Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. Highthroughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

Background Current state of knowledge suggests that disruption of neuronal information integration may be a unitary mechanism of anesthetic-induced unconsciousness. A neural system central for information integration is the thalamocortical system whose specific and nonspecific divisions may play the roles for representing and integrating information; respectively. How anesthetics affect the function of these systems individually is not completely understood. We studied the effect of propofol on thalamocortical functional connectivity in the specific and nonspecific systems using functional magnetic resonance imaging. Methods Eight healthy volunteers were instructed to listen to and encode 40 English words during wakeful baseline, light sedation, deep sedation, and recovery in the scanner. Functional connectivity was determined as the temporal correlation of blood oxygen level-dependent signals with seed regions defined within the specific and nonspecific thalamic nuclei. Results Thalamocortical connectivity at baseline was dominantly medial and bilateral frontal and temporal for the specific system and medial frontal and medial parietal for the nonspecific system. During deep sedation, propofol reduced functional connectivity by 43% (specific) and 79% (nonspecific), a significantly greater reduction of connections in the nonspecific than in the specific system and in the left hemisphere than in the right. Upon regaining consciousness, functional connectivity increased by 58% (specific) and 123% (nonspecific) during recovery, exceeding their values at baseline. Conclusions Propofol conferred differential changes in functional connectivity of the specific and nonspecific thalamocortical systems. The changes in nonspecific thalamocortical connectivity may correlate with loss and return of consciousness.

Current theories suggest that disrupting cortical information integration may account for the mechanism of general anesthesia in suppressing consciousness. Human cognitive operations take place in hierarchically structured neural organizations in the brain. The process of low-order neural representation of sensory stimuli becoming integrated in high-order cortices is also known as cognitive binding. Combining neuroimaging, cognitive neuroscience, and anesthetic manipulation, we examined how cognitive networks involved in auditory verbal memory are maintained in wakefulness, disrupted in propofol-induced deep sedation, and re-established in recovery. Inspired by the notion of cognitive binding, an fMRI-guided connectivity analysis was utilized to assess the integrity of functional interactions within and between different levels of the task-defined brain regions. Task-related responses persisted in the primary auditory cortex (PAC), but vanished in the inferior frontal gyrus (IFG) and premotor areas in deep sedation. For connectivity analysis, seed regions representing sensory and high-order processing of the memory task were identified in the PAC and IFG. Propofol disrupted connections from the PAC seed to the frontal regions and thalamus, but not the connections from the IFG seed to a set of widely distributed brain regions in the temporal, frontal, and parietal lobes (with exception of the PAC). These later regions have been implicated in mediating verbal comprehension and memory. These results suggest that propofol disrupts cognition by blocking the projection of sensory information to high-order processing networks and thus preventing information integration. Such findings contribute to our understanding of anesthetic mechanisms as related to information and integration in the brain.

The notion of uncontrollable stress causing reduced hippocampal size remains controversial in the posttraumatic stress disorder literature because human studies cannot discern the causality of effect. Here, we addressed this issue by employing structural magnetic resonance imaging in rats to measure the hippocampus and other brain regions before and after stress. Chronic restraint stress produced approximately 3% reduction in hippocampal volume, which was not observed in control rats. This decrease was not signficantly correlated with baseline hippocampal volume or body weight. Total forebrain volume and the sizes of the other brain regions and adrenal glands were all unaffected by stress. This longitudinal, within-subjects design study provides direct evidence that the hippocampus is differentially vulnerable and sensitive to chronic stress.

Functional magnetic resonance imaging (fMRI) was conducted to observe the effects of cocaine administration on the physiological fluctuations of fMRI signal in two brain regions. Seven long‐term cocaine users with an average age of 32 years and 8 years of cocaine use history were recruited for the study. A T2*‐weighted fast echo‐planar imaging (EPI) pulse sequence was employed at 1.5 T to acquire three sets of brain images for each subject under three conditions (at rest, after saline injection, and after cocaine injection [0.57 mg/kg]). Cross‐correlation maps were constructed using the synchronous, low frequency signal from voxel time courses after filtering respiratory, cardiac, and other physiological noise. A quantitative evaluation of the changes in functional connectivity was made using spatial correlation coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region of primary visual cortex and 43% reduction in SCC values in the region of primary motor cortex were observed after cocaine administration. This significant reduction in SCC values in these cortical regions is a reflection of changes in neuronal activity. It is suggested that the observed changes in low frequency components after acute cocaine administration during a resting, no‐task situation may be used as a baseline reference source when assessing the effects of cocaine on task‐driven activation or on mesolimbic dopamine pathways. Magn Reson Med 43:45–51, 2000. © 2000 Wiley‐Liss, Inc.