Using the Neuroscience of Fear Extinction for Anxiety Reduction

The best available treatment for social anxiety disorder is exposure therapy; however, 25% of
socially anxious patients do not respond to an adequate course of exposure therapy and it is
unclear why. Prior attempts to identify non-responders using clinical and demographic
features have been largely unsuccessful, highlighting the need to examine constructs that are
more closely tied to the mechanism of treatment (i.e., extinction learning and recall) and
the organ of dysfunction (i.e., the brain). The neurobiology of extinction learning and
recall is well understood from decades of animal and pre-clinical laboratory work, which has
highlighted the importance of the amygdala, dorsal anterior cingulate cortex (dACC), and
ventromedial prefrontal cortex (vmPFC). However, this knowledge has not been leveraged to
improve exposure therapy response, despite the assumption that response relies on extinction
learning and its successful recall.

Thus, a critical long-term goal is to improve exposure therapy response by tailoring therapy
based on the neurobiological profile of each patient. This project addresses that goal by
directly linking neurobiological profiles of extinction learning and recall with clinical
symptoms and therapy response. A major objective of this project is therefore to build a
mechanistic predictive model of exposure therapy response based on the neurobiology of
extinction learning and recall.

To accomplish this goal, the investigators will recruit 80 adults with social anxiety
disorder who will be randomized to 10 sessions of exposure-focused therapy or waitlist. The
primary clinical outcome measure will be the Liebowitz Social Anxiety Scale (LSAS), a
validated and widely used measure that assesses anxiety and avoidance symptoms. Pre-therapy,
participants will also undergo an experimental protocol for extinction learning and recall.
Participants will first view a neutral abstract image repeatedly paired with a loud aversive
noise, and another image that is never paired (fear acquisition phase). Following this,
participants will view the same images without aversive consequences (extinction learning
phase). Better extinction learning will be defined as greater reductions in skin conductance
within the extinction learning phase. Brain activation during extinction learning will be
assessed in the amygdala, dACC, and vmPFC. Finally, participants will view the same images
without aversive consequences one week later (extinction recall phase). Better extinction
recall will be defined as less skin conductance during extinction recall relative to fear
acquisition. The central hypothesis is that greater activation in the vmPFC during extinction
learning will predict both extinction recall and therapy response over and above symptom
severity.

Inclusion Criteria:

- age 18-50

- primary diagnosis of social anxiety disorder

- fluent spoken and written English

- able to provide informed consent.

Exclusion Criteria:

- history of mania or psychosis

- current moderate or severe substance use disorder

- current major depression greater than moderate severity

- high risk for suicide

- prior traumatic brain injury with loss of consciousness >5 minutes

- general medical condition or impediment to vision, hearing, or motor function likely
to interfere with assessments

- prior exposure therapy (>2 sessions)

- current use of psychotropic medication

- current psychotherapy other than couples counseling

- post-menopausal status

- pregnancy