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

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?

Figure 1. Cytoarchitectonic divisions of the human and monkey frontal lobe

Rostral and caudal axes are labelled and the numbers represent the update by Petrides and Pandya of the Brodmann and Walker cytoarchitecture maps. Several investigators have created maps of the frontal cortex based on morphological criteria such as the gross characteristics of cells, the arrangement of these cells in cortical layers, and gross characteristics of myelin in the cortex (for examples see REFS 152,153). However, area boundaries differ significantly between maps. For example, in the lateral prefrontal cortex, Brodmann’s area 9 is extensive and area 46 does not exist, whereas Walker includes area 46 and a much more restricted area 9 (REF. 153). Another issue concerns the correspondence between maps of monkey and human cortex. Indeed, a comparison between Brodmann’s monkey and human cortex maps reveals seemingly significant differences; for example, the human map includes area 46, but the monkey map does not^,. Likewise, in Walker’s map of the monkey cortex, area 46 is far more extensive than that depicted in Brodmann’s map of the human cortex. To resolve these discrepancies, Petrides and Pandya^,, performed an extensive comparison of the architecture of the frontal cortex between monkeys and humans. This revealed that both in monkeys and humans, areas 9 and 46 are in the mid-dorsolateral sector of the lateral prefrontal cortex. Also, in both species, area 9 lies dorsal to area 46. However, in humans, area 9 encircles area 46 caudally, which is not the case in monkeys. This caudal portion of area 9 in humans is similar to the caudal portion of area 46 in monkeys. This led Petrides and Pandya to create a new label, area 9/46, which they divided into a dorsal portion (area 9/46d) and a ventral portion (area 9/46v). The nomenclature they put forth in their maps is used in this Review. Figure is reproduced, with permission, from REF. © (2002) Wiley-Blackwell.

Figure 2. Functional gradients along the rostro-caudal axis

a | Summary of experimental findings from functional MRI (fMRI) studies and monkey electrophyiology along the rostro-caudal gradient. Across studies, there seems to be a trend for more-rostral regions to support more-abstract action rules. Anatomical locations of effects are approximate. b | Comparison of results from two fMRI studies showing functional gradients along the rostro-caudal axis of the human frontal lobe. Explicitly testing a rostro-caudal functional gradient, Koechlin et al. (shown in blue) and Badre et al. (shown in red) demonstrated highly convergent activation along a dorsal gradient from dorsal premotor cortex (PMd) (a,b; ~BA 6) to prePMd (c,d; ~BA 8) to mid-dorsolateral prefrontal cortex (PFC) (e,f; ~BA 9/46) to frontopolar cortex (g; ~BA 10), as cognitive control was required at progressively abstract levels. Although different forms of abstraction were tested — temporal abstraction in Koechlin et al. and policy abstraction in Badre et al. (see BOX 1) — the activation patterns observed in these two experiments were highly convergent. c | Race et al. aimed to locate a gradient of abstraction along the ventrolateral PFC by assessing repetition priming (that is, a reduction in signal change) at the stimulus (semantic), task (decision) and response levels. They showed that areas 44 and 8 (shown in orange) in caudal ventrolateral PFC showed repetition priming at the response level, that is, the signal change in these areas diminished when a motor response was repeated, regardless of the stimulus or decision associated with it. Area 45 (shown in blue) revealed repetition priming at the decision level even if the subsequent response differed. And area 47 (shown in red) demonstrated priming when the same item was encountered (semantic priming), regardless of the subsequent decision or response. These priming effects indicate a rostral-to-caudal gradient of decreasing abstraction. Part b is reproduced, with permission, from REF. © (2007) MIT Press. Part c is reproduced, with permission, from REF. © (2009) MIT press.

Figure 3. Architectonic stages of the prefrontal cortex

Diagrams showing the architectonic stages in the basoventral (a) and mediodorsal (b) prefrontal cortices. Each of these two broad cortical regions shows a gradient of laminar organization (for example, differentiation) from the most anterior to more-posterior portions of the frontal cortex. This axis of differentiation proceeds in a direction from the least-differentiated (anterior frontal regions such as area 10 and rostral area 46) to the most-differentiated cortex (posterior frontal regions such as caudal areas 46 and 8). Figure is modified, with permission, from REF. © (1989) Wiley.

Figure 4. Rostro-caudal connectivity of the frontal cortex

a. Intrinsic connections of the lateral prefrontal cortex (PFC; top) and a schematic summary of the connections of the principal frontal regions (area 10, shown in orange; area 9/46, shown in green; and area 6, shown in blue) that are proposed to be part of a rostro-caudal functional gradient based on functional studies (bottom). Area 4 depicts the primary motor cortex. b. Results from Vincent et al. showing that spontaneous activity in regions along the rostro-caudal axis of the prefrontal cortex (PFC) and in parietal and medial frontal cortex is correlated with activity in the frontopolar cortex (shown in light green). Also depicted in the figure is the spatial relationship of these regions to two other networks: the dorsal attention system (DAS) and the hippocampal-cortical memory system (HCMS), which were identified using visual motion area MT+ and the hippocampus as seeds, respectively. Importantly, these data provide evidence that the activities in regions of the frontal cortex that in other experiments were associated with control at increasing levels of abstraction are correlated with each other (and thus are part of a coherent rostro-caudal functional network, that is, the frontoparietal control system (FPCS)) but not with activity in other regions of the frontal cortex (that is, areas in the DAS and HCMS). Part b is reproduced, with permission, from REF. © (2008) The American Physiological Society.