Microstructural organization of human insula is linked to its macrofunctional circuitry and predicts cognitive control
Abstract
The human insular cortex is a heterogeneous brain structure which plays an integrative role in guiding behavior. The cytoarchitectonic organization of the human insula has been investigated over the last century using postmortem brains but there has been little progress in noninvasive in vivo mapping of its microstructure and large-scale functional circuitry. Quantitative modeling of multi-shell diffusion MRI data from 413 participants revealed that human insula microstructure differs significantly across subdivisions that serve distinct cognitive and affective functions. Insular microstructural organization was mirrored in its functionally interconnected circuits with the anterior cingulate cortex that anchors the salience network, a system important for adaptive switching of cognitive control systems. Furthermore, insular microstructural features, confirmed in Macaca mulatta, were linked to behavior and predicted individual differences in cognitive control ability. Our findings open new possibilities for probing psychiatric and neurological disorders impacted by insular cortex dysfunction, including autism, schizophrenia, and fronto-temporal dementia.
Data availability
All data used in this study is available in open-source databases. The human data comes from the Human Connectome Project, the primate data is available at the INDI Primate Data Exchange, and the three-dimensional neuronal models are available from the NeuroMorpho website. All custom code is available on GitHub accesible through the Zenodo DOI: 10.5281/zenodo.3759708. All code was developed based on open-source, publicly available software packages.
Article and author information
Author details
Funding
European Commission (NeuroLang -- 757672)
- Demian Wassermann
National Institutes of Health (HD094623,HD059205,MH084164)
- Vinod Menon
National Institutes of Health (MH105625)
- Weidong Cai
Inria (LargeBrainNets)
- Demian Wassermann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal data was obtained from the INDI-Prime primate data exchange database collection (http://fcon_1000.projects.nitrc.org/indi/indiPRIME.html) . All methods and procedures were approved by the Princeton University IACUC
Human subjects: Data was obtained from the HCP database. Informed consent for this study was not explicitly required. However, subjects signed a written informed consent when the database was constituted. IRB approval was obtained for the database construction with the following details: Mapping the Human Connectome: Structure, Function, and HeritabilityIRB # 201204036
Reviewing Editor
- Timothy E Behrens, University of Oxford, United Kingdom
Publication history
- Received: November 9, 2019
- Accepted: June 3, 2020
- Accepted Manuscript published: June 4, 2020 (version 1)
- Version of Record published: June 22, 2020 (version 2)
Copyright
© 2020, Menon 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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The human cerebral cortex is symmetrically organized along large-scale axes but also presents inter-hemispheric differences in structure and function. The quantified contralateral homologous difference, that is asymmetry, is a key feature of the human brain left-right axis supporting functional processes, such as language. Here, we assessed whether the asymmetry of cortical functional organization is heritable and phylogenetically conserved between humans and macaques. Our findings indicate asymmetric organization along an axis describing a functional trajectory from perceptual/action to abstract cognition. Whereas language network showed leftward asymmetric organization, frontoparietal network showed rightward asymmetric organization in humans. These asymmetries were heritable in humans and showed a similar spatial distribution with macaques, in the case of intra-hemispheric asymmetry of functional hierarchy. This suggests (phylo)genetic conservation. However, both language and frontoparietal networks showed a qualitatively larger asymmetry in humans relative to macaques. Overall, our findings suggest a genetic basis for asymmetry in intrinsic functional organization, linked to higher order cognitive functions uniquely developed in humans.