Fig. 3: sgACC/25 over-activation elevates threat-related arousal during threat extinction and extinction-recall.

Gray = control, orange = over-activation. Shading and error bars represent SEM. Infusions took place prior to extinction sessions, indicated by arrows above figures (a, b). n = 4. a During acquisition sessions, animals increased their vigilant scanning (VS) response from the pre-snake to post-snake phase in both the “to be saline” and “to-be overactivation” blocks (two-way repeated measures ANOVA, manipulation × phase, F1,3 = 1.4, p = 0.317; main effect of phase, F1,3 = 36.5, p = 0.009, η2 = 0.777). sgACC/25 over-activation blocked behavioral extinction (two-way repeated measures ANOVA, manipulation ×  CS pair, F4,12 = 3.6, p = 0.039, η2 = 0.087) with significant differences in scanning responses evident during the second (Sidak’s test, p = 0.039, d = 1.86), third (p = 0.007, d = 2.04) and fifth (p = 0.023, d = 1.05) CS pairs, but not the first (p = 0.974) or fourth (p = 0.0602). These effects persisted to the next day with sgACC/25 over-activation elevating VS across extinction recall (two-way repeated measures ANOVA, manipulation × CS pair, F4,12 = 4.0, p = 0.027, η2 = 0.039) evident across all CS pairs (Sidak’s test, first p < 0.001, d = 2.55; second p < 0.001, d = 1.39; third p < 0.001, d = 1.22; fourth p = 0.003, d = 1.08; fifth p = 0.026, d = 0.83). b Equally, the blood pressure (MAP) increase during acquisition was not different in the “to be saline” vs. “to be overactivation” blocks (two-way repeated measures ANOVA, manipulation × phase, F < 1, p = 0.695; main effect of phase, F1,3 = 44.5, p = 0.007, η2 = 0.503). sgACC/25 over-activation did not alter the rate of blood pressure extinction (two-way repeated measures ANOVA, manipulation × CS pair, F < 1, p = 0.668; main effect of CS pair, F4,12 = 16.0, p < 0.001, η2 = 0.069) but did elevate blood pressure responses across all CS pairs (two-way repeated measures ANOVA, main effect of manipulation, F1,3 = 11.8, p = 0.042, η2 = 0.180). Marmosets continued to extinguish their blood pressure responding during extinction recall (two-way repeated measures ANOVA, main effect of CS pair, F4,12 = 4.2, p = 0.023, η2 = 0.113) and again there was a systematic elevation in blood pressure responses following over-activation (two-way repeated measures ANOVA, main effect of infusion, F1,3 = 39.1, p = 0.008, η2 = 0.562). c Plotting second-by-second blood pressure values for all four animals during extinction revealed an increase across the entire session, not restricted to CS periods (linear mixed-model, manipulation ×  time, F < 1, p = 0.999; main effect of manipulation, F1,5330 = 1897, p < 0.001, d = 1.17). d Three out of four animals showed increased scanning during the baseline periods of the extinction session following over-activation, suggestive of a behavioral generalization response, but the increase was not significant (two-tailed paired t-test, p = 0.182). e A systematic elevation in blood pressure values was also evident for all four animals across the extinction recall session (linear mixed-model, manipulation ×  time, F < 1, p = 0.999; main effect of manipulation, F1,6547 = 720, p < 0.001, d = 1.34). f Again, three out of four animals also showed elevated baseline scanning following over-activation in the extinction recall session, but this change was not significant (two-tailed paired t-test, p = 0.087). Source data are provided as a Source Data file.