Sunday, May 4, 2025
5/4/2025
Disrupting fear:reconsolidation, cue specificity and memory strength - Fear learning and regulatory processes have been the subject of intense neuroscientific scrutiny in recent years, as substantial evidence suggests that psychopathology can emerge when these processes are compromised. Research has suggested a method based on the principles of memory reconsolidation may constitute the basis for an effective therapeutic approach for treatment of stress and anxiety disorders. This method involves activation of a fear memory by presentation of an isolated retrieval stimulus, causing the memory to become labile, followed by behavioral extinction, during which time the memory can be altered. But mixed results in the literature suggests this method may not always be effective (Lee et al., 2017). One factor impacting reconsolidation might be the specificity of the retrieval stimulus, with some evidence suggesting that a stimulus categorically distinct from the original fear cue might not enable reconsolidation update (Debiec et al., 2006; Debiec et al, 2013) or even activate brain structures necessary for reconsolidation to occur (Dunsmoor et al., 2011). This is a clinically relevant issue because an anxious individual undergoing exposure therapy is rarely exposed to a stimulus identical to the trauma or fear-relevant cue. Whether a dissimilar exemplar of a conditioned fear cue can effectively be employed in reconsolidation update paradigms to persistently attenuate learned fear has never been directly tested. Aim 1 of this project will utilize a Pavlovian fear conditioning paradigm to test the effect of cue specificity on reconsolidation update, as indexed by galvanic skin response (GSR) during a fear recovery test. Evidence also suggests that the strength of a fear memory could represent a limiting factor on reconsolidation update (Suzuki et al., 2004). However, no consensus operational definition for fear memory strength currently exists in the literature. Additionally, studies that have examined memory strength have focused mostly on responding during acquisition or within-session extinction, but not the clinically relevant target of fear recovery (Craske et al, 2008). Aim 2 will test the effect of two acquisition parameters, rate of reinforcement and number of learning trials (CS-US), on memory strength, as indexed by GSR responses during fear recovery. Furthermore, evidence suggests a dispositional factor, intolerance for uncertainty (IUS; Chin et al., 2016), may interact with reinforcement rate to mediate conditioned responding during acquisition. However, interactive effects during extinction or on long-term fear regulatory outcomes have yet to be tested. These studies will provide translationally-relevant data to researchers and clinicians interested in systematically manipulating memory strength in future studies and shed light on a factor that could account for some of the individual-level variance in fear recovery commonly observed in previous research. Collectively, these studies will contribute to efforts to develop more effective treatments for individual with stress and anxiety disorders.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).