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Is the rostro-caudal axis of the frontal lobe hierarchical?

Nature Reviews Neuroscience volume 10, pages 659–669 (2009)Cite this article

Key Points

  • Recent studies have reported rostro-caudal distinctions in frontal cortex activity based on the level of abstractness of action representations. Moreover, some have proposed that these differences reflect a hierarchical organization, whereby anterior frontal regions influence processing by posterior frontal regions during the realization of abstract action goals as motor acts. However, if such a processing hierarchy indeed exists, systematic rostro-caudal patterns should be evident in the anatomy and function of the frontal cortex.

  • Evidence from single-unit recording and lesion studies of behavioural rule learning, conditional action selection and response sequencing in non-human primates suggest that prefrontal cortex neurons code for more abstract rules and categories of responses than do premotor neurons, which are located in the more-caudal frontal cortex.

  • Studies using functional MRI of humans have consistently shown systematic within-subject differences in activation from premotor cortex (caudal) to the frontal pole (rostral) based on the degree of abstraction entailed by an action selection problem.

  • Data from effective connectivity analysis of functional MRI data in humans suggests a rostral-to-caudal flow of influence, which is indirectly consistent with a rostro-caudal hierarchy of processing. Recent, preliminary evidence from lesion studies provides the first direct support for such a hierarchy by showing deficits in more-abstract action selection after caudal frontal lesions but no deficits in more-concrete action selection after rostral frontal lesions.

  • There is a gradient of laminar organization within the frontal cortex from the most anterior (least differentiated) to posterior portions. In this scheme, less differentiated areas, such as those in rostral prefrontal cortex (PFC; areas 10, 9 and 46), have more diffuse projections and are thus well situated to be at the top of a hierarchy. In contrast, more differentiated areas, such as those in caudal PFC (areas 9/46 and 8), have more intrinsic connections and are well situated to be lower in a hierarchy.

  • Afferent and efferent projections within the frontal cortex follow a principle of contiguity along the rostro-caudal dimension, such that each region projects to immediately adjacent regions that are rostral and caudal to it. Thus, area 9/46d projects to area 10 and area 6. However, the frontal cortex is not fully connected. For example, no direct connections are found between 9/46d and 9/46v, even though they are adjacent to one another.

  • Non-adjacent regions follow an asymmetry principle from rostral to caudal within the frontal cortex. Thus, area 10 projects to area 6 but there are no projections from area 6 to area 10.

  • The most rostrally localized area 10 does not project directly to parietal, temporal and occipital areas, but more-caudal frontal regions (areas 9/46 and 6) do have massive bidirectional connections with these areas.

  • During development, separate regions along the rostro-caudal axis of the frontal cortex mature at different rates. Although the premotor cortex matures the earliest, development does not progress uniformly back to front. Rather, the most caudal and rostral portions of the frontal cortex mature first, followed by the interposed lateral frontal regions.

Abstract

The frontal lobes in the brain are a component of the cerebral system that supports goal-directed behaviour. However, their functional organization remains controversial. Recent studies have reported rostro-caudal distinctions in frontal cortex activity based on the abstractness of action representations. In addition, some have proposed that these differences reflect a hierarchical organization, whereby anterior frontal regions influence processing by posterior frontal regions during the realization of abstract action goals as motor acts. However, few have considered whether the anatomy and physiology of the frontal lobes support such a scheme. To address this gap, this Review surveys anatomical, neuroimaging, electrophysiological and developmental findings, and considers the question: could the organization of the frontal cortex be hierarchical?

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Figure 1: Cytoarchitectonic divisions of the human and monkey frontal lobe.
Figure 2: Functional gradients along the rostro-caudal axis.
Figure 3: Architectonic stages of the prefrontal cortex.
Figure 4: Rostro-caudal connectivity of the frontal cortex.

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Acknowledgements

Supported by the National Institutes of Health (MH63901 and NS40813) and the Veterans Administration Research Service.

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Authors and Affiliations

  1. Department of Cognitive & Linguistic Sciences, Brown University, Providence, 02912, Rhode Island, USA

    David Badre

  2. Department of Psychology, Brown University, Providence, 02912, Rhode Island, USA

    David Badre

  3. Helen Wills Neuroscience Institute, University of California, 94720, Berkeley, USA

    Mark D'Esposito

  4. Department of Psychology, University of California, 94720, Berkeley, USA

    Mark D'Esposito

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Correspondence to David Badre.

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Supplementary information

Supplementary information S1 (box)

Domain generality along rostro-caudal frontal cortex (PDF 271 kb)

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Glossary

Cognitive control

Also termed executive function, cognitive control allows flexible behaviour by guiding thought and action based on goals, plans and intentions.

Double dissociation

When two experimental manipulations have different effects on two dependent variables (for example, on the left and right hemisphere or on the medial and lateral prefrontal cortex).

Domain (stimulus/input domains)

A type of information, such as spatial versus verbal versus object-related information. Domains are often associated with independent or modular input systems.

Action rule

A type of knowledge that specifies how to behave given a particular state. A stimulus-to-response mapping is a simple rule.

Semantic

Conceptual knowledge, beliefs and facts about the world. In the verbal domain, semantic refers to word meanings.

Phonology (phonological)

The sound structure of a word in terms of the smallest sound units that distinguish different words in a language.

Repetition priming

Facilitated processing of a stimulus upon repetition, which happens even following an extended delay.

Structural equation modelling

A statistical approach for testing proposed causal relationships between variables.

Seeding

A step in functional connectivity analysis whereby a region of interest is defined to which connectivity of all other regions is estimated.

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Badre, D., D'Esposito, M. Is the rostro-caudal axis of the frontal lobe hierarchical?. Nat Rev Neurosci 10, 659–669 (2009). https://doi.org/10.1038/nrn2667

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