Pain anticipation has previously been shown to involve activity in sensorimotor regions but also in the insula, anterior cingulate cortex and PCC

(Porro et al., 2002, 2003; Wager et al., 2004; Koyama et al., 2005; Brown et al., 2008; Atlas et al., 2010; Drabant et al., 2011; Worthen et al., 2011; Seifert et al., 2012). Secondly, we used dynamic visual stimuli instead of static pictures, which possibly enhanced the threatening aspect of the needle (Ehrsson et al., 2007). Activity within the PCC has been repeatedly associated with Alectinib in vitro processing of threat-related stimuli (for a recent meta-analysis see Hayes & Northoff, 2012). Finally, the focus of our analysis was on the interval before the needle or the Q-tip hit the hand. These differences Dabrafenib cell line in experimental protocols may have accounted for the different effects of visual stimulation on ABA in the present compared with some previous studies (Perry et al., 2010; Whitmarsh & Jensen, 2011). The effect of viewing a needle prick on anticipatory ABA was robustly localised to the PCC. The PCC has frequently been related to the default mode network and to different cognitive processes such as memory, attention, and change detection (for reviews

see Vogt, 2005; Pearson et al., 2011). The PCC is also involved in visual aversive conditioning (Maddock & Buonocore, 1997), pain anticipation (Porro et al., 2003; Brown et al., 2008; Seifert et al., 2012), and the initial detection of threat (Mobbs et al., 2009, 2010). Furthermore, Galeterone larger PCC activity has been observed during the anticipation of aversive

compared with neutral pictures (Grupe et al., 2013). Based on its anatomical connections, comprising amongst others the anterior cingulate cortex and cingulate motor regions (Vogt et al., 2006), the PCC has been supposed to play a role in orienting the body to motivationally salient stimuli (McCoy & Platt, 2005; Vogt, 2005). Salient sensory stimuli, especially threatening stimuli, presented near the body have been shown to evoke defensive responses (for reviews see Graziano & Cooke, 2006; Legrain et al., 2011). Thus, in the present study, the effects on ABA and PDR may reflect the preparation of adequate defensive behavior when viewing a needle approaching the body. In agreement with our previous study (Höfle et al., 2012), we observed a positive correlation between the effects in the PDR and perceived unpleasantness across participants. Interestingly, we found a difference in timing between the effect in the PCC and PDR. The effect in the PCC started at about −0.7 s, whereas it started at about −0.2 s in the PDR. This observation might be due to the more sluggish response of the PDR, which takes several hundred milliseconds to differentiate between stimulus content. For instance, in our previous study, we found that the pupil starts differentiating between painful and nonpainful electrical stimulation at about 0.4 s after electrical stimulus onset (Höfle et al., 2012).