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Randomized Controlled Trial
. 2024 May;241(5):1079-1092.
doi: 10.1007/s00213-024-06541-9. Epub 2024 Jan 29.

L-DOPA and oxytocin influence the neural correlates of performance monitoring for self and others

Myrthe Jansen  1   2 , Sandy Overgaauw  3   4 , Ellen R A de Bruijn  3   4
Affiliations
Randomized Controlled Trial

L-DOPA and oxytocin influence the neural correlates of performance monitoring for self and others

Myrthe Jansen et al. Psychopharmacology (Berl). 2024 May.

Abstract

Rationale: The ability to monitor the consequences of our actions for others is imperative for flexible and adaptive behavior, and allows us to act in a (pro)social manner. Yet, little is known about the neurochemical mechanisms underlying alterations in (pro)social performance monitoring.

Objective: The aim of this functional magnetic resonance imaging (fMRI) study was to improve our understanding of the role of dopamine and oxytocin and their potential overlap in the neural mechanisms underlying performance monitoring for own versus others' outcomes.

Method: Using a double-blind placebo-controlled cross-over design, 30 healthy male volunteers were administered oxytocin (24 international units), the dopamine precursor L-DOPA (100 mg + 25 mg carbidopa), or placebo in three sessions. Participants performed a computerized cannon shooting game in two recipient conditions where mistakes resulted in negative monetary consequences for (1) oneself or (2) an anonymous other participant.

Results: Results indicated reduced error-correct differentiation in the ventral striatum after L-DOPA compared to placebo, independent of recipient. Hence, pharmacological manipulation of dopamine via L-DOPA modulated performance-monitoring activity in a brain region associated with reward prediction and processing in a domain-general manner. In contrast, oxytocin modulated the BOLD response in a recipient-specific manner, such that it specifically enhanced activity for errors that affected the other in the pregenual anterior cingulate cortex (pgACC), a region previously implicated in the processing of social rewards and prediction errors. Behaviorally, we also found reduced target sizes-indicative of better performance-after oxytocin, regardless of recipient. Moreover, after oxytocin lower target sizes specifically predicted higher pgACC activity when performing for others.

Conclusions: These different behavioral and neural patterns after oxytocin compared to L-DOPA administration highlight a divergent role of each neurochemical in modulating the neural mechanisms underlying social performance monitoring.

Keywords: Dopamine; Functional magnetic resonance imaging (fMRI); Oxytocin; Prosocial; Social performance monitoring.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the timetable for each session (A) and the Cannonball task (B). (A) During each session participants received a pill followed by a nasal spray exactly 15 min later (either a placebo pill followed by a placebo spray, a placebo pill followed by a spray containing oxytocin, or a L-DOPA pill followed by placebo spray). Participants performed the Cannonball task in the scanner approximately 59 min (SD = 2.5) after pill administration and 44 min (SD = 3.3) after administration of the nasal spray. Subjective drug effects (alertness, mood and anxiety) were assessed using the Bond and Lader (1974) mood rating scale (B&L) right before administration of the pill (T1), approximately one hour later (T2), and at the end of the visit (T3). (B) The goal of the Cannonball task is to stop a horizontally moving cannon (triangle) by a button press, to precisely line it up with a stationary target (square). Participants played this task in two conditions: for their own monetary bonus and for the bonus of another participant, whereby errors resulted in a monetary deduction from an initial bonus. At the beginning of each trial a black screen with a white fixation cross was presented, the duration of which was jittered using a randomized jitter list with the following durations in ms: 750, 750, 1000, 1000, 1000, 1250, 1250, 1500, 1500, 5500. Subsequently, the target and cannon appeared on the screen. Target location was randomly determined on each trial, whereas the cannon was always horizontally centered. Immediately after presentation, the cannon starts moving either to the right or the left for a maximum of 3500 ms or until a button is pressed. In case of a missed response, the words ‘TOO LATE’ appeared on the screen. 500 ms after a response was made, an unambiguous feedback signal (thumb up/thumb down) was presented for 750 ms, indicating whether the response was correct or incorrect. Each run lasted 80 trials, and after every 10 trials participants were reminded of the recipient condition (“You are playing for the bonus of the other participant” vs “You are playing for your own bonus”). The task was presented using E-prime 3.0 software (Psychology Software Tools, Pittsburgh, PA)
Fig. 2
Fig. 2
Mean target size (in pixels) for correct and incorrect trials across drug and recipient conditions. As accuracy rate was kept constant by reducing or increasing the target sizes, smaller target sizes reflect better performance. The Fig. demonstrates the main effects of correctness (smaller target sizes for errors), recipient (smaller target sizes for self) and drug (smaller target sizes after oxytocin). Error bars represents standard error of the mean
Fig. 3
Fig. 3
Region-of-interest (ROI) mask (A) and interactions between L-DOPA and correctness in the left (B) and right (C) ventral striatum. (A) We created a single ROI mask by combining anatomical masks of the ventral striatum and anterior insula with a 10-mm sphere of the posterior medial prefrontal cortex [x = 4, y = 32, z = 38]. (B & C) Whole-brain image and extracted parameter estimates of the significant interaction between L-DOPA and correctness in the left and right ventral striatum (left: x = -9, y = 9, z = -8], k = 89, Z = 4.61, p = 0.001 SVC-FWE; right: x = 11, y = 8, z = -11, k = 7, Z = 3.65, p = 0.043 SVC-FWE). Contrasts are displayed at P < 0.001 for illustration purposes [x = -9, y = 9, z = -8]. *p < 0.05, **p < 0.01
Fig. 4
Fig. 4
Whole-brain image and extracted parameter estimates for the interaction between oxytocin, recipient and correctness in the left pregenual anterior cingulate cortex. (A) Whole-brain image and extracted parameter estimates show enhanced activation for errors that affect the other after oxytocin (x = -15, y = 42, z = 12, k = 12, Z = 5.00, p = 0.007 FWE). Contrasts are displayed at p < 0.001 for illustration purposes [x = -12, y = 42, z = 12]. *p < 0.05, **p < 0.01
Fig. 5
Fig. 5
Scatterplot depicting the association between target size and mean parameter estimates in the pregenual anterior cingulate cortex after oxytocin and placebo per recipient condition. Plot shows that better performance (as indicated by lower target sizes) is associated with higher activity in the pregenual anterior cingulate cortex specifically when playing for others after oxytocin
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