Dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange

Abstract

Dopamine and serotonin are hypothesized to guide social behaviours. In humans, however, we have not yet been able to study neuromodulator dynamics as social interaction unfolds. Here, we obtained subsecond estimates of dopamine and serotonin from human substantia nigra pars reticulata during the ultimatum game. Participants, who were patients with Parkinson's disease undergoing awake brain surgery, had to accept or reject monetary offers of varying fairness from human and computer players. They rejected more offers in the human than the computer condition, an effect of social context associated with higher overall levels of dopamine but not serotonin. Regardless of the social context, relative changes in dopamine tracked trial-by-trial changes in offer value-akin to reward prediction errors-whereas serotonin tracked the current offer value. These results show that dopamine and serotonin fluctuations in one of the basal ganglia's main output structures reflect distinct social context and value signals.

Fig. 1. Experimental framework.

a, Illustration of electrode trajectory and recording site. GP, globus pallidus; STN, subthalamic nucleus; SNr/SNc, substantia nigra pars reticulata/compacta; RN, raphe nucleus. Brain slice created with Biorender.com. b, The game involved 60 trials of the one-shot ultimatum game where participants had to accept or reject splits of a US$20 stake proposed by either a human (30 trials) or a computer (30 trials) avatar. On around a third of trials, participants were asked to indicate how they felt about the game. Each participant underwent two surgical sessions 14–28 days apart; the human and computer conditions were blocked within a session and their order was counterbalanced across sessions.

Fig. 2. Behavioural results.

a, Proportion accept (y axis) given offer value (x axis) and condition (colours). b, Reaction time (y axis) given choice (colours). c, Emotion (y axis; 0–100) given condition (colours). b,c, Each dot is a dataset. a–c, Data are represented as mean ± s.e.m. across datasets (n = 8).

Fig. 3. Overall dopamine levels depend on social context.

a, Overall dopamine/serotonin (y axis) separated by condition (colour) and its order within a session (x axis). b, Overall dopamine/serotonin (y axis) across time separated by condition order (left column versus right column). a,b, Overall estimates were computed as the sum of neuromodulator samples within a 1 s window (ten samples) after offer presentation. We limited the estimates to this window for consistency with the relative analysis in Fig. 4 and to ensure that all estimates were based on the same number of samples regardless of variation in reaction times and trial events (for example, variable duration of proposer screen and emotion ratings). The effect of condition on dopamine remained regardless of the specific time window (for example, a 6 s window centred on offer presentation; N-M1, t(454) = 2.63, P = 0.009, β ± 95% CI = 1.00 ± 0.75). Data are represented as mean ± s.e.m. across datasets (n = 4 for each order). Each dataset (session) was z-scored separately.

Fig. 4. Relative changes in dopamine and serotonin reflect distinct value signals.

To visualize the value effects (see main text for statistical analysis), we grouped the value of the current offer (top row) and the difference in value between the current and the previous offer (bottom row) into three bins using terciles and then plotted relative dopamine/serotonin (y axis) for each bin (x axis). Relative estimates were computed by first subtracting the sample at offer presentation as a local baseline and then taking the sum of neuromodulator samples within a 1 s window (ten samples) after offer presentation. Data are represented as mean ± s.e.m. across datasets (n = 8). Each dataset (session) was z-scored separately.