Functional gradients in the human lateral prefrontal cortex revealed by a comprehensive coordinate-based meta-analysis

  1. Majd Abdallah  Is a corresponding author
  2. Gaston E Zanitti
  3. Valentin Iovene
  4. Demian Wassermann  Is a corresponding author
  1. Inria Saclay - Île-de-France Research Centre, France

Abstract

The lateral prefrontal cortex (LPFC) of humans enables flexible goal-directed behavior. However, its functional organization remains actively debated after decades of research. Moreover, recent efforts aiming to map the LPFC through meta-analysis are limited, either in scope or in the inferred specificity of structure-function associations. These limitations are in part due to the limited expressiveness of commonly-used data analysis tools, which restricts the breadth and complexity of questions that can be expressed in a meta-analysis. Here, we adopt NeuroLang, a novel approach to more expressive meta-analysis based on probabilistic first-order logic programming, to infer the organizing principles of the LPFC from 14,371 neuroimaging studies. Our findings reveal a rostrocaudal and a dorsoventral gradient, respectively explaining the most and second most variance in meta-analytic connectivity across the LPFC. Moreover, we identify a unimodal-to-transmodal spectrum of coactivation patterns along with a concrete-to-abstract axis of structure-function associations extending from caudal to rostral regions of the LPFC. Finally, we infer inter-hemispheric asymmetries along the principal rostrocaudal gradient, identifying hemisphere-specific associations with topics of language, memory, response inhibition, and sensory processing. Overall, this study provides a comprehensive meta-analytic mapping of the LPFC, grounding future hypothesis generation on a quantitative overview of past findings.

Data availability

All data and scripts used in this study are openly available to be accessed and freely used by the community. The source code of NeuroLang is freely available on GitHub at https://github.com/NeuroLang/NeuroLang.

The following previously published data sets were used

Article and author information

Author details

  1. Majd Abdallah

    Inria Saclay - Île-de-France Research Centre, Palaiseau, France
    For correspondence
    majd.abdallah@inria.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8371-1793
  2. Gaston E Zanitti

    Inria Saclay - Île-de-France Research Centre, Palaiseau, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5549-9548
  3. Valentin Iovene

    Inria Saclay - Île-de-France Research Centre, Palaiseau, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Demian Wassermann

    Inria Saclay - Île-de-France Research Centre, Palaiseau, France
    For correspondence
    demian.wassermann@inria.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5194-6056

Funding

European Research Council (10.3030/757672)

  • Majd Abdallah

European Research Council (10.3030/757672)

  • Demian Wassermann

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The current study uses brain activation data from the Individual Brain Charting Dataset (IBC). In the original paper of IBC, the authors indicate that they received written consent from the subjects involved in the study. To quote from Pinho et al. Individual Brain Charting, a high-resolution fMRI dataset for cognitive mapping. Sci Data. 2018 : "The experimental procedures were approved by a regional ethical committee for medical protocols in Île-de-France ("Comité de Protection des Personnes" - no. 14-031) and a committee to ensure compliance with data-protection rules ("Commission Nationale de l'Informatique et des Libertés" - DR-2016-033). They were undertaken with the informed written consent of each participant according to the Helsinki declaration and the French public health regulation. Participants were reimbursed on the basis of 80 per MRI acquisition with extra-fees for any additional session."

Copyright

© 2022, Abdallah 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

  • 997
    views
  • 191
    downloads
  • 13
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Majd Abdallah
  2. Gaston E Zanitti
  3. Valentin Iovene
  4. Demian Wassermann
(2022)
Functional gradients in the human lateral prefrontal cortex revealed by a comprehensive coordinate-based meta-analysis
eLife 11:e76926.
https://doi.org/10.7554/eLife.76926

Share this article

https://doi.org/10.7554/eLife.76926

Further reading

    1. Neuroscience
    Franziska Auer, Katherine Nardone ... David Schoppik
    Research Article

    Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.

    1. Neuroscience
    Zhujun Shao, Mengya Zhang, Qing Yu
    Research Article

    When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.