AN FMRI STUDY EXAMINING THE EFFECTS OF ACUTE D-CYCLOSERINE ADMINISTRATION ON BRAIN ACTIVATIONS AND COGNITIVE FUNCTIONING IN SPIDER PHOBIA

Abstract

Specific phobias are among the most commonly diagnosed psychiatric disorders. Exposure and Response Prevention (ERP) has become the treatment of choice for specific phobias, and is believed to operate on the basis of fear extinction. Animal studies have shown that acute administration of D-cycloserine (DCS) prior to exposure to a feared stimulus enhances extinction of that fear. Clinical studies in humans have recently demonstrated that DCS facilitates the effects of ERP therapy, presumably through enhancement of memory encoding and consolidation. However, the neural mechanisms underlying these potential benefits of DCS are not understood. The current study used fMRI to examine brain function in subjects with specific phobia and healthy control participants, with and without DCS. The primary objectives of this study were to examine the effects of DCS on 1) neural activity during phobic symptom provocation and 2) neuropsychological functioning. Results provide evidence that DCS enhances activity in prefrontal cortex (PFC), anterior cingulate cortex (ACC), and insular cortex during phobic symptom provocation. This suggests that DCS may enhance cognitive control and interoceptive integration during emotional processing. Neuropsychological assessment provided evidence that specific phobia is associated with subtle differences in cognitive functioning, most notably on decision-making and strategic organization. DCS also had an effect on cognitive functioning, but the direction of influence depended upon clinical anxiety symptoms. The current study is the first investigation of acute DCS effects on neural processing during phobic symptom provocation. It is also the first study to examine acute DCS effects on neuropsychological functioning. Results provide direction for future research examining the use of acute DCS administration in enhancing fear extinction, exposure therapy, and cognitive functioning in general.