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/.

Two experiments assess adult age differences in the extent of inhibition or negative priming generated in a selective-attention task. Younger adults consistently demonstrated negative priming effects; they were slower to name a letter on a current trial that had served as a distractor on the previous trial relative to one that had not occurred on the previous trial. Whether or not inhibition dissipated when the response to stimulus interval was lengthened from 500 ms in Experiment 1 to 1,200 ms in Experiment 2 depended upon whether young subjects were aware of the patterns across trial types. Older adults did not show inhibition at either interval. The age effects are interpreted within the Hasher-Zacks (1988) framework, which proposes inhibition as a central mechanism determining the contents of working memory and consequently influencing a wide array of cognitive functions.

Working memory (WM), the process by which information is coded into memory, actively maintained and subsequently retrieved, declines with age. To test the hypothesis that age-related changes in prefrontal cortex (PFC) may mediate this WM decline, we used functional MRI to investigate age differences in PFC activity during separate WM task components (encoding, maintenance, retrieval). We found greater PFC activity in younger than older adults only in dorsolateral PFC during memory retrieval. Fast younger subjects showed less dorsolateral PFC activation during retrieval than slow younger subjects, whereas older adults showed the opposite pattern. Thus age-related changes in dorsolateral PFC and not ventrolateral PFC account for WM decline with normal aging.

Using an event-related functional MRI design, we explored the relative roles of dorsal and ventral prefrontal cortex (PFC) regions during specific components (Encoding, Delay, Response) of a working memory task under different memory-load conditions. In a group analysis, effects of increased memory load were observed only in dorsal PFC in the encoding period. Activity was lateralized to the right hemisphere in the high but not the low memory-load condition. Individual analyses revealed variability in activation patterns across subjects. Regression analyses indicated that one source of variability was subjects' memory retrieval rate. It was observed that dorsal PFC plays a differentially greater role in information retrieval for slower subjects, possibly because of inefficient retrieval processes or a reduced quality of mnemonic representations. This study supports the idea that dorsal and ventral PFC play different roles in component processes of working memory.Working memory (WM), the cognitive system that allows individuals to maintain and manipulate information held temporarily in mind, may be divided into separate processes such as those required for the retention of information and those required for allocating attention and coordinating information that is being temporarily maintained (1, 2). Evidence has accumulated to support the notion that PFC may be organized to support different WM processes. Imaging studies have observed that ventral PFC is engaged by simple rehearsal (or maintenance) processes (3, 4). Studies that use more complex WM tasks have shown PFC activations that often occur bilaterally and in regions dorsal to those found in studies of simple retention (Brodmann's areas 9 and 46) (5). One theory has proposed that PFC is functionally divided in a dorsal/ventral fashion according to the type of cognitive operation that must be performed on information held in WM (6). Empirical studies have supported the notion that ventral PFC mediates maintenance processes whereas dorsal PFC is recruited when additional processing of information, such as manipulation or monitoring, is necessary (7,8).Studies that use more complex tasks, such as n-back and dual-tasks (e.g., refs. 9-11, 5), have not clearly distinguished the role of PFC in these different WM processes because information processing demands increase concurrently with maintenance demands. In fact, one study that used a task with no overt requirements to manipulate information held in WM suggested a role for dorsal PFC in WM maintenance. Rypma et al. (12) observed dorsal PFC activation in a WM task in which subjects were required to maintain one, three, or six letters for 5 seconds. When subjects were required to maintain three letters in WM, relative to one letter, activation in frontal regions was limited to left ventral PFC (Brodmann's area 44). When subjects were required to maintain six letters, relative to one letter, additional activation of dorsal PFC was observed, similar to that observed during tasks in which successful perfo...

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Working memory refers to the short-term retention of information that is no longer accessible in the environment, and the manipulation of this information, for subsequent use in guiding behavior. In this review, we will present data from a series of event-related functional magnetic-resonance-imaging (fMRI) studies of delayed-response tasks that were designed to investigate the role of different regions of the prefrontal cortex (PFC) during different working-memory component processes. From these data, we conclude that: (1) lateral PFC is anatomically organized according to the types of cognitive operations that one performs when attempting to temporarily maintain and manipulate information; and (2) consistent with the picture that has emerged from the monkey electrophysiological literature, human lateral PFC is involved in several encoding- and response-related processes as well as mnemonic and nonmnemonic processes that are engaged during the temporary maintenance of information. Thus, lateral PFC activity cannot be ascribed to the function of a single, unitary cognitive operation.