The Brain's Default Network Anatomy,Function,and Relevance to Disease RANDY L.BUCKNER,JESSICA R.ANDREWS-HANNA, AND DANIEL L.SCHACTER -Department of Psycholog,Harvard University,Cambridge,Massachusetts,USA Center for Brain Science,Harvard University,Cambridge,Massachusetts,USA Athinoula A.Martinos Center for Biomedical Imaging.Massachusetts General Hospital Boston,Massachusetts,USA tment of Radiology,Harvard Medical School,Boston,Massachusetts,USA "Howard Hughes Medical Institute,Chevy Chase,Maryland 20815,USA Thirty years of brain imaging research has con ed to define the brain's default nety ed brain system i int modes of co ly defined b a pre y activ are ports the ginsight in fun r the futu ing t he I of oth omy The m dial te al lobe su inf tal s the ant me The two sub of the al obs L C igat inte twork for understanding mental disorders including autism,sc phrenia.and alzheimer's rdefauit mode default system;default netor MRI;PET;hippocampus;memoryi zophrenia;Alzheime A common observation in brain imaging research within the default network (Buckner Carroll 2007) is that a specific set of brain regionsreferred to as ations prompt one to ask such question ecngagrdtcndidala mmon?and what is the significanice of t al 2001 Raichle this network to adaptive function?The default net ing this phenomenon further reveals that other kinds of situations,beyond freethinking,engage the default net- non to c work.For example,remembering the past,envisioning be important to understanding discases of the mind (eg,Lustig et al.2003,Greicius et al.2004,Kennedy et a 2006.Bluhm et al.2007). Address forThe Brain’s Default Network Anatomy, Function, and Relevance to Disease RANDY L. BUCKNER, a,b,c,d,e JESSICA R. ANDREWS-HANNA, a,b,c AND DANIEL L. SCHACTERa aDepartment of Psychology, Harvard University, Cambridge, Massachusetts, USA bCenter for Brain Science, Harvard University, Cambridge, Massachusetts, USA c Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts, USA dDepartment of Radiology, Harvard Medical School, Boston, Massachusetts, USA eHoward Hughes Medical Institute, Chevy Chase, Maryland 20815, USA 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 cog￾nition. Here we synthesize past observations to provide strong evidence that the default net￾work 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 sup￾ports 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 autobio￾graphical memory retrieval, envisioning the future, and conceiving the perspectives of oth￾ers. 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 informa￾tion 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 sub￾systems 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 fu￾ture, navigate social interactions, and maximize the utility of moments when we are not oth￾erwise 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. Key words: default mode; default system; default network; fMRI; PET; hippocampus; memory; schizophrenia; Alzheimer Introduction A common observation in brain imaging research is that a specific set of brain regions—referred to as the default network—is engaged when individuals are left to think to themselves undisturbed (Shulman et al. 1997, Mazoyer et al. 2001, Raichle et al. 2001). Prob￾ing this phenomenon furtherreveals that other kinds of situations, beyond freethinking, engage the default net￾work. For example, remembering the past, envisioning Address for correspondence: Dr. Randy Buckner, Harvard University, William James Hall, 33 Kirkland Drive, Cambridge, MA 02148. rbuckner@wjh.harvard.edu future events, and considering the thoughts and per￾spectives of other people all activate multiple regions within the default network (Buckner & Carroll 2007). These observations prompt one to ask such questions as: What do these tasks and spontaneous cognition share in common? and what is the significance of this network to adaptive function? The default net￾work is also disrupted in autism, schizophrenia, and Alzheimer’s disease, further encouraging one to con￾sider how the functions of the default network might be important to understanding diseases of the mind (e.g., Lustig et al. 2003, Greicius et al. 2004, Kennedy et al. 2006, Bluhm et al. 2007). Motivated by these questions, we provide a com￾prehensive review and synthesis of findings about the Ann. N.Y. Acad. Sci. 1124: 1–38 (2008). !C 2008 New York Academy of Sciences. doi: 10.1196/annals.1440.011 1