Development of anxiety: the role of threat appraisal and fear learning

Abstract

Anxious individuals exhibit threat biases at multiple levels of information processing. From a developmental perspective, abnormal safety learning in childhood may establish threat-related appraisal biases early, which may contribute to chronic disorders in adulthood. This review illustrates how the interface among attention, threat appraisal, and fear learning can generate novel insights for outcome prediction. This review summarizes data on amygdala function, as it relates to learning and attention, highlights the importance of examining threat appraisal, and introduces a novel imaging paradigm to investigate the neural correlates of threat appraisal and threat-sensitivity during extinction recall. This novel paradigm can be used to investigate key questions relevant to prognosis and treatment. Depression and Anxiety, 2011.© 2010 Wiley-Liss, Inc.

Figure 1. Influences on Fear Learning

Figure 1 Legend: As illustrated in the highlighted box, fear learning primarily involves the amygdala and the ventromedial prefrontal cortex (vmPFC). Through repeated pairing of the conditioned stimulus (CS+) and unconditioned stimulus (UCS), the neural representation of the CS+ is activated in tandem with the amygdala response to the UCS. Following learning, the CS+ alone excites the amygdala and its projections to brain regions mediating the autonomic (e.g., heart-rate, respiration, and sweating response), endocrine (cortisol response), and behavioral (e.g., freezing, flight/fight response) constituents of the fear response. When the CS+ is presented in the absence of the UCS during extinction, the vmPFC is proposed to inhibit this amygdala activation. While fear learning principally involves the amygdala and vmPFC, attention, appraisal, and safety/threat discrimination processes and associated brain regions interact with fear learning to influence the fear response. The ventrolateral prefrontal cortex (vlPFC) and anterior cingulate cortex (ACC) influence the control of attention orienting and resource allocation. The dorsomedial prefrontal cortex (dmPFC) and dorsolateral prefrontal cortex (dlPFC) elaborate the learned classification via threat appraisal and emotion regulation processes. The hippocampus provides context and fear generalization information. Together, these processes and the underlying brain network influence the fear response.

Figure 2. Unconditioned Stimulus Selection

Figure 2 Legend: Thirty-five adults (mean age=27.9) rated similar anxiety levels following a 95dB, 3 second exposure to white noise, 2Hz tone, alarm and a scream (all p>0.3). Mean and standard deviations are displayed.

Figure 3. Morph Images used for Generalization

Figure 3 Legend: Several types of stimuli may be used to assess generalization gradients. A) Circles. The circles at the extremes are the images used in the fear conditioning procedure. Circles of varying size created a continuum of stimuli between these two extremes. [79]. B) Faces. The faces at the extremes are the pure images of the light-haired and dark-haired women with neutral facial expressions used in the fear conditioning procedure. The light-haired woman is morphed into the dark-haired woman using 10% increments, providing a continuum of similarity between the two women. The continuum of circles or faces can be used to assess fear generalization gradients following conditioning.

Figure 4. Threat Appraisal Paradigm

Figure 4 Legend: On Day 1, participants undergo fear acquisition and extinction procedures using the screaming lady paradigm in the psychophysiology laboratory using similar methods as Lau et al., 2008 [20]. Two women with neutral facial expressions are shown. One woman (CS+) is paired with a screaming lady (UCS); whereas, the other woman (CS-) never gets paired with the UCS. Approximately two weeks later, participants return and undergo extinction recall in the magnetic resonance imaging (MRI) scanner. Participants are shown a continuum of neutral face stimuli that vary between the CS+ and CS- while attending to their emotional state. A generalization gradient in brain activation in the ventromedial prefrontal cortex is expected. CS=conditioned stimulus, UCS=unconditioned stimulus, vmPFC=ventromedial prefrontal cortex.