# Mismatch vs. standard intervention during memory reconsolidation blockade with propranolol: effect on psychophysiological reactivity during traumatic imagery

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $167,500

## Abstract

PROJECT SUMMARY / ABSTRACT
The proposed R21 project will attempt to further develop a novel intervention for posttraumatic stress
symptoms inspired by the science of memory reconsolidation. Work in normal humans has shown that when a
stable, consolidated memory is reactivated (i.e., retrieved) under appropriate conditions, it reverts to an
unstable state, a process referred to herein as deconsolidation. In such a state, the memory is susceptible to
the action of various “amnestic” agents that may inhibit its reconsolidation, thereby weakening it. The β-
adrenergic blocker propranolol (PPNL) possesses such amnestic properties. More recent research has found
that in order to initiate deconsolidation, there must be a prediction error, or mismatch, between what is
expected and what occurs when the memory is reactivated.
Prior placebo-controlled, randomized clinical trials (PBO-RCT) from our laboratory have found that when
propranolol is administered concomitant with the reactivation of a psychologically traumatic memory, the
memory is weakened, as revealed by subsequent lower physiological (heart rate, skin conductance, facial
electromyogram) responding during script-driven mental imagery. Clinical applicability was evaluated in a
PBO-RCT, in which PTSD participants receiving propranolol underwent six weekly sessions of 10-20 min of
“standard” (STD) traumatic memory reactivation stimulated by reading a narrative. At post-treatment, these
participants showed a greater reduction of PTSD symptoms compared to participants who had taken PBO. The
goal of the proposed study is to test whether intentionally incorporating innovative mismatch (MM) into
traumatic memory reactivation can improve upon physiological responding during script-driven mental imagery.
Participants will be randomized to one of 2 treatment arms: STD/PPNL and MM/PPNL. A baseline assessment
will measure psychophysiological responsivity to script-driven mental imagery (target measure). PPNL will be
administered 90-min prior to each of six weekly 10-20 min. traumatic memory reactivation sessions. In the MM
condition, a different, unexpected mismatch (e.g., singing the narrative) will be incorporated into the
reactivation. In the STD condition, the participant will read the narrative the same way each time. The focus of
the R21 proposal will be to assess whether the MM/PPNL group shows lower subsequent physiological
responses than the STD/PPNL group.

## Key facts

- **NIH application ID:** 10868730
- **Project number:** 5R21MH131987-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** SCOTT P. ORR
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $167,500
- **Award type:** 5
- **Project period:** 2023-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868730

## Citation

> US National Institutes of Health, RePORTER application 10868730, Mismatch vs. standard intervention during memory reconsolidation blockade with propranolol: effect on psychophysiological reactivity during traumatic imagery (5R21MH131987-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10868730. Licensed CC0.

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