Vasopressin increases human risky cooperative behavior

Abstract

The history of humankind is an epic of cooperation, which is ubiquitous across societies and increasing in scale. Much human cooperation occurs where it is risky to cooperate for mutual benefit because successful cooperation depends on a sufficient level of cooperation by others. Here we show that arginine vasopressin (AVP), a neuropeptide that mediates complex mammalian social behaviors such as pair bonding, social recognition and aggression causally increases humans' willingness to engage in risky, mutually beneficial cooperation. In two double-blind experiments, male participants received either AVP or placebo intranasally and made decisions with financial consequences in the "Stag hunt" cooperation game. AVP increases humans' willingness to cooperate. That increase is not due to an increase in the general willingness to bear risks or to altruistically help others. Using functional brain imaging, we show that, when subjects make the risky Stag choice, AVP down-regulates the BOLD signal in the left dorsolateral prefrontal cortex (dlPFC), a risk-integration region, and increases the left dlPFC functional connectivity with the ventral pallidum, an AVP receptor-rich region previously associated with AVP-mediated social reward processing in mammals. These findings show a previously unidentified causal role for AVP in social approach behavior in humans, as established by animal research.

Keywords: cooperation; fMRI; intranasal administration; neuroeconomics; vasopressin.

Fig. 1.

The Stag hunt task. (A) Stag hunt game payoff matrix. The cooperative action Stag potentially generates the highest possible payoff, but only if one’s partner cooperates as well. Rabbit choice secures a lower (but certain) payoff, regardless of the partner’s action. The payoff dominant equilibrium (200/200) is at the Top Left, and the risk-dominant equilibrium (160/160) is at the Bottom Right. (B) Stag hunt game payoff matrix of the strategy method. Participants indicated a security level (parameter S-value) at which they would switch between the risk-dominant Rabbit strategy to the payoff-dominant Stag strategy and also indicated the direction of switching.

Fig. 2.

AVP increased cooperative behavior. (A) AVP subjects switched from Stag to Rabbit at a higher security level (S-value), indicating higher cooperation rates and reduced aversion to social risk under AVP treatment. Note that, as all subjects switched from Stag to Rabbit, the cumulative distribution was equivalent to the rate of Rabbit choice at any given security level. (B) Mean cooperation rates of both groups in experiment 2 (fMRI). AVP subjects were significantly more cooperative; the effect increased when the incentive to cooperate was high.

Fig. 3.

AVP caused choice-dependent changes in brain activity. (A) Mean response times across action choices. The placebo group was significantly slower when choosing Stag compared with Rabbit (paired-sample t = 2.62, P < 0.01); the effect disappeared in the AVP group (t = −2.144, P < 0.03). (B) A cluster in the left dlPFC showed increased BOLD activation for the contrast Stag > Rabbit choices in the placebo group relative to the AVP group. (C) A region-of-interest analysis in the area shown in B revealed a significant drug × choice interaction. AVP decreased the BOLD signal (percentage signal change, y axis) in the left dlPFC during Stag choices (t = −2.34, P < 0.05) and increased activity in the latter brain region during Rabbit choices (t = 1.87, P < 0.05), relative to the placebo group. This finding indicates that cooperation (choosing Stag) required less mental effort under AVP treatment, in accordance with the behavioral and RT data. (D) Intranasal AVP enhanced the left dlPFC functional connectivity with (i) the left ventral pallidum, the cingulate gyrus, and the medial and superior frontal gyrus during Stag choices and (ii) increased the left dlPFC functional connectivity with the left parahippocampal gyrus, left amygdala, and ACC during Rabbit choices.