guadalupe Garcia-Gomar², James Shine³, Marta Bianciardi², Bratislav Misic⁴

¹McGill University, Montreal, QC, ²Harvard Medical School, Boston, MA, ³University of Sydney, Sydney, NA, ⁴McGill University, Montreal, Quebec

Justine Hansen  
McGill University
Montreal, QC

Simone Cauzzo  
Harvard Medical School
Boston, MA

Kavita Singh  
Harvard Medical School
Boston, MA

Maria Guadalupe Garcia-Gomar  
Harvard Medical School
Boston, MA

Mac Shine  
University of Sydney
Sydney, NA

Marta Bianciardi  
Harvard Medical School
Boston, MA

Bratislav Misic  
McGill University
Montreal, Quebec

The brain is a network of functionally interacting neural populations. Studying the functional architecture of the brain in awake humans is possible with multiple imaging technologies, although these technologies are often biased towards the cortex where signal quality is highest [1]. Perhaps the biggest missing piece of modern in vivo brain network reconstruction is the brainstem. This early evolutionary structure is crucial for survival and consciousness, and integrates signals from throughout the nervous system. Furthermore, multiple neurotransmitter systems originate in brainstem nuclei and project throughout the cortex, shaping cortical activity [2]. However, knowledge about brainstem function primarily comes from either lesion studies or studies in model organisms, and these studies are often limited to specific nuclei or pathways. Exciting recent imaging advances have improved the feasibility of measuring brainstem activity, making it now possible to augment the cortical functional connectome with an anatomically comprehensive representation of the brainstem [3-5].

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 [3-5]. 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. Using meta-analytic cortical functional activation patterns from NeuroSynth, we derive a psychological signature for each brainstem community [6]. 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 [7]. Finally, we identify cortical regions that are similarly functionally connected with the brainstem, as well as the brainstem nuclei with which these cortical regions are connected. 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.

We identify a compact set of brainstem-cortex hubs, including the periaqueductal grey, dorsal raphe, laterodorsal tegmental nucleus, and inferior medullary reticular formation (Figure 1a). On the other hand, cortical regions are functionally connected with the brainstem following an anterior-posterior gradient that is correlated with cellular architecture and MEG-derived oscillatory dynamics (Figure 1b-e). Next, 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 find that neuromodulatory nuclei within each module are likely mediating the link between brainstem module and cortical activation pattern. 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 (Figure 2a, b). Unimodal cortex is connected with caudal brainstem, and transmodal cortex with rostral brainstem (Figure 2c).

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.

Connectivity (eg. functional, effective, structural)

fMRI Connectivity and Network Modeling ¹

Multivariate Approaches

Anatomy and Functional Systems ²

Transmitter Receptors

Brainstem

Cognition

FUNCTIONAL MRI

HIGH FIELD MR

MEG

Multivariate

Neurotransmitter

Positron Emission Tomography (PET)

RECEPTORS

Sub-Cortical