Over the Edge: Extending the duration of a reconsolidation intervention for spider fear

Abstract

Pharmacologically disrupting fear memory reconsolidation dramatically reduces fear behaviour. For example, 2–3 min of tarantula exposure followed by 40 mg of propranolol HCl (i.e., a reconsolidation intervention) abruptly decreased spider avoidance, an effect that persisted one year later. However, the success of reconsolidation interventions is not guaranteed: Pavlovian fear-conditioning research shows that the window to target memory reconsolidation is small and easy to miss. If exposure is too long to trigger reconsolidation, but too short for extinction learning, an inactive transitional limbo state occurs, rendering the fear memory unchanged and insensitive to amnesic agents. In this pre-registered study, we aimed to find this behaviourally-controlled boundary condition. Spider-fearful participants underwent a ~3 min (n = 23) or ~14 min (n = 20) exposure to a tarantula, intended to trigger reconsolidation or the limbo state respectively, followed by 40 mg of propranolol. We expected greater spider fear reduction after 3 than 14 min of exposure. Unexpectedly, there were no group differences on any outcome measures. In both groups, Bayesian analysis revealed a marked reduction in fear behaviour towards a generalisation stimulus (a house spider) accompanied by lower self-reported distress, with a sharp decline in spider fear scores two days after treatment that persisted one year later. Possible explanations include that the boundary conditions of reconsolidation are wider in older and stronger memories than experimentally-induced fears, or that alternative processes caused the treatment effects. Although the mechanism is unclear, these results carry a tentative promising message for the potential of brief reconsolidation-targeting interventions to mitigate irrational fears.

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“…The crucial role of central noradrenergic signaling in the process cascade ( 41 ) suggests that the β-adrenergic blocker propranolol is a viable option for effectively interfering with memory reconsolidation in humans. Indeed, preclinical research has compellingly shown that β-adrenergic blockade during reconsolidation can disrupt fear memories in healthy individuals (e.g., ( 42 ); see for a review ( 43 )) and in people with a fear of spiders (( 44 , 45 ); but see ( 46 )). Even though these findings point to a revolutionary new treatment for emotional memory disorders, the success of reconsolidation interventions is not guaranteed ( 47 ).…”