Measuring human context fear conditioning and retention after consolidation

Abstract

Fear conditioning is a laboratory paradigm commonly used to investigate aversive learning and memory. In context fear conditioning, a configuration of elemental cues (conditioned stimulus [CTX]) predicts an aversive event (unconditioned stimulus [US]). To quantify context fear acquisition in humans, previous work has used startle eyeblink responses (SEBRs), skin conductance responses (SCRs), and verbal reports, but different quantification methods have rarely been compared. Moreover, preclinical intervention studies mandate recall tests several days after acquisition, and it is unclear how to induce and measure context fear memory retention over such a time interval. First, we used a semi-immersive virtual reality paradigm. In two experiments (N= 23 andN= 28), we found successful declarative learning and memory retention over 7 d but no evidence of other conditioned responses. Next, we used a configural fear conditioning paradigm with five static room images as CTXs in two experiments (N= 29 andN= 24). Besides successful declarative learning and memory retention after 7 d, SCR and pupil dilation in response to CTX onset differentiated CTX+/CTX−during acquisition training, and SEBR and pupil dilation differentiated CTX+/CTX−during the recall test, with medium to large effect sizes for the most sensitive indices (SEBR: Hedge'sg= 0.56 andg= 0.69; pupil dilation: Hedge'sg= 0.99 andg= 0.88). Our results demonstrate that with a configural learning paradigm, context fear memory retention can be demonstrated over 7 d, and we provide robust and replicable measurement methods to this end.

The impact of doxycycline on human contextual fear memory

“…We employed a configural conditioning task that seeks to maximize configural associations (Stout et al 2018 , 2019 ), thus suggesting hippocampal involvement. In a preceding methodological investigation, we demonstrated successful fear memory recall after 7 days in this paradigm (Xia et al 2023 ).…”

“…After the trial protocol was registered and recruitment for the present study commenced, we conducted two methodological experiments to investigate the effect size for memory retention in the employed configural fear conditioning protocol (Xia et al 2023 ). These experiments revealed effect sizes between d = 0.58 and d = 0.71 in SEBR, and between d = 0.91 and d = 1.02 in pupil dilation.…”

“…Prior methodological work (Xia et al 2023 ) with the same experimental paradigm identified SEBR and pupil dilation as indices for configural fear memory retention 7 days after fear learning, and skin conductance response (SCR) and pupil dilation as indices for fear acquisition. Pre-processing and scoring methods were in line with the most sensitive procedures identified in this previous work.…”

Attenuating human fear memory retention with minocycline: a randomized placebo-controlled trial

“…The effect sizes for this power analysis were based on a study using cued delay fear conditioning [ 38 ]. After the trial protocol was registered, we derived effect sizes for the CS + /CS- difference in a methodological study [ 36 ] using the same configural fear conditioning paradigm as in the current trial. This study revealed a smaller effect size of d = 0.71 for the CS + /CS- FPS difference.…”

“…Thus, in the present study, we used a presumably hippocampus-dependent configural fear conditioning paradigm [ 33 – 35 ] and investigated the effect of minocycline on configural memory retention. We identified the optimal quantification of memory retention in this paradigm in a preceding methodological investigation [ 36 ]. Accordingly, we pre-registered fear-potentiated startle eye-blink responses (FPS) during configural memory recall as primary outcome, and pupil dilation as secondary outcome.…”