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 goaldirected behaviors. F unctional 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. 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.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...

During performance of attention-demanding cognitive tasks, certain regions of the brain routinely increase activity, whereas others routinely decrease activity. In this study, we investigate the extent to which this task-related dichotomy is represented intrinsically in the resting human brain through examination of spontaneous fluctuations in the functional MRI blood oxygen level-dependent signal. We identify two diametrically opposed, widely distributed brain networks on the basis of both spontaneous correlations within each network and anticorrelations between networks. One network consists of regions routinely exhibiting task-related activations and the other of regions routinely exhibiting task-related deactivations. This intrinsic organization, featuring the presence of anticorrelated networks in the absence of overt task performance, provides a critical context in which to understand brain function. We suggest that both task-driven neuronal responses and behavior are reflections of this dynamic, ongoing, functional organization of the brain.functional MRI ͉ functional connectivity ͉ spontaneous activity

The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease.

Control regions in the brain are thought to provide signals that configure the brain's moment-to-moment information processing. Previously, we identified regions that carried signals related to taskcontrol initiation, maintenance, and adjustment. Here we characterize the interactions of these regions by applying graph theory to resting state functional connectivity MRI data. In contrast to previous, more unitary models of control, this approach suggests the presence of two distinct task-control networks. A frontoparietal network included the dorsolateral prefrontal cortex and intraparietal sulcus. This network emphasized start-cue and error-related activity and may initiate and adapt control on a trial-by-trial basis. The second network included dorsal anterior cingulate/medial superior frontal cortex, anterior insula/frontal operculum, and anterior prefrontal cortex. Among other signals, these regions showed activity sustained across the entire task epoch, suggesting that this network may control goaldirected behavior through the stable maintenance of task sets. These two independent networks appear to operate on different time scales and affect downstream processing via dissociable mechanisms.attention ͉ connectivity ͉ executive control ͉ functional MRI ͉ task set H umans possess unrivaled cognitive flexibility. When performing goal-directed tasks, humans are thought to adopt task sets that flexibly configure information processing in response to changing task demands. The brain's task-control system is thought to consist of functionally diverse regions that are anatomically separate from downstream processing systems (1).Previously, we studied mixed blocked/event-related fMRI data across a wide range of tasks (2). Because mixed fMRI designs can disambiguate sustained set-maintenance activity from more transient set and trial-related activity (3, 4), we were able to identify regions that carried three different putative task-control signals: (i) activity time-locked to the beginning of task periods (control initiation), (ii) set-maintenance signals sustained across the entire task period, and (iii) error-related activity (for feedback and control adjustment). Using cross-studies analyses, we identified a collection of regions thought to support these various task-control signals.The dorsal anterior cingulate cortex/medial superior frontal cortex (dACC/msFC) and bilateral anterior insula/frontal operculum (aI/fO) were the only regions that showed all three task-control signals (set initiation, maintenance, and feedback and adjustment) across a wide range of tasks. Therefore, we proposed that the dACC/msFC and aI/fO might

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its discovery was an unexpected consequence of brain-imaging studies first performed with positron emission tomography in which various novel, attention-demanding, and non-self-referential tasks were compared with quiet repose either with eyes closed or with simple visual fixation. The default mode network consistently decreases its activity when compared with activity during these relaxed nontask states. The discovery of the default mode network reignited a longstanding interest in the significance of the brain's ongoing or intrinsic activity. Presently, studies of the brain's intrinsic activity, popularly referred to as resting-state studies, have come to play a major role in studies of the human brain in health and disease. The brain's default mode network plays a central role in this work.