PROJECT SUMMARY/ABSTRACT
Anxiety-related psychopathology is a serious detriment to mental health in the United States, with total
lifetime prevalence a staggering 31.2%. The most commonly used clinical technique in the treatment of
many forms of anxiety-related psychopathology is exposure therapy. However, some patients do not benefit
from treatment and experience return of fear. One potential explanation is that exposure techniques are
designed to primarily address only a circumscribed set of stimuli and experiences. Consequently, reductions
in fear tend not to generalize to the broader, more nebulous network of fear associations typically seen in
pathological anxiety. In line with the RDoC Initiative and NIMH Strategic Objective 1 to define the
mechanism of complex behaviors, the Aims of this application investigate the neurobehavioral mechanisms
of higher-order generalization processes through which networks of abstract or indirect associations
develop and spread. To do this, we draw on and combine two experimental literatures, associative learning
(e.g., Pavlovian conditioning) and episodic memory, to precisely model and test the complex interplay of
emotion, learning, and memory that results in dense and difficult to treat higher-order fear associations. Aim
1 of this proposal will investigate the neural mechanisms of how neutral and conditioned fear memories are
integrated and retrieved in post-traumatic stress disorder (PTSD) and control participants. Advanced fMRI
neuroimaging techniques will be used to quantify the degree of integration and its relation to fear learning
and generalization. Although Pavlovian conditioning models are useful for testing fear generalization, the
burden of anxiety-related psychopathology is comprised of more than internal fear and anxiety experiences.
Behavioral avoidance and its interference in everyday life is also a key component of these pathologies, and
generalized forms of avoidance are particularly impairing and difficult to treat. Further, avoidance is quick to
generalize across stimuli based on abstract concepts, such as categorical similarity (e.g., learning to avoid
all people in a specific social group). Accordingly, Aim 2 will test how fear and avoidance generalize across
stimuli of varying degrees of conceptual similarity and identify key anxiety-related individual differences in
these processes. In this behavioral test, psychophysiological and self-report indices will be submitted to
sophisticated multilevel and latent profile analyses to optimize prediction of maladaptive forms of avoidance
generalization. The combined Aims laid out in this proposal will significantly bolster current knowledge of the
neural, cognitive, and behavioral mechanisms of higher-order and conceptual generalization and link these
mechanisms to clinical anxiety and related traits. Completion of these Aims will advance knowledge of the
neuroscience of emotional learning and memory and contribute to future treatments of anxiety-related
psychopathology.
