Structural connections between the noradrenergic and cholinergic system shape the dynamics of functional brain networks

N L Taylor; A D'Souza; B R Munn; J Lv; L Zaborszky; E J Müller; G Wainstein; F Calamante; J M Shine

doi:10.1016/j.neuroimage.2022.119455

Structural connections between the noradrenergic and cholinergic system shape the dynamics of functional brain networks

Neuroimage. 2022 Oct 15:260:119455. doi: 10.1016/j.neuroimage.2022.119455. Epub 2022 Jul 7.

Authors

N L Taylor¹, A D'Souza², B R Munn¹, J Lv³, L Zaborszky⁴, E J Müller¹, G Wainstein¹, F Calamante⁵, J M Shine⁶

Affiliations

¹ Brain and Mind Centre, The University of Sydney, Sydney, Australia.
² Brain and Mind Centre, The University of Sydney, Sydney, Australia; Sydney School of Medicine, Central Clinical School, The University of Sydney, Australia.
³ Brain and Mind Centre, The University of Sydney, Sydney, Australia; School of Biomedical Engineering, The University of Sydney, Sydney, Australia.
⁴ School of Arts and Sciences, Rutgers University, New Jersey, USA.
⁵ Brain and Mind Centre, The University of Sydney, Sydney, Australia; School of Biomedical Engineering, The University of Sydney, Sydney, Australia; Sydney Imaging, The University of Sydney, Sydney, Australia.
⁶ Brain and Mind Centre, The University of Sydney, Sydney, Australia. Electronic address: mac.shine@sydney.edu.au.

Abstract

Complex cognitive abilities are thought to arise from the ability of the brain to adaptively reconfigure its internal network structure as a function of task demands. Recent work has suggested that this inherent flexibility may in part be conferred by the widespread projections of the ascending arousal systems. While the different components of the ascending arousal system are often studied in isolation, there are anatomical connections between neuromodulatory hubs that we hypothesise are crucial for mediating key features of adaptive network dynamics, such as the balance between integration and segregation. To test this hypothesis, we estimated the strength of structural connectivity between key hubs of the noradrenergic and cholinergic arousal systems (the locus coeruleus [LC] and nucleus basalis of Meynert [nbM], respectively). We then asked whether the strength of structural LC and nbM inter-connectivity was related to individual differences in the emergent, dynamical signatures of functional integration measured from resting state fMRI data, such as network and attractor topography. We observed a significant positive relationship between the strength of white-matter connections between the LC and nbM and the extent of network-level integration following BOLD signal peaks in LC relative to nbM activity. In addition, individuals with denser white-matter streamlines interconnecting neuromodulatory hubs also demonstrated a heightened ability to shift to novel brain states. These results suggest that individuals with stronger structural connectivity between the noradrenergic and cholinergic systems have a greater capacity to mediate the flexible network dynamics required to support complex, adaptive behaviour. Furthermore, our results highlight the underlying static features of the neuromodulatory hubs can impose some constraints on the dynamic features of the brain.

Keywords: Attractor landscape; Basal nucleus of Meynert; Diffusion MRI; Locus coeruleus; Neuromodulation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Basal Nucleus of Meynert*
Brain*
Cholinergic Agents
Humans
Locus Coeruleus / diagnostic imaging
Magnetic Resonance Imaging / methods

Substances

Cholinergic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding