Generalized Fear-Conditioning & Avoidance: Neurobiology & Transdiagnostic Import

NIH RePORTER · NIH · R01 · $196,739 · view on reporter.nih.gov ↗

Abstract

Project Summary: The objective of this project is to neurally, behaviorally, psychologically, and clinically characterize fundamental Pavlovian and instrumental dimensions of potential threat through which emotional and behavioral responses to threat cues generalize to resembling, safe stimuli. Such generalization is aligned with the potential threat construct due to the threat ambiguity, or uncertain threat value, inherent in these safe `generalization' stimuli. The Pavlovian dimension of interest is generalization of conditioned fear: a fundamental Pavlovian process through which fear transfers, or generalizes, to safe stimuli resembling a conditioned threat-cue (CS+). The targeted instrumental dimension is generalized avoidance: active decisions to withdraw from safe stimuli resembling the CS+ that are motivationally prompted by Pavlovian generalization. Given lab-based findings have linked heightened Pavlovian generalization to a variety of traditional anxiety disorders (PTSD, GAD, panic), overgeneralization represents a promising dimension of potential threat with transdiagnostic relevance to anxiety pathology. One central aspect of this project is testing personality and psychiatric factors (e.g., trait fear, internalizing, externalizing) that may account for the relevance of generalization and its neurobiology across traditional anxiety disorders. A second key aspect, is studying neural processes by which Pavlovian generalization evokes instrumental generalized avoidance of benign stimuli (resembling danger cues), which, when excessive, is likely to impair day-to-day functioning in anxiety patients. Unfortunately, human fear- conditioning experiments in clinical samples, have focused almost exclusively on passive-emotional, Pavlovian conditioning, to the virtual exclusion of studying active-behavioral, instrumental avoidance. The current fMRI project fills this gap by applying a novel Pavlovian-instrumental generalization paradigm to neurally and behaviorally elucidate Pavlovian processes leading to generalized instrumental avoidance. Personality moderators (e.g., dispositional resilience) of relations between Pavlovian and instrumental generalization will also be examined. The studied adult samples will display a wide range of symptom severity across traditional anxiety disorders and will include trauma survivors (N=114), and anxiety-clinic patients and healthy comparisons (N=159). Central goals of this proposal include: 1) elucidating the neurobiology of Pavlovian and instrumental generalization and their interaction, 2) testing relations between neural substrates of Pavlovian and instrumental generalization and broad psychiatric dysfunction (Aims2-3); and 3) assessing the degree to which relations between these dimensions of generalization and broad dysfunction are driven by transdiagnostic, psychometrically validated personality traits. This third and final goal is critical to the project, because individual difference measures capturi...

Key facts

NIH application ID
9942503
Project number
5R01MH107382-05
Recipient
UNIVERSITY OF MINNESOTA
Principal Investigator
Shmuel Mordechai Lissek
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$196,739
Award type
5
Project period
2016-07-20 → 2022-08-31