Sexual Violence is Horrible, But First Look at Causes Outside the Brain

"At the brain level, empathy for social exclusion of personalized women recruited areas coding the affective component of pain (i.e., anterior insula and cingulate cortex), the somatosensory components of pain (i.e., posterior insula and secondary somatosensory cortex) together with the mentalizing network (i.e., middle frontal cortex) to a greater extent than for the sexually objectified women. This diminished empathy is discussed in light of the gender-based violence that is afflicting the modern society" (Cogoni et al., 2018).

A new brain imaging paper on Cyberball, social exclusion, objectification, and empathy went WAY out on a limb and linked the results to sexual violence, despite the lack of differences between male and female participants. It's quite a leap from watching a video of women in differing attire, comparing levels of empathy when “objectified” vs. “personalized” women are excluded from the game, and actually perpetrating violence against women in the real world.

modified from Fig. 1 (Cogoni et al., 2018). (A) objectified women in little black dresses; (B) personalized women in pants and t-shirt. Note: the black bar didn't appear in the actual videos.


I'm not a social psychologist (so I've always been a bit skeptical), but Cyberball is a virtual game designed as a model for social rejection and ostracism (Williams et al., 2000). The participant is led to believe they are playing an online ball-tossing game with other people, who then proceed to exclude them from the game. It's been widely used to study exclusion, social pain, and empathy for another's person's pain.

The present version went beyond this simple animation and used 15–21 second videos (see still image in Fig. 1) with the “self” condition represented by a pair of hands. More important, though, was a comparison of the two “other person” conditions.

“Each video displayed either a ‘social inclusion’ or a ‘social exclusion’ trial.  ...  At the end of each trial, the participant was asked to rate the valence of the emotion felt by themselves (self condition), or by the other person (other conditions), during the game on a  Likert-type rating scale going from −10 = ‘very negative’ over 0 to +10 = ‘very positive’.”

The participants were 19 women and 17 men, who showed no differences in their emotion ratings. Curiously, the negative emotion ratings on exclusion trials did not differ between the Self, Objectified, and Personalized conditions. So there appears to be no empathy gap for objectified women who were excluded from Cyberball. The difference was on the inclusion trials, when the subjects didn't feel as positively towards women in little black dresses when they were included in the game (in comparison to when women in pants were included, or when they themselves were included).

Fig. 3 (Cogoni et al., 2018).


At this point, I won't delve deeper into the neuroimaging results, because the differences shown at the top of the post were for the exclusion condition, when behavioral ratings were the all same. And any potential sex differences in the imaging data weren't reported.¹ Or else I'm confused. At any rate, perhaps an fMRI study of perpetrators would be more informative in the future. But ultimately, culture and social conditions and power differentials (all outside the brain) are the major determinants of violence against women.

from Truisms, by Jenny Holzer

When discussing the objectification of women in the present era, it's hard to escape the Harvey Weinstein scandal. One of the main purposes of Miramax² was to turn young women inro sex objects. Powerful essays by Lupita Nyong’o, Salma Hayek, and Brit Marling (to name just a few) describe the indignities, sexual harassment, and outright assault they endured from this highly influential career-maker or breaker. Further, they describe the identical circumstances, the lingering doubt, the self-blame, and the commodification of themselves. Here's Marling:

Hollywood was, of course, a rude awakening to that kind of idealism. I quickly realized that a large portion of the town functioned inside a soft and sometimes literal trafficking or prostitution of young women (a commodity with an endless supply and an endless demand). The storytellers—the people with economic and artistic power—are, by and large, straight, white men. As of 2017, women make up only 23 percent of the Directors Guild of America and only 11 percent are people of color.
. . .

Once, when I was standing in line for some open-call audition for a horror film, I remember catching my reflection in the mirror and realizing that I was dressed like a sex object. Every woman in line to audition for “Nurse” was, it seemed. We had all internalized on some level the idea that if we were going to be cast we’d better sell what was desired—not our artistry, not our imaginations—but our bodies.

Dacher Keltner wrote about empathy deficits of the rich and famous in Sex, Power, and the Systems That Enable Men Like Harvey Weinstein. But he emphasized the abuse of power: “The challenge, then, is to change social systems in which the abuses of power arise and continue unchecked.” 


Footnotes

¹ Although they listed a variety of reasons, the authors didn't do themselves any favors with this explanation for the lack of sex differences:

“Although this issue is still debated, in this study we refer to gender violence as a phenomenon that mainly entails not only active participation, but also passive acceptance or compliance and therefore involving both men and women’ behaviors.”

² And Hollywood in general...


References

Cogoni C, Carnaghi A, Silani G. (2018). Reduced empathic responses for sexually objectified women: an fMRI investigation. Cortex  99: 258–272.  {PDF}

Williams KD, Cheung CK, Choi W. (2000). Cyberostracism: effects of being ignored over the Internet. J Pers Soc Psychol. 79:748-62.


Further Reading: The Cyberball Collection (by The Neurocritic)

Suffering from the pain of social rejection? Feel better with TYLENOL®

Vicodin for Social Exclusion

Existential Dread of Absurd Social Psychology Studies

The Mental Health of Lonely Marijuana Users

Acetaminophen Probably Isn't an "Empathy Killer"

Advil Increases Social Pain (if you're male)

Oh, and... Spanner or Sex Object?

What Can Brain Imaging Tell Us About Violent Extremism?

Before answering that question, I'll tell you about an incredibly impressive ethnographic study and field survey. For a one year period, the investigators (Pretus, Hamid et al., 2018) conducted field work within the community of young Moroccan men in Barcelona, Spain. As the authors explain, the Moroccan diaspora is an immigrant community susceptible to jihadist forms of radicalization:

Spain hosts Europe’s second largest Moroccan diaspora community (after France) and its least integrated, whereas Catalonia hosts the largest and least integrated Moroccan community in Spain. Barcelona ... was most recently the site of a mass killing ... by a group of young Moroccan men pledging support for the Islamic State. According to a recent Europol’s latest annual report on terrorism trends, Spain had the second highest number of jihadist terrorism-related arrests in Europe (second only to France) in 2016...

After months of observation in selected neighborhoods, the researchers approached prospective participants about completing a survey, with the assurance of absolute anonymity. No names were exchanged, and informed consent procedures were performed orally, to prevent any written record of participation. The very large sample included 535 respondents (average age 23.47 years, range 18–42), who were all Sunni Muslim Moroccan men.

The goal of the study was to look at sacred values in these participants, and whether these values might affect their willingness to engage in violent extremism. “Sacred values are immune or resistant to material tradeoffs and are associated with deontic (duty-bound) reasoning...” (Pretus, Hamid et al., 2018). The term sacred values doesn't necessarily refer to religious beliefs. One of the most common is the basic human value, “it is wrong to kill another human being.” But theoretically speaking, we could include statements such as, “it is wrong to kill endangered species for sport (or for any other reason).”

In this study, Sacred Values included:

• Palestinian right of return
• Western military forces being expelled from all Muslim lands
• Strict sharia as the rule of law in all Muslim countries
• Armed jihad being waged against enemies of Muslims
• Forbidding of caricatures of Prophet Mohammed
• Veiling of women in public

What were the Nonsacred Values? We don't know. I couldn't find examples anywhere in the paper. It's crucial that we know what these were, to help understand the “sacralization” of nonsacred values, which was observed in an fMRI experiment (described later). So I turned to the Supplemental Material of Berns et al. (2012), inferring that the statements below are good examples of nonsacred values in a population of adults in Atlanta.

• You are a dog person.
• You are a cat person.

• You are a Pepsi drinker.
• You are a Coke drinker.

• You believe that Target is superior to Walmart.
• You believe that Walmart is superior to Target.

But what if the nonsacred values in the present study of violent extremism were a little more contentious and meaningful?

• You are a fan of FC Barcelona.
• You are a fan of AC Milan.

Anyway, to choose participants for the fMRI experiment, the investigators first divided the entire group into those who were more (n=267) or less (n=268) vulnerable to recruitment into violent extremism (see Appendix for details). An important comparison would have been to directly contrast brain activity in these two groups, but that wasn't done here. Out of the 267 men more vulnerable to violent extremism, 38 agreed to participate in the fMRI study. These 38 were more likely to Endorse Militant Jihadism (score 4.24 out of 7) than the general fMRI pool (3.35) and the non-fMRI pool (2.43).¹ 

A battery of six sacred and six nonsacred values was constructed individually for each person and presented in the scanner, along with a number of grammatical variants, for a list of 50 different items per condition. The 38 participants were randomly assigned to one of two manipulations in a between-subjects design: exclusion (n=19) and inclusion (n=19) in the ever-popular ball-tossing video game of Cyberball. [PDF]²

Unfortunately, this reduced the study's statistical power. Nonetheless, a major goal of the experiment was to examine how social exclusion affects the processing of sacred values. I don't know if Cyberball studies are ever conducted in a within-subjects design (perhaps with an intervening task), or if exposure to one of the two conditions is too “contaminating”. At any rate, in real life, discrimination against Muslim immigrants is isolating and causes exclusion from social and economic benefits. Feelings of marginalization can result in greater radicalization and support for (and participation in) extremist groups. At this point in time, I don't think neuroimaging can add to the extensive knowledge gained from years of field work.

Nevertheless, the investigators wanted to extend the findings of Berns et al. (2012) to a very different population. The earlier study wanted to determine whether sacred values are processed in a deontological way (based on strict rules of right and wrong) or in a utilitarian fashion (based on cost/benefit analysis of outcome). As interpreted by those authors, processing sacred values was associated with increased activation of left temporoparietal junction (semantic storage) and left ventrolateral prefrontal cortex (semantic retrieval). Berns et al. suggested that “sacred values affect behaviour through the retrieval and processing of deontic rules and not through a utilitarian evaluation of costs and benefits.” Based on those results, the obvious prediction in the present study is that sacred values should activate left temporoparietal junction (L TPJ) and left ventrolateral prefrontal cortex (L VLPFC).

Fig. 3A (Pretus, Hamid et al., 2018).


Fig. 3A shows that only the latter half of that prediction was observed, and there was no explanation for the lack of activation in L TPJ. Instead, there was a finding in R TPJ in the excluded group which I won't discuss further.

Of note, the excluded participants rated themselves as being more likely to fight and die for nonsacred values, compared to the included participants. This was termed “sacralization” and now you can see why it's so important to know the nonsacred values. Are we talking about fighting and dying for Pepsi vs. Coke? For FC Barcelona vs. AC Milan? Not to be glib, but this would help us understand why social exclusion (in an artificial experimental setting) would radicalize these participants (in an artificial experimental setting).

Fig. 3B (Pretus, Hamid et al., 2018). Nonsacred values activate Left Inferior Frontal Gyrus (IFG, aka VLPFC) in the excluded group, but not in the included group. This was interpreted as a neural correlate of “sacralization”.


Another interpretation of Fig. 3B is that the exclusion manipulation was distracting, making it more difficult for these participants to process stimuli expressing nonsacred values (due to increased encoding demands, syntactic processing, etc.). Exclusion increased emotional intensity ratings, and decreased feelings of belongingness and being in control. This distraction could have carried over to the task of rating one's willingness to fight and die in defense of values.

Even if we say the brain imaging results weren't especially informative, the extensive ethnographic study and field surveys were a highly valuable source of data on a marginalized group of young Muslim men at risk of recruitment by violent extremist groups. It's a vicious cycle: terrorist attacks result in greater discrimination and persecution of innocent Muslim men, which has the unintended effect of further radicalization in some of the most vulnerable individuals. To conclude, I acknowledge that my comments may be out of turn because I have no authority or expertise, and because I'm from a country with an appalling record of discriminating against Muslims.


Footnotes

¹ I was a bit confused by some of these scores, because they changed from one paragraph to the next, and differed from what was in Table 1. Perhaps one was a composite score, and the other from an individual questionnaire.

² I've written extensively about whether Cyberball is a valid proxy for social exclusion, but I won't get into that here.


References

Berns GS, Bell E, Capra CM, Prietula MJ, Moore S, Anderson B, Ginges J, Atran S. (2012). The price of your soul: neural evidence for the non-utilitarian representation of sacred values. Philos Trans R Soc Lond B Biol Sci. 367(1589):754-62.

Pretus C, Hamid N, Sheikh H, Ginges J, Tobeña A, Davis R, Vilarroya O, Atran S. (2018). Neural and Behavioral Correlates of Sacred Values and Vulnerability to Violent Extremism. Front Psychol. 9:2462.


Appendix

Modified from Table 1 (Pretus, Hamid et al., 2018).

[The] measures included (1) a modified inventory on general radicalization (support for violence as a political tactic) based on a prior longitudinal study on violent extremist attitudes among Swiss adolescents (Nivette et al., 2017); (2) a scale on personal grievances and previously used on imprisoned Islamist militants in the Philippines, and Tamil Tigers in Sri Lanka (Webber et al., 2018); (3) a scale on collective narcissism which has been shown to shape in-group authoritarian identity and support for military aggression against outgroups (de Zavala et al., 2009); (4) a self-report delinquency inventory adapted from Elliott et al. (1985), based on the disproportionate number of Muslim European delinquents who join jihadist terrorist groups (Basra and Neumann, 2016); and (5) a series of items assessing endorsement of militant jihadism (“The fighting of the Taliban, Al Qaida, ISIS is justified,” “The means of jihadist groups are justified,” “Attacks against Western nations by jihadist groups are justified,” “Attacks against Muslim nations by jihadist groups are justified,” “Attacks against civilians by jihadist groups are justified,” “Spreading Islam using force is every part of the world is an act of justifiable jihad,” and “A Caliphate must be resurrected even by force”) that we combined into a reliable composite score, “Endorsement of Militant Jihadism”...

Vicodin for Social Exclusion

Cyberball (with apologies to Kipling D. Williams).

Cyberball (not the Atari version) is a virtual game designed by social psychologists to be a model for social rejection and ostracism (Williams et al., 2000). The study participant is led to believe they are playing an online ball-tossing game with other people, who then proceed to exclude them from the game. The resultant negative feelings are meant to be a proxy for ostracism based on fundamental attributes such as race, disability, physical appearance, homelessness, etc. This simple game has lead to a burgeoning cottage industry on social pain and its close resemblance to physical pain.


Social Pain and Physical Pain Are Not Interchangeable

That statement may sound obvious to you, but an increasing number of neuroimaging studies would have us believe otherwise. Whenever I read an article proclaiming that "the brain bases of social pain are similar to those of physical pain" (Eisenberger et al., 2003), I am reminded of how phenomenologically DIFFERENT they are. Waking up from general anesthesia and feeling undermedicated for surgery that took your body apart and put it back together again feels absolutely nothing like being rejected by your long-term partner. Your anterior insula and anterior cingulate cortex might be very busy in both cases, but they're also activated in many different situations (Yarkoni et al, 2011).

Indeed, of the 2238 total papers in the BrainMap neuroimaging database, 735 of them contain the search term 'anterior cingulate' (see also Shackman et al., 2011). Besides pain and emotion, the behavioral domains that activate this brain region include motor learning, language, speech, explicit memory, working memory, bladder control, thirst, sexuality, and perception in all five senses. Sure, the affective components of pain might show some overlap with physical pain (Kross et al., 2011), but distinct networks are likely responsible for the unique aspects of these different qualia.¹


The Aversive Brain

Hayes and Northoff (2012) described a core brain network involved in the processing of aversive stimuli (or states) that can be either painful or non-painful in nature. They relied on evidence from both the human and animal literatures. Aversion here refers to more than social and physical pain, and includes avoidance of stimuli that are unpleasant, frightening or disgusting. Meta-analysis of human neuroimaging data showed overlap in some of the structures involved in non-painful aversion and physical pain (shown in green below), which accounted for 35% of Aversion-related voxels and 24% of Pain-related voxels. These overlapping regions included mid-cingulate cortex, posterior cingulate cortex, anterior insula, right ventrolateral prefrontal cortex (PFC), dorsomedial PFC, thalamus, midbrain, secondary motor cortex, and areas related to memory (right hippocampus/parahippocampal gyrus) and even reward (dorsal striatum).²

It is important to note here that some of the social pain darlings (mid-cingulate cortex, anterior insula, right ventrolateral PFC) are also activated by unpleasant pictures, sounds, and smells.

- click on image for a larger view -

Fig. 2 (Hayes & Northoff, 2012). Overlap of pain- and aversion-related networks in humans. Results of meta-analyses for human pain- (blue) and aversion- (yellow) related studies (top row), overlapping activations (green; top row and isolated in bottom row), and a corresponding table of associated brain regions. All results are family-wise error rate whole-brain corrected at p < 0.05


Furthermore, although there was substantial overlap between Aversion and Pain, 65% and 76% of all activations (respectively) were not shared. Structures uniquely activated by Aversion included the amygdala, hypothalamus, more anterior regions of the anterior cingulate, and another reward-related area (ventral striatum). Brain regions uniquely activated by Pain included the cerebellum, rostral pons, somatosensory cortex, posterior insula, and yet another dopamine-rich, reward-related area (ventral tegmental area).³

Dave J Hayes, co-author of the study, wrote about this fruitful cross species network approach to The Aversive Brain in his blog.


But Depression Hurts, doesn't it?

It sure does according to Lilly, who would also like us to believe that their drug Cymbalta (duloxetine, an SNRI antidepressant) will cure your aches and pains along with your depression. But Duloxetine Does Not Relieve Painful Physical Symptoms in Depression, according to a meta-analysis of five available studies (Spielmans, 2008).

How much overlap is there between brain activity associated with physical pain and feelings of sadness? To answer this question, I performed a meta-analysis of my own that made use of the BrainMap database of published neuroimaging experiments. Using GingerALE software, I did two activation likelihood estimate (ALE) meta-analyses to look at brain regions activated by experimental manipulations to induce physical pain and sadness (see Laird et al., 2005 for methodological details of ALE). In brief, the procedure involves three steps to determine the likelihood of activation across experiments:

1. ALE and Testing Significance: Compute the ALE values for each voxel in the brain and performs a test to determine the null distribution of the ALE statistic at each voxel.
2. Thresholding: Take the P values from the previous step and computes the threshold for the ALE map using the Tom Nichol’s FDR algorithm.
3. Cluster Analysis: Perform cluster analysis on the thresholded map, based on the minimum volume that is specified in the previous step.

Using Sleuth to search the BrainMap database revealed 94 papers related to pain perception or pain monitoring/discrimination, which involved 1334 subjects, 345 experimental contrasts, and 3455 locations. ⁴ The search for sadness identified 58 papers involving 1159 subjects, 193 experimental contrasts, and 1204 locations. The pinkish-colored regions in the figure below show the overlap between sadness (in blue) and pain (in red) — which is not very extensive! The slices were selected to highlight overlap in anterior cingulate (Left), mid-insula and basal ganglia (Middle), and anterior insula (Right).

The main points here are that:

• Sadness is represented quite differently from physical pain.
• The shared physical pain-social pain network also includes aversive responses to unpleasant sensory stimuli. Which are not painful.

So any treatment designed to ease the unpleasantness of physical pain would not help the concomitant  feelings of sadness, at least not directly. But treatments for social pain could generalize to the non-painful aversion network: disgusting and disturbing things might not seem as bad, either.

Have there been any effective manipulations to ease social pain? One unlikely study claimed that acetaminophen reduced the pain of social rejection (Dewall et al., 2010).  I was quite skeptical of this study, as outlined in Suffering from the pain of social rejection? Feel better with TYLENOL®:

 In Experiment 1, 30 participants (24 women, 6 men) took one 500 mg acetaminophen pill immediately after waking up and another 500 mg an hour before going to sleep (1,000 mg per day for 3 weeks). The other 32 participants (24 women, 8 men) took the same dosing of placebo for 3 weeks. Each evening, subjects filled out the the Hurt Feelings Scale (the "today" version) to report how much social pain they had experienced that day. Despite the fact that the half life of acetaminophen is 4 hours, it took about 10 days for the drug group to report significantly lower hurt feelings than the placebo group. The difference on day 21 was greatest (p < .005). However, the difference in change-over-time slopes between the two groups was only marginally significant (p ≤ .10). The explanation of the time course for these effects was unclear...

 Or as Time writer Maia Szalavitz said in a comment on the post:

This study would have made sense if they used opioids, which are known to reduce the emotional aspect of physical pain. There's also a high concentration of opioid receptors in the cingulate. Of course, the result wouldn't have been novel or surprising: junkies wouldn't exist if opioids didn't kill emotional pain.

Indeed, if acetaminophen could numb emotional pain, this would have been discovered by addicts by now. The fact that the drug remains boringly OTC suggests that this effect is either so small it can only be detected in the lab or nonexistent as the blog suggests.

Buffer the Pain Away ⁵

This brings us to a new study (by one of the same authors) that administered transcranial direct current stimulation (tDCS) over right ventrolateral PFC and reported a reduction in negative feelings caused by exclusion in a game of Cyberball  (Riva et al., 2012). This article, like the acetaminophen one, was published Psychological Science.

Rather than launch into a full-scale summary of this study, I refer the interested reader to a post by Andrew Wilson — Psychological Science...meet me at camera 3, which is not about this paper but summarizes some of the general issues that can be seen in 2-3 page short reports in Psych Science.

As for the specific findings of Riva et al. (2012), beyond asking whether all five of the rating scales confirmed the result (rather than just the two reported), I wonder about the specificity of the response to social exclusion. In other words, would tDCS reduce reactions to aversive stimuli in general (as noted above)? What do you think, does right frontal tDCS improve functioning in other domains? What do we know about its mechanisms of action?

And finally, do you buy the premise that social exclusion hurts, literally?


Footnotes

¹ According to the Stanford Encyclopedia of Philosophy:

Philosophers often use the term ‘qualia’ ... to refer to the introspectively accessible, phenomenal aspects of our mental lives. ... Disagreement typically centers on which mental states have qualia, whether qualia are intrinsic qualities of their bearers, and how qualia relate to the physical world both inside and outside the head. The status of qualia is hotly debated in philosophy largely because it is central to a proper understanding of the nature of consciousness. Qualia are at the very heart of the mind-body problem. 

² Presumably, the vast majority of subjects were not masochists or gluttons for punishment.

³ Another complicating factor is that this so-called "Pain Matrix" might not be specific to pain at all, but may instead reflect responses to highly salient stimuli in different modalities (Iannetti & Mouraux, 2010).

⁴ Compare this to 6 yrs ago, when my analysis for physical pain yielded only 35 studies (see Hypnosis and Pain Control).

⁵ OR you could F**k the Pain Away...

...as Peaches would say.


References

Dewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM, Eisenberger NI. (2010). Acetaminophen reduces socialpain: behavioral and neural evidence. Psychol Sci. 21:931-7.

Eisenberger NI, Lieberman MD, Williams KD. (2003). Does rejection hurt? An FMRI study of social exclusion. Science 302:290-2.

Hayes, D., Northoff, G. (2012). Common brain activations for painful and non-painful aversive stimuli. BMC Neuroscience, 13 (1) DOI: 10.1186/1471-2202-13-60

Iannetti GD, Mouraux A. (2010). From the neuromatrix to the pain matrix (and back). Exp Brain Res. 205:1-12.

Kross E, Berman MG, Mischel W, Smith EE, Wager TD. (2011). Social rejection sharessomatosensory representations with physical pain. Proc Natl Acad Sci 108(15):6270-5.

Laird AR, Fox PM, Price CJ, Glahn DC, Uecker AM, Lancaster JL, Turkeltaub PE, Kochunov P, Fox PT. (2005). ALE meta-analysis: controlling the false discovery rate and performing statistical contrasts. Hum Brain Mapp. 25:155-164.

Riva, P., Romero Lauro, L., DeWall, C., Bushman, B. (2012). Buffer the Pain Away: Stimulating the Right Ventrolateral Prefrontal Cortex Reduces Pain Following Social Exclusion. Psychological Science DOI: 10.1177/0956797612450894

Shackman AJ, Salomons TV, Slagter HA, Fox AS, Winter JJ, Davidson RJ. (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Nat Rev Neurosci. 12:154-67.

Spielmans GI. (2008). Duloxetine does not relieve painful physical symptoms in depression: a meta-analysis.  Psychother Psychosom. 77:12-6.

Williams KD, Cheung CK, Choi W. (2000). Cyberostracism: effects of being ignored over the Internet. J Pers Soc Psychol. 79:748-62.

Yarkoni T, Poldrack RA, Nichols TE, Van Essen DC, Wager TD. (2011). Large-scale automated synthesis of human functional neuroimaging data. Nat Methods 8:665-70.

Advil Increases Social Pain (if you're male)

Headache, Guillaume DELEBARRE (Guigui-Lille)

A recent neuroessay in the New York Times asked, Can Tylenol Help Heal a Broken Heart?

What’s crazy about the pain of a broken heart is that your body perceives it as physical pain.

No it does not. Do you feel heartbroken every time you stub your toe?


Well... I guess the social pain = physical pain isomorphism is a one way street. Anyway, the author continued:

In research published in 2010, scientists found that acetaminophen can reduce physical and neural responses associated with the pain of social rejection, whether in romantic relationships, friendships or otherwise.

The pain reliever Tylenol (acetaminophen) lessens the pain of social rejection, according to the 2010 study in Psychological Science [except when it doesn't].¹ Acetaminophen also purportedly soothes the existential angst of watching a David Lynch film, blunts your emotions, and kills your empathy.²

So if you’re hurting from heartache, try popping some Tylenol.

Do not pop Tylenol after a breakup. It can cause serious liver damage if you take too much.


But What About Advil?

A 2014 study in the journal Personal Relationships was the first to break the stranglehold of acetaminophen (Vangelisti et al., 2014). The paper made few headlines (an exception was the Daily Mail), and it was not cited by the Tylenol researchers after its publication. Yet I saw no difference in quality, and even found more to like about it compared to the Tylenol papers (all of which appeared in higher impact journals). One of the Advil authors was Dr. James Pennebaker, chair of Psychology at the University of Texas. Dr. Pennebaker is well-known for his research on text analysis and what word choice can reveal about sex, age, social class, personality, mood, and affective state.

The focus of the study by Dr. Anita Vangelisti and colleagues was on potential sex differences in the effects of a physical pain reliever on social pain. They cited evidence suggesting that women are more sensitive to physical pain, and men might be more responsive to pain relievers like ibuprofen (Walker & Carmody, 1998).

Proposed explanations for sex differences in pain and analgesia include the bullet list below (Mogil & Bailey, 2010). These could potentially influence the effects of ibuprofen (and acetaminophen) on social pain.³

• Sociocultural – manly and stoic machismo
• Psychological – greater negative affect and catastrophizing in women
• Experiential – women may have more experience with clinical pain, which affects current pain perception
• Opioid receptors – and especially their interactions with gonadal hormones
• Other potential biological factors – a long list

Advil Worsened Social Pain in Men

Ibuprofen did indeed increase ratings of social pain in male participants, but decreased ratings in female participants Vangelisti et al. (2014). For more details, read on.

Read more »

Acetaminophen Probably Isn't an "Empathy Killer"

Left: Belgian physician Dr. Wim Distelmans, a cancer specialist, professor in palliative care and the president of the Belgian federal euthanasia commission. Right: Generic acetaminophen.


What (or who) is an “Empathy Killer“? An Angel of Death Kevorkian-type who helps terminally ill patients with ALS or cancer put an end their excruciating pain? This is a very selfless act that shows extreme empathy for the suffering of others.

Or is an “Empathy Killer” a medication that dulls your numerical ratings of empathic concern for fictional characters ever so slightly? If you guessed the latter, you are correct. Here's the actual title of a new paper in SCAN: “From Painkiller to Empathy Killer: Acetaminophen (Paracetamol) Reduces Empathy for Pain.”

Oh the headlines. Truly painful.

Paracetamol doesn't just kill pain - it makes us less CARING

America's Most Common Drug Ingredient Could Be Making You Less Empathetic


Why Would a Headache Medication Make You Less Empathetic?

A popular line of research in Social Cognitive and Affective Neuroscience examines the commonalities between physical and social/psychological pain. IF there is indeed an overlap,¹ one might ask some provocative questions about the underlying neural mechanisms. Do drugs that ease physical pain also soothe the pain of social rejection and existential angst?² Several recent papers have reported that acetaminophen does exactly that (Dewall et al., 2010; Randles et al., 2013; Durso et al., 2015) — although some pundits may beg to differ.³

The latest psychological study on this popular over-the-counter painkiller looks at empathy for another person's pain (Mischkowski et al., 2016). This work is based on the premise that the same neural machinery responsible for feeling our own physical and psychological pain (ACC, AI, mirror neurons — don't ask — but see Zaki et al., 2016) is invoked when observing the pain of others.


The Mystery of the Sliding Scales

[NOTE: Perceived Pain scores standardized in Tables 1, 3, 4 but not Table 2]

Can Tylenol (aka Parecemetol) lessen the pain you feel for others? I'll go out on a limb here and say probably not. Or not much, especially in a real-world sense. Here's why.

First, you have to understand that the experimental ratings of empathy were based on two different scales that varied from 1 (No pain at all) to 5 (Worst possible pain) OR from -4 (Worst possible pain) to +4 (Most possible pleasure). For the latter scale, the authors “reverse-coded participants’ ratings, so higher ratings indicated higher empathy for pain.”

Participants in Experiment 1 were given a placebo drink (n=40) or 1000 mg liquid acetaminophen (n=40). An hour later, they read short scenarios depicting other people in physical pain (e.g., cutting a finger) or social pain (e.g., getting rejected from college). Two major scores were obtained for perceived pain and personal distress. My reading is that these should yield a mean score between 1 and 5 for each measure.

ADDENDUM (May 18 2016): As pointed out by two Anonymous commenters, the Perceived Pain scores were standardized in Table 1. The same measure was not standardized in Table 2.

PERCEIVED PAIN — For each scenario, we measured perceived pain with two measures. First, participants rated the pain of each protagonist using a scale from 1 (No pain at all) to 5 (Worst possible pain). Second, participants rated on three items how much each protagonist felt hurt, wounded, and pained on scales ranging from 1 (Not at all) to 5 (Extremely). We averaged items to create perceived hurt feeling measures across physical and social pain scenarios... Within each scenario type, both perceived pain ratings correlated highly... Therefore, we standardized and averaged these measures into indices of perceived physical and social pain.

PERSONAL DISTRESS — Participants also rated their personal distress when reading each scenario. On a scale from 1 (Not at all) to 5 (Extremely), participants rated the extent to which they felt uncomfortable, pained, bothered, unpleasant, distress, as well as wanted to cringe while imagining the feelings of each scenario protagonist. We averaged items to create separate personal distress measures for physical and social pain scenarios...

My guess is that the authors made a mistake in their Tables, or else I misunderstood the scoring scheme. Let's take a look (click on image for a larger view).

For the first Dependent Variable, participants rated their own positive and negative feelings on the PANAS. General Affect ratings didn't differ between drug and placebo.

Next, look at Perceived Pain for Physical Pain Scenarios and Social Pain Scenarios. I won't belabor the p values here. Instead, focus on the red rectangles. [My mistake, Perceived Pain scores were standardized in Table 1. However, this does not affect my next comment.] These values are both close to zero (perhaps not significantly different from zero). But they don't seem to be on the 1 to 5 scale described above. The Personal Distress values ranged from “kind of a little bit” distressed for drug (2.15 and 2.00) to “kind of a little bit more” distressed for placebo (2.75 and 2.45). The participants who received acetaminophen are hardly in the land of the cruel and heartless psychopath. How much would these slight variations in personal distress ratings translate to real world empathy? We simply don't know.

Next, let's figure out the sliding scale issue. In Experiment 2:

Participants read the same eight physical and social pain empathy scenarios as in Experiment 1. After reading each scenario, participants rated perceived pain of the protagonist, using a scale from -4 (Worst possible pain) to +4 (Most possible pleasure). We reverse-coded participants’ ratings, so higher ratings indicated higher empathy for pain.

So here we have a scale that does include negative numbers, perhaps that scale was used for Perceived Pain in Exp. 1. Except ratings in Exp. 2 seems to use the 1 to 5 scale? It's hard to tell at this point. [Perceived Pain scores were not standardized in Table 2.] At any rate, the differences are small, and not significant for some of the comparisons.

There were other conditions involving noise blasts and watching a person being excluded from a round of cyberball (an old-school ball-tossing video game). Some of the values here were confusing as well. Or maybe I'm just confused... [Yes, I was confused. Perceived Pain scores were standardized in Tables 3 and 4.]

Noise blasts rated on a scale from 1 (Not unpleasant at all) to 10 (Extremely unpleasant).


Once again, in Table 4 we see mean values for Perceived Pain that are very close to zero. What does it mean? I will be happy to correct any erroneous interpretations of these Tables.

Now that I have corrected my mistakes, I still think it's hyperbole to say these differences mean that acetaminophen is an empathy killer in real life.

Neuroskeptic points out: 

Something odd about some of the datapoints... In Table 1, the mean for "perceived pain" for placebo is equal to the mean for acetaminophen * -1 (e.g. 0.22 vs -0.22, 0.19 vs. -0.19). The same is true in Table 4, two different values (e.g. 0.06 vs. -0.06, 0.04 vs -0.04).

Furthermore, does an Empathic Concern for Ostracized Player score of 1.68 (compared to 2.05) mean you're a less caring person? That acetaminophen has dulled your empathy? An empathy score of 2.05 (out of 5) while on placebo isn't exactly a heart-rending level of concern...

Cyberball 4.0

I could be wrong, but I don't think the Tylenol-fueled collapse of civilization is neigh. Next up? Ibuprofen! ⁴


Footnotes

¹ Many have argued that the physical-emotional pain isomorphism is vastly overstated (e.g., Hayes and Northoff, 2012; The Neurocritic, 2012; Iannetti et al., 2013; Woo et al., 2014; Wager et al., 2016).

² Well sure, you say, people have been self-medicating with opiates and alcohol for centuries. BUT here I mean mild nonprescription medications not known for having psychoactive properties.

³ Yeah, I've written about this a lot.

Tylenol Doesn't Really Blunt Your Emotions

Suffering from the pain of social rejection? Feel better with TYLENOL®

Existential Dread of Absurd Social Psychology Studies

Does Tylenol Exert its Analgesic Effects via the Spinal Cord?

Vicodin for Social Exclusion

⁴ I've wanted to see that study for years.


References

Dewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM, Eisenberger NI. (2010). Acetaminophen reduces social pain: behavioral and neural evidence. Psychological Science 21:931-937.

Durso G, Luttrell A, Way B. (2015). Over-the-Counter Relief From Pains and Pleasures Alike: Acetaminophen Blunts Evaluation Sensitivity to Both Negative and Positive Stimuli. Psychological Science 26:750-758.

Mischkowski, D., Crocker, J., & Way, B. (2016). From Painkiller to Empathy Killer: Acetaminophen (Paracetamol) Reduces Empathy for Pain. Social Cognitive and Affective Neuroscience DOI: 10.1093/scan/nsw057

Randles D, Heine SJ, Santos N. (2013). The common pain of surrealism and death: acetaminophen reduces compensatory affirmation following meaning threats. Psychological Science 24:966-73.

Zaki J, Wager TD, Singer T, Keysers C, Gazzola V. (2016). The Anatomy of Suffering: Understanding the Relationship between Nociceptive and Empathic Pain. Trends Cogn Sci. 20(4):249-59.

Suffering from the pain of social rejection? Feel better with TYLENOL®

It's not just for headaches anymore! The active ingredient in TYLENOL® (acetaminophen, also known as paracetamol) has been shown to ease the pain of social rejection. Wouldn't it be great if you could pop an over-the-counter medication to lessen the hurt of being excluded from that grad student party? Of being ostracized by all your old friends? Even disowned by your family and becoming homeless? The journal article, which was promoted by press release six months ago, has finally appeared online (Dewall et al., 2010). An excerpt from the December 2009 press release is below.

A Pill for Psychological Pain?

. . .

“The idea—that a drug designed to alleviate physical pain should reduce the pain of social rejection—seemed simple and straightforward based on what we know about neural overlap between social and physical pain systems. To my surprise, I couldn’t find anyone who had ever tested this idea,” [psychologist C. Nathan] DeWall said.

Perhaps because there's no clear mechanistic basis for such an idea? The authors themselves never proposed one either. One might expect that a psychopharmacological experiment with a drug that can cause serious liver damage would be conducted with a specific hypothesis in mind and some basic knowledge about how the drug is thought to work, but we didn't see that here. Granted, that would not be typical fare for Psych Sci. So instead the rationale given by Dewall et al. (2010) is partially linguistic, partially based on a neuroimaging study (Eisenberger et al., 2003):

Studies suggest that the similar linguistic descriptions of social and physical pain extend beyond metaphor, and demonstrate overlap in the neurobiological systems underlying physical pain and social pain (DeWall & Baumeister, 2006; Eisenberger, Lieberman, & Williams, 2003; Way, Taylor, & Eisenberger, 2009). In the present experiments, we examined one functional consequence of the hypothesis that social and physical pain rely on shared neurobiological systems—whether acetaminophen, a common physical pain reliever, also reduces social pain.

The "shared neurobiological systems" are thought to be located in the dorsal anterior cingulate cortex (ACC), a brain structure that contains discrete regions responsive to physical pain (Kwan et al., 2000). Interestingly, externally applied vs. self-administered thermal pain activate anatomically distinct areas of the ACC (Mohr et al., 2005). Furthermore, it is not at all clear whether the same regions of ACC represent social pain and the affective components of physical pain. In a study designed to dissociate expectancy violations from social rejection, the dorsal ACC was activated when expectations were violated, while ventral ACC (quite distant from the physical pain regions) was activated by social rejection (Somerville et al., 2006).


Figure 2 (Somerville et al., 2006). Differential ACC response to expectancy violation and social feedback. (a) A three-dimensional rendering of the medial surface of the brain illustrates a functional dissociation between dorsal (dACC) and ventral (vACC) anterior cingulate. A whole-brain voxel-by-voxel ANOVA was used to identify voxels that showed a significant main effect (P less than 0.001, uncorrected) of expectancy violation (blue) and a main effect of feedback type (yellow).

At any rate, participants in the Eisenberger et al. (2003) study took part in a computerized ball-tossing game while being scanned. Initially, two fictitious players included the scanned subject in the game, but then started to exclude him/her. This was the “social exclusion” condition, which was compared to the inclusion condition. But it happens to be the case that this paper was singled out as one of the worst of the "voodoo correlation" violators by Vul and his colleagues [PDF], since it reported a statistically unlikely value based on a non-independent analysis:

Eisenberger, Lieberman, and Williams (2003), writing in Science, described a game they created to expose individuals to social rejection in the laboratory. The authors measured the brain activity in 13 individuals at the same time as the actual rejection took place, and later obtained a self-report measure of how much distress the subject had experienced. Distress was correlated at r=.88 with activity in the anterior cingulate cortex (ACC).

A correlation of r=.88 between dACC activity and self-reported distress is implausibly high... But I'll stop here, and point to Lieberman, Berkman, and Wager's (2009) reply to Vul et al.

That brings us to the present study by Dewall et al. (2010). In Experiment 1, 30 participants (24 women, 6 men) took one 500 mg acetaminophen pill immediately after waking up and another 500 mg an hour before going to sleep (1,000 mg per day for 3 weeks). The other 32 participants (24 women, 8 men) took the same dosing of placebo for 3 weeks. Each evening, subjects filled out the the Hurt Feelings Scale (the "today" version) to report how much social pain they had experienced that day. Despite the fact that the half life of acetaminophen is 4 hours, it took about 10 days for the drug group to report significantly lower hurt feelings than the placebo group. The difference on day 21 was greatest (p < .005). However, the difference in change-over-time slopes between the two groups was only marginally significant (p ≤ .10). The explanation of the time course for these effects was unclear:

Acetaminophen has a relatively short half-life, lasting approximately 4 hr, which means that it is unlikely that acetaminophen had a cumulative effect in our experiments. Our finding that acetaminophen reduced hurt feelings over time could be due to a combination of not feeling hurt and having a greater ability to reappraise the rejection experience.

In Experiment 2, the dose was upped to 2,000 mg acetaminophen per day for 3 weeks. Instructions were given to refrain from drinking entirely, since alcohol can potentiate liver damage when taken with acetaminophen. In 2009, an FDA panel made a recommendation to lower the maximum daily dose from 4,000 mg (to an unspecified value). The panel also endorsed limiting the maximum single dose of the drug to 650 mg, down from the current 1,000 mg dose (which was given in Exp. 2). At the end of the three week period, the cyberball exclusion fMRI study was run. The acetaminophen group showed less activity in dACC in response to social exclusion, but they did not report lower hurt feelings.

Hmm. As an aside, here's another puzzling observation. If it's been claimed that "social exclusion hurts" (Macdonald & Leary, 2005), then why does the experience of social exclusion result in higher tolerance for physical pain and higher pain thresholds (DeWall & Baumeister, 2006)?

Next, I have a series of questions for the authors:

• Did you consider the negative consequences of acetaminophen?
• Did your IRB have anything to say about this (there was NO info in the paper on institutional approval or the signed consent procedure with participants)?
• How did you decide on your dosing regimen?
• Why 3 weeks, when the half-life is only 4 hrs?
• Instructions say "do not use for more than 10 days without doctor's permission." Was an MD involved in the study?
  
• What do you know about the mechanism of action? For more info, see Acetaminophen from Frank J. Dowd.
• And most critically, why did you choose acetaminophen, rather than aspirin, ibuprofen, or naproxen?
• Related to this, why did the first version of the manuscript have "Tylenol" in the title? ¹

I was also alarmed by the wild extrapolation from exclusion in a laboratory video game to purported increases in aggressive violence:

Furthermore, many studies have shown that being rejected can trigger aggressive and antisocial behavior, which could lead to further complications in social life (DeWall, Twenge, Gitter, & Baumeister, 2009; Warburton, Williams, & Cairns, 2006). If acetaminophen reduces the distress of rejection, the behavioral consequences of rejection, such as antisocial behavior, may be reduced as well. Indeed, our fMRI results showed that acetaminophen diminished reactivity in the dACC and amygdala, brain regions that have been linked to aggression (Denson, Pedersen, Ronquillo, & Nandy, 2009; Eisenberger, Way, Taylor, Welch, & Lieberman, 2007). It would therefore be worthwhile to explore whether acetaminophen reduces the aggressive consequences of social rejection.

I'm sure the 24 women in the placebo condition felt like committing mass murder after being excluded from a game of cyberball. Better put them on TYLENOL®.

The Medscape article on the study had prominent kudos from Bruce G. Charlton, MD, who:

...applauded the investigators' research efforts.

"It is particularly difficult to get research funding to study old, cheap, unpatented, over-the-counter drugs, so I congratulate the authors on doing this," he said.

Dr. Charlton, who [was] editor-in-chief of Medical Hypotheses and professor of theoretical medicine at the University of Buckingham, United Kingdom, agreed that different sorts of pain are often related, so there is good reason to assume that acetaminophen or paracetamol may benefit those who suffer any type of pain of unpleasant feelings, including some types of depression.

However, he noted that the same effect would likely apply to aspirin, nonsteroidal anti-inflammatory drugs, and opiates, "about which there is more evidence," he said.

One last question arose when I checked funding for the study:

This work was funded by grants from the National Institute of Mental Health (MH-65999) and the Gulf Atlantic Group, Inc.

The grant number was misreported, it's MH065559, not MH-65999.

And funding from the Gulf Atlantic Group, Inc.?? Trying to trace that entity has been like navigating a maze, an endless series of shell corporations:

http://haverlandprince.com/
http://www.texpacfunding.com/
http://www.gainagroup.com/
http://pcigroupltd.com/

But maybe it's really Gulf Atlantic Funding Group Inc ? -- no, that's mortgages.

OR how about: Gulf Atlantic Group Incorporated in Tallahassee, FL (where one of the authors is located)?

Or maybe it was just another typo...

ADDENDUM

¹ Original name of the article was: DeWall C. N., MacDonald, G., Webster, G. D., Masten, C., Baumeister, R. F., Powell, C., Combs, D., Schurtz, D. R., Stillman, T. F., Tice, D. M., & Eisenberger, N. I. (in press). Tylenol reduces social pain: Behavioral and neural evidence. Psychological Science.

Here are two other papers that use the brand name Tylenol:

DeWall, C. N., Stillman, T. F., MacDonald, G., Webster, G. D., Finkel, E. J., Tice, D. M., & Baumeister, R. F. (2010). Can Tylenol boost self-esteem? Effects of acetaminophen on perceived social threat and social self-esteem. Manuscript in preparation. (Intended outlet: Journal of Personality and Social Psychology).

DeWall, C. N. (2008). Effects of Daily Acetaminophen on Social Emotions: Can Two Tylenol Overcome Heartbreak? Paper presented at the Annual Meeting of the Society of Personality and Social Psychology. Albuquerque, NM.

References

DeWall CN, Baumeister RF (2006). Alone but feeling no pain: Effects of social exclusion on physical pain tolerance and pain threshold, affective forecasting, and interpersonal empathy. Journal of Personality and Social Psychology, 91, 1–15.

Dewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM, & Eisenberger NI (2010). Acetaminophen Reduces Social Pain: Behavioral and Neural Evidence. Psychological Science PMID: 20548058

Eisenberger NI, Lieberman MD, Williams KD. (2003). Does rejection hurt? An FMRI study of social exclusion. Science 302:290-2.

Kwan CL, Crawley AP, Mikulis DJ, Davis KD. (2000). An fMRI study of the anterior cingulate cortex and surrounding medial wall activations evoked by noxious cutaneous heat and cold stimuli. Pain 85:359-74.

Lieberman M, Berkman E, Wager T. (2009). Correlations in Social Neuroscience Aren't Voodoo: Commentary on Vul et al. (2009) Perspectives on Psychological Science, 4 (3), 299-307

Macdonald G, Leary MR. (2005). Why does social exclusion hurt? The relationship between social and physical pain. Psychol Bull. 131:202-23.

Mohr C, Binkofski F, Erdmann C, Büchel C, Helmchen C. (2005). The anterior cingulate cortex contains distinct areas dissociating external from self-administered painful stimulation: a parametric fMRI study. Pain 114:347-57.

Somerville LH, Heatherton TF, Kelley WM. (2006). Anterior cingulate cortex responds differentially to expectancy violation and social rejection. Nat Neurosci. 9, 1007-1008.

Vul E, Harris C, Winkielman P, Pashler H (2009). Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition [PDF]. Perspectives on Psychological Science 4(3), 274-290.

Way BM, Taylor SE, Eisenberger NI (2009). Variation in the mu-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection. Proceedings of the National Academy of Sciences 106, 15079–15084.