Neurobiology of Generalized Fear-Conditioning & Avoidance in Anxiety Disorders
Condition: Anxiety Disorders
MeSH terms: Anxiety Disorders
Study type: Observational

Summary: 
      Anxiety disorders are among the most prevalent, costly, and disabling mental illnesses. One
      central, yet largely understudied, abnormality in anxiety disorders is the heightened
      tendency to display fear and avoidance in reaction to benign or safe events that resemble
      feared situations. The current project maps brain circuits associated with this abnormality
      in order to contribute to future brain-based diagnosis and treatments for clinical anxiety.
    

Detailed description: 
      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, overgeneralization
      represents a promising dimension of potential threat with relevance across traditional
      anxiety disorders. 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 neuroimaging 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 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 psychometrically validated personality traits relevant across traditional anxiety
      disorders. This third and final goal is critical to the project, because individual
      difference measures capturing empirically-validated psychological constructs will likely
      track relations between fundamental conditioning processes (e.g., generalization) and general
      dysfunction, better than traditional, polythetic, diagnostic entities, that, by and large, do
      not reflect any single coherent psychological process.
    

Intervention name(s): Test of fear conditioning
Intervention type(s): Behavioral
Intervention description(s): Behavioral and brain correlates of conditioned fear generalization and avoidance will be assessed using fMRI and related to levels of anxiety related psychopathology.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Male and female adults presenting with anxiety symptoms at the Anxiety Disorders Clinic in
        the Department of Psychiatry at U of MN, as well as demographically matched healthy
        comparisons
      
Keywords: fear-conditioning; behavioral avoidance; anxiety disorders; fMRI