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

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

Pregabalin effects on neural response to emotional faces

Pregabalin has shown promise in the treatment of anxiety disorders. Previous functional magnetic resonance imaging (fMRI) studies indicate agents used to treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and medial prefrontal cortex (mPFC) activation during emotional processing. Our prior study has shown that during anticipation of an emotional stimulus, pregabalin attenuates amygdala and insula activation but increases medial PFC activation. In this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin attenuates amygdala, insula, and medial PFC during emotional face processing. Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural activation during an emotional face-matching task. Linear mixed model analysis revealed that pregabalin dose-dependently attenuated left amygdala activation during fearful face-matching and left anterior insula activation during angry face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC. Thus, pregabalin shares some similarity to SSRIs and benzodiazepines in attenuating anger and fear-related insula and amygdala activation during emotional face processing. However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose. Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders

Combat PTSD and implicit behavioral tendencies for positive affective stimuli: A brief report

Background: Prior cognitive research in PTSD has focused on automatic responses to negative affective stimuli, including attentional facilitation or disengagement and avoidance action tendencies. More recent research suggests PTSD may also relate to differences in reward processing, which has lead to theories of PTSD relating to approach-avoidance imbalances. The current pilot study assessed how combat-PTSD symptoms relate to automatic behavioral tendencies to both positive and negative affective stimuli. Method: Twenty male combat veterans completed the Approach-Avoidance Task (AAT), Clinician Administered PTSD Scale, Beck Depression Inventory-II, and State-Trait Anger Expression Inventory-II. During the AAT, subjects pulled (approach) or pushed (avoid) a joystick in response to neutral, happy, disgust, and angry faces based on border color. Bias scores were calculated for each emotion type (avoid-approach response latency differences). Main and interaction effects for psychological symptom severity and emotion type on bias score were assessed using linear mixed models. Results: There was a significant interaction between PTSD symptoms and emotion type, driven primarily by worse symptoms relating to a greater bias to avoid happy faces. Post-hoc tests revealed that veterans with worse PTSD symptoms were slower to approach as well as quicker to avoid happy faces. Neither depressive nor anger symptoms related to avoid or approach tendencies of emotional stimuli.Conclusion: PTSD severity was associated with a bias for avoiding positive affective stimuli. These results provide further evidence that PTSD may relate to aberrant processing of positively valenced, or rewarding stimuli. Implicit responses to rewarding stimuli could be an important factor in PTSD pathology and treatment. Specifically, these findings have implications for recent endeavors in using computer-based interventions to influence automatic approach-avoidance tendencies