Dissociable memory modulation mechanisms facilitate fear amnesia at different timescales
- School of Psychological and Cognitive Sciences and Beijing Key Laboratory of Behavior and Mental Health, Peking University, China
- School of Psychology, Shaanxi Normal University, China
- Department of Anxiety Disorders, Shenzhen Kangning Hospital, Shenzhen Mental Health Institute, China
- Departments of Psychiatry and Neuroscience, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, United States
- IDG/McGovern Institute for Brain Research, Peking University, China
Figures
Figure 1 with 1 supplement
Skin conductance response (SCR) responses to conditioned stimuli in two groups of Study 1 indicating short-term memory amnesia.
(a) Experimental design and timeline. (b) SCRs of fear-conditioned stimuli (CS+) and the control stimulus (CS–) across fear acquisition, extinction, and test phases for two groups (reminder and no-reminder). (c) Mean differential SCRs (CS+ minus CS–) in the acquisition phase (trials in the latter half). (d) Differential SCRs (CS+ minus CS–) in the extinction phase (last trial). (e) Differential fear recovery index between CS+ and CS– in the test phase. ***p<0.001, *p<0.05. NS: nonsignificant. Two sample t-test, error bars represent standard errors (n = 30 & 27 for the reminder and no-reminder groups, respectively).
Figure 1—figure supplement 1
Skin conductance response (SCR) responses to conditioned stimuli in two groups of Study 1 with all responders (learners+non-learners).
(a) Experimental design and timeline. (b) Mean SCRs of fear-conditioned stimuli (CS+) and the control stimulus (CS–) across fear acquisition, extinction, and test phases for two groups (reminder and no-reminder). (c) Mean differential SCRs (CS+ minus CS–) in the acquisition phase (latter half trials). (d) Mean differential SCRs (CS+ minus CS–) in the extinction phase (last trial). (e) Differential fear recovery index (FRI) for the reminder and no-reminder groups (CS+ FRI minus CS– FRI). ***p<0.001, **p<0.01. NS: nonsignificant. Mann-Whitney U test, error bars represent standard errors (n = 36 & 31 for the reminder and no-reminder groups, respectively).
Figure 2 with 1 supplement
Skin conductance response (SCR) responses to conditioned stimuli in three groups of Study 2 indicating amnesia at different timescales.
(a) Experimental design and timeline. (b) SCRs of fear-conditioned stimuli CS1+ (reminder) and CS2+ (no-reminder), and the control stimulus (CS–) across the fear acquisition, extinction, and test phases for each group (30 min, 6 hr and 24 hr groups). (c) Mean differential SCRs (CS1+ minus CS– and CS2+ minus CS–) in the acquisition phase (trials in the latter half). (d) Differential SCRs in the extinction phase (last trial). (e) Differential fear recovery index between CS+ and CS– in the test phase. ***p<0.001. **p<0.01. *p<0.05. NS: nonsignificant. ANOVA and post-hoc t-test, error bars represent standard errors (n = 27, 26 and 26 for the 30min, 6h and 24h groups, correspondingly).
Figure 2—figure supplement 1
Skin conductance response (SCR) responses to conditioned stimuli in three groups of Study 2 with all responders (learners+non-learners).
(a) Experimental design and timeline. (b) SCRs of fear-conditioned stimuli CS1+ (reminder) and CS2+ (no-reminder), and the control stimulus (CS–) across the fear acquisition, extinction, and test phases for each group (30 min, 6 hr and 24 hr tests). (c) Mean differential SCRs (CS+ minus CS–) in the acquisition phase (latter half trials). (d) Differential SCRs (CS+ minus CS–) in the extinction phase (last trial). (e) Differential fear recovery index (FRI) for the reminder and no-reminder groups (CS+ FRI minus CS– FRI). ***p<0.001; *p<0.05. NS: nonsignificant. ANOVA and post-hoc t-test, error bars represent standard errors (n = 29, 26 and 27 for the 30min, 6h and 24h groups, correspondingly).
Figure 3
Fear recovery as a function of thought-control abilities.
(a) Thought control ability was significantly correlated with fear recovery index in the 30 min group (p=0.003, Bonferroni correction), but not in the 6 hr (b) or 24 hr group (c, Ps>0.7). The violin graphs indicate the distribution of fear recovery index across subjects (Figure 2e). **p<0.01. NS: nonsignificant.
Figure 4
Skin conductance response (SCR) responses to conditioned stimuli in the continuous theta-burst stimulation (cTBS) study (Study 3), indicating that both intact dorsolateral prefrontal cortex (dlPFC) and cue reminder are required for short-term memory amnesia.
(a) Experimental design and timeline. (b) SCRs of fear-conditioned stimuli CS1+ (reminder) and CS2+ (no-reminder), and the control stimulus (CS–) across the fear acquisition, extinction, and test phases for each group (R-PFC, R-VER, NR-PFC, and NR-VER groups). (c) Mean differential SCRs (CS1+ minus CS– and CS2+ minus CS–) in the acquisition phase (trials in the latter half). (d) Differential SCRs in the extinction phase (last trial). (e) Differential fear recovery index between CS+ and CS– in the test phase. ***p<0.001. *p<0.05. NS: nonsignificant. ANOVA and post-hoc t-test, error bars represent standard errors (n = 19, 18, 18 & 20 for the P-PRC, R-VER, NR-PFC and NR-VER groups, respectively).
Figure 5
The correlation between the differential fear recovery index and thought-control ability in four continuous theta-burst stimulation (cTBS) groups.
(a) There was no significant correlation between differential fear recovery index and thought-control abilities in the R-PFC group (p>0.4). (b) However, in the R-VER group, the correlation between thought-control ability scores and the differential fear recovery index was significant (p=0.008, Bonferroni correction), with high thought-control ability participants showing less fear recovery for both CS+ (CS1+ and CS2+). Such correlation was not observed in the (c) NR-PFC or the (d) NR-VER group (Ps>0.4). **p<0.01, NS: nonsignificant.
Figure 6
Time courses of short- and long-term amnesia.
(a) At the short interval (30 min to 1 hr), fear recovery of the reminded CS (CS1+) is inhibited (green). As time progresses (from 6 hr to 24 hr), the amnesia effect is likely due to the fear memory reconsolidation effect emerging later (orange). Actual skin conductance response (SCR) data in black solid line. (b) Fear amnesia of the non-reminded CS (CS2+) is only evident at the 30 min interval and such effect starts to decay as test interval increases (green). However, long-term amnesia does not generalize to CS2+ (orange, cue dependence). The observed SCR data (gray solid line) paralleled the prediction from both the short-term and the long-term effects as the interval length increased (from 30 min to 24 hr). (c) Schematics depicting the effect of cue reminder on fear memory retention. After both CS1+ (black) and CS2+ (gray) successfully elicit fear responses in the acquisition phase, CS1+ is reminded (black) before both CS+ go through the extinction training. The lack of both CS1+ and CS2+ fear responses in the short-term memory (STM) test (30 min) might be explained by the dorsolateral prefrontal cortex (dlPFC) dependent direct suppression effect (dotted circle of US representation). On the other hand, the cue-specific fear amnesia effect in the long-term memory (LTM) test (24 hr) of CS1+ but not CS2+ could be attributed to the reconsolidation effect specific to CS1+. *p<0.05. Error bars represent standard errors.
Author response image 1
Author response image 2
Tables
Author response table 1
| Test time/Group | Morning | Afternoon | Night | Total# Subjects |
|---|---|---|---|---|
| 30 min | 10 | 9 | 8 | 27 |
| 6 h | 0 | 12 | 14 | 26 |
| 24 h | 8 | 9 | 9 | 26 |
Additional files
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Supplementary file 1
Participant exclusion criteria.
- https://cdn.elifesciences.org/articles/98652/elife-98652-supp1-v1.docx
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MDAR checklist
- https://cdn.elifesciences.org/articles/98652/elife-98652-mdarchecklist1-v1.docx
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Dissociable memory modulation mechanisms facilitate fear amnesia at different timescales
eLife 13:RP98652.
https://doi.org/10.7554/eLife.98652.4
