Volume 26, Issue 19, Pages 2690-2695 (October 2016) Disrupting Reconsolidation Attenuates Long-Term Fear Memory in the Human Amygdala and Facilitates Approach Behavior  Johannes Björkstrand, Thomas Agren, Fredrik Åhs, Andreas Frick, Elna-Marie Larsson, Olof Hjorth, Tomas Furmark, Mats Fredrikson  Current Biology  Volume 26, Issue 19, Pages 2690-2695 (October 2016) DOI: 10.1016/j.cub.2016.08.022 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 Exposure during Reconsolidation Attenuates Amygdala-Related Return of Fear Experimental conditions: after fear activation followed by seven exposure trials on day 1, the memory was tested on day 2 (A). Exposure to spiders on day 1 was performed either within the reconsolidation window after 10 min (10 min group) or outside the window after 6 hr (6 hr group) after fear activation. Another spider cue was activated but not presented during exposure (B). An additional cue was presented eight times during exposure day 1 but was not preceded by activation (C). On day 2, a new fourth spider slide was introduced (D). Within each group, subjects were exposed to all experimental conditions, and pictures were counter-balanced across subjects. Results: fMRI demonstrated increased amygdala activation from day 1 to day 2 in the 6 hr group (n = 23) as compared to the 10 min group (n = 22) for the activated and repeatedly exposed stimulus (xyz = −27, −7, −14; Z = 3.45; p < 0.0001; pcorrected = 0.006; 1,053 mm3; xyz = 27, −1, −14; Z = 2.34; p = 0.010; pcorrected = 0.107; 432 mm3) (A). For the activated but not exposed spider cue, amygdala reactivity tended to be higher in the 6 hr group than the 10 min group (xyz = −24, −7, −14; Z = 2.42; p = 0.008; pcorrected = 0.091; 243 mm3) (B). The exposed but not activated slide also elicited enhanced amygdala responsivity in the 6 hr group as compared to the 10 min group (xyz = −24, −7, −14; Z = 3.17; p = 0.001; pcorrected = 0.014; 1,053 mm3; xyz = 24, −10, −11, Z = 2.79; p = 0.003; pcorrected = 0.039; 378 mm3) (C). The new slide introduced on day 2 elicited higher amygdala activation in the 6 hr group as compared to the 10 min group (xyz = −24, −7, −14; Z = 2.82; p = 0.002; pcorrected = 0.035; 567 mm3) (D). The measure of amygdala activity is blood-oxygen-level-dependent (BOLD) activity. Brighter colors represent larger effects with higher significance. Brain coordinates are according to Montreal Neurological Institute (MNI). See also Figures S1–S3 and Table S1. Current Biology 2016 26, 2690-2695DOI: (10.1016/j.cub.2016.08.022) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 2 Disrupted Reconsolidation Facilitates Approach and Amygdala Activity Predicts Behavior Subjects chose between avoiding or viewing a spider slide while being paid nothing or 0.1, 0.5, 1, 2, or 5 SEK (Swedish Krona; 1 SEK ≈ 0.11 USD). (A) Approach behavior was facilitated by disrupted reconsolidation because the 10 min group (n = 21), as compared to the 6 hr group (n = 23), approached more spiders during high-gain conditions (F(5, 210) = 3.23; p = 0.008), being significant for the 2 and 5 SEK conditions (t(42) > 2.86; p < 0.005), and non-significant for the other conditions (t(42) < 1.70; n.s). Error bars indicate the SEM. (B) In the 6 hr group (top), which received undisrupted reconsolidation, amygdala activity during re-exposure was inversely related to approach behavior (xyz = −24, −1, −23; Z = 3.05; p = 0.001; pcorrected = 0.018; 540 mm3), whereas in the 10 min group, which received disrupted reconsolidation, no such relationship was observed. (C) The amygdala areas coupled to disrupted reconsolidation (Figure 1A) overlapped with areas predicting approach behavior in a 378 mm3 volume in the 6 hr group. See also Figure S4. Current Biology 2016 26, 2690-2695DOI: (10.1016/j.cub.2016.08.022) Copyright © 2016 Elsevier Ltd Terms and Conditions