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The missing cortex?

In a new paper {1}, Mazzola and colleagues present a further account of their well-known studies of electrical stimulation of the cortex (see ref {2}), in which they identify sensations of pain arising from a region of cortex around the medial parietal operculum and posterior insula cortex. 

Their research raises a fundamental question -– is this really the missing pain cortex? Do these rather small, inconsistent, and sometimes unpleasant sensory as opposed to frankly painful experiences reflect the activity of the elusive 'SIII'. It's a fascinating question and forces us to ask ourselves what it would take for us to conclude that this area is actually the long lost cortex. One the one hand, it seems likely that many nociceptive-specific ascending pathways project here (see ref {3} for a review) and stimulation here seems sufficient to cause to pain, but on the other, it's hardly the robust and convincing result you might expect for a sensory and emotional experience that can overwhelm our consciousness. 

So what should we expect to characterize a pain cortex? Is it specificity for pain? Or the necessity and sufficiency to support conscious appreciation of pain? Or the engagement in complex computations involved in processing pain? Or all three of these? The region is certainly not exclusive for pain, but there may be some degree of specificity (see ref {4} for a recent investigation). Necessity is hinted at by lesion studies (for an example, see ref {5}), and sufficiency is implied by this study. Perhaps what is most lacking is a clear demonstration that the area performs a specific computational function involved in the perception of pain. And herein lies a possible clue to the difficulty finding it, since pain is a comparatively simple, primitive sensation (compared to vision or hearing, for instance), there may not be an awful lot of complex computation to do, hence necessitating only a small bit of (shared) cortex. The only obvious alternative account is that pain perception has a genuinely distributed coding across two or more regions of cortex. If this is the case, perhaps simultaneous stimulation of these regions (for example, anterior cingulate and posterior insula cortex) might produce more pain than either alone.


1. Mazzola L, Isnard J, Peyron R, Mauguière F. Stimulation of the human cortex and the experience of pain: Wilder Penfield's observations revisited. Brain. 2012 Feb; 135(Pt 2): 631-4. PMID: 22036962 DOI: 10.1093/brain/awr265

2.Somatotopic organization of pain responses to direct electrical stimulation of the human insular cortex. Mazzola L, Isnard J, Peyron R, Guénot M, Mauguière FPain 2009 Nov; 146(1-2): 99-104 PMID: 19665303 DOI: 10.1016/j.pain.2009.07.014

3.Interoception: the sense of the physiological condition of the body. Craig ADCurrent opinion in neurobiology 2003 Aug; 13(4): 500-5  PMID: 12965300
4.The human operculo-insular cortex is pain-preferentially but not pain-exclusively activated by trigeminal and olfactory stimuli. Lötsch J, Walter C, Felden L, Nöth U, Deichmann R, Oertel BGPloS one 2012; 7(4): e34798  PMID: 22496865 DOI: 10.1371/journal.pone.0034798
5.Isolated insular infarction eliminates contralateral cold, cold pain, and pinprick perception. Birklein F, Rolke R, Müller-Forell WNeurology 2005 Nov 8; 65(9): 1381 PMID: 16275823 DOI: 10.1212/01.wnl.0000181351.82772.b3

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