Avoidant symptoms in PTSD predict fear circuit activation during multimodal fear extinction

Convergent evidence suggests that individuals with posttraumatic stress disorder (PTSD) exhibit exaggerated avoidance behaviors as well as abnormalities in Pavlonian fear conditioning. However, the link between the two features of this disorder is not well understood. In order to probe the brain basis of aberrant extinction learning in PTSD, we administered a multimodal classical fear conditioning/extinction paradigm that incorporated affectively relevant information from two sensory channels (visual and tactile) while participants underwent fMRI scanning. The sample consisted of fifteen OEF/OIF veterans with PTSD. In response to conditioned cues and contextual information, greater avoidance symptomatology was associated with greater activation in amygdala, hippocampus, vmPFC, dmPFC, and insula, during both fear acquisition and fear extinction. Heightened responses to previously conditioned stimuli in individuals with more severe PTSD could indicate a deficiency in safety learning, consistent with PTSD symptomatology. The close link between avoidance symptoms and fear circuit activation suggests that this symptom cluster may be a key component of fear extinction deficits in PTSD and/or may be particularly amenable to change through extinction-based therapie

The Neurosteroids Allopregnanolone and DHEA Modulate Neurocircuits implicated in Emotion Regulation and Posttraumatic Stress Disorder.

The neurosteroids dehydroepiandrosterone (DHEA) and allopregnanolone are integral components of the stress response and exert positive modulatory effects on emotion in human and animal studies. Though these antidepressant and anxiolytic effects have been well established, little research to date has examined their neural correlates. In particular, brain imaging techniques have not yet been used to assess the impact of neurosteroid administration on emotion regulation neurocircuitry. In a parallel line of research, growing evidence supports that intrinsic connectivity networks involved in emotion regulation are disrupted in anxiety disorders. However, the impact of neurosteroids on these intrinsic connectivity networks is unknown. Thus, the current studies aim to describe the impact of neurosteroids on emotion regulation neurocircuits and amygdala intrinsic connectivity by measuring the effects of neurosteroid administration on the Shifted-Attention Emotional Appraisal Task and on resting-state fMRI. We demonstrate that during emotion regulation, DHEA and allopregnanolone reduce activity in regions associated with generation of negative emotion and enhance activity in regions linked to regulatory processes. Further, we demonstrate that these neurosteroids modulate amygdala intrinsic connectivity in ways that run counter to aberrations observed in posttraumatic stress disorder. Thus, our results provide initial neuroimaging evidence that DHEA and allopregnanolone may be useful as pharmacological interventions for anxiety disorders and invite further investigation into the brain basis of neurosteroid emotion regulatory effects.PHDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/100064/1/rekaufma_1.pd

A Pilot Study of Mindfulness-based Exposure Therapy in OEF/OIF Combat Veterans with PTSD: Altered Medial Frontal Cortex and Amygdala Responses in Social-Emotional Processing

Combat-related PTSD is common among returning veterans, and is a serious and debilitating disorder. While highly effective treatments involving trauma exposure exist, difficulties with engagement and early drop may lead to sub-optimal outcomes. Mindfulness training may provide a method for increasing emotional regulation skills that may improve engagement in trauma-focused therapy. Here we examine potential neural correlates of mindfulness training and in vivo exposure (non-trauma focused) using a novel group therapy (Mindfulness-based Exposure Therapy) in Afghanistan (OEF) or Iraq (OIF) combat veterans with PTSD. OEF/OIF combat veterans with PTSD (N=23) were treated with MBET (N = 14) or a comparison group therapy (Present-centered group therapy [PCGT], N = 9). PTSD symptoms were assessed at pre- and post-therapy with Clinician Administered PTSD scale (CAPS). Functional neuroimaging (3 Tesla fMRI) before and after therapy examined responses to emotional faces (angry, fearful, and neutral faces). Patients treated with MBET had reduced PTSD symptoms (effect size d = .92) but effect was not significantly different from PCGT (d = .43). Improvement in PTSD symptoms from Pre- to Post treatment in both treatment groups was correlated with increased activity in rostral ACC, dorsal medial PFC, and left amygdala. The MBET group showed greater increases in amygdala and fusiform gyrus responses to Angry faces, as well as increased response in left medial PFC to Fearful faces. These preliminary findings provide intriguing evidence that MBET group therapy for PTSD may lead to changes in neural processing of social-emotional threat related to symptom reduction