Vol 45312 June 200doi:10.1038/nature06976 nature REVIEWS What we can do and what we cannot do with fMR Nikos K.Logothetis' Functional magnetic resonance imaging(fMRI)is currently the mainstay of neuroimaging in cognitive neuroscience. fwareiRomertechnolcegymegeaguistionprotoc ental design,anc d analysis methods promise to push Here I give an overview of the current state of fMRI,and draw on neu imagingand physiological data to present thecu understanding of the haemodynamic signals and the constraints they impose on neuroimaging data interpretation. ing (MRD is th sition M on b linic in the l aticndpgnosticmcdicincandmorg ccntyinb ans,including the central nervous 信ana mind has no components to speak of.Even if true.the challenge meural activityi the had a real impa on basi in each of which cognitive capacity,however abstract,is cognitive database oblem but a contrast ag ng to a ut nitive task or timldorcogniti MRI can go reve ing the rm module er topics ing plasticty,drug action,experiment )as we In humans.fMRI is used routinely not just to study tions term fur ffongeontrolofactio d and spati ht furthe ed m yto po g toindicate tha h fmriwe can The principal adv ges of fMRI lie in its noninvasive natur tests has be renology that i oded to signal whose ificity and tempo oral response ar SiobohphycahdngaoatAmoepoia 'Max Planck Institute for Biological Cy :72076T cal Engir ng.University of Manchester.Manchester M13 9PL UK REVIEWS What we can do and what we cannot do with fMRI Nikos K. Logothetis1 Functional magnetic resonance imaging (fMRI) is currently the mainstay of neuroimaging in cognitive neuroscience. Advances in scanner technology, image acquisition protocols, experimental design, and analysis methods promise to push forward fMRI from mere cartography to the true study of brain organization. However, fundamental questions concerning the interpretation of fMRI data abound, as the conclusions drawn often ignore the actual limitations of the methodology. Here I give an overview of the current state of fMRI, and draw on neuroimaging and physiological data to present the current understanding of the haemodynamic signals and the constraints they impose on neuroimaging data interpretation. Magnetic resonance imaging (MRI) is the most important imaging advance since the introduction of X-rays by Conrad Ro¨ntgen in 1895. Since its introduction in the clinic in the 1980s, it has assumed a role of unparalleled importance in diagnostic medicine and more recently in basic research. In medicine, MRI is primarily used to produce structural images of organs, including the central nervous system, but it can also provide information on the physico-chemical state of tissues, their vasculariza￾tion, and perfusion. Although all of these capacities have long been widely appreciated, it was the emergence of functional MRI (fMRI)—a technique for measuring haemodynamic changes after enhanced neural activity—in the early 1990s that had a real impact on basic cognitive neuroscience research. A recent database (ISI/Web of Science) query using the keywords ‘fMRI’ or ‘functional MRI’ or ‘func￾tional magnetic resonance imaging’ returned over 19,000 peer￾reviewed articles. Given that the first fMRI study without exogenous contrast agents was published in 1991, this corresponds to approxi￾mately 1,100 papers per year, or over 3 papers per day. This average obscures the actual rate of publications, as in 1992 there were four publications in total, increasing to about eight per day by 2007. About 43% of papers explore functional localization and/or cognitive anatomy associated with some cognitive task or stimulus—construct￾ing statistical parametric maps from changes in haemodynamic res￾ponses from every point in the brain. Another 22% are region of interest studies examining the physiological properties of different brain structures, analogous to single-unit recordings; 8% are on neuro￾psychology; 5% on the properties of thefMRI signal; and the rest is on a variety of other topics including plasticity, drug action, experimental designs and analysis methods. In humans, fMRI is used routinely not just to study sensory pro￾cessing or control of action, but also to draw provocative conclusions about the neural mechanisms of cognitive capacities, ranging from recognition and memory to pondering ethical dilemmas. Its popular fascination is reflected in countless articles in the press speculating on potential applications, and seeming to indicate that with fMRI we can read minds better than direct tests of behaviour itself. Unsurprisingly, criticism has been just as vigorous, both among scientists and the public. In fact, fMRI is not and will never be a mind reader, as some of the proponents of decoding-based methods suggest, nor is it a worth￾less and non-informative ‘neophrenology’ that is condemned to fail, as has been occasionally argued. Perhaps the extreme positions on both sides result from a poor understanding of the actual capacities and limitations of this tech￾nology, as well as, frequently, a confusion between fMRI shortcom￾ings and potential flaws in modelling the organizational principles of the faculties under investigation. For example, a frequently made assumption is that the mind can be subdivided into modules or parts whose activity can then be studied with fMRI. If this assumption is false, then even if the brain’s architecture is modular, we would never be able to map mind modules onto brain structures, because a unified mind has no components to speak of. Even if true, the challenge remains in coming up with the correct recursive decompositions— in each of which any given cognitive capacity, however abstract, is divided into increasingly smaller functional units that are localized to specific brain parts, which in turn can be detected and studied with fMRI. This is not a neuroimaging problem but a cognitive one. Hierarchical decompositions are clearly possible within different sensory modalities and motor systems. Their mapping, which reflects the brain’s functional organization, is evidently possible and certainly meaningful beyond any reasonable doubt1 . Here, I offer an assessment of fMRI methodology itself, leaving aside such epistemological and ontological issues. I take the modular organization of many brain systems as a well established fact, and discuss only how far fMRI can go in revealing the neuronal mechan￾isms of behaviour by mapping different system modules and their dynamic inter-relationships. In this context the term module cap￾tures the classical local neuronal circuits repeated iteratively within a structure (for example, the columns or swirling, slab-like tangential arrangements of the neocortex), as well as the entities within which modules might be grouped by sets of dominating external connec￾tions. The often used term functional segregation refers to such specialized and spatially separated modules. Segregated entities that are interconnected might further result in nested distributed systems, the activity of which, often termed functional integration, can only be visualized by large-scale neuroimaging. The principal advantages of fMRI lie in its noninvasive nature, ever-increasing availability, relatively high spatiotemporal resolu￾tion, and its capacity to demonstrate the entire network of brain areas engaged when subjects undertake particular tasks. One disadvantage is that, like all haemodynamic-based modalities, it measures a sur￾rogate signal whose spatial specificity and temporal response are subject to both physical and biological constraints. A more important 1 Max Planck Institute for Biological Cybernetics, 72076 Tuebingen, Germany, and Imaging Science and Biomedical Engineering, University of Manchester, Manchester M13 9PL, UK. 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