A default mode of brain function.
Journal: 2001/April - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
Abstract:
A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
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Proc Natl Acad Sci U S A 98(2): 676-682

A default mode of brain function

Mallinckrodt Institute of Radiology and Departments of Neurology and Psychiatry, Washington University School of Medicine, St. Louis, MO 63110
To whom reprint requests should be addressed at: Washington University School of Medicine, 4525 Scott Avenue, Room 2116, St. Louis, MO 63110. E-mail: ude.ltsuw.gpn@cram.
Contributed by Marcus E. Raichle
Contributed by Marcus E. Raichle
Accepted 2000 Oct 26.

Abstract

A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

Abstract

Functional brain imaging studies in normal human subjects with positron-emission tomography (PET) and functional MRI (fMRI) have consistently revealed expected task-induced increases in regional brain activity during goal-directed behaviors (for brief reviews see refs. 1 and 2). These changes are detected when comparisons are made between a task state, designed to place demands on the brain, and a control state, with a set of demands that are uniquely different from those of the task state.

Researchers have also frequently encountered task-induced decreases in regional brain activity even when the control state consists of lying quietly with eyes closed or passively viewing a stimulus. Whereas cortical increases in activity have been shown to be task specific and, therefore, vary in location depending on task demands, many decreases (Fig. (Fig.1)1) appear to be largely task independent, varying little in their location across a wide range of tasks (3). This consistency with which certain areas of the brain participate in these decreases made us wonder whether there might be an organized mode of brain function that is present as a baseline or default state and is suspended during specific goal-directed behaviors.

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Regions of the brain regularly observed to decrease their activity during attention demanding cognitive tasks. These data represent a metaanalysis of nine functional brain imaging studies performed with PET and analyzed by Shulman and colleagues (49). In each of the studies included, the subjects processed a particular visual image in the task state and viewed it passively in the control state. One hundred thirty-two individuals contributed to the data in these images. These decreases appear to be largely task independent. The images are oriented with the anterior at the top and the left side to the reader's left. The numbers beneath each image represent the millimeters above or below a transverse plane running through the anterior and posterior commissures (26).

The primary issue this paper will address is whether these unexplained decreases merely arise from unrecognized increases (i.e., activation in the jargon of functional brain imaging) present only in the “control state.” Thus, on this argument, any control state, no matter how carefully it is selected, is just another task state with its own unique areas of activation. Unfortunately, in most instances there is insufficient information about the control state to judge whether the observed decrease arose in this manner.

We believe conceptual progress has suffered because of our inability to exclude explanations of the above type for regional decreases in brain activity and, more generally, to understand whether a specific level of activity in a given area of the brain can be considered its baseline. At the heart of the problem is the lack of agreed-upon characteristics defining a baseline state. In response to this dilemma we began with a generally accepted, quantitative circulatory and metabolic definition of brain activation (see Background, below). From this definition we specified criteria for a baseline state (i.e., the absence of activation by this definition). In so doing, we were able to determine that areas consistently exhibiting decreases in activity during specific goal-directed behaviors (3) did so from this baseline state. We believe these findings are consistent with our idea of a baseline or default state of the brain, the functions of which are revealed by those areas whose activities are suspended during many transient, attention-demanding, goal-directed activities.

The values for OEF, CBF, and CMRO2 are expressed as local-to-global ratios (see Methods). For the 19 subjects in group I the global values for OEF and CBF (± SD) were 0.40 ± 0.09 (dimensionless) and 46 ± 8 ml/(min × 100 g), respectively. The mean arterial oxygen content for this group was 16.6 ± 0.16 ml/ml. From these data quantitative images of the CMRO2 were created that yielded a mean cerebral hemisphere value of 2.94 ± 0.41 ml/(min × 100 g) or 1.31 ± 0.18 μmol/(min × g). The asterisks denote values that differ significantly from the global mean after correction for multiple comparisons.

The values for OEF, CBF, and CMRO2 are expressed as local-to-global ratios (see Methods). For the 19 subjects in group II the global values for OEF and CBF (± SD) were 0.30 ± 0.09 (dimensionless) and 48 ± 10 ml/(min × 100 g), respectively. The mean arterial oxygen content for this group was 17.0 ± 0.02 ml/ml. From these data quantitative images of the CMRO2 were created that yielded a mean cerebral hemisphere value of 2.17 ± 0.41 ml/(min × 100 g) or 0.97 ± 0.17 μmol/(min × g). The asterisks denote values that differ significantly from the global mean after correction for multiple comparisons.

Note that these are all increases in the OEF signifying areas of deactivation in the baseline state of resting but awake with eyes closed. With the exception of Brodmann area 11 located in the right gyrus rectus, these areas cluster in visual areas of the occipital and parietal cortices. The conventions used are similar to those of Tables Tables11 and and22.

Note that these are all increases in the OEF signifying areas of deactivation in the baseline state of resting but awake with eyes closed. These areas cluster in visual areas of occipital and parietal cortices. The conventions used are similar to those of Tables Tables11 and and22.

Acknowledgments

This work was supported by National Institutes of Health Grants NS06833, DA07261, and NS10196 and the Charles A. Dana Foundation.

Acknowledgments

Abbreviations

OEFoxygen extraction fraction
fMRIfunctional MRI
PETpositron-emission tomography
CBFcerebral blood flow
CMRO2cerebral metabolic rate for oxygen
MPFCmedial prefrontal cortex
Abbreviations

Footnotes

This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on April 30, 1996.

Footnotes

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