1. M. J. Kane, L. H. Brown, J. C. McVay, P. J. Silvia, I. Myin-Germeys, and T. R. Kwapil, “For Whom the Mind Wanders, and When: An Experience-Sampling Study of Working Memory and Executive Control in Daily Life,” Psychological Science 18 (2007): 614–621.
2. For a recent version of this critique and other potential issues with the interpretation of the default network, see A. M. Morcom and P. C. Fletcher, “Does the Brain Have a Baseline? Why We Should Be Resisting a Rest,” Neuroimage 37 (2007): 1073–1082. There are several replies to this article discussing many of the arguments.
3. G. L. Shulman, J. A. Fiez, M. Corbetta, R. L. Buckner, F. M. Miezen, M. E. Raichle, and S. E. Petersen, “Common Blood Flow Changes Across Visual Tasks: II. Decreases in Cerebral Cortex,” Journal of Cognitive Neuroscience 9 (1997): 648–663.
4. The pivotal report that introduced the concept of the default network is M. E. Raichle, A. M. MacLeod, A. Z. Snyder, W. J. Powers, D. A. Gusnard, and G. L. Shulman, “A Default Mode of Brain Function,” Proceedings of the National Academy of Sciences, USA 98 (2001): 676–682.
5. This technique was based on work in positron-emission tomography, as described in K. J. Friston, C. D. Frith, P. F. Liddle, and R. S. J. Frackowiak, “Functional Connectivity: The Principal-Component Analysis of Large (PET) Data Sets,” Journal of Cerebral Blood Flow and Metabolism 13 (1993): 5–14. The application of intrinsic activity correlations to MRI data during a resting period is described by B. Biswal, F. Z. Yetkin, V. M. Haughton, and J. S. Hyde, “Functional Connectivity in the Motor Cortex of Resting Human Brain Using Echo-planar MRI,” Magnetic Resonance in Medicine 34 (1995): 537–541.
6. M. D. Greicius, B. Krasnow, A. L. Reiss, and V. Menon, “Functional Connectivity in the Resting Brain: A Network Analysis of the Default Mode Hypothesis,” Proceedings of the National Academy of Sciences, USA 100 (2003): 253–258.
7. The initial demonstration of default network regions as highly interconnected hub regions was provided in P. Hagmann, L. Cammoun, X. Gigandet, R. Meuli, C. J. Honey, V. J. Weeden, and O. Sporns, “Mapping the Structural Core of Human Cerebral Cortex,” PLoS Biology 6 (2008): e159. An application of this idea and its potential relevance to Alzheimer’s disease is described by R. L. Buckner, J. Sepulcre, T. Talukdar, F. M. Krienen, H. Liu, T. Hedden, et al., “Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer’s Disease,” Journal of Neuroscience 29 (2009): 1860–1873.
8. M. F. Mason, M. I. Norton, J. D. Van Horn, D. M. Wegner, S. T. Grafton, and C. N. Macrae, “Wandering Minds: The Default Network and Stimulus-Independent Thought,” Science 315 (2007): 393–395.
9. J. M. Moran, T. F. Heatherton, and W. M. Kelley, “Modulation of Cortical Midline Structures by Implicit and Explicit Self-Relevance Evaluation,” Social Neuroscience 4 (2009): 197–211.
10. R. N. Spreng and C. L. Grady, “Patterns of Brain Activity Supporting Autobiographical Memory, Prospection, and Theory of Mind, and Their Relationship to the Default Mode Network,” Journal of Cognitive Neuroscience 22 (2010): 1112–1123.
11. Y. I. Sheline, D. M. Barch, J. L. Price, M. M. Rundle, S. N. Vaishnavi, A. Z. Snyder, et al., “The Default Mode Network and Self-referential Processes in Depression,” Proceedings of the National Academy of Sciences, USA 106 (2009): 1942–1947.
12. D. R. Addis, L. Pan, M. A. Vu, N. Laiser, and D. L. Schacter, “Constructive Episodic Simulation of the Future and the Past: Distinct Sub-systems of a Core Brain Network Mediate Imagining and Remembering,” Neuropsychologia 47 (2009): 2222–2238.
13. J. R. Andrews-Hanna, J. S. Reidler, J. Sepulcre, R. Poulin, and R. L. Buckner, “Functional-Anatomic Fractionation of the Brain’s Default Network,” Neuron 65 (2010): 550–562.
14. For a review of the default network’s involvement in multiple disorders, see S. J. Broyd, C. Bemanuele, S. Debener, S. K. Helps, C. J. James, and E. J. Sonuga-Barke, “Default-Mode Brain Dysfunction in Mental Disorders: A Systematic Review,” Neuroscience and Biobehavioral Reviews 33 (2009): 279–296.
15. Alzheimer’s Association, “2010 Alzheimer’s Facts and Figures,” Alzheimer’s and Dementia 6 (2010): 158–194.
16. There are now several amyloid agents available for use in neuroimaging. The first of these new-generation agents is described by W. E. Klunk, H. Engler, A. Nordberg, Y. Wang, G. Blomqvist, D. P. Holt, et al., “Imaging Brain Amyloid in Alzheimer’s Disease with Pittsburgh Compound-B,” Annals of Neurology 55 (2004): 306–319. For reporting on recent advances using amyloid imaging, see http://www.alzforum.org/new/detail.asp?id=2389 and http://www.nytimes.com/2010/06/24/health/research/24scans.html.
17. The article that pointed out this remarkable similarity and posited several hypotheses that still drive investigation is R. L. Buckner, A. Z. Snyder, B. J. Shannon, G. LaRossa, R. Sachs, A. F. Fotenos, et al., “Molecular, Structural, and Functional Characterization of Alzheimer’s Disease: Evidence for a Relationship Between Default Activity, Amyloid, and Memory,” Journal of Neuroscience 25 (2005): 7709–7717.
18. C. Lustig, A. Z. Snyder, M. Bhakta, K. C. O’Brien, M. McAvoy, M. E. Raichle, et al., “Functional Deactivations: Change with Age and Dementia of the Alzheimer Type,” Proceedings of the National Academy of Sciences, USA 100 (2003): 14504–14509. M. D. Greicius, G. Srivastava, A. L. Reiss, and V. Menon, “Default-Mode Network Activity Distinguishes Alzheimer’s Disease from Healthy Aging,” Proceedings of the National Academy of Sciences, USA 101 (2004): 4637–4642.
19. R. A. Sperling, P. S. Laviolette, K. O’Keefe, J. O’Brien, D. M. Rentz, M. Pihlajamaki, et al., “Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons Without Dementia,” Neuron 63 (2009): 178–188. T. Hedden, K. R. Van Dijk, J. A. Becker, A. Mehta, R. A. Sperling, K. A. Johnson, and R. L. Buckner, “Disruption of Functional Connectivity in Clinically Normal Older Adults Harboring Amyloid Burden,” Journal of Neuroscience 29 (2009): 12686–12694.
20. Although diagnostic specificity and robustness to differences in analytic methods remain to be confirmed, the possibility of using such images to detect Alzheimer’s is described by W. Koch, S. Teipel, S. Mueller, J. Benninghoff, M. Wagner, A. L. Bokde, et al., “Diagnostic Power of Default Mode Network Resting State fMRI in the Detection of Alzheimer’s Disease,” Neurobiology of Aging (2010), e-publication ahead of print.
21. Recent reporting on setbacks in clinical trials includes:
22. A working group convened by the National Institute on Aging at the National Institutes of Health and the Alzheimer’s Association has proposed a new set of criteria for the earliest stages of Alzheimer’s disease that include certain neuroimaging techniques. See http://www.alzforum.org/new/detail.asp?id=2521 and http://www.telegraph.co.uk/health/healthnews/7965818/Alzheimers-disease-being-tackled-too-late-Lancet.html for reporting on why these criteria may represent an important step for diagnosis and evaluation of treatments. These criteria are still in the discussion and review stage; detailed information on the proposal can be found at http://www.alz.org/research/diagnostic_criteria.
The following lay-friendly articles provide an in-depth review of the concepts discussed here:
R. L. Buckner, J. R. Andrews-Hanna, and D. L. Schacter, “The Brain’s Default Network: Anatomy, Function, and Relevance to Disease,” Annals of the New York Academy of Sciences 1124 (2008): 1–38.
M. E. Raichle, “The Brain’s Dark Energy,” Scientific American 302 (2010): 44–49.
D. Zhang and M. E. Raichle, “Disease and the Brain’s Dark Energy,” Nature Reviews Neurology 6 (2010): 15–28.