A default mode of brain function: A brief history of an evolving idea

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1088 M.E. Raichle, A.Z. Snyder / NeuroImage 37 (2007) 1083–1090directly than was done in the main text. Our responses are intendedto clarify certain points and to provide additional background thatsome may find useful in discussions of the default mode, thedefault system, the physiologic baseline and intrinsic activity.M&F: a default or intrinsic mode of functioning derives fromthe observation that “a consistent network of brain regionsshows high levels of activity when no explicit task is performedand subjects are asked simply to rest.”A default mode of functioning was initially inferred on thebasis of two related observations: first, certain areas of the brainconsistently decrease activity when subjects engage in goaldirectedtasks as compared to simply resting quietly with the eyesclosed or visually fixating; and, second, this network of areas wasnot physiologically 'activated' in the resting state. While initiallyattributed specifically to a specific system, now often called thedefault network, we now appreciate that all parts of the brainexhibit a default mode of functioning that largely reflects theirongoing intrinsic activity.M&F: “The importance of this putative 'default mode' isasserted on the basis of the substantial energy demandassociated with the resting state and of the suggestion thatrest entails a finely tuned balance between metabolic demandand regionally regulated blood supply.”A finely tuned balance between metabolic demand andregionally regulated blood supply is not unique to the restingstate or the default system. It is characteristic of all areas of thebrain at all times. It is important to appreciate in this regard thatblood flow is not simply regulated in relation to oxygenconsumption as traditionally envisioned. Rather, a complexinterplay between glycolysis, oxidative phosphorylation, bloodflow and cellular physiology (in astrocytes and neurons alike) isplayed out in the course of functional activities (Raichle andMintun, 2006).The brain's substantial energy demand (20% of the entirebody's) is a more broadly important matter (Raichle, 2006). Recentevidence clearly indicates that a majority of this cost is directlyrelated to the functioning of the brain. In this regard it should benoted that transmitter cycling is a correlate of transmitter releaseand uptake, and, hence neuronal signaling. Transmitter cycling hascomputational significance.M&F: The case for a default mode comprises three relatedideas. The first is that the resting state constitutes an absolutebaseline, and is therefore a fixed point relative to which allcognitive and physiological states can and should beconsidered.To restate, the baseline as defined in our work is a physiologicalreferent not a behavioral one. It is, therefore, only appropriatelyapplied to PET and not to fMRI. On the other hand, 'control state'and 'control condition' (whichever term is preferred) can beequally well applied to PET and fMRI. We remain convinced thatusing a low level control state in addition to other more complexones enhances the interpretability of functional imaging data (e.g.,consider the interpretational complexities in the study by Simpsonand colleagues (Simpson et al., 2001) that are discussed in greaterdetail in Gusnard and Raichle, 2001).M&F: “The second is the notion that the level of neural activityin this resting state is substantial and therefore functionallyimportant, with changes produced by task demands representingjust the ‘tip of the iceberg’.”Correct. Event-related changes in cerebral blood flow andglucose uptake are no more than 10% of the physiologic baselinein typical cognitive paradigms. Concomitant changes in energyutilization are on the order of 1% (for addition discussion seeRaichle and Mintun, 2006).M&F: “It would follow that cognitively driven fluctuationscannot be interpreted except in the context of the defaultsystem.”This is true of all parts of the brain because they all exhibitongoing intrinsic activity, a default mode if you will. Task-relatedresponses in any part of the nervous system should ultimately beunderstood in relation to local intrinsic activity.M&F: “We conclude that despite the interesting characteristicsof rest as baseline in terms of oxygen balance, these are notrelevant to studies that seek to understand how neural activityunderpins cognitive processing.”Traditional views of brain energy metabolism posited that allenergy for brain function came from the metabolism of glucose tocarbon dioxide and water. The discovery that this simple relationshipis not correct (Fox et al., 1988) not only provided thephysiological basis for fMRI but also opened up new ways ofthinking about the neural events underlying cognitive processing.Links such as this across levels of analysis and intellectual inquiryshould be at the heart of any enterprise that hopes to understandhow brain instantiates behavior.M&F: “While we accept that a high level of energy expenditureof the brain at ‘rest’ indicates that the resting state is active, wedo not agree that this activity has a special status comparedwith that in any other task, or that the brain energy budget isinformative about the nature of the ‘default mode’.”The important distinction is not between “rest” and “task” butrather between intrinsic and evoked activity. To define “rest” assimply a task with unspecified cognitive content obscures what webelieve to be the important and essential distinction betweenintrinsic and evoked activity. That upwards of 90% of the brain'sfunctional activity, as measured in energy terms, is devoted tointrinsic and not evoked activity inescapably leads one to give tothe study of intrinsic activity an increased level of attention, wellabove that which it has heretofore received. To do otherwise is toprematurely limit the level of understanding achievable in ourquest to understand how brain instantiates behavior. Determiningthe contribution of intrinsic activity to behavior is challenging but,in our view, should be a major neuroscience objective.M&F: “We conclude that even if there is empirical consistencyin the patterns of activity observed at rest, and a subjectiveappeal to the notion that when we rest we are in a default statebecause there is no explicit task to perform, these areinsufficient grounds for affording the resting state a privilegedstatus in accounts of human behavior.”Again, our argument is quite simply that the fundamentaldistinction to be made is between intrinsic and evoked activity.Resting quietly but awake in a scanner affords one an opportunityto view intrinsic activity but we would not argue that this is theonly way. Sleep and general anesthesia (Vincent et al., in press)
M.E. Raichle, A.Z. Snyder / NeuroImage 37 (2007) 1083–10901089also come to mind. As experimental strategies develop distinctionsbetween intrinsic and evoked during task performance may alsobecome increasingly feasible in the context of functionalneuroimaging (e.g., see Fox et al., 2006). But we should alwayskeep in mind that this work cannot precede effectively in avacuum. Success will require a dialogue with other levels ofanalysis.M&F: In most instances the aims of cognitive neuroscience arebest served by the study of specific task manipulations ratherthan “rest.”We would agree that the aims of cognitive neuroscience willcontinue to be served by the study of specific task manipulationsbut not exclusively so. To base the agenda on this approach alonemisses the exciting opportunities afforded by an integration ofapproaches across disciplines and levels of analysis. To do so alsohas the potential to blind one to the real reason we have a brain,which is not to reminisce about the past nor react in the momentbut, rather, to envision the future.ReferencesAbbott, L.F., Chance, F.S., 2005. Drivers and modulators from push–pulland balanced synaptic input. Prog. Brain Res. 149, 147–155.Aguirre, G.K., Detre, J.A., et al., 2002. Experimental design and the relativesensitivity of BOLD and perfusion fMRI. NeuroImage 15 (3), 488–500.Amedi, A., Malach, R., et al., 2005. Negative BOLD differentiates visualimagery and perception. Neuron 48 (5), 859–872.Antrobus, J.S., 1968. Information theory and stimulus-independent thought.Br. J. Psychol. 59 (4), 423–430.Arieli, A., Sterkin, A., et al., 1996. Dynamics of ongoing activity:explanation of the large variability in evoked cortical responses.Science 273 (5283), 1868–1871.Attwell, D., Iadecola, C., 2002. The neural basis of functional brain imagingsignals. Trends Neurosci. 25 (12), 621–625.Attwell, D., Laughlin, S.B., 2001. An energy budget for signaling in the greymatter of the brain. J. Cereb. Blood Flow Metab. 21 (10), 1133–1145.Binder, J.R., Frost, J.A., et al., 1999. Conceptual processing during theconscious resting state. A functional MRI study. J. Cogn. Neurosci. 11 (1),80–95.Brain, R., 1961. The neurology of language. Speech Pathol. Ther. 4, 47–59.Buckner, R.L., Vincent, J.L., in press. Unrest at rest: an argument forstudying sontaneous brain activity. NeuroImage.Buzsaki, G., 2006. Rhythms of the Brain. Oxford Univ. Press, New York.Buzsaki, G., Draguhn, A., 2004. Neuronal oscillations in cortical networks.Science 304 (5679), 1926–1929.Cacioppo, J.T., Berntson, G.G., et al. (Eds.), 2002. Foundations of SocialNeuroscience. MIT Press, Cambridge, MA.Cacioppo, J.T., Visser, P.S., et al. (Eds.), 2006. Social Neuroscience: PeopleThinking About People. MIT Press, Cambridge, MA.Detre, J.A., Wang, J., 2002. Technical aspects and utility of fMRI usingBOLD and ASL. Clin. Neurophysiol. 113 (5), 621–634.Drevets, W.C., Burton, H., et al., 1995. Blood flow changes in humansomatosensory cortex during anticipated stimulation. Nature 373 (6511),249–252.Foster, D.J., Wilson, M.A., 2006. Reverse replay of behavioural sequencesin hippocampal place cells during the awake state. Nature 440 (7084),680–683.Fox, P.T., Raichle, M.E., 1986. Focal physiological uncoupling of cerebralblood flow and oxidative metabolism during somatosensory stimulationin human subjects. Proc. Natl. Acad. Sci. U. S. A. 83 (4), 1140–1144.Fox, P.T., Raichle, M.E., et al., 1988. Nonoxidative glucose consumptionduring focal physiologic neural activity. Science 241 (4864), 462–464.Fox, M.D., Snyder, A.Z., et al., 2005. The human brain is intrinsicallyorganized into dynamic, anticorrelated functional networks. Proc. Natl.Acad. Sci. U. S. A. 102 (27), 9673–9678.Fox, M.D., Snyder, A.Z., et al., 2006. Coherent spontaneous activityaccounts for trial-to-trial variability in human evoked brain responses.Nat. Neurosci. 9 (1), 23–25.Ghatan, P.H., Hsieh, J.C., et al., 1998. Coexistence of attention-basedfacilitation and inhibition in the human cortex. NeuroImage 7 (1),23–29.Gusnard, D.A., Raichle, M.E., 2001. Searching for a baseline: functionalimaging and the resting human brain. Nat. Rev., Neurosci. 2 (10),685–694.Hahn, T.T., Sakmann, B., et al., 2006. Phase-locking of hippocampalinterneurons' membrane potential to neocortical up-down states. Nat.Neurosci. 9 (11), 1359–1361.Haider, B., Duque, A., et al., 2006. Neocortical network activity in vivois generated through a dynamic balance of excitation and inhibition.J. Neurosci. 26 (17), 4535–4545.Hebb, D.O., 1965. Alice in Wonderland or psychology among the biologicalsciences. In: Harlow, H.F., Woolsey, C.N. (Eds.), Biological andBiochemical Bases of Behavior. The Univ. of Wisconsin Press,Madison, WI.Ingvar, D.H., 1985. Memory of the future: an essay on the temporalorganization of conscious awareness. Hum. Neurobiol. 4 (3), 127–136.Isomura, Y., Sirota, A., et al., 2006. Integration and segregation of activity inentorhinal–hippocampal subregions by neocortical slow oscillations.Neuron 52 (5), 871–882.James, W., 1890. The Principles of Psychology. Henry Holt & Company,New York.Kant, I., 1781, 2004. Critique of Pure Reason. New York, Barnes and NoblePublishing, Inc.Kawashima, R., O'Sullivan, B.T., et al., 1995. Positron-emission tomographystudies of cross-modality inhibition in selective attentional tasks:closing the “mind's eye”. Proc. Natl. Acad. Sci. U. S. A. 92 (13),5969–5972.Kay, L.M., 2005. Theta oscillations and sensorimotor performance. Proc.Natl. Acad. Sci. U. S. A. 102, 3863–3868.Kenet, T., Bibitchkov, D., et al., 2003. Spontaneously emerging corticalrepresentations of visual attributes. Nature 425 (6961), 954–956.Kersten, D., Mamassian, P., et al., 2004. Object perception as Bayesianinference. Annu. Rev. Psychol. 55, 271–304.Kim, S.G., Rostrup, E., et al., 1999. Determination of relative CMRO2 fromCBF and BOLD changes: significant increase of oxygen consumptionrate during visual stimulation. Magn. Reson. Med. 41 (6), 1152–1161.Knill, D.C., Pouget, A., 2004. The Bayesian brain: the role of uncertainty inneural coding and computation. Trends Neurosci. 27 (12), 712–719.Kwong, K.K., Belliveau, J.W., et al., 1992. Dynamic magnetic resonanceimaging of human brain activity during primary sensory stimulation.Proc. Natl. Acad. Sci. U. S. A. 89 (12), 5675–5679.Laughlin, S.B., Sejnowski, T.J., 2003. Communication in neuronalnetworks. Science 301 (5641), 1870–1874.Lauritzen, M., 2005. Reading vascular changes in brain imaging: is dendriticcalcium the key? Nat. Rev., Neurosci. 6 (1), 77–785.Lebrun-Grandie, P., Baron, J.C., et al., 1983. Coupling between regionalblood flow and oxygen utilization in the normal human brain. A studywith positron tomography and oxygen 15. Arch. Neurol. 40 (4), 230–236.Leopold, D.A., Murayama, Y., et al., 2003. Very slow activity fluctuations inmonkey visual cortex: implications for functional brain imaging. Cereb.Cortex 13 (4), 422–433.Llinas, R., 2001. I of the Vortex. The MIT Press, Cambridge, MA.Logothetis, N.K., Pauls, J., et al., 2001. Neurophysiological investigation ofthe basis of the fMRI signal. Nature 412 (6843), 150–157.Luczak, A., Bartho, P., et al., 2007. Sequential structure of neocorticalspontaneous activity in vivo. Proc. Natl. Acad. Sci. U. S. A. 104,347–352.Martin, W.R., Powers, W.J., et al., 1987. Cerebral blood volume measuredwith inhaled C15O and positron emission tomography. J. Cereb. BloodFlow Metab. 7 (4), 421–426.
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A default mode of brain function: A brief history of an evolving idea

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