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:
- 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.
- Thresholding: Take the P values from the previous step and computes the threshold for the ALE map using the Tom Nichol’s FDR algorithm.
- 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.
