Cognitive Brain Research 17 (2003) 255–262 www.elsevier.com / locate / cogbrainres Research report Increased cerebral functional connectivity underlying the antinociceptive effects of hypnosis a a b b Marie-Elisabeth Faymonville , Laurence Roediger , Guy Del Fiore , Christian Delgueldre , b a a b,c b,c, * Christophe Phillips , Maurice Lamy , Andre Luxen , Pierre Maquet , Steven Laureys a ` ` Department of Anesthesiology and Intensive Care Medicine, CHU Sart Tilman, University of Liege, 4000 Liege, Belgium b ` ` Cyclotron Research Center, Sart Tilman B30, University of Liege, 4000 Liege, Belgium c ` ` Department of Neurology, CHU Sart Tilman, University of Liege, 4000 Liege, Belgium Accepted 7 March 2003 Abstract The neural mechanisms underlying the antinociceptive effects of hypnosis are not well understood. Using positron emission tomography (PET), we recently showed that the activity in the anterior cingulate cortex (midcingulate area 24a9) covaries with the hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation [Faymonville et al., Anesthesiology 92 (2000) 1257–1267]. In the present study, we assessed changes in cerebral functional connectivity related to the hypnotic state, compared 15 to simple distraction and the resting state. Nineteen highly hypnotizable right-handed volunteers were studied using H O-PET. The 2 experimental conditions were hot noxious or warm non-noxious stimulation of the right hand during resting state, mental imagery and hypnotic state. Using a psychophysiological interaction analysis, we identified brain areas that would respond to noxious stimulations under the modulatory action of the midcingulate cortex in, and only in, the hypnotic state. Hypnosis, compared to the resting state, reduced pain perception by 50%. Pain perception during rest and mental imagery was not significantly different. Analysis of PET data showed that the hypnotic state, compared to normal alertness (i.e., rest and mental imagery), significantly enhanced the functional modulation between midcingulate cortex and a large neural network encompassing bilateral insula, pregenual anterior cingulate cortex, pre-supplementary motor area, right prefrontal cortex and striatum, thalamus and brainstem. These findings point to a critical role for the midcingulate cortex in the modulation of a large cortical and subcortical network underlying its influence on sensory, affective, cognitive and behavioral aspects of nociception, in the specific context of hypnosis.  2003 Elsevier B.V. All rights reserved. Theme: Neural basis of behaviour Topic: Cognition; Motivation and emotion; Neural plasticity Keywords: Hypnotic state; Pain; Psychophysiological interaction analysis; Positron emission tomography; Regional cerebral blood flow 1. Introduction main, however, not fully understood. Studies of the antinociceptive effects of hypnosis have labored under a Hypnosis combined with slight conscious sedation (i.e., double burden: both hypnotic experience and pain ex- hypnosedation) and local anesthesia is now considered a perience are highly subjective phenomena. Factors that valuable alternative to general anesthesia in specific indica- evoke pain reduction range from extrinsic psychosocial tions [18,20,21,30,31,37]. Since 1992 we have used hy- (e.g., interactions between clinician and patient) to intrinsic pnosis routinely in more than 3300 surgical procedures. psychophysiological (e.g., modulation of pain signal trans- The underlying neuromodulatory effects of hypnosis re- mission [47] ). Recent positron emission tomography (PET) studies have demonstrated that the decreased per- ception of pain during hypnosis is related to changes in the *Corresponding author. Cyclotron Research Center, Sart Tilman B30, activity (i.e., regional cerebral blood flow—rCBF) mea- ` ` University of Liege, 4000 Liege, Belgium. http: / / www.ulg.ac.be / crc. sured in the midcingulate cortex (area 249 [19,48] ). We Tel.: 132-4-366-3687; fax: 132-4-366-2946. E-mail address: steven.laureys@ulg.ac.be (S. Laureys). here test the hypothesis that hypnosis-induced analgesia 0926-6410 / 03 / $ – see front matter  2003 Elsevier B.V. All rights reserved. doi:10.1016 / S0926-6410(03)00113-7