The pain matrix reloaded A salience detection system for the body Vale ´ ry Legrain a,b, *, Gian Domenico Iannetti c , Le ´ on Plaghki b , Andre ´ Mouraux b a Department of Experimental-Clinical and Health Psychology, Ghent University, Belgium b Institute of Neuroscience (IoNS), Universite ´ catholique de Louvain, Belgium c Department of Neuroscience, Physiology & Pharmacology, University College London, United Kingdom Contents 1. Introduction ..................................................................................................... 112 2. Relationship between magnitude of responses in the ‘‘pain matrix’’ and intensity of pain ....................................... 112 3. The effect of novelty and orienting of attention......................................................................... 115 4. Activation of the ‘‘pain matrix’’ by non-nociceptive inputs ................................................................ 116 5. A salience detection system ........................................................................................ 118 6. A salience detection system for the body .............................................................................. 119 7. Towards a neuropsychology of threat detection ........................................................................ 120 8. Conclusion ...................................................................................................... 121 Acknowledgements ............................................................................................... 121 References ...................................................................................................... 121 Progress in Neurobiology 93 (2011) 111–124 ARTICLE INFO Article history: Received 5 March 2010 Received in revised form 8 October 2010 Accepted 20 October 2010 Available online 30 October 2010 Keywords: Pain Nociception Salience Attention Multimodal Peripersonal space ABSTRACT Neuroimaging and neurophysiological studies have shown that nociceptive stimuli elicit responses in an extensive cortical network including somatosensory, insular and cingulate areas, as well as frontal and parietal areas. This network, often referred to as the ‘‘pain matrix’’, is viewed as representing the activity by which the intensity and unpleasantness of the percept elicited by a nociceptive stimulus are represented. However, recent experiments have reported (i) that pain intensity can be dissociated from the magnitude of responses in the ‘‘pain matrix’’, (ii) that the responses in the ‘‘pain matrix’’ are strongly influenced by the context within which the nociceptive stimuli appear, and (iii) that non-nociceptive stimuli can elicit cortical responses with a spatial configuration similar to that of the ‘‘pain matrix’’. For these reasons, we propose an alternative view of the functional significance of this cortical network, in which it reflects a system involved in detecting, orienting attention towards, and reacting to the occurrence of salient sensory events. This cortical network might represent a basic mechanism through which significant events for the body’s integrity are detected, regardless of the sensory channel through which these events are conveyed. This function would involve the construction of a multimodal cortical representation of the body and nearby space. Under the assumption that this network acts as a defensive system signaling potentially damaging threats for the body, emphasis is no longer on the quality of the sensation elicited by noxious stimuli but on the action prompted by the occurrence of potential threats. ß 2010 Published by Elsevier Ltd. Abbreviations: ACC, anterior cingulate cortex; AIP, anterior intraparietal area; BOLD, blood oxygen level dependent; CRPS, complex regional pain syndrome; DNIC, diffuse noxious inhibitory controls; EEG, electroencephalography; ERFs, event-related magnetic fields; ERPs, event-related potentials; fMRI, functional magnetic resonance imaging; MEG, magnetoencephalography; PET, positron emission tomography; SI, primary somatosensory cortex; SII, secondary somatosensory cortex; VIP, ventral intraparietal area; WDR, wide dynamic range. * Corresponding author at: Department of Experimental-Clinical and Health Psychology, Ghent University, Henri Dunantlaan 2, 9000 Ghent, Belgium. Tel.: +32 9 264 91 43; fax: +32 9 264 64 89. E-mail address: valery.legrain@ugent.be (V. Legrain). Contents lists available at ScienceDirect Progress in Neurobiology journal homepage: www.elsevier.com/locate/pneurobio 0301-0082/$ – see front matter ß 2010 Published by Elsevier Ltd. doi:10.1016/j.pneurobio.2010.10.005