Neural Correlates of Empathy for Physical and Psychological Pain Vera Flasbeck and Martin Brune

Neural Correlates of Empathy for Physical and Psychological Pain

Vera Flasbeck and Martin Brüne

LWL University Hospital, Department of Psychiatry, Psychotherapy and Preventive Medicine, Division of Cognitive Neuropsychiatry and Psychiatric Preventive Medicine, Ruhr-University Bochum, Germany

Abstract: Empathy is known as the ability to share and understand someone else’s feelings. Previous research has either addressed the neural correlates of empathy for pain or social exclusion, but no study has examined empathy for physical and psychological (social) pain simultaneously. Forty-seven participants completed our novel “Social Interaction Empathy Task” during electroencephalogram (EEG) recording. Participants had to observe and rate the intensity of physical and psychological pain in social interactions from a first- and thirdperson perspective. At the behavioral level, subjects did not differentiate between the perspectives and rated physically painful scenarios as more painful than psychologically painful and neutral interactions. Psychologically painful pictures were also rated as more painful than neutral pictures. Analysis of event-related potentials (ERPs) revealed an early and a late response with a higher ERP response to physical and psychological pain compared to neutral interactions. Moreover, a significant difference emerged between the two dimensions of painful interactions. Furthermore, we found that the activity over frontal regions for discrimination of painful interactions was lateralized to the right hemisphere. Moreover, we detected significant correlations with the self-rated perspective taking ability. This suggests the psychological and physical pain qualities are processed differently but both are related to empathic traits. We further suggest that the right hemisphere may be specifically involved in the processing of empathy-related tasks.

Keywords: empathy, ERP, physical pain, social exclusion, perspective taking

Empathy is a complex mental state which enables us to share and to understand someone else’s emotions (Gonzalez-Liencres, Shamay-Tsoory, & Brüne, 2013; Shamay-Tsoory, 2011; Shamay-Tsoory, Aharon-Peretz, & Perry, 2009). It requires an affective component to match the emotional state of someone else and a cognitive component involving the capacity to differentiate self from others (for reviews, see Gonzalez-Liencres et al., 2013; Singer, 2006). Empathy for another’s pain has become a common tool for the investigation of empathic abilities in human beings. Neuroimaging research has revealed overlapping brain areas that are activated during empathy for another’s pain and the first-hand experience of pain, whereby these affective parts of the “pain matrix” comprise the bilateral anterior insular cortex and medial/ anterior cingulate cortex (ACC; Botvinick et al., 2005; Jackson, Brunet, Meltzoff, & Decety, 2006; Lamm, Decety, & Singer, 2011; Singer et al., 2004). Moreover, the activity of the affective brain regions correlates with the judgment of pain intensity and with self-rated empathic abilities (Jackson, Meltzoff, & Decety, 2005; Saarela et al., 2007). Several studies have tried to differentiate between a firstperson perspective and a third-person perspective during the empathy task. That is, individuals were asked to

indicate how they would feel in the observed situation (i.e., first-person perspective, FPP) and how the observed character would feel (i.e., third-person perspective, TPP). While some studies reported differences between the perspectives with a higher pain rating and faster reactions in the FPP (Li & Han, 2010; van der Heiden, Scherpiet, Konicar, Birbaumer, & Veit, 2013), other studies did not find any difference. For example, Jackson et al. (2006) reported that pain empathy evoked overlapping brain activity in both perspectives, but also a higher involvement of the secondary somatosensory cortex, ACC, and insula in the FPP and higher recruitment of the right temporoparietal junction in the TPP condition (Jackson et al., 2006). In addition, Abu-Akel, Palgi, Klein, Decety, and Shamay-Tsoory (2015) examined empathy for pain in both FPP and TPP under oxytocin treatment and could not detect differences between the perspectives in the placebo group. However, after administration of oxytocin participants rated the pain as more intense in the TPP compared to the FPP suggesting a modulatory effect of oxytocin on empathy (Abu-Akel et al., 2015). Another approach to investigate empathy for pain and its temporal dynamics entailed the analysis of event-related brain potentials (ERPs). Fan and Han were the first to

examine empathy for pain by presenting images of hands in neutral or physically painful situations. The participants’ attention was required for some of the task conditions and in some conditions withdrawn from the pain cues (Fan & Han, 2008). Painful stimuli elicited a positive shift of the ERP compared to neutral stimuli at short-latencies over frontal and central areas and at long-latencies over central-parietal regions. Moreover, the empathic responses could be modulated by attention and stimulus reality (cartoon or pictures) of the pain cues. The ERP pattern and the positive shifts of ERP components for painful stimuli relative to neutral stimuli could be replicated in further studies (Decety, Yang, & Cheng, 2010; Han, Fan, & Mao, 2008; Li & Han, 2010). Another dimension of pain, namely psychological or social pain, has been investigated in neuroimaging studies, demonstrating that social exclusion during a virtual balltossing game activates parts of the pain matrix, including the ACC, insula, and the right ventromedial prefrontal cortex (Bolling et al., 2011; Eisenberger, Lieberman, & Williams, 2003; Kross, Berman, Mischel, Smith, & Wager, 2011; Masten et al., 2009), whereby the intensity of activity in these regions was correlated with the magnitude of subjective distress. A few event-related studies utilizing the Cyberball game (Williams, Cheung, & Choi, 2000) showed that social exclusion led to an increase in ERP compared to neutral trials at N2 and P3b (Crowley et al., 2009; Weschke & Niedeggen, 2013). Hence, physical and social pain seem to share some elements concerning their neural representation, especially in affective areas that probably reflect the unpleasantness of the stimuli (for review, see Eisenberger, 2012). To our knowledge, no study exists that has compared the ERPs of both empathy for psychological or social pain and physical pain in the same experiment to further investigate the commonalities and differences between the empathic responses to the two pain types. Moreover, in light of critique of the Cyberball game suggesting that it reflects expectancy violation and conflict-based neural alarm activation rather than social pain per se (Themanson, Khatcherian, Ball, & Rosen, 2013; Weschke & Niedeggen, 2015), we designed a novel “Social Interaction Empathy Task,” where healthy participants had to rate the pain intensity of images depicting social interactions containing psychological (social) or physical pain from a FPP and a TPP during electroencephalogram (EEG) recording. This allowed us to directly compare the processing of the empathic responses to different pain qualities which could add important information to the discussion of shared brain areas involved in empathy for physical and social pain. We further aimed to investigate whether empathic abilities affect processing of the different painful social interactions.

We anticipated differences between ERPs of neutral and physical and psychologically painful interactions. Furthermore, we expected associations with self-rated empathic abilities. In addition, we investigated whether the neural correlates of empathy for pain in social interactions showed any lateralization and perspective effects. We hypothesized higher association of right frontal brain activity with empathy for pain than with the left hemisphere, based on previous work suggesting that greater right frontal activity is associated with negative affect and withdrawal, whereas the left frontal brain is more recruited by positive affect and approach motivation (Harmon-Jones, 2003).

Material and Methods

Participants

Forty-seven female healthy participants were recruited for the study. The participants’ age ranged from 18 to 50 years and the mean age was 26.47 (SD = 6.44). The mean IQ was 117 (SD = 16.69) as assessed by the verbal intelligence test MWT-A (Mehrfachwahl-Wortschatz-Intelligenztest; Lehrl, Merz, Burkard, & Fischer, 1991). Exclusion criteria were an IQ below 90, neurological and psychiatric diseases, addiction disorders, severe somatic disorders, and pregnancy. The study was approved by the Ethics Committee of the Medical Faculty of the Ruhr-University Bochum. All subjects gave full informed consent in writing.

Social Interaction Empathy Task

The paradigm used in this study was designed to address the question how participants distinguish between physical and psychological pain in social interactions and how the ERPs differ during the processing of the different pain qualities. The paradigm used in this study consists of images depicting situations in which a woman and a man interacted that were presented to the subjects. The pictures showed either physically or psychologically painful situations or neutral situations (i.e., no pain). For each condition there was a set of six different photos. Prior to the experiment the painfulness depicted in the images was rated by 15 healthy volunteers (pilot rating procedure is described in Flasbeck, Enzi, & Brüne, 2017). One neutral picture was subsequently excluded from the study due to its ambiguity. All pictures were taken in the same room with the same persons with the aim to keep the complexity of the pictures constant across conditions. Physically painful photos showed a scene in which a man accidentally hit a woman’s finger with a hammer, another showed the man kicking the woman’s leg instead of a ball, and another

Figure 1. Description of a scenario of the “Social Interaction Empathy Task.” Every trial started with a fixation cross, followed by a picture showing either a psychologically or a physically painful or a neutral social interaction. After another fixation cross phase the pain rating scale appeared whereby the participants should type their pain rating on a range from 1 (= “not painful at all”) until 9 (= “very painful”) from the first-person perspective or in the other part from the third-person perspective.

photo depicted the man pinching the hand of a woman in a door. Further scenes showed a man cutting a woman’s hand with a bread knife and with a scissor and a man scalding the woman with coffee. All images were prepared in ways strongly suggesting that the pain was caused by accident, not intentionally. Psychologically painful pictures showed the woman being abandoned by her partner and being stood up. Other pictures showed the man laughing at the woman, shouting at her, and sending her away, respectively. Another image showed the man disliking/ refusing the woman’s present. Neutral situations showed the two persons taking a meal, inspecting a shirt, and talking. Other pictures showed the man writing while the woman is having a drink, and the man making a phone call while the woman is reading a book. An example for each condition (physical and psychological pain and neutral) is given in Figure 1. The random presentation of the selected photos was carried out using Presentation® software (Neurobehavioral Systems, Inc. Version 14.9, Albany, CA). After each picture, participants had to rate the pain intensity on a scale from 1 (= “not painful at all”) to 9 (= “very painful”). In detail, every trial started with a fixation cross for 500–1,000 ms, followed by a photo showing one picture out of the three conditions for 3,000 ms, after which another fixation cross

appeared for 800–1,600 ms. Finally, the pain rating scale was shown for 3,000 ms whereby participants had to push a button indicating the subjective pain rating on the abovementioned scale (Figure 1). If they did not respond within 3,000 ms the experiments continued and the next trial started. Responses were only included in the analysis if they were given spontaneously or during the 3,000 ms period. Late responses or missed trials were not counted. Reaction time was only included in the analysis, if the judgment occurred within the 3,000 ms period. In total, there were 48 trials for each condition (8 repetitions of 6 different physical painful pictures, 8 repetitions of6 different psychological painful, 10 (two pictures 9) repetitions of 5 different neutral pictures). The duration of the experiment was approximately 19 min in total. The experiment consisted of two parts composed of the above-mentioned trials, which differ in the perspective the participants were asked to adopt. In the first part the participants had to rate the pain intensity according to their own feelings when asked to imagine themselves being in the presented situation. That is, they had to rate from the firstperson or self-perspective. In the second part the participants were asked to rate the pain intensity the woman shown in the same pictures feels, that is, from a thirdperson or other-perspective. In both parts the woman was

the person experiencing the somatic or psychological pain and the participants were asked to put themselves in her shoes. The order of the two conditions was randomized and separated by a short break. Participants were doing the task while EEG was recorded. For the analysis of pain empathy, we included the pain ratings, the reaction time (RT) and the EEG data.

EEG Recording and Analysis

The EEG was recorded from 32 scalp electrodes mounted on an elastic cap in accordance with the 10–20 system by the BrainVision Recorder software (Version 1.20.001; Brain Products, Munich, Germany) and was referenced using the electrodes on the mastoids. Eye blinks and movements were controlled with an electrode located 2 cm diagonally lateral below the left eye. During recording the impedance was kept at 5 kΩ and the data acquisition was conducted with a sampling rate of 250 Hz. ERP analysis was carried out using BrainVision Analyzer 2.0 (Version 2.01.3931; Brain Products). For all conditions high and low band-pass filter were applied (0.1 and 100 Hz), and eye and muscle movements removed using Independent Component Analysis (ICA), implementing 512 ICA steps. Two hundred milliseconds before stimulus onset was used as a baseline for the calculation of ERPs which were conducted for the different conditions separately. The extracted ERPs lasted for 1,000 ms and were computed separately for Fz, F3, F4, Cz, C3, C4, Pz, P3, and P4 electrodes. Artifact rejection above 100 μV and below
100 μV was performed and ERPs were averaged over trials for each condition, perspective, and participant. Due to visual inspection of grand-averaged ERPs we decided to focus on the time frame between 330 and 450 ms after stimulus onset and the time frame of 500–700 ms reflecting a late positive potential (LPP). Mean voltage amplitudes were extracted and processed with statistical software.

Examination of Self-Reported Empathy

The German version of the Interpersonal Reactivity Index (IRI; Davis, 1983), called “Saarbrücker PersönlichkeitsFragebogen” (Paulus, 2006), was used for assessment of self-reported empathic abilities. The Questionnaire consists of two cognitive subscales, namely “perspective taking” (PT) and “Fantasy” (FS), and two affective subscales: “empathic concern” (EC) and “personal distress” (PD).

Statistical Analysis

Statistical analysis was conducted using SPSS Statistics version 24 (IBM Corp., Armonk, NY). Prior to statistical

Figure 2. Pain rating results of the social interaction empathy task. Participants discriminated between painful conditions and the neutral situation and between physical and psychological pain, whereas physically painful pictures were rated as the most painful situations; ***p < .001.

calculations EEG data outliers were removed, outliers defined as the deviation of more than three standard deviations. For analysis of pain rating and reaction time 3  2 repeated-measures analyses of variance (ANOVAs) were carried out for within-subject factors “condition” (physically painful, psychologically painful, neutral) and “perspective” (first-person perspective, third-person perspective). For analysis of EEG data 3  3  2  2  3 repeatedmeasures ANOVA was conducted with the within-subject factors “lateral position” (left lateral F3, C3, P3; medial Fz, Cz, Pz; right lateral F4, C4, P4), anterior-posterior level (frontal F3, Fz, F4; central C3, Cz, C4; parietal P3, Pz, P4), time (early 330–450 ms after onset; late 500–700 ms after onset), perspective (first-person perspective, third-person perspective), and condition (physically painful, psychologically painful, neutral). For investigation of frontal lateralization effects, repeated-measures ANOVAs were used with the factors “condition” (physically painful, psychologically painful, neutral), “perspective” (first-person perspective, thirdperson perspective), and lateralization (left hemisphere F3, right hemisphere F4). The ANOVA results reported were Greenhouse-Geisser corrected. Dependent two-tailed t-tests were used for post hoc comparisons for significant effects and interactions. Correlations between the ERP results and IRI scores were calculated using Pearson’s correlation coefficient. To investigate whether the ERPs reflect pain quantities of the different conditions or different pain processing we calculated correlations between pain rating (physically painful, psychologically painful, and neutral) and ERPs (ERPs of physically painful, psychologically painful, and neutral pictures). To avoid errors due to multiple comparisons correlations were Bonferroni-Holm corrected for each electrode. For all other tests a significance level of p < .05 was chosen.

Figure 3. Grand-averaged ERPs of physically painful, psychologically painful, and neutral pictures over the frontal F3, F4, and Fz electrodes, the central C3, C4, and Cz electrodes, and the parietal P3, P4, and Pz electrodes. ERPs were recorded during the first-person perspective part. The voltage topographies (right) illustrate the amplitude distribution for 360 ms and 600 ms after pictures onset.

Results

Social Interaction Empathy Task: Pain Ratings

Repeated-measures ANOVA with the factors “condition” (physically painful, psychologically painful, neutral), and “perspective” (FPP, TPP) revealed the main effect of condition, F (1.88, 86.44) = 279.69, p < .001, indicating different ratings of pain intensity between the conditions. As there was no effect of perspective further analysis was computed with perspectives pooled for each condition.

Post hoc comparisons showed that neutral pictures (M = 1.30, SD = 0.70) were rated as less painful than physically (M = 6.73, SD = 1.41) and psychologically (M = 4.48, SD = 1.61) painful pictures (neutral vs. physically painful: t 46 =
23.64, p < .001; neutral vs. psychologically painful: t 46 =
15.58, p < .001). In addition, physically painful

situations were judged as more painful compared to psychologically painful pictures (t 46 = 8.80, p < .001; Figure 2).

Social Interaction Empathy Task: Reaction Time

Repeated-measures ANOVA revealed again a main effect of condition, F (1.75, 80.46) = 8.09, p = .001, but no effect of perspective. Further comparisons of condition with the perspectives pooled indicated that participants responded more rapidly to neutral pictures (RT neutral pictures M = 0.67, SD = 0.14 s) compared to both painful conditions (RT physically painful pictures M = 0.72, SD = 0.15 s, RT psychologically painful pictures M = 0.74, SD = 0.17 s; RT neutral vs. RT physical pain: t 46 =
2.49, p = .017; RT neutral vs. RT psychological pain: t 46 =
3.57, p = .001).

Figure 4. Grand-averaged ERPs and topographic maps recorded during the third-person perspective part for physically painful, psychologically painful, and neutral pictures over frontal F3, F4, and Fz electrodes, central C3, C4, and Cz electrodes, and parietal P3, P4, and Pz electrodes.

Electrophysiological Data

Figures 3 and 4 show the grand-averaged ERPs to the pictures of the three conditions at the lateral and medial central, frontal, and parietal electrodes, respectively. All pictures evoked a negative component between 90 and 150 ms after picture onset (N120), followed by a peak at 170 ms (between 150 and 200 ms). Negative components followed, peaking at 270 ms (N270) and at 360 ms after stimulus onset. These ERP components were most prominent over the frontal and central electrodes. Furthermore, a late positive potential (LPP) between approximately 500–700 ms could be detected over all electrodes, reaching the maximum over the parietal electrodes. For further analysis, we focused on the early anterior component at 330–450 ms after stimulus onset and on the LPP. Repeated-measures ANOVA revealed main effects of the anterior posterior level, F (1.14, 46.82) = 75.58, p < .001, the time, F (1, 41) = 15.35, p < .001, and the condition, F (1.99, 81.65) = 75.66, p < .001. No main effects were found

for the lateral position and the perspective. Post hoc comparisons regarding the anterior posterior level effect showed that frontal electrodes recorded more negative potentials when compared to central and parietal electrodes (frontal vs. central electrodes: t 42 =
4.06, p < .001; frontal vs. parietal electrodes: t 41 =
8.61, p < .001). Central electrodes recorded also more negative potentials than parietal electrodes which recorded positive potentials (central vs. parietal electrodes: t 42 =
12.23, p < .001; see Figure 3). The main effect of time indicates more positive potentials at LPP compared to the earlier phase independent of the electrodes, which is also visible in Figures 3 and 4. Further analysis of the main effect condition showed that painful conditions induced a positive shift compared to the neutral condition. More precisely, physically painful pictures lead to significantly more positive potentials compared to neutral pictures (physical pain vs. neutral: t 42 =
12.18, p < .001) and psychologically painful pictures (physical pain vs. psychological pain: t 41 = 5.66, p < .001). Moreover, psychologically painful pictures evoked also higher

potentials than neutral pictures (psychological pain vs. neutral: t 42 <
7.01, p = .001). In addition, we found a Lateral Position  Anterior Posterior Level interaction, F (2.61, 106.93) = 4.38, p = .008, an Anterior Posterior Level  Time interaction, F (1.15, 46.93) = 7.82, p = .006, a Lateral Position  Condition interaction, F (3.65, 149.83) = 8.22, p < .001, and an Anterior Posterior Level  Condition interaction, F (2.46, 100.90) = 8.9, p < .001. We also found three-way interactions but decided to spare them due to the complexity of the interpretation. The Anterior Posterior Level  Time interaction finding demonstrated that the earlier component reached the peak over the frontal electrodes (frontal electrodes vs. central electrodes: t 43 =
3.09, p = .004; frontal electrodes vs. parietal electrodes: t 42 =
8.14, p < .001) and LPP reached the maximum over the parietal electrodes (parietal electrodes vs. frontal electrodes: t 43 =
8.73, p < .001; parietal electrodes vs. central: t 42 =
11.05, p < .001; central electrodes differed also significantly from the remaining electrodes: central vs. parietal electrode at early phase: t 44 =
12.29, p < .001; central vs. frontal electrode at LPP: t 43 =
4.72, p < .001). In addition, the earlier components were more negative over frontal and central electrodes when compared to the late component (frontal early vs. LPP: t 42 =
3.06, p = .004; central early vs. LPP: t 44 =
5.91, p < .001: parietal ns). Post hoc comparisons of the Lateral Position  Condition interaction revealed a difference for neutral pictures when comparing left and medial electrodes (t 43 = 2.73, p = .009). Besides, neutral pictures evoked more negative potentials compared to physically painful and psychologically painful pictures over medial and right electrodes (medial electrodes: physical pain vs. neutral: t 45 = 2.67, p < .001; psychological pain vs. neutral: t 44 = 1.55, p < .001; right electrodes: physical pain vs. neutral: t 45 = 2.22, p < .001; psychological pain vs. neutral: t 44 = 1.79, p < .001). Over right and medial electrodes, the potentials evoked by psychologically painful pictures also differed from activity when seeing physical pain (central: physical pain vs. psychological pain: t 45 = 5.60, p < .001; right: physical pain vs. psychological pain: t 45 = 2.47, p = .017). When looking at the left electrode, only a difference between the pain types and physical pain and neutral pictures emerged (physical pain vs. psychological pain: t 42 = 5.10, p < .001; physical pain vs. neutral: t 42 = 6.51, p < .001). Because of the above-mentioned findings and the topographic map (Figures 3 and 4) we suggested to find a frontal lateralization and conducted repeated-measures ANOVA with the factors “condition” (physically painful, psychologically painful, neutral), “perspective” (first-person perspective, third-person perspective), and lateralization (left hemisphere F3, right hemisphere F4) for the time frame of 330–450 ms after picture onset. Again, we found a reliable main effect of condition, F (1.95, 83.87) = 11.43, p < .001, and a Lateralization  Condition interaction, F (1.89, 81.33) = 4.23, p = .017. The interaction displays a difference between neutral and painful (painful conditions pooled) ERPs only at the right hemisphere (F4 electrode), but not over the left F3 (F4: pain vs. neutral: t 45 =
4.78, p < .001; F3: pain vs. neutral: ns). A closer look at the painful conditions indicated that the ERPs of physically and psychologically painful pictures showed a positive shift compared to neutral pictures over F4 (physical pain vs. neutral: t 46 =
5.11, p < .001; psychological pain vs. neutral: t 46 =
3.26, p = .002). In addition, the ERPs of physical pain differed from psychologically pain (physical pain vs. psychological pain: t 46 =
2.09, p = .042). Over F3, we found only difference between neutral and physically painful pictures (t 45 =
2.59, p = .013). Analysis of the Anterior Posterior Level  Condition interaction revealed that all conditions differ from all other conditions at central and parietal levels, but not at the frontal level (central: physical vs. psychological pain: t 44 = 7.40, p < .001; physical pain vs. neutral: t 44 = 13.55, p < .001; psychological pain vs. neutral: t 45 = 6.30, p < .001, parietal: physical vs. psychological pain: t 44 = 7.62, p < .001; physical pain vs. neutral: t 45 = 14.74, p < .001; psychological pain vs. neutral: t 44 = 7.82, p < .001). Over the frontal electrodes, ERPs of physical and psychological pain did not differ (physical vs. psychological pain: ns; physical pain vs. neutral: t 43 = 4.62, p < .001; psychological pain vs. neutral: t 43 = 3.86, p < .001). One reason might be that the differentiation of mental and physical pain takes place at the right hemisphere which was covered by the other electrodes in this comparison.

Correlation Analysis

We detected significant correlations between the ERP results and self-rated empathic abilities assessed by IRI questionnaires. ERPs over the left central and medial parietal electrodes of painful conditions correlated significantly with the perspective taking scale of the IRI (C3 psychological pain –PT: r = .37, p = .011; Pz physical pain: r = .32, p = .039), suggesting a modulation effect of perspective taking abilities on processing of painful social interactions. If the differences in ERPs reflect different pain intensities instead of processing of the different social interactions, we expected to find correlations between pain rating and ERPs. We calculated correlations between pain ratings of physically painful, psychologically painful, and neutral interactions (perspectives pooled) and ERPs of physically painful, psychologically painful, and neutral pictures and could not find any significant association.

Discussion

The aim of the present study was to investigate and characterize the neural correlates of empathy for physical and psychological pain. Previous studies of empathy for pain investigated either empathy for physical pain or social pain, which was mainly assessed via social exclusion, respectively. Therefore, we developed the “Social Interaction Empathy Task” which enabled us to investigate ERPs to both pain dimensions and neutral interactions at the same time. Due to the different ratings of pain intensity, we anticipated differences in ERP between physical and psychological pain and neutral interactions. Because participants judged physically painful pictures as more painful than psychologically painful and neutral images we assumed that ERPs to physical pain would differ most strongly from neutral pictures.

In the present study, the higher pain ratings were accompanied by longer reaction times needed for the evaluation of painful pictures, suggesting that painful interactions captured the participants’ attention more than neutral scenarios. Consistent with our hypotheses concerning ERP responses, we found a main effect of condition indicating that physical pain evoked a positive shift relative to neutral and psychological pain. Moreover, psychological pain also differed significantly from neutral conditions. In accordance with other studies, we found an early component over frontal-central areas and a late component reaching the maximum over the parietal electrodes (Fan & Han, 2008). In our study we did not find any effect of perspective on pain rating, reaction time, or ERP responses. The study of Li and Han, using the painful and neutral pictures of hands that should be rated from the first- and third-person perspective, reported interactions of pain with perspective in reaction time, accuracy, and ERP at 370–420 ms over the central-parietal area, whereas there was no main effect of perspective (Li & Han, 2010). Another study could not find significant differences between the first- and third-person perspective in a behavior task testing empathy for pain (Abu-Akel et al., 2015). In contrast, a functional magnetic resonance imaging (fMRI) study could demonstrate that pain rating from both the FPP and TPP activated the neural network of pain processing. In addition, the FPP yielded a higher involvement of the secondary somatosensory cortex, ACC, and insula, whereas the right temporo-parietal junction was more activated during the TPP (Jackson et al., 2006). Taken together, these results suggest that perspective effects critically depend on the methodological approach and task sensitivity.

In our study, the analysis of hemispheric differences revealed an asymmetrical frontal involvement in pain empathy. We found differences in ERPs between neutral

and painful conditions only at the right hemisphere, but not at the left frontal hemisphere. The difference in ERP responses to the observation of physical and psychological painful conditions showed the same pattern as observed for the other electrodes. These findings are inconsistent with the results of Fan and Han (2008) reporting a larger effect of pain empathy over the left hemisphere. Here, it is important to note that the “classical” empathy for pain tasks is difficult to compare to the social interaction empathy task because the social complexity of the task might lead to different processing of pain. Thus, the higher involvement of the right hemisphere could be due to the social component of the task which in turn leads to higher activity of the right dorsolateral prefrontal cortex (DLPFC). There are different theories existing describing the role of the DLPFC in overriding self-interest motives or the involvement of the DLPFC in regulating emotional responses. Supporting the first theory, Knoch et al. demonstrated that repetitive transcranial magnetic stimulation (rTMS) of the right but not left DLPFC reduced the rejections of unfair co-players in the Ultimatum Game, indicating that subjects’ impact of fairness and self-interest goals (here the economic profit) were shifted (Knoch, Pascual-Leone, Meyer, Treyer, & Fehr, 2006). It was also shown with fMRI that unfair offers evoked activity in the DLPFC and the insula (Sanfey, Rilling, Aronson, Nystrom, & Cohen, 2003). Another study reported that rTMS over the right DLPFC increased costly punishment in the Dictator Game, whereas empathy moderated this effect (Brüne et al., 2012). Regarding the second theory, it was reported that the DLPFC and the ACC were involved in down- and upregulation of negative emotions (Ochsner et al., 2004). In addition, Harmon-Jones concluded that the asymmetrical frontal cortical activity is not solely related due to experience and expression of emotions with a higher involvement of the left hemisphere in positive and the right hemisphere in negative emotions, but also caused by motivation (Harmon-Jones, 2003). Aside from these theories, De Greck reported stronger hemodynamic responses in Chinese participants in the left DLPFC during empathy with anger compared to German participants (de Greck et al., 2012). Consequently, further studies are necessary to investigate the functional role of the frontal cortical areas.

Our correlation analysis showed that perspective taking abilities were related to the ERPs of painful pictures. Importantly, we did not find correlations between pain rating and ERPs, suggesting that ERPs do not reflect the pain intensity but pain quality, that is, the differential processing of physical and psychological pain.

To conclude, we found an early and a late empathic response with a higher ERP response to physical than to psychological pain. Moreover, we found painful situations

being discernible at right frontal cortical areas, and correlations of lateral central and parietal ERPs emerged with empathic abilities. However, our findings imply a limitation insofar as our results are not generalizable for both sexes because we recruited exclusively female participants. Future research should also include males and focus on the neuronal basis of differences between psychological and physical pain and disentangle the influence of the perspective that participants adopt regarding empathy and pain processing

Ethical Standards The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Conflict of Interest None.

Acknowledgment We thank Elke Köhler for supporting the EEG recordings and good cooperation.

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Received March 18, 2016 Accepted January 7, 2017 Published online November 21, 2017

Martin Brüne LWL University Hospital Department of Psychiatry, Psychotherapy and Preventive Medicine Division of Cognitive Neuropsychiatry and Psychiatric Preventive Medicine Ruhr-University Bochum Alexandrinenstr. 1 44791 Bochum Germany martin.bruene@rub.de