Understanding how fears are acquired is an important step in translating basic research to the treatment of fear-related disorders. However, understanding how learned fears are diminished may be even more valuable. We explored the neural mechanisms of fear extinction in humans. Studies of extinction in nonhuman animals have focused on two interconnected brain regions: the amygdala and the ventral medial prefrontal cortex (vmPFC). Consistent with animal models suggesting that the amygdala is important for both the acquisition and extinction of conditioned fear, amygdala activation was correlated across subjects with the conditioned response in both acquisition and early extinction. Activation in the vmPFC (subgenual anterior cingulate) was primarily linked to the expression of fear learning during a delayed test of extinction, as might have been expected from studies demonstrating this region is critical for the retention of extinction. These results provide evidence that the mechanisms of extinction learning may be preserved across species.

SUMMARY Recent efforts to translate basic research to the treatment of clinical disorders have led to a growing interest in exploring mechanisms for diminishing fear. This research has emphasized two approaches: extinction of conditioned fear, examined across species; and cognitive emotion regulation, unique to humans. Here, we sought to examine the similarities and differences in the neural mechanisms underlying these two paradigms for diminishing fear. Using an emotion regulation strategy, we examine the neural mechanisms of regulating conditioned fear using fMRI and compare the resulting activation pattern with that observed during classic extinction. Our results suggest that the lateral PFC regions engaged by cognitive emotion regulation strategies may influence the amygdala, diminishing fear through similar vmPFC connections that are thought to inhibit the amygdala during extinction. These findings further suggest that humans may have developed complex cognition that can aid in regulating emotional responses while utilizing phylogenetically shared mechanisms of extinction.

IMPORTANCE Clinically apparent atrial fibrillation increases the risk of ischemic stroke. In contrast, perioperative atrial fibrillation may be viewed as a transient response to physiological stress, and the long-term risk of stroke after perioperative atrial fibrillation is unclear. OBJECTIVE To examine the association between perioperative atrial fibrillation and the long-term risk of stroke. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using administrative claims data on patients hospitalized for surgery (as defined by surgical diagnosis related group codes), and discharged alive and free of documented cerebrovascular disease or preexisting atrial fibrillation from nonfederal California acute care hospitals between 2007 and 2011. Patients undergoing cardiac vs other types of surgery were analyzed separately. MAIN OUTCOMES AND MEASURES Previously validated diagnosis codes were used to identify ischemic strokes after discharge from the index hospitalization for surgery. The primary predictor variable was atrial fibrillation newly diagnosed during the index hospitalization, as defined by previously validated present-on-admission codes. Patients were censored at postdischarge emergency department encounters or hospitalizations with a recorded diagnosis of atrial fibrillation. RESULTS Of 1 729 360 eligible patients, 24 711 (1.43%; 95% CI, 1.41%–1.45%) had new-onset perioperative atrial fibrillation during the index hospitalization and 13 952 (0.81%; 95% CI, 0.79%–0.82%) experienced a stroke after discharge. In a Cox proportional hazards analysis accounting for potential confounders, perioperative atrial fibrillation was associated with subsequent stroke both after noncardiac and cardiac surgery. Type of SurgeryCumulative Rate of Stroke 1 Year AfterHospitalization, % (95% CI)Hazard Ratio (95% CI)PerioperativeAtrial FibrillationNo PerioperativeAtrial FibrillationNoncardiac1.47 (1.24–1.75)0.36 (0.35–0.37)2.0 (1.7–2.3)Cardiac0.99 (0.81–1.20)0.83 (0.76–0.91)1.3 (1.1–1.6) The association with stroke was significantly stronger for perioperative atrial fibrillation after noncardiac vs cardiac surgery (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Among patients hospitalized for surgery, perioperative atrial fibrillation was associated with an increased long-term risk of ischemic stroke, especially following noncardiac surgery.

Classical fear conditioning has been used as a model paradigm to explain fear learning across species. In this paradigm, the amygdala is known to play a critical role. However, classical fear conditioning requires first-hand experience with an aversive event, which may not be how most fears are acquired in humans. It remains to be determined whether the conditioning model can be extended to indirect forms of learning more common in humans. Here we show that fear acquired indirectly through social observation, with no personal experience of the aversive event, engages similar neural mechanisms as fear conditioning. The amygdala was recruited both when subjects observed someone else being submitted to an aversive event, knowing that the same treatment awaited themselves, and when subjects were subsequently placed in an analogous situation. These findings confirm the central role of the amygdala in the acquisition and expression of observational fear learning, and validate the extension of cross-species models of fear conditioning to learning in a human sociocultural context. Our findings also provides new insights into the relationship between learning from, and empathizing with, fearful others. This study suggests that indirectly attained fears may be as powerful as fears originating from direct experiences.