Abstract
Prolonged exposure (PE) is an empirically supported efficacious treatment for posttraumatic stress disorder (PTSD). In this focused review, we briefly review the neurobiological networks in PTSD relevant to PE, discuss the theoretical basis of PE, review the neurobiological mechanisms underlying the effectiveness of PE and identify the enhancements that can be applied to increase treatment response and retention. Based on the reviewed studies, it is clear that PTSD results in disrupted network of interconnected regions, and PE has been shown to increase the connectivity within and between these regions. Successful extinction recall in PE is related to increased functional coherence between the ventromedial prefrontal cortex (vmPFC), amygdala and the hippocampus. Increased connectivity within the dorsolateral PFC (dlPFC) following PE is associated with more effective downregulation of emotional responses in stressful situations. Pre-existing neural connectivity also in some cases predicts response to exposure treatment. We consider various enhancements that have been used with PE, including serotonin reuptake inhibitors (SSRIs), D-cycloserine (DCS), allopregnanolone (ALLO) and propranolol, repetitive transcranial magnetic stimulation (rTMS), oxytocin and MDMA. Given that neural connectivity appears to be crucial in mechanisms of action of PE, rTMS is a logical target for further research as an enhancement of PE. Additionally, exploring the effectiveness and mechanisms of action of oxytocin and MDMA in conjunction with PE may lead to improvement in treatment engagement and retention.