ArticlesDistraction modulates connectivity of the cingulo-frontal cortex and the midbrain during pain—an fMRI analysisValet, Michaela,∗; Sprenger, Tilla; Boecker, Henninga,b; Willoch, Frodeb; Rummeny, Ernstc; Conrad, Bastiana; Erhard, Petera,b,c; Tolle, Thomas R.aAuthor Information aDepartment of Neurology, Technische Universität München, Klinikum rechts der Isar, Möhlstraβe 28, 81675 München, Germany bDepartment of Nuclear Medicine, Technische Universität München, Klinikum rechts der Isar, Möhlstraβe 28, 81675 München, Germany cDepartment of Radiology, Technische Universität München, Klinikum rechts der Isar, Möhlstraβe 28, 81675 München, Germany ∗Corresponding author. Tel.: +49-89-4140-4628; fax: +49-89-4140-4659 E-mail: email@example.com Submitted August 1, 2003; revised February 3, 2004; accepted February 17, 2004. Pain: June 2004 - Volume 109 - Issue 3 - p 399-408 doi: 10.1016/j.pain.2004.02.033 Buy Metrics Abstract Neuroimaging studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have delineated a human pain network in vivo. Despite the recognition of cerebral structures engaged in pain transmission, the cerebral mechanisms involved in pain modulation are still not well understood. Here, we investigated healthy volunteers using fMRI during experimental heat pain and distraction induced by a visual incongruent color-word Stroop task. A factorial design permitted categorical and covariation analysis of four conditions, namely innocuous and noxious heat; with and without distraction. Pain without distraction evoked an activation pattern similar to that observed in previous neuroimaging pain studies. Distraction was associated with a significant reduction of the visual analogue scale (VAS) ratings for pain intensity and unpleasantness and a reduction of pain-related activation in multiple brain areas, particularly in the so-called ‘medial pain system’. Distraction significantly increased the activation of the cingulo-frontal cortex including the orbitofrontal and perigenual anterior cingulate cortex (ACC), as well as the periaquaeductal gray (PAG) and the posterior thalamus. Covariation analysis revealed functional interaction between these structures during pain stimulation and distraction, but not during pain stimulation per se. According to our results, the cingulo-frontal cortex may exert top–down influences on the PAG and posterior thalamus to gate pain modulation during distraction. © 2004 Lippincott Williams & Wilkins, Inc.