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

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.

Keywords

• lateral prefrontal cortex
• meta-analysis
• rostrocaudal gradient
• probabilistic logic programming
• neuroinformatics
• specificity