title: Evidence for thalamic involvement in the thermal grill illusion: an FMRI study.
abstract: BACKGROUND
  Perceptual illusions play an important role in untangling neural mechanisms underlying conscious phenomena. The thermal grill illusion (TGI) has been suggested as a promising model for exploring percepts involved in neuropathic pain, such as cold-allodynia (pain arising from contact with innocuous cold). The TGI is an unpleasant/painful sensation from touching juxtapositioned bars of cold and warm innocuous temperatures.
  
  
  OBJECTIVE
  To develop an MRI-compatible TGI-unit and explore the supraspinal correlates of the illusion, using fMRI, in a group of healthy volunteers.
  
  
  METHODS
  We constructed a TGI-thermode allowing the rapid presentation of warm(41°C), cold(18°C) and interleaved(41°C+18°C = TGI) temperatures in an fMRI-environment. Twenty volunteers were tested. The affective-motivational ("unpleasantness") and sensory-disciminatory ("pain-intensity") dimensions of each respective stimulus were rated. Functional images were analyzed at a corrected α-level <0.05.
  
  
  RESULTS
  The TGI was rated as significantly more unpleasant and painful than stimulation with each of its constituent temperatures. Also, the TGI was rated as significantly more unpleasant than painful. Thermal stimulation versus neutral baseline revealed bilateral activations of the anterior insulae and fronto-parietal regions. Unlike its constituent temperatures the TGI displayed a strong activation of the right (contralateral) thalamus. Exploratory contrasts at a slightly more liberal threshold-level also revealed a TGI-activation of the right mid/anterior insula, correlating with ratings of unpleasantness (rho = 0.31).
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first fMRI-study of the TGI. The activation of the anterior insula is consistent with this region's putative role in processing of homeostatically relevant feeling-states. Our results constitute the first neurophysiologic evidence of thalamic involvement in the TGI. Similar thalamic activity has previously been observed during evoked cold-allodynia in patients with central neuropathic pain. Our results further the understanding of the supraspinal correlates of the TGI-phenomenon and pave the way for future inquiries into if and how it may relate to neuropathic pain.
authors.affiliation: Department of Clinical Neuroscience, Osher Center for Integrative Medicine, Stockholm Brain Institute, Karolinska Institutet, Stockholm, Sweden. fredrik.lindstedt@ki.se
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lindstedt
authors.forename: Bo
authors.initials: B
authors.lastname: Johansson
authors.forename: Sofia
authors.initials: S
authors.lastname: Martinsen
authors.forename: Eva
authors.initials: E
authors.lastname: Kosek
authors.forename: Peter
authors.initials: P
authors.lastname: Fransson
authors.forename: Martin
authors.initials: M
authors.lastname: Ingvar
mesh_terms: D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010146:Pain; D058748:Pain Perception / Q000502:physiology; D013696:Temperature; D013788:Thalamus / Q000503:physiopathology*; D013697:Thermosensing / Q000502:physiology
references.citation: Nature. 2008 Jun 12;453(7197):869-78
references.pmid: 18548064
references.citation: Pain. 2008 Oct 31;139(3):653-659
references.pmid: 18723286
references.citation: Neurology. 2005 Apr 12;64(7):1175-83
references.pmid: 15824343
references.citation: J Neurosci. 2004 Jul 7;24(27):6098-105
references.pmid: 15240801
references.citation: Open Neuroimag J. 2010 Nov 24;4:182-6
references.pmid: 21347202
references.citation: Mol Interv. 2002 Oct;2(6):392-403, 339
references.pmid: 14993415
references.citation: Pain. 1991 Dec;47(3):329-336
references.pmid: 1784503
references.citation: Pain. 1987 Mar;28(3):297-307
references.pmid: 2952934
references.citation: Neuroimage. 2006 Oct 1;32(4):1804-14
references.pmid: 16861005
references.citation: Nature. 1982 Jun 3;297(5865):406-8
references.pmid: 7078650
references.citation: J Pain. 2002 Apr;3(2):79-94
references.pmid: 14622792
references.citation: Arch Neurol. 1988 Dec;45(12):1312-20
references.pmid: 3196191
references.citation: Pain. 2000 Jan;84(1):77-87
references.pmid: 10601675
references.citation: Am J Respir Crit Care Med. 2008 May 1;177(9):1026-32
references.pmid: 18263796
references.citation: J Neurosci. 2007 May 2;27(18):4995-5004
references.pmid: 17475808
references.citation: Neurophysiol Clin. 2009 Dec;39(6):275-82
references.pmid: 19962655
references.citation: Brain. 1996 Apr;119 ( Pt 2):363-75
references.pmid: 8800933
references.citation: J Neurophysiol. 2003 Sep;90(3):1877-86
references.pmid: 12702705
references.citation: Annu Rev Neurosci. 2003;26:1-30
references.pmid: 12651967
references.citation: Neuroimage. 2011 Jan 15;54(2):1324-35
references.pmid: 20851770
references.citation: J Neurosci. 2009 Nov 25;29(47):14924-31
references.pmid: 19940188
references.citation: J Neurophysiol. 2005 Sep;94(3):1676-87
references.pmid: 15901758
references.citation: Nat Neurosci. 2004 Feb;7(2):189-95
references.pmid: 14730305
references.citation: Trends Cogn Sci. 2006 Feb;10(2):59-63
references.pmid: 16406760
references.citation: Trends Cogn Sci. 2004 Jun;8(6):239-41
references.pmid: 15165543
references.citation: J Neurophysiol. 2000 Jul;84(1):484-94
references.pmid: 10899221
references.citation: Curr Opin Anaesthesiol. 2008 Oct;21(5):586-9
references.pmid: 18784483
references.citation: Nat Neurosci. 2000 Feb;3(2):184-90
references.pmid: 10649575
references.citation: Brain Struct Funct. 2010 Jun;214(5-6):563-77
references.pmid: 20512381
references.citation: Curr Biol. 2010 Oct 26;20(20):1819-22
references.pmid: 20869246
references.citation: Eur J Neurosci. 1998 Nov;10(11):3462-9
references.pmid: 9824459
references.citation: Neurophysiol Clin. 2000 Oct;30(5):263-88
references.pmid: 11126640
references.citation: J Comp Neurol. 2003 May 12;459(4):329-33
references.pmid: 12687702
references.citation: Vis Neurosci. 2000 Jan-Feb;17(1):55-62
references.pmid: 10750826
references.citation: J Neurosci. 2004 Jan 7;24(1):248-56
references.pmid: 14715957
references.citation: Nat Neurosci. 2000 Mar;3(3):284-91
references.pmid: 10700262
references.citation: Pain. 2008 Apr;135(3):215-216
references.pmid: 18282660
references.citation: J Neurol Neurosurg Psychiatry. 2010 Jun;81(6):611-8
references.pmid: 20522870
references.citation: J Neurophysiol. 2004 Aug;92(2):1248-51
references.pmid: 15277602
references.citation: Neuron. 2007 Aug 2;55(3):339-41
references.pmid: 17678847
references.citation: Brain. 1998 Feb;121 ( Pt 2):345-56
references.pmid: 9549510
references.citation: Science. 1994 Jul 8;265(5169):252-5
references.pmid: 8023144
references.citation: Trends Neurosci. 2003 Jun;26(6):303-7
references.pmid: 12798599
references.citation: Brain. 2010 Nov;133(11):3409-22
references.pmid: 20852265
references.citation: Pain. 2008 Apr;135(3):291-299
references.pmid: 18258367
references.citation: Neurourol Urodyn. 2007 Oct;26(6 Suppl):899-903
references.pmid: 17654564
references.citation: J Gen Physiol. 1967 Jan;50(3):519-32
references.pmid: 11526844
references.citation: J Neurosci. 2009 May 13;29(19):6167-75
references.pmid: 19439594
references.citation: Neuron. 2007 Aug 2;55(3):465-78
references.pmid: 17678858
references.citation: Brain Res Rev. 2010 Oct 5;65(1):14-27
references.pmid: 20553761
references.citation: Pain. 1988 Aug;34(2):109-116
references.pmid: 3174149
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15222-7
references.pmid: 10611366
references.citation: Curr Pain Headache Rep. 2007 Jun;11(3):183-9
references.pmid: 17504645
references.citation: J Physiol. 2009 Dec 1;587(Pt 23):5633-52
references.pmid: 19822550
references.citation: Neuroimage. 2007;37 Suppl 1:S80-8
references.pmid: 17512757
references.citation: Nature. 1996 Nov 21;384(6606):258-60
references.pmid: 8918874
references.citation: PLoS One. 2011 Mar 15;6(3):e17752
references.pmid: 21423614
references.citation: J Neurosci. 2011 Mar 9;31(10):3795-804
references.pmid: 21389234
references.citation: Somatosens Mot Res. 1993;10(4):467-74
references.pmid: 8310783
references.citation: Pain. 2005 Mar;114(1-2):160-7
references.pmid: 15733641
references.citation: Pain. 2011 Jan;152(1):123-130
references.pmid: 20980103
references.citation: Pain. 2008 Sep 15;138(3):577-586
references.pmid: 18374485
references.citation: Brain Res. 1982 Nov 11;251(1):77-81
references.pmid: 7172011
references.citation: Pain. 2005 Jul;116(1-2):26-32
references.pmid: 15935558
references.citation: Neurology. 1997 May;48(5):1196-9
references.pmid: 9153442
references.citation: J Neurosci. 2009 Sep 16;29(37):11424-5
references.pmid: 19759291
references.citation: Neuroimage. 2005 May 1;25(4):1325-35
references.pmid: 15850749
references.citation: Eur J Pain. 2003;7(1):63-71
references.pmid: 12527319
references.citation: J Neurosci. 2006 Apr 19;26(16):4444-50
references.pmid: 16624964
references.citation: J Neurophysiol. 2002 Jan;87(1):615-20
references.pmid: 11784775
references.citation: Brain. 2006 Apr;129(Pt 4):963-76
references.pmid: 16434417
references.citation: J Appl Physiol. 1962 Nov;17:1003-8
references.pmid: 13997855
references.citation: Neuroscience. 2005;133(2):533-42
references.pmid: 15896917
references.citation: Brain Topogr. 2005 Fall;18(1):27-35
references.pmid: 16193264
references.citation: Neuroimage. 2003 Mar;18(3):650-9
references.pmid: 12667842