tDCS Modulation of Visually Induced Analgesia Flavia Mancini1, Nadia Bolognini2,3, Patrick Haggard1, and Giuseppe Vallar2,3 Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/24/12/2419/1778471/jocn_a_00293.pdf by MIT Libraries user on 17 May 2021 Abstract ■ Multisensory interactions can produce analgesic effects. In par- the centro-parietal areas thought to be involved in the sensory ticular, viewing oneʼs own body reduces pain levels, perhaps be- processing of pain. Participants were required to rate the intensity cause of changes in connectivity between visual areas specialized of painful electrical stimuli while viewing either their left hand or for body representation, and sensory areas underlying pain per- an object occluding the left hand, both before and immediately ception. We tested the causal role of the extrastriate visual cortex after tDCS. We found that the analgesic effect of viewing the body in triggering visually induced analgesia by modulating the excitabil- was enhanced selectively by anodal stimulation of the occipital ity of this region with transcranial direct current stimulation cortex. The effect was specific for the polarity and the site of stim- (tDCS). Anodal, cathodal, or sham tDCS (2 mA, 10 min) was admin- ulation. The present results indicate that visually induced analgesia istered to 24 healthy participants over the right occipital or over may depend on neural signals from the extrastriate visual cortex. ■ INTRODUCTION 2001) and areas activated by painful stimuli. In this study, The experienced level of pain strongly depends on the we tested the causal role of the extrastriate visual cortex in context in which nociceptive stimuli occur. Attention, ex- triggering the cross-modal modulation of pain perception. pectations, and motivation are well-known examples of To achieve this aim, we modulated the level of excitability contextual modulation (Wiech, Ploner, & Tracey, 2008). of the extrastriate visual cortex by transcranial direct cur- In addition to modulation of pain by psychological con- rent stimulation (tDCS) and examined the resulting effect texts, multisensory perceptual contexts may also modu- on visually induced analgesia. late pain. For example, simply looking at oneʼsown tDCS is a noninvasive technique of brain stimulation body can be analgesic. In neurologically unimpaired par- that can modulate cortical excitability by polarizing brain ticipants, passive vision of the hand reduces pain ratings tissue in a polarity-dependent fashion, with anodal stim- and the N2/P2 complex of laser-evoked potentials for ulation generally increasing excitability, and cathodal stim- the same stimuli (Longo, Betti, Aglioti, & Haggard, 2009). ulation generally reducing excitability (Brunoni et al., 2012; Furthermore, viewing oneʼs own hand increases contact Paulus, 2011; Nitsche et al., 2003; Nitsche & Paulus, 2001). heat pain thresholds by 3.2°C, relative to viewing a neutral When delivered to specific cortical areas, tDCS can alter object (Mancini, Longo, Kammers, & Haggard, 2011). This physiological, perceptual, and higher-order cognitive pro- “visually induced analgesia” can be considered a form of cesses (Vallar & Bolognini, 2011; Antal, Nitsche, & Paulus, multisensory modulation in which the visual representa- 2001; Nitsche & Paulus, 2001). tDCS alters activity of corti- tion of the body has effects on pain processing. cal areas situated under the electrodes, but also of distant Interactions between visual and somatosensory areas areas, probably through interconnections of the primary seem to mediate this modulatory effect of viewing the stimulated area with these structures (Polania, Nitsche, & body. A recent functional MRI experiment demonstrated Paulus, 2011). that changes in the effective connectivity between visual The behavioral task was to rate the intensity of a pain- and pain centers in the cerebral cortex underlie visually ful sensation elicited by trains of electrical shocks applied induced analgesia (Longo, Iannetti, Mancini, Driver, & to the left hand in two different visual contexts: participants Haggard, 2012). In particular, that study showed increased were required to look at their own left hand (“hand-view” functional coupling between visual and parietal areas that condition) or at an object occluding that hand (a wooden are activated by the visual perception of oneʼsownbody, block, “object-view” condition). In two separate experi- including the “extrastriate body area” (EBA) in the lateral ments, we investigated the effect of anodal (Experiment 1) occipital cortex (Downing, Jiang, Shuman, & Kanwisher, and cathodal (Experiment 2) tDCS over the occipital cortex (extrastriate visual) and the centro-parietal cortex, which contributes to sensory processing of nociceptive stimuli 1University College London, 2University of Milano-Bicocca, (Valentini et al., 2012; Liang, Mouraux, & Iannetti, 2011; 3IRCCS Istituto Auxologico Italiano Tracey, 2011). We expected that tDCS over the occipital © 2012 Massachusetts Institute of Technology Published under a Journal of Cognitive Neuroscience 24:12, pp. 2419–2427 Creative Commons Attribution 3.0 Unported (CC BY 3.0) license Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00293 by guest on 25 September 2021 cortex would not modulate pain generally, but specifically By virtue of its concentric design and small anode– influence the analgesic effect of viewing the body (increas- cathode distance, this somatosensory stimulating electrode ing or decreasing analgesia, depending on the tDCS polar- produces high current density at low current intensities. It ity). Conversely, tDCS over the centro-parietal cortex might can therefore depolarize the superficial layer of the dermis induce analgesia independent of the visual context, accord- containing nociceptive A-delta fibers (Kaube, Katsarava, ing to previous reports that demonstrate analgesic effects Kaufer, Diener, & Ellrich, 2000); however, A-beta fibers also of both anodal and cathodal stimulation of the motor cor- might be concomitantly stimulated (de Tommaso et al., tex without any explicit visual task (for reviews, see Vallar & 2011). Pinprick-like painful sensation is generally produced Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/24/12/2419/1778471/jocn_a_00293.pdf by MIT Libraries user on 17 May 2021 Bolognini, 2011; Lefaucheur et al., 2008). at currents between 0.6 and 1.6 mA. Mean onset latencies of blink reflexes and pain-related evoked potentials for such stimulation were found to be compatible with con- METHODS duction velocities of A-delta fibers (Katsarava et al., 2006; Participants Katsarava, Ellrich, Diener, & Kaube, 2002). Twenty-four naive right-handed (Oldfield, 1971) partici- At the beginning of each session, the individual thresh- pants (mean age = 23.4 years, SD = 4.4 years; 17 women) old for painful pinprick sensations was identified by two took part in the two experiments (n = 12 each). All were ascending and descending stimulation sequences in 0.1 mA free of medical disorders, substance abuse or depen- steps. The mean threshold was 0.52 mA (SD =0.26mA). dence, CNS effective medication, and psychiatric and neu- Two different intensities (+0.20 and +0.70 mA above rological disorders (Poreisz, Boros, Antal, & Paulus, 2007) individual pain thresholds) were then selected and used and participated on the basis of informed consent. Guide- in the main experiments (low-intensity stimulus: mean = lines of the ethical committees of the University of Milano- 0.70 mA, SD = 0.26 mA; high-intensity stimulus: mean = Bicocca (Milan, Italy) and the Declaration of Helsinki (BMJ 1.18 mA, SD =0.32mA). 1991; 302: 1194) were followed. Procedure Stimuli Participants sat at a table with their hands resting palm For stimulation, we used a custom planar concentric elec- down on the desktop, gazing toward their left hand trode, consisting of a central metal cathode (diameter = (Figure 1). A black cape hid from sight their arms and 0.5 mm), an isolation insert (diameter = 5 mm), and an right hand, so that participants could see only their left external anode ring (diameter = 6 mm), and providing a hand. Two visual conditions, “hand-view” and “object- stimulation area of 19.6 mm2. The electrode was applied view,” were presented in different blocks in an ABBA along the digital nerve path, approximately on the second order (initial condition counterbalanced across partici- metacarpal space of the left hand. In each trial, a 500-msec pants and sessions). In the “hand-view” condition, partici- train of electrical shocks at 10 Hz was generated by a Digi- pants gazed toward their left hand. In the “object-view” timer DS7A electrical stimulator (www.digitimer.com/) condition, the left hand was occluded by a box, and par- under computer control. ticipants looked at a hand-sized wooden block placed on Figure 1. Stimuli and procedure. Two sessions of the same behavioral task were administered before and after 10 min of 2 mA tDCS over either the right occipital or the centro-parietal cortex. During the behavioral task, participants were required to look at their own left hand or at an object in the same spatial location while verbally rating the intensity of electrical shocks delivered on their left hand. 2420 Journal of Cognitive Neuroscience Volume 24, Number 12 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00293 by guest on 25 September 2021 top of it (approximately 3 cm above the hand). Partici- the reference electrode was placed over