MDMA Increases Cooperation and Recruitment of Social Brain Areas When Playing Trustworthy Players in an Iterated Prisoner's Dilemma

TY - JOUR

T1 - MDMA Increases Cooperation and Recruitment of Social Brain Areas When Playing Trustworthy Players in an Iterated Prisoner's Dilemma

AU - Gabay, Anthony

AU - Kempton, Matthew

AU - Gilleen, James

AU - Mehta, Mitul

N1 - I am joint senior author on this paper.

PY - 2019/1/9

Y1 - 2019/1/9

N2 - Social decision-making is fundamental for successful functioning, and can be affected in psychiatric illness and by serotoninergic modulation. The Prisoner’s Dilemma (PD) is the archetypal paradigm to model cooperation and trust. However, the effect of serotonergic enhancement is poorly characterised, and its influence on the effect of variations in opponent behaviour unknown. To address this, we conducted a study investigating how the serotonergic enhancer MDMA modulates behaviour and its neural correlates during an iterated PD with both trustworthy and untrustworthy opponents.We administered 100mg MDMA or placebo to 20 male participants in a double-blind, placebo-controlled, crossover study. While being scanned, participants played repeated rounds with opponents who differed in levels of cooperation. On each round participants chose to compete or cooperate and were asked to rate their trust in the other player. Cooperation with trustworthy, but not untrustworthy, opponents was enhanced following MDMA but not placebo (respectively: OR=2.01 95% CI 1.42–2.84, p<0.001; OR=1.37 95% CI 0.78–2.30 n.s.). Specifically, MDMA enhanced recovery from, but not the impact of, breaches in cooperation. During trial outcome, MDMA increased activation of four clusters incorporating precentral and supramarginal gyri, superior temporal cortex, central operculum/posterior insula, and supplementary motor area. There was a treatment-by-opponent interaction in right anterior insula and dorsal caudate. Trust ratings did not change across treatment sessions. MDMA increased cooperative behaviour when playing trustworthy opponents. Underlying this was a change in brain activity of regions linked to social cognition. Our findings highlight the context-specific nature of MDMA’s effect on social decision-making.© 2020, The Author(s). This is an author produced version of a paper published in JOURNAL OF NEUROSCIENCE uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

AB - Social decision-making is fundamental for successful functioning, and can be affected in psychiatric illness and by serotoninergic modulation. The Prisoner’s Dilemma (PD) is the archetypal paradigm to model cooperation and trust. However, the effect of serotonergic enhancement is poorly characterised, and its influence on the effect of variations in opponent behaviour unknown. To address this, we conducted a study investigating how the serotonergic enhancer MDMA modulates behaviour and its neural correlates during an iterated PD with both trustworthy and untrustworthy opponents.We administered 100mg MDMA or placebo to 20 male participants in a double-blind, placebo-controlled, crossover study. While being scanned, participants played repeated rounds with opponents who differed in levels of cooperation. On each round participants chose to compete or cooperate and were asked to rate their trust in the other player. Cooperation with trustworthy, but not untrustworthy, opponents was enhanced following MDMA but not placebo (respectively: OR=2.01 95% CI 1.42–2.84, p<0.001; OR=1.37 95% CI 0.78–2.30 n.s.). Specifically, MDMA enhanced recovery from, but not the impact of, breaches in cooperation. During trial outcome, MDMA increased activation of four clusters incorporating precentral and supramarginal gyri, superior temporal cortex, central operculum/posterior insula, and supplementary motor area. There was a treatment-by-opponent interaction in right anterior insula and dorsal caudate. Trust ratings did not change across treatment sessions. MDMA increased cooperative behaviour when playing trustworthy opponents. Underlying this was a change in brain activity of regions linked to social cognition. Our findings highlight the context-specific nature of MDMA’s effect on social decision-making.© 2020, The Author(s). This is an author produced version of a paper published in JOURNAL OF NEUROSCIENCE uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

KW - social decision-making

KW - fmri

KW - psychopharmacology

KW - MDMA

U2 - 10.1523/JNEUROSCI.1276-18.2018

DO - 10.1523/JNEUROSCI.1276-18.2018

M3 - Article

SN - 0270-6474

VL - 39

SP - 307

EP - 320

JO - JOURNAL OF NEUROSCIENCE

JF - JOURNAL OF NEUROSCIENCE

IS - 2

ER -