Is Mourning Rewarding? (revisited)

Can we reduce the persistent, unbearable pain of losing a loved one to 15-20 voxels of brain activity in the nucleus accumbens (O'Connor et al., 2008)? No? Then what if I told you that unrelenting grief — and associated feelings of sheer panic, fear, terminal aloneness, and existential crisis — isn't “suffering”. It's actually rewarding!

Well I'm here to tell you that it isn't.

Looking back on a post from 2011, you never realize it's going to be you.¹

The top figure shows that activity in the nucleus accumbens was greater in response to grief-related words vs. neutral words in a group of 11 women with “Complicated” Grief (who lost a mother or sister to breast cancer in the last 5 years), compared to a group of 10 women with garden-variety Non-complicated Grief (O'Connor et al., 2008). Since the paper was published in 2008, and the standards for conducting fMRI studies have changed (larger sample sizes are necessary, no more “voodoo correlations”), I won't go on about that here.


When Grief Gets Complicated?

Grief is never simple, it's always complicated. The death of a cherished loved one can create a situation that seems totally intolerable. Almost everyone agrees that navigating such loss doesn't rely on one acceptable road map. Yet here it is. Normal people are supposed to move through a one year mourning period of “sorrow, numbness, and even guilt and anger. Gradually these feelings ease, and it's possible to accept loss and move forward.” If you don't, well then it's Complicated. This is a stigmatizing and limiting view of what it means to grieve the loss of a loved one.²

But is there really such there a thing as Complicated Grief? Simply put, it's “a chronic impairing form of grief brought about by interference with the healing process.” There are “maladaptive thoughts and dysfunctional behaviors” according to The Center for Complicated Grief. However, it's not named as an actual disorder in either of the major psychiatric manuals. In ICD-11, preoccupation with and longing for the deceased, accompanied by significant emotional distress and functional impairment beyond six months, is called Prolonged Grief Disorder. In DSM-5, Complicated Grief has morphed into Persistent Complex Bereavement Disorder, a not-exactly-reified condition subject to further study.


Dopamine ≠ Reward

Dopamine and its putative reward circuitry are way more complex than a simple one-to-one mapping. Studies in rodents have demonstrated that the nucleus accumbens (NA) can code for negative states, as well as positive ones, as shown by the existence of “hedonic coldspots” that generate aversive reactions, in addition to the usual hotspots (Berridge & Kringelbach, 2015). These studies involved microinjections of opioids into tiny regions of the NA.

If a chronically anguished state is portrayed as rewarding, it's time to recalibrate these terms. As I said in 2011:

If tremendous psychological suffering and loss are associated with activity in brain regions such as the ventral tegmental area and nucleus accumbens, isn't it time to abandon the simplistic notion of dopamine as the feel-good neurotransmitter? To quote the authors of Mesolimbic Dopamine in Desire and Dread (Faure et al., 2008):

It is important to understand how mesocorticolimbic mechanisms generate positive versus negative motivations. Dopamine (DA) in the nucleus accumbens is well known as a mechanism of appetitive motivation for reward. However, aversive motivations such as pain, stress, and fear also may involve dopamine in nucleus accumbens (at least tonic dopamine signals).

Grief-Related Words Are Rewarding

So what happens when you take a disputed diagnostic label and combine it with reverse inference in a neuroimaging study? (when you operate under the assumption that activity in a particular brain region must mean that a specific cognitive process or psychological state was present).

The NA activity was observed while the participants viewed grief words vs. neutral words that were superimposed over a photograph: a photo of the participant's deceased mother or a photo of someone else's mother. And it didn't matter whose mother was pictured, the difference was due to the words, not the images.³



Sample stimulus provides an [unintentional?] example of the emotional Stroop effect.


That's pretty hard to explain by saying that “the pangs of grief would continue to occur with NA activity, with reward activity in response to the cues motivating reunion with the deceased” if the effect is not specific to an image of the deceased.


Yearning and the Subgenual Cingulate

Why beat a dead horse, you ask? Because a recent study (McConnell et al., 2018) did not heed the advice above (sample size should be increased, beware reverse inference). The participants were 9 women with Complicated Grief (CG), 7 women with Non-complicated Grief (NG), and 9 Non-Bereaved (NB). The NA finding did not replicate, nor were there any differences between CG and NG and NB (over the entire brain). A post-hoc analysis then extracted a single question from a 19-item inventory and found that yearning for the dead spouse in all 16 Bereaved participants was correlated with activity in the subgenual cingulate (“depression-land” or perhaps “rumination-land”), for the comparison of an anticipation period vs. presentation of spouse photo. There were 5 spouse photos and 5 photos of strangers (note that it was not possible to predict which would be presented). The authors recognized the limitations of the study, yet pathologized yearning in Complicated and Non-complicated Grief alike.

I realize that the general motivation behind these experiments might be admirable, but you really can't come to any conclusions about how grief — a highly complex emotional response unique to each individual — might be represented in the brain.


Footnotes

¹ See There Is a Giant Hole Where My Heart Used To Be from October 2, 2018.

The posts on illness and death that I never wrote:

• Update on Antiemetics
 
• The Neurology of Liver Failure

(yes, I was really serious about these)

² I was skeptical when someone sent me this book, It's OK That You're Not OK: Meeting Grief and Loss in a Culture That Doesn't Understand (by Megan Devine). I thought it was going to be overly 'self-helpy'. But it's actually been immensely helpful.

³ The idea of creating a self-relevant stimulus set was utterly horrifying to me.


References

Berridge KC, Kringelbach ML. (2015). Pleasure systems in the brain. Neuron 86(3):646-64.

Faure A, Reynolds SM, Richard JM, Berridge KC. (2008). Mesolimbic dopamine in desire and dread: enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens. J Neurosci. 28:7184-92.

McConnell MH, Killgore WD, O'Connor MF. (2018). Yearning predicts subgenual anterior cingulate activity in bereaved individuals. Heliyon 4(10):e00852.

O'Connor MF, Wellisch DK, Stanton AL, Eisenberger NI, Irwin MR, Lieberman MD. (2008). Craving love? Enduring grief activates brain's reward center. Neuroimage 42:969-72.