Investigating the effect of memory strength within reactivation-extinction paradigm on cue-dependent amnesia

• Published in: Neuroscience Vol. 582; pp. 11 - 21
• Main Authors: Paul, Tripureshwari, Asthana, Manish Kumar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.08.2025
• Subjects: Adult; Amnesia - physiopathology; Amnesia - psychology; Conditioning, Classical - physiology; Cues; Extinction, Psychological - physiology; Fear - physiology; Fear - psychology; Female; Galvanic Skin Response - physiology; Humans; Male; Memory - physiology; Memory reconsolidation; Memory strength; Prediction error; Reinforcement, Psychology; Retrieval-extinction; Young Adult; Memory strength; Retrieval-extinction; Memory reconsolidation; Prediction error
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2025.07.014

•Boundary conditions of cue-dependent amnesia affect the conditional response.•Memory strength may hinder cue-dependent amnesia, and Prediction Errors during retrieval may serve as a prerequisite for decrease in conditioned fear responses.•Strong memories produced stronger conditioned responses in comparison to weaker memories.•Prediction error can serve as one of the factors affecting the fear return.•Prediction Error is unsuccessful in inducing cue-dependent amnesia for the group with stronger memories, hence leading to fear retention. Strong emotional memories serve as core symptoms of major psychological disorders. Paradigms based on memory reconsolidation have demonstrated superior results compared to standard methods. However, many studies have failed to replicate the findings in humans, highlighting the potential boundary conditions of memory, such as the strength of memory and prediction error (PE) that limits the effectiveness of the retrieval extinction paradigm. In the current study, we use a three-day fear conditioning paradigm. Three geometrical figures (CSs) were paired with two aversive tones and images (US) at partial (50%) and continuous (100%) reinforcement rates. The results showed that SCR generated higher conditioned responses during acquisition for continuous reinforcement than partial reinforcement. We find that there was a general decrease in SCR of fear reinstatement in groups treated with PE than standard methods. Also, group-wise comparison shows that fear returns in 100% reinforcement even if treated with PE in comparison to 50% reinforcement. The results demonstrate that memory strength and PE serve as boundary conditions for memory reconsolidation. This data is significant as it is the first study to examine memory strength within the so-called reactivation-extinction procedure in the context of the reconsolidation framework in human subjects.