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.
Reviewing Editor
- Timothy E Behrens, University of Oxford, United Kingdom
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
Version 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.
Metrics
-
- 3,081
- Page views
-
- 521
- Downloads
-
- 43
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.
-
- Neuroscience
Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (Lonchura striata domestica). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points, where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases, where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.