Functional connectivity in the resting brain: a network analysis of the default mode hypothesis.
Journal: 2003/February - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
Abstract:
Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.
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Proc Natl Acad Sci U S A 100(1): 253-258

Functional connectivity in the resting brain: A network analysis of the default mode hypothesis

Departments of Psychiatry and Behavioral Sciences and Neurology and Neurological Sciences, Program in Neurosciences, and Stanford Brain Research Center, Stanford University School of Medicine, Stanford, CA 94305-5719
To whom correspondence should be addressed. E-mail: ude.drofnats@suicierg.
Edited by Marcus E. Raichle, Washington University School of Medicine, St. Louis, MO, and approved November 12, 2002
Edited by Marcus E. Raichle, Washington University School of Medicine, St. Louis, MO, and approved November 12, 2002
Received 2002 Aug 21

Abstract

Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.

Abstract

Functional brain imaging has been widely used to study the neural basis of perception, cognition, and emotion. Such studies have traditionally focused on brain regions showing task-related increases in neural activity, i.e., greater activity during an experimental task than during a baseline state, typically rest or a sensory-motor control task with reduced cognitive demand. Recently, however, increasing attention has been focused on brain regions in which neural activity is greater during the baseline state than during an experimental task. Interest in this phenomenon, sometimes referred to as “deactivation,” has been sparked by the finding that particular brain regions, including two midline regions, the posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently demonstrate such task-related decreases in activity across a broad range of cognitive tasks (1, 2). Using quantitative positron emission tomography, Raichle et al. (3) determined that these brain regions are in their baseline state when subjects rest with their eyes closed. They hypothesized that this set of brain regions constitutes an organized network, whose activity is ongoing during rest and suspended during performance of externally cued tasks, that supports a “default mode of brain function.”

At present, however, it is not known whether brain regions that show task-related decreases in activity, such as the PCC and vACC, constitute tightly linked nodes in a single, tonically active resting-state network. The default mode hypothesis is based on the finding of relative decreases in neural activity during task performance compared with a baseline state. Direct evidence for temporal coherence of resting-state neural activity between regions in this hypothetical network is lacking. Detection of temporal coherence in such a network would (i) provide more compelling evidence for the existence of a default mode network, and (ii) enhance our understanding of neural activity in baseline states, thereby refining interpretations of “activation” and “deactivation” in functional imaging studies (4). More broadly, mapping such a network may provide insight into the neural underpinnings of a critical but poorly understood component of human consciousness variably referred to as “a conscious resting state” (2, 5), “stimulus-independent thought” (6), or a default mode of brain function (3).

A number of key questions remain, however, chief among them being whether the postulated network exists in the resting brain. If so, which brain regions are linked in the network, and what inferences can be made about the mental processes subserved by these regions? Is the network altered or disrupted during simple sensory processing tasks? How is the network modulated during performance of externally cued cognitive tasks?

To address these questions, we formulated the following hypotheses: (i) If the default mode network exists, then analyzing the resting-state connectivity of one of its key components should generate a (partial) map of the larger network. (ii) If the network is minimally disrupted during passive sensory processing tasks, then the connectivity maps generated during rest should be replicable in a passive visual processing task. (iii) If the network activity is suspended during performance of cognitively demanding externally cued tasks, then resting-state activity in the network may be inversely correlated with activity in brain regions that show task-related activations.

To test these hypotheses, we used functional MRI (fMRI) to examine brain activity in a group of 14 subjects under three different conditions: performance of a cognitive (working memory) task; passive viewing of a visual stimulus; and resting state with eyes closed. The working memory task was used to define regions in the PCC and vACC that showed task-related decreases in activity and regions in the lateral prefrontal cortex that showed task-related increases in activity. We then applied a functional connectivity MRI (fcMRI) analysis to the resting-state and visual processing data. Unlike fMRI analyses, fcMRI does not rely on a comparison of experimental and baseline conditions; rather, it detects interregional temporal correlations of blood oxygen level-dependent (BOLD) signal fluctuations. Regions whose BOLD signal fluctuations show a high degree of temporal correlation are presumed to constitute a tightly coupled neural network. To date, most fcMRI studies have explored primary motor and sensory networks (79). Recently, fcMRI has been successfully applied in examining interactions between brain regions involved in language (10). In this study, we determined the connectivity patterns of the PCC and the vACC during the resting state and the visual processing task. We also examined correlations in resting-state activity between the “activated” lateral prefrontal regions and regions implicated in the default mode network.

Brain regions that showed significant connectivity to the PCC ROI centered at [2, −51, 27]. The height and extent thresholds were set at P < 0.001. BA, Brodmann's area.

Brain regions that showed significant connectivity to the vACC ROI centered at [2, 38, −2]. The height and extent thresholds were set at P < 0.001. BA, Brodmann's area.

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Acknowledgments

This work was made possible through grants from the National Institutes of Health (MH19938, MH01142, HD31715, HD40761, and MH62430), the Ruth K. Broad Biomedical Research Foundation, and the Sinclair Fund.

Acknowledgments

Abbreviations

ROIregion of interest
PCCposterior cingulate cortex
vACCventral anterior cingulate cortex
fcMRIfunctional connectivity MRI
VLPFCventrolateral prefrontal cortex
DLPFCdorsolateral prefrontal cortex
IPCinferior parietal cortex
ITCinferolateral temporal cortex
MPFCmedial prefrontal cortex
OFCorbitofrontal cortex
PHGparahippocampal gyrus
Abbreviations

Footnotes

This paper was submitted directly (Track II) to the PNAS office.

Footnotes

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