Background: Early life assaultive violence exposure is a potent risk factor for PTSD and other mood and anxiety disorders. Neurocircuitry models posit that increased risk is mediated by heightened emotion processing in a salience network including dorsal anterior cingulate cortex, anterior insula, and amygdala. However, the processes of reinforcement learning (RL) also engage the salience network and are implicated in responses to early life trauma and PTSD. To define their relative roles in response to early life trauma and PTSD symptoms, the current study compared engagement of the salience network during emotion processing and reinforcement learning as a function of early life assault exposure.Methods: Adolescent girls (n=30 physically or sexually assaulted; n = 30 healthy comparison) aged 11-17 completed two tasks during fMRI: a facial emotion processing task and RL tasks using either social or non-social stimuli. Independent component analysis was used to identify a salience network and characterize its engagement in response to emotion processing and prediction error (PE) encoding during the RL tasks.Results: Assault was related to greater reactivity of the salience network during emotion processing. By contrast, we found that assaulted girls demonstrated lesser encoding of negative PEs in the salience network, particularly during the social RL tasks. The dysfunction of salience network activity during emotion processing and PE encoding was not associated with PTSD symptoms. Conclusions:These results suggest that hyper-vs hypo-activity of the salience network among trauma-exposed youth depends on the cognitive-affective domain.

This study tested whether L-DOPA delivered during the consolidation window following fear extinction learning reduces subsequent fear responding among women with PTSD. Adult women diagnosed with PTSD completed a contextual fear acquisition and extinction task during fMRI and then immediately received either placebo (n = 34), 100/25 mg L-DOPA/carbidopa (n = 28), or 200/50 mg L-DOPA/carbidopa (n = 29). Participants completed a restingstate scan before the task and again 45 min following drug ingestion to characterize effects of L-DOPA on extinction memory neural reactivation patterns during consolidation. Twenty-four hours later, participants returned for tests of context renewal, extinction recall, and reinstatement during fMRI with concurrent skin conductance responding (SCR) assessment. Both active drug groups demonstrated increased reactivation of extinction encoding in the amygdala during the post-task resting-state scan. For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the 100 mg group compared to placebo. For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo. There was no evidence in SCR or neural activity that L-DOPA improved extinction recall. Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network. These results support a role for dopamine during the consolidation window in boosting reactivation of amygdala extinction encodings and reducing reinstatement, but not improving extinction recall, in women with PTSD.

Posttraumatic stress disorder (PTSD) is characterized by heightened avoidance, cognitive inflexibility, and impaired reward processing. Maladaptive behavior in PTSD may reflect an imbalance between approach and avoidance, but no research has investigated approach-avoidance conflict (AAC) in PTSD. The current study investigated approach-avoidance behavior in PTSD using a trauma-related AAC (trAAC) task in two independent samples. In Study 1, 43 women with a current diagnosis of PTSD and 18 healthy comparison subjects were recruited from the community. In Study 2, 53 women with trauma exposure and a range of PTSD symptoms were recruited from a correctional institution. Trials were separated into two phases: conflict (the option most likely to win points was most likely to show a trauma-related image) and congruent (the option most likely to win points was least likely to show a trauma-related image). In Study 1, reward obtainment varied with the task manipulation (i.e., fewer points earned during conflict compared to congruent Phase) in PTSD but not healthy subjects. These results indicate that when avoidance is advantageous (congruent phase), individuals with PTSD show increased task performance, whereas when avoidance is maladaptive (conflict phase), individuals with PTSD show increased sacrifice of reward. In Study 2, higher PTSD symptoms predicted decreased reward earning during the conflict phase, again indicating a sacrifice of reward when avoidance is maladaptive. Across both studies, PTSD associated with increased AAC and sacrifice of reward in the presence of trauma-related stimuli. These studies shed light on AAC in PTSD and could inform more targeted therapy approaches.

Highlights PTSD is often treated with psychotherapies based on principles of fear acquisition and extinction. Increased AEA has resulted in enhanced extinction learning and recall among healthy adults. These effects have not yet been comprehensively examined in a PTSD population. Results suggest that genetic variation within the FAAH gene affects how fear learning is tuned in women with PTSD.

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