fMRI Study Examining Effects of D-cycloserine in Specific Phobia

An fMRI Study Investigating the Effects of Acute D-cycloserine Administration on Brain Activations and Cognitive Functioning in Spider Phobia.

The research team hopes to use brain imaging and mental testing to learn more about specific phobias and the treatment of phobia. When given directly prior to therapy sessions, D-cycloserine has been shown to enhance the effects of therapy. This study hopes to identify reasons why D-cycloserine has this effect by measuring brain activity.

Exposure and Response Prevention (ERP) therapy has become the treatment of choice for specific phobias. ERP involves systematic and repeated exposure to a feared or anxiety-provoking stimulus, leading to habituation and extinction of the fear response. Animal models of fear extinction have shown that acute administration of D-cycloserine (DCS) prior to exposure to a feared stimulus enhances extinction of that fear. A recent study in human subjects with height phobia (a specific phobia) has also demonstrated that DCS facilitates the effects of ERP therapy. Current theories postulate that DCS facilitates fear extinction by enhancing the learning process and increasing consolidation of memories, but the neural mechanisms underlying this process are not understood. The proposed research aims to elucidate these mechanisms by using fMRI to measure brain activation during 1) symptom provocation and verbal learning two hours post-medication, and 2)repeated symptom provocation and verbal recognition one week post-medication. This research will also examine the effects of DCS on cognitive functioning using neuropsychological testing both two house and one week post-medication.

Regions of interest (ROIs) were specified based on previous research and included amygdala, insula, dorsal anterior cingulate cortex (ACC), dorsolateral PFC (dlPFC), and hippocampus. Multiple regression analyses were used to examine differences in response between experimental conditions (spider versus butterfly images). For significant clusters of activation within ROIs, the average max percent signal change is reported. For other regions, the average max percent signal change is reported within a sphere centered at coordinates identified via previous research.

Cognitive Functioning Measured Using the Wechsler Memory Scale III (Logical Memory and Faces Subtests)

This scale measures the learning and memory of functioning adults. Logical Memory I and II and Faces I and II subtests were administered to participants. The tasks measure verbal and visual memory, respectively. Scoring is based on the number of story details or faces correctly recalled during immediate (Logical Memory I, Faces I) and 30 minute delayed (Logical Memory II, Faces II) conditions. Total score ranges from 0-75 on Logical Memory I, 0-50 on Logical Memory II, 0-48 on Faces I, and 0-48 on Faces II. For all subtests, higher scores indicate better memory performance.

The RCFT assesses the a person's ability to use cues to retrieve information. The test measures visuospatial construction and memory. A person is asked to draw a figure. The figure is broken down into 18 elements. The score is based on their presence, completeness, and correct placement. Each element is scored from 0-2. The Copy, Immediate, and Delay results are scored on a 36 point scale. The higher the score, the better the person performed on the test with a 0 being the minimum and 36 being the maximum score. The organization score is scored according to whether the participant drew five cohesive units of the figure together, for a range of 0-6 and a higher score indicating better organizational performance.

This test measures a person's emotional decision making. Participants are presented with virtual decks of cards on a computer. Participants are told that each card they draw will "win" them game money. However, sometimes cards result in "losing" game money. The task includes 100 trials and the total score represents the number of cards drawn from "bad" decks as compared to "good" or safe decks. Thus, the score ranges from -100 to +100, with higher sores representing better performance.

The Wisconsin Card Sorting Task measures executive functioning and cognitive flexibility. The task uses a deck of 64 cards that the participant must sort according to specified rules. The test is stopped when when six sequences of 10 correct responses have been achieved, or after the deck has been completed twice, which provides a cumulative total of 128 trials. We report the number of errors on the task, which has a range of 0 -128, with a higher score representing worse performance.

Inclusion Criteria: Right-handed Adults between 18 and 55 years of age Subjects in the phobic group will additionally meet diagnostic (DSM-IV) criteria for spider phobia. Individuals of both genders and all races will be included Exclusion Criteria: Women who are breastfeeding or pregnant Individuals with medical conditions unsuitable for MR scanning Individuals reporting a history of epilepsy or seizures Individuals reporting an allergy to cycloserine Individuals diagnosed with asthma or who report previous anaphylactic reaction to insect stings/bites, medication, food, or other material and/or event Individuals reporting present or past diagnosis of a developmental disorder, neurological disorder, or head injury *Individuals found to have Axis I psychopathology as defined by the DSM-IV (other than spider phobia) Individuals currently taking any psychotropic medication