Edited by:
Reviewed by:
*Correspondence:
This article was submitted to Clinical and Health Psychology, a section of the journal Frontiers in Psychology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Disruption of fear conditioning, its extinction and its retrieval are at the core of posttraumatic stress disorder (PTSD). Such deficits, especially fear extinction delay, disappear after alternating bilateral stimulations (BLS) during eye movement desensitization and reprocessing (EMDR) therapy. An animal model of fear recovery, based on auditory cued fear conditioning and extinction learning, recently showed that BLS facilitate fear extinction and fear extinction retrieval. Our goal was to determine if these previous results found in animals can be reproduced in humans. Twenty-two healthy participants took part in a classical fear conditioning, extinction, and extinction recall paradigm. Behavioral responses (fear expectations) as well as psychophysiological measures (skin conductance responses, SCRs) were recorded. The results showed a significant fear expectation decrease during fear extinction with BLS. Additionally, SCR for fear extinction retrieval were significantly lower with BLS. Our results demonstrate the importance of BLS to reduce negative emotions, and provide a successful model to further explore the neural mechanisms underlying the sole BLS effect in the EMDR.
Posttraumatic stress disorder (PTSD) (
Eye movement desensitization and reprocessing is an eight-step standardized protocol of cognitive, emotional, and physical assessment associations of actual distress to traumatic scenery. Also included is imaginal exposure during BLS. These are either auditory, visual, or somaesthetic stimuli alternating between the two sides of the body (
Fear mechanism deficits are thought to be at the core of PTSD (
Despite varying results based on the protocols (with and without context during the fear conditioning), this model has received strong support. Studies have shown that PTSD patients had faster fear conditioning and slower fear extinction (
Adding BLS during fear extinction learning has been used as a model mimicking the core feature of EMDR therapy. It has alleviated early extinction and long-lasting fear recovery of conditioned fear in mice (
Nevertheless, whether or not a BLS facilitation effect on fear extinction could also be found in humans has not been demonstrated. To further verify if the BLS effect obtained in mice can be replicated in humans, we evaluated 22 healthy participants using a paradigm that included fear conditioning and fear extinction on the first day, and fear extinction recall the following day. We recorded the participants’ behavioral and psychophysiological responses to assess their fear expectations and these responses were recorded by means of skin conductance measurements which have the advantage of reflecting sympathetic nervous system activity, as well as its involved fear response brain structure modulations such as by the amygdala (
Twenty-two healthy participants with no neurological or psychiatric disorders were recruited via screening lists at the
The investigation was carried out in accordance with the latest version of the Declaration of Helsinki. Participants provided written informed consent in agreement with local ethical committee guidelines set forth by the South Mediterranean 2 Committee who approved the protocol.
The experimental protocol was administrated over two separate days in keeping with the example of previous studies (
Example that illustrates the experimental protocol including habituation, fear acquisition (= fear conditioning), extinction, and fear extinction recall with two conditions during the extinction phase,
The BLS were administered using auditory tones alternately delivered to the right and left ears at a frequency of 1 Hz using Sony’s MDRZX110 headset. Auditory tones had broadband sounds similar to those used by many EMDR practitioners with the Tac/AudioScan from NeuroTek Corporation.
On day one, participants underwent the habituation, acquisition, and extinction phases of the two tasks in order to obtain their fear conditioned responses. The BLS were administered during one of the two extinction phases in a pseudo-randomized order. On day two, participants underwent the Recall phases to test for fear extinction retrieval.
Participants were comfortably seated 60 cm from a 17′′ computer screen. In one task, the stimuli were geometric figures of a triangle and a circle, both gray-colored and with identical luminance against a dark-blue background (
For the other task, the conditioned stimuli were represented by two volumes; a cube and a cylinder, each gray-colored and with identical luminance against a dark-red background. In this case, the CS+ was the cylinder and the CS- was the cube. On each task, the CS+ and the CS- pictures were presented for 4s. The mean inter-trial interval was 8 s (ranging from 6 to 10 s).
On day one, the conditioning task consisted of three different phases: habituation, acquisition, and extinction. The US was a 500-ms electrical stimulation. Electrical stimulation intensity was individually pre-set using an up-down staircase method to achieve a level of “unpleasant but not painful” sensations. The electrical stimulation intensity was kept at a constant all along the conditioning phase.
After viewing each image, participants used a 5-button keypad to respond as quickly as possible to: “how much do you expect this stimulus to be paired with an electrical stimulation: 0, 25, 50, 75, or 100%?”
For the extinction phase, no further instructions were shown. This phase consisted of 16 CS+ and 16 CS-. The CS+ was uncoupled with the US.
One of the two extinction phases was associated with auditory BLS. The two tasks and the BLS were presented in a counterbalanced order for all participants and each performed the two conditioning tasks.
On day two, participants performed the extinction recall task related to the two previous conditioning tasks. Participants were presented with the 24 CS+ and the 24 CS- as defined from day one (
In addition to behavioral responses, SCRs were recorded during all sessions with the Biopac system (MP30). This procedure obtained objective phasic psychophysiological indices of the participant’ sympathetic responses (
We used an electric stimulator, developed in partnership with the
Fear expectation mean percentages and SCR amplitudes were calculated by averaging four subsequent consecutive values resulting from the CS+ and CS- conditions. The averaged four responses, along the conditioning, extinction and recall phases provided nine mean values for each CS-type: one corresponding to habituation (H; the four last), four to conditioning (C1, C2, C3, and C4) and four to extinction (E1, E2, E3, and E4). Results obtained for CS- were subtracted to those for CS+.
Because the data did not follow the normality law and/or did not respect the variance equality, non-parametric tests were performed using sigma plot software (v12). Five participants had no electrodermal conditioning, that is, they had no SCR larger than 0.01 for any of the CS during acquisition. Therefore, our subsequent analyses included the 13 remaining participants with SCR.
To test for the main effect of Time, Friedman repeated the measures ANOVA on ranks on the difference between CS+ and CS- for the fear expectation values (percentages) and the SCR amplitudes of the nine time periods. Tukey’s HSD tests were used for
As displayed on the
As displayed on the
The present study findings replicate in humans the fear extinction facilitation by BLS previously found in mice (
The BLS effect was found during extinction for the percentage of fear expectation but not during fear extinction recall. Conversely, the BLS effect exists during fear extinction recall but not during extinction for SCR indicating a dissociation between the behavioral and the psychophysiological responses. This lack of BLS effect on the SCRs during the fear extinction may be related to habituation of the electrodermal measure (
The lack of BLS effect on fear expectation during the fear extinction retrieval could be due to the weak fear expectation difference between CS+ and CS- (<10% on average) suggesting that participants minimally expected fear.
Further experiments could improve the protocol of fear extinction recall to avoid such a ceiling effect. This could be achieved by enhancing the fear expectations during the fear conditioning, then increasing the duration of the conditioning phase and reinforcement rate of the US to elicit larger fear expectation responses at the recall. Nevertheless, the fact that SCR amplitudes were larger
The significant Time effect found on the percentage of fear expectation substantiates the validity of our fear conditioning protocol. In particular, this effect of Time showed an increased fear expectation until the end of the fear conditioning, and a decrease along the fear extinction for the difference between CS+ and CS-. There are similar observations for the fear extinction recall since the fear expectation for the CS+ minus CS- was higher at the beginning than at the end of the fear extinction recall.
This Time effect was less evident for the SCR amplitudes and could be due to two reasons. Firstly, the statistical power for the SCR results was weaker when compared to that of the behavioral responses. This is because the number of participants included in the SCR’s analyses was reduced when compared to the behavioral sample (five of the participants did not show any apparent SCRs to the stimuli). Moreover, according to the standard errors, it seems that there was greater variability of the SCR than of the behavioral responses.
Secondly, as reported above, the SCRs are potentially susceptible to habituation (
As with mice (
Given that the SCR are modulated by the amygdala (
In agreement with this hypothesis, recent reviews argue that BLS may be essential to the EMDR therapy (
Some authors theorize that the EMDR effect mostly relies upon the taxing memory effect of eye movements (
In our experiment, the BLS effect during fear extinction may rely on such a taxation of vividness and emotionality of the electric stimulation memory, or may provoke memory reconsolidation. Our model may serve to explore and solve this issue considering the sole effect of the BLS.
Future studies should also further consider variables such as age and gender that could be potential limitations to the interpretation of the BLS effect.
This experiment demonstrated the facilitating effect of BLS on fear extinction learning and its retrieval. Further experiments using the present protocol coupled with functional MRI, and applying the refinements suggested above, would be effective to explore the brain mechanisms involved in the “BLS effect,” and likely in the EMDR, to decrease negative emotions related to a traumatic memory. In addition, further experiments could also verify, as in
SK, SB, CS, BN, P-FR, EG, and CV-M substantially contributed to the design and to the experiment and the acquisition, analysis and the interpretation of the data, and to drafting and final approval of the version of the manuscript to be published. The agreement is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We gratefully acknowledge all the participants for their time and involvement, as well as the staff at the fMRI center in
bilateral alternating stimulations
conditioned stimulus
eye movement desensitization and reprocessing
skin conductance responses
unconditioned stimulus.