(a) VmPFC responses that reflected CS+ trials during extinction training when subjects no longer expected an US that are contrasted with trials in which an US was expected (i.e., extinction learning). One-sided independent t-test L-DOPA > Placebo, MNI xyz: 10, 35,–7; Z = 4.76; pFWE-SVC=0.002; displayed at threshold punc<0.005; colour bar represents t-values. Estimates in the vmPFC were enhanced after administration of L-DOPA as compared to placebo (a.u. = arbitrary units; error-bar indicate the standard error of the mean). (b) Higher individual vmPFC responses across groups that reflected decreasing US expectancy for the CS+ (i.e., extinction learning) were associated with lower conditioned responses (SCR CS+ > CS−) during retrieval test 24 hr later (two-sided Pearson correlation). (c) The effect of L-DOPA treatment on conditioned responses (SCR CS+ > CS−) during retrieval test was fully mediated via the activity of the vmPFC in extinction learning. Drug treatment (L-DOPA vs. Placebo) had an effect on vmPFC activity (β = −2.2957, standard error = 0.4227, t(38)=-5.431, p=0.000003), and vmPFC activity had a negative effect on conditioned responses during retrieval test (β = −0.01898, standard error = 0.008888, t(38) = –2.135, p=0.0392). We found no evidence for an effect of drug treatment (L-DOPA vs. Placebo) on conditioned responses during retrieval test (β = 0.02644, standard error = 0.03238, t(38) = 0.816, p=0.419), but when including vmPFC activity into that model, this mediator was significant (β = −0.02478, standard error = 0.01192, t(38) = –2.079, p=0.0446; effect of group p=0.4). There was further evidence for a full mediation of drug treatment (L-DOPA vs. Placebo) on conditioned responses by an indirect effect of vmPFC activity within a mediation model using quasi-bayesian procedures (β = 0.0563, 95% confidence intervals = 0.007–0.12, p=0.038, N = 40,1000 samples, N = 40); bootstrapping yielded comparable results (β = 0.056, 95% confidence intervals = 0.007–0.14, p=0.044). a.u. = arbitrary units, vmPFC = ventromedial prefrontalcortex, CS = conditioned stimulus, US = unconditioned stimulus, SCR = skin conductance responses.