Elsevier

NeuroImage

Volume 185, 15 January 2019, Pages 398-407
NeuroImage

Functionally dissociating ventro-dorsal components within the rostro-caudal hierarchical organization of the human prefrontal cortex

https://doi.org/10.1016/j.neuroimage.2018.10.048Get rights and content

Highlights

  • Near-infrared spectroscopy (NIRS) allows inference of directed functional networks.

  • NIRS reveals rostro-caudally directed interactions in prefrontal cortex (PFC).

  • Rostro-caudally directed interactions are segregated in a dorsal and ventral stream.

  • Rostro-caudal directed interactions peak in mid-dorsolateral PFC as apex of control.

  • NIRS-based analyses complement evidence from functional magnetic resonance imaging.

Abstract

Cognitive control is proposed to rely on a rostral-to-caudal hierarchy of neural processing within the prefrontal cortex (PFC), with more rostral parts exerting control over more caudal parts. Anatomical and functional data suggest that this hierarchical organization of the PFC may be separated into a ventral and a dorsal component. Furthermore, recent studies indicate that the apex of the hierarchy resides within the mid-lateral rather the rostral PFC. However, investigating the hierarchical aspect of rostro-to-caudal processing requires quantification of the directed interactions between PFC regions.

Using functional near-infrared spectroscopy (fNIRS) in a sample of healthy young adults we analyzed directed interactions between rostral and caudal PFC during passive watching of nature documentaries. Directed coherence (DC) as a measure of directed interaction was computed pairwise between 38 channels evenly distributed over the lateral prefrontal convexity.

Results revealed an overall predominance of rostral-to-caudal directed interactions in the PFC that further dissociated along a ventro-dorsal axis: Dorsal regions exerted stronger rostro-caudally directed interactions on dorsal than on ventral regions and vice versa. Interactions between ventral and dorsal PFC were stronger from ventral to dorsal areas than vice versa. Results further support the notion that the mid-dorsolateral PFC constitutes the apex of the prefrontal hierarchy.

Taken together these data provide novel evidence for parallel dorsal and ventral streams within the rostro-caudal hierarchical organization of the PFC. FNIRS-based analyses of directed interactions put forward a new perspective on the functional architecture of the prefrontal hierarchy and complement previous insights from functional magnetic resonance imaging.

Introduction

Within the lateral prefrontal cortex (PFC), different levels of cognitive control are assumed to be hierarchically organized along a rostro-caudal axis, with rostral parts of the PFC performing highly abstract levels of behavioral control and caudal parts carrying out concrete action selection in a temporally confined context (Badre et al., 2009; Blumenfeld et al., 2013; Koechlin et al., 2003, 1999; Voytek et al., 2015). Evidence for this hierarchical organization of neural processing has been provided by task-based functional magnetic resonance imaging (fMRI) studies (Badre & D'Esposito, 2007; Bahlmann et al., 2015; Koechlin et al., 1999, for a review see Badre & D'Esposito, 2009) but is also supported by lesion data (Azuar et al., 2014) and transcranial magnetic stimulation (Nee and D'Esposito, 2016). However, other studies showed that rostral PFC regions can also be recruited by concrete action selection (Crittenden and Duncan, 2014) and that the temporal, rather than the spatial activation profile of specific PFC regions is modulated by maintenance demands, irrespective of the level of abstraction (Reynolds et al., 2012). Tracer studies in monkeys further demonstrated that the structural network in the PFC does not follow a strict rostro-caudal organization (Goulas et al., 2014). The extent to which the PFC is organized along a rostro-caudal axis hence constitutes a matter of debate.

Beyond functional gradients along a rostro-caudal axis, the structural and functional organization of the PFC has also been subject to anatomically detailed characterizations along a ventro-dorsal axis (see Tanji and Hoshi, 2008 and Petrides, 2005 for reviews). In this respect, it has been demonstrated that potentially separable rostro-caudal streams of processing are present in the ventral and dorsal convexity of the lateral PFC (Blumenfeld et al., 2018, 2013). Using a resting-state fMRI paradigm, Blumenfeld et al. (2013) found parallel ventral and dorsal networks that were interconnected in caudal but not in rostral PFC regions. Bahlmann et al. (2015) further suggested that rostro-caudally organized functional networks in ventral and dorsal PFC adapt their ventro-dorsal segregation dynamically to be operative on the highest level of the rostro-caudal axis that is currently engaged in the task, whereas on lower levels processing is integrated across ventral and dorsal areas. The lateral PFC thus seems to comprise parallel rostro-caudal pathways which appear anatomically separable along a ventro-dorsal axis but functionally interact to subserve goal-directed behavior. While this functional interaction has been proposed to be orchestrated by the rostral-most part of the lateral PFC (e.g. Ramnani and Owen, 2004; Wendelken et al., 2012; for a recent review on the function of the frontopolar cortex see Mansouri et al., 2017), recent evidence suggests that the apex of the prefrontal hierarchy actually resides in the mid-lateral rather than the rostral PFC (Margulies et al., 2016; Nee and D'Esposito, 2016; for a review see Badre and Nee, 2018).

Taken together, an abundance of fMRI studies demonstrate the gradual activation along the rostro-caudal and the ventro-dorsal axes of the PFC by task-related factorial designs (e.g. Bahlmann et al., 2015) as well as the functional connectivity between the respective regions by correlation analyses of resting-state activity (e.g. Taren et al., 2011). These studies argue for a hierarchical functional organization of the PFC. However, to fully understand the mechanisms and functional pathways that subserve cognitive functions requires to complement these correlation- and activation-based analyses by the inference of the actual direction of influences and the demonstration of the implied propagation of neural activity along a rostro-to-caudal gradient of hierarchical control within the lateral PFC. While the slow hemodynamic response is well captured by sampling intervals between 0.5 and 2 Hz as provided by conventional fMRI (Logothetis, 2008), functional interactions between brain regions appear on a much smaller temporal scale (Stokes et al., 2013). Reliably inferring directed functional connections from such very short delays between neural activity in different regions requires much faster sampling of at least 10 Hz (Mader et al., 2008; Roebroeck et al., 2005). Simplifying the problem of inferring directionality down to the detection of short delays between oscillations (Granger, 1969), the need for a sufficiently high temporal resolution can be easily illustrated by plotting two noisy sine waves with a small phase shift using different sampling rates. A phase shift which is entirely obscure when sampled at .5 Hz can become highly apparent when sampled at 10 Hz (Supplementary Fig. S1).

Similar to fMRI, functional near-infrared spectroscopy (fNIRS) relies on the neuro-vascular coupling and measures the hemodynamic response but in contrast to fMRI it is based on the differential absorption properties of oxygenated and deoxygenated hemoglobin (Scholkmann et al., 2014; Strangman et al., 2002). Multiple light sources and detectors transcranially measure absorption changes elicited by changes in cortical oxygenation at sample frequencies up to 250 Hz (Scholkmann et al., 2014). Thus, fNIRS overcomes the limited temporal resolution of fMRI and provides sufficiently high spatial resolution (here 2.1 cm) to allow for inference of directed functional interactions along rostro-caudal and ventro-dorsal axes in the PFC.

Here we used fast optical imaging with multi-channel fNIRS and measures of directed coherence (DC) (Schelter et al., 2006) to estimate the propagation of neural activity across the PFC and to provide complementary evidence for the predicted influences within and between parallel rostro-caudal signaling pathways in the ventral and dorsal PFC (Bahlmann et al., 2015; Blumenfeld et al., 2013; Bunge et al., 2005; Wendelken et al., 2012). We expected to reveal (i) a predominant rostral to caudal direction of influences within the PFC and (ii) a separation into a ventral and a dorsal component.

Section snippets

Experimental design

Subjects between 19 and 26 years of age were recruited from the University of Freiburg provided that they were German native speakers and fulfilled MRI safety criteria. Exclusion criteria concerned current or previous psychiatric/neurological disease, use of psychotropic medication, and color blindness. Thirty-one subjects participated in two 24-min fNIRS measurements (one week apart) and additionally underwent MRI and neuropsychological assessments that were conducted as a part of a larger

Results

Due to the high number of observations all fixed effects terms in both models were significant (p < .05); we therefore only report significant digits (Clymo, 2014) of least square means of DC values (DCLSM) ± standard errors and post-hoc tests of interest in the text and refer the reader to Supplementary Table S1 for a detailed overview of effect statistics. In the following, ΔDCLSM denotes contrasts (pairwise comparisons) of DCLSM values and ΔΔDCLSM denotes interaction contrasts (pairwise

Discussion

Taking advantage of the sufficiently high temporal and spatial resolution of multi-channel fNIRS, the present study used directed coherence as a measure of influences between brain regions to assess the functional networks of the PFC (Medvedev, 2014). Showing that activity in caudal PFC is modulated by activity in its more rostral parts, the present data provide complementary evidence for the intrinsic rostro-caudal functional hierarchy within the PFC, as predicted by extant models of

Conclusion

Using the methodological framework of fast sampling multi-channel fNIRS and a frequency-domain measure of directed functional connectivity, we provide explicit evidence for a rostral-to-caudal processing hierarchy in the PFC. Consistent with extant models of prefrontal organization, this hierarchy is dissociated into a ventral and a dorsal component and peaks in the mid-dorsolateral PFC, which exerts the highest level of cognitive control (Badre and Nee, 2018).

Conflicts of interest

The authors declare no competing financial interests.

Acknowledgement

This work was supported by a grant of the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation (DFG, grant number EXC 1086).

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