Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.

People can consciously re-experience past events and pre-experience possible future events. This fMRI study examined the neural regions mediating the construction and elaboration of past and future events. Participants were cued with a noun for 20s and instructed to construct a past or future event within a specified time period (week, year, 5-20 years). Once participants had the event in mind, they made a button press and for the remainder of the 20s elaborated on the event. Importantly, all events generated were episodic and did not differ on a number of phenomenological qualities (detail, emotionality, personal significance, field/observer perspective). Conjunction analyses indicated the left hippocampus was commonly engaged by past and future event construction, along with posterior visuospatial regions, but considerable neural differentiation was also observed during the construction phase. Future events recruited regions involved in prospective thinking and generation processes, specifically right frontopolar cortex and left ventrolateral prefrontal cortex, respectively. Furthermore, future event construction uniquely engaged the right hippocampus, possibly as a response to the novelty of these events. In contrast to the construction phase, elaboration was characterized by remarkable overlap in regions comprising the autobiographical memory retrieval network, attributable to the common processes engaged during elaboration, including self-referential processing, contextual and episodic imagery. This striking neural overlap is consistent with findings that amnesic patients exhibit deficits in both past and future thinking, and confirms that the episodic system contributes importantly to imagining the future.

10.1073͞pnas.0504604102), the authors note that Eq. 1 was incorrectly given as P ϭ f ssͩ ͩ1 ϩ m ͪ ϩ Dͩ 2 ϩ m ͪͪ both in the text and in Fig. 2. The correct equation is as follows:The corrected figure and its legend appear below. The error does not affect the conclusions of the article. Fig. 2.Comprehensive characterization of the promoter library. Several orthogonal metrics were used to characterize the promoter library and ensure the consistent behavior of all its members for various genes and culturing conditions. We show here three metrics that were chosen for quantifying transcriptional of the promoters: (i) the dynamics of GFP production based on fluorescence, (ii) measurement of the relative mRNA transcript levels in the cultures, and (iii) testing of the MIC for chloramphenicol in an additional library of constructs where the promoter drove the expression of chloramphenicol acetyltransferase. The overall strong correlation between the various metrics suggests a broad-range utility of the promoter library for a variety of genes and conditions. (A) Mouse C127 cells were transduced with retrovirus expressing BPV-1 E7 with a FLAG͞HA epitope tag at either the C terminus (E7-C) or N terminus (E7-N), or with no tag (E7). Cells were lysed, and proteins were immunoprecipitated by using either an anti-FLAG antibody (Left) or an anti-BPV-1 E7 antibody (Right). Proteins were resolved by SDS͞PAGE on a 15% polyacrylamide gel and probed by immunoblotting using the anti-E7 antibody. (B) Cells were assayed for anchorage-independent growth with transduced BPV-1 oncogenes: C127 control cells, cells expressing BPV-1 E7 alone, BPV-1 E6 alone, E6 and E7, E6 and C-terminal FLAG͞HA-tagged E7 (E7-C), and E6 and N-terminal FLAG͞HA-tagged E7 (E7-N). Cells were suspended in 0.3% Noble agar, DMEM, and 10% FBS and grown for 14 days. Representative fields are shown at ϫ10 magnification. For further details, see Cortical analysis related to visual object recognition is traditionally thought to propagate serially along a bottom-up hierarchy of ventral areas. Recent proposals gradually promote the role of top-down processing in recognition, but how such facilitation is triggered remains a puzzle. We tested a specific model, proposing that low spatial frequencies facilitate visual object recognition by initiating top-down processes projected from orbitofrontal to visual cortex. The present study combined magnetoencephalography, which has superior temporal resolution, functional magnetic resonance imaging, and a behavioral task that yields successful recognition with stimulus repetitions. Object recognition elicited differential activity that developed in the left orbitofrontal cortex 50 ms earlier than it did in recognition-related areas in the temporal cortex. This early orbitofrontal activity was directly modulated by the presence of low spatial frequencies in the image. Taken together, the dynamics we revealed provide strong support for the proposal of how top-down facilitation of object recognition is initiated, and our observations a...