Elsevier

NeuroImage

Volume 42, Issue 3, September 2008, Pages 1178-1184
NeuroImage

The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis

https://doi.org/10.1016/j.neuroimage.2008.05.059Get rights and content

Abstract

Recent research has shown that intrinsic brain activity as observed by functional magnetic resonance imaging (fMRI) manifest itself as coherent signal changes in networks encompassing brain regions that span long-range neuronal pathways. One of these networks, the so called default mode network, has become the primary target in recent investigations to link intrinsic activity to cognition and how intrinsic signal changes may be altered in disease. In this study we assessed functional connectivity within the default mode network during both rest and a continuous working memory task on a region-by-region basis using partial correlation analysis, a data-driven method that provides insight into effective connectivity within neuronal networks. Prominent features of functional connectivity within the default mode network included an overall strong level of interaction between the precuneus/posterior cingulate region and the rest of the default mode network, as well as a high degree of interaction between the left and right medial temporal lobes combined with weak interactions between the medial temporal lobes and the rest of the default mode network. Additionally, we found support for strong interactions between the precuneus/posterior cingulate cortex and the left inferior parietal lobe as well as between the dorsal and ventral sections of the medial prefrontal cortex. The suggested pivotal role of the precuneus/posterior cingulate cortex in the default mode network is discussed.

Introduction

Intrinsic functional brain connectivity as revealed by low-frequency spontaneous signal fluctuations in fMRI signal intensity time-courses has received increased attention in the neuroscience community. A first demonstration of the existence of so called resting-state networks was given by Biswal et al. (1995) by showing that brain activity in the primary sensorimotor brain areas are synchronized across the hemispheres during rest. Subsequent functional connectivity studies focusing on the detection of low-frequency fMRI signal changes using explorative, data-driven analysis methods have suggested that there exist up to 10 resting-state networks that span long-range cortico-cortical as well as well as cortical–subcortical networks in the human brain (Beckmann et al., 2005, Damoiseaux et al., 2006). Moreover, recent investigations have presented experimental data suggesting that resting-state networks prevail during sleep (Fukunaga et al., 2006, Horovitz et al., 2008) and anaesthetic conditions (Vincent et al., 2007, Greicius et al., in press).

From a cognitive neuroscience point of view, particular attention has been paid to one of the resting-state networks, the so called default mode network (DMN, Raichle et al., 2001). There are several reasons for this interest, one being that positron emission tomography (PET) investigations have revealed that the precuneus/posterior cingulate cortex (pC/PCC) and the medial prefrontal cortex (MPFC), both previously shown to be part of the DMN, show an elevated level of metabolic activity (Raichle et al., 2001). Another reason is the recurrent observation that attention-demanding tasks cause a decrease in activity in the DMN (Shulman et al., 1997, Mazoyer et al., 2001). Finally, studies targeting the neuronal basis for self-related mental tasks have shown consistent signal increases in the DMN compared to tasks without elements of self-related mental processing (see Buckner et al., 2008 for a review). From a clinical perspective, the DMN has become a primary objective in the endeavour to characterize and localize differences in resting-state network activity as biological markers for abnormalities in brain connectivity for a wide spectrum of psychiatric disorders. For example, previous studies using seed-based ROI correlation analyses have shown that intrinsic fMRI signal fluctuations in the precuneus/posterior cingulate cortex (pC/PCC) is altered in schizophrenia (Bluhm et al., 2007), while intrinsic functional correlation between the pC/PCC, MPFC and the right inferior parietal lobe (IPL) is altered in autism (Kennedy and Courchesne, 2008). Moreover, a recent study has shown a significant decrease in intrinsic resting-state functional correlation between the MPFC and the PCC in ADHD subjects compared to healthy controls (Castellanos et al., 2008). Using pairwise correlation measures in the healthy brain, Buckner et al. (2008) have obtained results that suggest that the pC/PCC, MPFC and the bilateral IPL together constitute a “core hub” in the DMN. The regions of this “core hub” showed strong intra-regional correlation with each other and weaker correlation with the remaining regions in the DMN such as the temporal cortex (TC) and the medial temporal lobe (MTL).

While substantial information has been gained in terms of the spatial location of brain regions that participate in resting-state networks and how these networks are altered during cognitive work and disease (e.g. see Fox and Raichle, 2007, Buckner et al., 2008), less is known of the functional connectivity within the DMN. Investigations that previously have studied default mode activity have typically relied on voxel-based differences in correlation strength calculated on the basis of reference signal intensity time-courses extracted from seed regions of interest (ROIs) positioned in one or several default mode brain areas. Although this approach has been successfully applied to investigate the putative role of the DMN in both health and disease, it provides little information regarding differences in functional interactions at the level of individual brain areas (or equivalently network nodes) in the DMN. In other words, a pairwise correlation analysis of DMN activity does not take into account the covariance structure of the entire DMN and potentially interesting information is lost. Moreover, all seed-based ROI analysis approaches to connectivity investigations are to some extent vulnerable to user-introduced bias in terms of the choices of seed regions made by the investigator.

The goal of the present work was to investigate functional connectivity within the DMN and at the same time addressing the methodological limitations described above. Functional connectivity within the DMN during both rest and a working memory task was assessed in a two-step procedure. First, estimates of regional fMRI signal intensity time-courses in the DMN were extracted based on information contained in statistical maps created by an independent component analysis. Second, functional connectivity within the DMN was assessed using a partial correlation technique that estimates the level of interaction between any two network nodes after removal of the common influences from all other nodes. The partial correlation analysis showed that the pC/PCC was the only node that exhibited interactions with virtually all other network nodes. The cognitive implications and uses of the observed patterns of interactions within the DMN are discussed.

Section snippets

Materials and methods

The results presented in this study constitute a re-analysis of dataset that has been described previously (Fransson, 2006) using new analytical tools. We here provide basic information regarding the participants, task and scanning procedures. For a more detailed account, we refer the reader to Fransson (2006).

Results

At a group level, intrinsic activity during rest in the DMN was faithfully represented by the extracted independent component analysis as shown in Fig. 1. Pertinent to our network analysis, consistent activity was found in the pC/PCC, bilateral lateral temporal cortex, MTL, inferior parietal cortex and the dorsal as well as the ventral aspects of the MPFC. Our network modelling results are presented in Fig. 2. Connectivity within the DMN during rest and the continuous verbal 2-back task is

Discussion

In this study, we have presented an investigation to gain insights on how intrinsic activity is routed at the level of individual brain regions in the default mode network. The usage of a data-driven analysis approach allowed us to estimate functional connectivity without making any prior assumptions on how intrinsic activity is implemented within the DMN. Importantly, compared to calculating the pairwise (marginal) correlation coefficients for all brain regions in the DMN, the partial

Acknowledgment

P.F. was supported by a grant from the Karolinska Institute research foundation.

References (47)

  • MarrelecG. et al.

    Partial correlation for functional brain interactivity investigation in functional MRI

    NeuroImage

    (2006)
  • MarrelecG. et al.

    Using partial correlation to enhance structural equation modelling of functional MRI data

    Magn. Reson. Imaging

    (2007)
  • MazoyerB. et al.

    Cortical networks for working memory and executive function sustain the conscious resting state in man

    Brain Res. Bull.

    (2001)
  • Tzourio-MazoyerN. et al.

    Automated anatomical labelling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain

    NeuroImage

    (2002)
  • WagnerA.D. et al.

    Parietal lobe contributions to episodic memory retrieval

    Trends Cogn. Sci.

    (2005)
  • BeckmannC.F. et al.

    Probabilistic independent component analysis for functional magnetic resonance imaging

    IEEE Trans. Med. Imag.

    (2004)
  • BeckmannC.F. et al.

    Investigations into resting-state connectivity using independent component analysis

    Phil. Trans. R. Soc. B

    (2005)
  • BiswalB.B. et al.

    Functional connectivity in the motor cortex of resting human brain using echo-planar MRI

    Magn. Reson. Med.

    (1995)
  • BluhmR.L. et al.

    Spontaneous low-frequency fluctuations in the BOLD signal in Schizophrenic patients: anomalities the default network

    Schiophr. Bull.

    (2007)
  • BucknerR.L. et al.

    The brain's default network: anatomy, function and relevance to disease.

    Ann. New York Acad. Sci.

    (2008)
  • CavannaA.E. et al.

    The precuneus: a review of its functional anatomy and behavioural correlates

    Brain

    (2006)
  • DamoiseauxJ.S. et al.

    Consistent resting-state networks across healthy subjects

    Proc. Natl. Acad. Sci. U. S. A.

    (2006)
  • Damoiseaux J.S., Beckmann C.F., Sanz Arigita E.J., Barkhof F., Scheltens P.H., Stam C.J., Smith S.M., Rombouts...
  • Cited by (0)

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