Neural correlates of sleep-induced benefits on traumatic memory processing.

Recent findings indicate that sleep after trauma compared to sleep loss inhibits intrusive memory development, possibly by promoting adequate memory consolidation and integration. However, the underlying neural mechanisms are still unknown. Here, we examined the neural correlates underlying the effects of sleep on traumatic memory development in 110 healthy participants using a trauma film paradigm and an implicit memory task with fMRI recordings in a between-subjects design. To further facilitate memory integration, we used targeted memory reactivation (TMR) to reactivate traumatic memories during sleep. We found that sleep (i.e., nap) compared to wakefulness reduced the number of intrusive traumatic memories for the experimental trauma groups. TMR during sleep only descriptively reduced the intrusions further. On the level of brain activity, increased activity in the anterior and posterior cingulate cortex, retrosplenial cortex and precuneus was found in the experimental trauma group compared to the control group after wakefulness. After sleep, on the other hand, these findings could not be found in the experimental trauma groups compared to the control group. Sleep compared to wakefulness increased activity in the cerebellum, fusiform gyrus, inferior temporal lobe, hippocampus, and amygdala during implicit retrieval of trauma memories in the experimental trauma groups. Activity in the hippocampus and the amygdala predicted subsequent intrusions. Results demonstrate the beneficial behavioral and neural effects of sleep after experimental trauma and provide indications for early neural predictor factors. This study has implications for understanding the important role of sleep for personalized treatment and prevention in posttraumatic stress disorder.

Experimental trauma rapidly modifies functional connectivity.

Traumatic events can produce emotional, cognitive and autonomous physical responses. This may ultimately lead to post-traumatic stress disorder (PTSD), a psychiatric syndrome which requires comprehensive treatment. Trauma exposure alters functional connectivity; however, onset and nature of these changes are unknown. Here, we explore functional connectivity changes at rest directly after experimental trauma exposure. Seventy-three healthy subjects watched either a trauma or a control film. Resting state functional magnetic resonance imaging measurements were conducted before and directly after the film. Seed-based analyses revealed trauma-related changes in functional connectivity, specifically including decreases of connectivity between amygdala and middle temporal gyrus and increases between hippocampus and precuneus. These central effects were accompanied by trauma-related increases in heart rate. Moreover, connectivity between the amygdala and middle temporal gyrus predicted subsequent trauma-related valence. Our results demonstrate rapid functional connectivity changes in memory-related brain regions at rest after experimental trauma, selectively relating to changes in emotions evoked by the trauma manipulation. Results could represent an early predictive biomarker for the development of trauma-related PTSD and thus provide an indication for the need of early targeted preventive interventions.

Structural brain differences predict early traumatic memory processing.

Intrusive memories are a key symptom of post-traumatic stress disorder (PTSD). They emerge early after trauma exposure and are predictive for PTSD development. There is a high relevance in evaluating the neurobiological mechanisms of early stages of intrusive symptom development to provide a further understanding of PTSD. In the present study, we explore structural differences in healthy young female subjects preceding experimental trauma exposure and their relationship to early intrusive memory development using a traumatic film paradigm. With voxel-based morphometry, we demonstrate that smaller insular volume was associated with an increased number of early intrusive film memories. Moreover, larger lingual gyrus/cerebellar and inferior frontal gyrus/precentral gyrus volumes were also related to an increased number of early intrusive film memories. Our results identify unique brain areas associated with early experimental trauma memory processing and highlight the necessity of evaluating early symptom stages relevant for personalized PTSD prevention and treatment.

Dopaminergic D1 Receptor Stimulation Affects Effort and Risk Preferences.

BACKGROUND: Activation of D1 receptors has been related to successful goal-directed behavior, but it remains unclear whether D1 receptor activation causally tips the balance of weighing costs and benefits in humans. Here, we tested the impact of pharmacologically stimulated D1 receptors on sensitivity to risk, delay, and effort costs in economic choice and investigated whether D1 receptor stimulation would bias preferences toward options with increased costs in a cost-specific manner. METHODS: In a randomized, double-blind, placebo-controlled, parallel-group phase 1 study, 120 healthy young volunteers received either placebo or 1 of 3 doses (6 mg, 15 mg, or 30 mg) of a novel, selective D1 agonist (PF-06412562). After drug administration, participants performed decision tasks measuring their preferences for risky, delayed, and effortful outcomes. RESULTS: Higher doses of the D1 agonist increased the willingness to exert physical effort for reward as well as reduced the preference for risky outcomes. We observed no effects on preferences for delayed rewards. CONCLUSIONS: The current results provide evidence that D1 receptor stimulation causally affects core aspects of cost-benefit decision making in humans.

Neural correlates of experimental trauma memory retrieval.

OBJECTIVES: Traumatic memories such as intrusions and flashbacks play a major role in the development and maintenance of post-traumatic stress disorder (PTSD). A thorough understanding of the neural mechanisms underlying traumatic memories is indispensable for precise diagnosis, for personalized treatment and prevention. In particular, the identification of early neural predictor variables for intrusion development shortly after trauma exposure requires detailed investigation. EXPERIMENTAL DESIGN: Here, we examined the neural correlates of early experimental trauma memory retrieval in a traumatic film paradigm in 42 young healthy females, using both implicit and explicit retrieval tasks. PRINCIPAL OBSERVATIONS: We show that implicit experimental trauma retrieval specifically involved the retrosplenial cortex and the anterior cingulate cortex (ACC), while both retrieval tasks resulted in trauma-related activity in the posterior cingulate cortex (PCC) and the precuneus. Importantly, neural activity early after experimental trauma exposure predicted later intrusion development, with independent contributions from activity in the retrosplenial cortex (implicit retrieval) and the PCC (explicit retrieval). Additional analyses revealed a stronger connectivity between the bilateral amygdala and the supplementary motor area, precentral and paracentral lobule for the control group compared to the experimental trauma group. CONCLUSIONS: Our study gives new insights in the neural correlates of experimental trauma memory retrieval and their predictive value for subsequent symptom development. Our results could provide the basis for personalized early treatment and prevention of PTSD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. Hum Brain Mapp 38:3592-3602, 2017. © 2017 Wiley Periodicals, Inc.