Anatomical and functional connectivity support the existence of a salience network node within the caudal ventrolateral prefrontal cortex
Three large-scale brain networks are considered essential to cognitive flexibility: the ventral and dorsal attention (VANet and DANet) and salience (SNet) networks. The ventrolateral prefrontal cortex (vlPFC) is a known component of the VANet and DANet, but there is an important gap in the current knowledge regarding its involvement in the SNet. In this study, we used a translational and multimodal approach to fulfill this gap and demonstrate the existence of a SNet node within the vlPFC. First, we used tract-tracing methods in non-human primates (NHP) to quantify the anatomical connectivity strength between the different vlPFC areas and the frontal and insular cortices. The strongest connections with the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) locations comprising the two main cortical SNet nodes were derived from the caudal area 47/12. This location also has strong axonal projections to subcortical structures of the salience network, including the dorsomedial thalamus, hypothalamus, sublenticular extended amygdala, and periaqueductal gray. Second, we used a seed-based functional connectivity analysis in NHP resting-state functional MRI (rsfMRI) data to validate the caudal area 47/12 as an SNet node. Third, we used the same approach in human rsfMRI data to identify a homologous structure in caudal area 47/12, also showing strong connections with the SNet cortical nodes, thus confirming the caudal area 47/12 as the SNet node in the vlPFC. Taken together, the vlPFC contains nodes for all three cognitive networks, the VANet, DANet, and SNet. Thus, the vlPFC is in a position to switch between these three cognitive networks, pointing to a key role as an attentional hub. Its tight additional connections to the orbitofrontal, dorsolateral, and ventral premotor cortices, places the vlPFC at the center for switching behaviors based on environmental stimuli, computing value and cognitive control.
All anatomical data analysed during this study are included in the manuscript and supporting files.Functional connectivity analyses utilized publicly available datasets:PRIME-DE:https://fcon_1000.projects.nitrc.org/indi/indiPRIME.htmlGSP:https://www.nature.com/articles/sdata201531
PRIMatE Data Exchange (PRIME-DE)PRIMatE Data Exchange (PRIME-DE).
Article and author information
National Institutes of Health (MH106435)
- Suzanne N Haber
National Institutes of Health (MH045573)
- Suzanne N Haber
National Natural Science Foundation of China (81790652)
- Hesheng Liu
National Institutes of Health (MH111439)
- Charles E Schroeder
National Institutes of Health (MH109429)
- Charles E Schroeder
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All tracer experiments and animal care were approved by the University Committee on Animal Resources at University of Rochester (protocol number UCAR-2008-122R).The NKI Institutional Animal Care and Use Committee (IACUC) protocol approved all imaging methods and procedures in NHP (protocol numbers AP2016-568 and AP2019-642). All experiments were conducted following the National Guide for the Care and Use of Laboratory Animals.
- Birte U Forstmann, University of Amsterdam, Netherlands
- Preprint posted: October 3, 2021 (view preprint)
- Received: December 13, 2021
- Accepted: May 4, 2022
- Accepted Manuscript published: May 5, 2022 (version 1)
- Version of Record published: May 13, 2022 (version 2)
© 2022, Trambaiolli et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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