A default mode of brain function

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.

Figures

Figure 1

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).

Figure 2

Quantitative maps of blood flow (Upper) and oxygen consumption (Lower) in the subjects from group I while they rested quietly but awake with their eyes closed. The quantitative hemisphere mean values for these images are presented in Table 1. Note the large variation in blood flow and oxygen consumption across regions of the brain. These vary most widely between gray and white matter. Despite this variation, blood flow and oxygen consumption are closely matched, as also reflected in the image of the oxygen extraction fraction (i.e., the ratio of oxygen consumption to blood flow; see Fig. 4).

Figure 3

A schematic representation of the metabolic and circulatory relationships occurring in areas of the brain with transient increases (Activation) or decreases (Deactivation) in the level of neural activity from a baseline or equilibrium state. Typically increases (Right) are characterized by increases in the cerebral blood flow (CBF) and the cerebral blood volume (CBV), with much smaller changes in the cerebral metabolic rate for oxygen (CMRO2). As a result, there is a fall in the oxygen extraction fraction (OEF) and an increase in the amount of oxygen attached to hemoglobin exiting the brain (HbO2). This latter change is responsible for the blood oxygen level–dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI). Decreases from baseline (Left) are characterized as the opposite pattern of change.

Figure 4

Maps of the fraction of oxygen extracted by the brain from arterial blood (oxygen extraction fraction or OEF expressed as a percentage of the available oxygen delivered to the brain). The data come from 19 normal adults (group I, Table 1) resting quietly but awake with their eyes closed. The data were obtained with PET. Despite an almost 4-fold difference in blood flow and oxygen consumption between gray and white matter, the OEF is relatively uniform, emphasizing the close matching of blood flow and oxygen consumption in the resting, awake brain. Areas of increased OEF can be seen in the occipital regions bilaterally (see text for discussion).

Figure 5

Regions of the brain regularly observed to decrease their activity during attention-demanding cognitive tasks shown in sagittal projection (Upper) as compared with the blood flow of the brain while the subject rests quietly but is awake with eyes closed (Lower). The data in the top row are the same as those shown in Fig. 1, except in the sagittal projection, to emphasize the changes along the midline of the hemispheres. The data in the bottom row represent the blood flow of the brain and are the same data shown in horizontal projection in the top row of Fig. 2. The numbers below the images refer to the millimeters to the right (positive) or left (negative) of the midline.