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An electroconvulsive therapy procedure impairs reconsolidation of episodic memories in humans

Abstract

Despite accumulating evidence for a reconsolidation process in animals, support in humans, especially for episodic memory, is limited. Using a within-subjects manipulation, we found that a single application of electroconvulsive therapy following memory reactivation in patients with unipolar depression disrupted reactivated, but not non-reactivated, memories for an emotional episode in a time-dependent manner. Our results provide evidence for reconsolidation of emotional episodic memories in humans.

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Figure 1: ECT disrupts reconsolidation.

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Acknowledgements

We would like to thank O. Buno Heslinga for help with patient recruitment, S. Vosters for help with creating and piloting stimulus material, A. van Stegeren for advice on the creation of the stimulus material, and F. Battaglia, C. Doeler and E. Hermans for commenting on previous versions of the manuscript. This work was supported by research grants from the Netherlands Organization for Scientific Research (NWO 918.66.613) and the European Research Council (ERC-2010-AdG 268800) to G.F. B.A.S. is supported by a Marie Curie Career Integration grant (FP7-PEOPLE-2011-CIG 304248) and grant SAF2011-27766 from the Spanish Ministry of Science and Innovation.

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Authors

Contributions

All of the authors contributed to the design of the study. M.C.W.K. acquired and analyzed the data. M.C.W.K., B.A.S. and G.F. wrote the manuscript. I.T., G.A.v.W. and J.A.v.W. reviewed and approved the manuscript.

Corresponding author

Correspondence to Marijn C W Kroes.

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Competing interests

I.T. has received speaker fees from SERVIER Nederland Pharma B.V.

Integrated supplementary information

Supplementary Figure 1 Study design.

Patients were assigned to one of three groups (A, B, C). During a first study session all groups were shown two emotional slide-show stories. During a second session memory for one of the two stories was reactivated. Immediately after memory reactivation patient in groups A and B received ECT. In patients of group B memory was tested immediately upon recovery from ECT (Test, blue). In patients of groups A and C memory was tested one day after reactivation (Test, red and orange respectively).

Supplementary Figure 2 Stimulus material

Patients were presented with two slide shows that form arousing episodic stories of negative valence. Top: the original “Cahill Story”, bottom: the newly developed story. Both stories consist of 11 slides and each slide is accompanied by an auditory narrative.

Supplementary Figure 3 Memory reactivation scores

All groups showed evidence of memory reactivation, i.e., memory performance at reactivation was above chance level as indexed by the memory reactivation score (one-sample t-test across all groups, (t(36) = 7.53, P < 0.001), and groups did not differ in memory reactivation scores (y-axis; Kruskal-Wallis for group (A,B,C), H(2) = 1.77, P = 0.412; group A (red) mean: 3.08, s.e.m.: 0.35; group B (blue): mean: 2.62, s.e.m.: 0.96; group C (orange) mean: 3.23; s.e.m.: 1.24). Therefore, the observed between-group differences in reactivated memories are not due to differences in strength of memory reactivation, and adequate memory reactivation principally allows the initiation of a reconsolidation process. Dashed line indicates chance level (25%), error bars depict s.e.m.

Supplementary Figure 4 DSST results

DSST scores in minutes (y-axis). A group (A, B, C) x time point (study, test) repeated measures ANOVA on DSST scores revealed no main effect of time point (F1, 33 = 1.72, P = 0.199), group (F2, 33 = 0.69, P = 0.509) or group x time point interaction (F2, 33 = 1.64, P = 0.209). Thus, General cognitive functioning does not differ between groups. Hence, group differences in memory performance are unlikely to be due to group differences in general cognitive functioning. Error bars depict s.e.m.

Supplementary Figure 5 Story phase results

Memory scores (y-axis) per phase for group A. Emotional narratives accompanied both slide-stories learnt by patients. Each story can be separated into three phases (x-axis) of which the middle is considered most emotional and results in enhanced memory when compared to the same images accompanied by a neutral narrative. Testing for a reactivation (reactivated story (solid bars), non-reactivated story (open-bars)) x phase (1,2,3) effect within group A revealed a main effect of reactivation (F1, 12 = 8.75 P = 0.012), but no main effect of phase (F2, 24 = 0.48, P = 0.624), or reactivation x phase interaction (F2, 24 = 2.40, P = 0.112). Thus we observe no interaction between relative emotionality of the studies material and the disturbance of reactivated memory. Error bars depict s.e.m.

Supplementary Figure 6 Memory performance is associated with illness and ECT parameters

We assessed whether screening scores or elements of ECT treatment were related to memory performance. Top: Cumulative illness rating scale scores (CIRS, y-axis) correlated with memory performance (x-axis) over all groups (Pearson r = –0.32, N = 38, P = 0.047), thus the lower the comorbid physical problems or illnesses the better memory performance. Middle: Limiting the analyses to group A and group B, we tested whether ECT treatment parameters were related to memory performance. An independent t-test showed that memory impairment was greater for bifrontotemporal electrode placement compared to right unilateral stimulation (t(24) = 2.28, P = 0.032, right unilateral mean: 36.27, s.e.m: 2.45; bifrontotemporal mean: 28.91, s.e.m.: 1.96). Bottom: Given that bilateral stimulation leads to more memory impairment, we specifically tested for a modulation of reconsolidation by electrode placement in group A. No effect was observed (P > 0.05), but this null finding may reflect the size of our sample (unilateral N=4, bilateral N=9). The reconsolidation impairment observed in group A was still evident when controlling for electrode placement. The relation between electrode placement and memory performance suggests that the observed memory impairments are a result of the electrical stimulation and/or the convulsion itself and not other elements of the ECT treatment such as the anaesthesia. Error bars depict s.e.m.

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Kroes, M., Tendolkar, I., van Wingen, G. et al. An electroconvulsive therapy procedure impairs reconsolidation of episodic memories in humans. Nat Neurosci 17, 204–206 (2014). https://doi.org/10.1038/nn.3609

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