Recent research on changing fears has examined targeting reconsolidation. During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological manipulations at this stage result in an inability to retrieve the memories at later times, suggesting they are erased or persistently inhibited. Unfortunately, the use of these pharmacological manipulations in humans can be problematic. Here we introduce a non-invasive technique to target the reconsolidation of fear memories in humans. We provide evidence that old fear memories can be updated with non-fearful information provided during the reconsolidation window. As a consequence, fear responses were no longer expressed, an effect that lasted at least a year and was selective only to reactivated memories without affecting others. These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear.

Humans expect positive events in the future even when there is no evidence to support such expectations. For example, people expect to live longer and be healthier than average, they underestimate their likelihood of getting a divorce, and overestimate their prospects for success on the job market. We examined how the brain generates this pervasive optimism bias. Here we report that this tendency was related specifically to enhanced activation in the amygdala and in the rostral anterior cingulate cortex when imagining positive future events relative to negative ones, suggesting a key role for areas involved in monitoring emotional salience in mediating the optimism bias. These are the same regions that show irregularities in depression, which has been related to pessimism. Across individuals, activity in the rostral anterior cingulate cortex was correlated with trait optimism. The current study highlights how the brain may generate the tendency to engage in the projection of positive future events, suggesting that the effective integration and regulation of emotional and autobiographical information supports the projection of positive future events in healthy individuals, and is related to optimism.

Accounts of decision-making have long posited the operation of separate, competing valuation systems in the control of choice behavior. Recent theoretical and experimental advances suggest that this classic distinction between habitual and goal-directed (or more generally, automatic and controlled) choice may arise from two computational strategies for reinforcement learning, called model-free and model-based learning. Popular neurocomputational accounts of reward processing emphasize the involvement of the dopaminergic system in model-free learning and prefrontal, central executive-dependent control systems in model-based choice. Here we hypothesized that the hypothalamic-pituitaryadrenal (HPA) axis stress response-believed to have detrimental effects on prefrontal cortex function-should selectively attenuate model-based contributions to behavior. To test this, we paired an acute stressor with a sequential decision-making task that affords distinguishing the relative contributions of the two learning strategies. We assessed baseline working-memory (WM) capacity and used salivary cortisol levels to measure HPA axis stress response. We found that stress response attenuates the contribution of model-based, but not model-free, contributions to behavior. Moreover, stress-induced behavioral changes were modulated by individual WM capacity, such that low-WM-capacity individuals were more susceptible to detrimental stress effects than high-WMcapacity individuals. These results enrich existing accounts of the interplay between acute stress, working memory, and prefrontal function and suggest that executive function may be protective against the deleterious effects of acute stress.A number of accounts of human and animal decision-making posit the coexistence of separate valuation systems that control choice (1-4), which, broadly speaking, represent automatic or habitual vs. deliberative or controlled modes. The circumstances under which one system may dominate over the other and thereby exert control over behavior has been a question of interest in both neuroscience and psychology, in part because of the implications of such differential control for disorders of compulsion such as drug abuse (5, 6). Acute stress may afford unique leverage in isolating the properties of these systems, because it is believed to prompt a shift from more cognitive or deliberative processes to more automatic processes presumed to be underpinned by phylogenetically older brain structures (7).Accordingly, a spate of recent work suggests that acute stressindexed by changes in levels of cortisol, a neuroendocrine marker of stress response-engenders reliance on putative habitual and/ or automatic processes in human decision-making (8-13), consistent with the assumption that the physiological stress response impairs central executive functions subserving more deliberative choice. However, distinguishing such processes is both experimentally and theoretically fraught, because in dual process theories, which system controls a particular behavior is t...

Cognitive emotion regulation has been widely shown in the laboratory to be an effective way to alter the nature of emotional responses. Despite its success in experimental contexts, however, we often fail to use these strategies in everyday life where stress is pervasive. The successful execution of cognitive regulation relies on intact executive functioning and engagement of the prefrontal cortex, both of which are rapidly impaired by the deleterious effects of stress. Because it is specifically under stressful conditions that we may benefit most from such deliberate forms of emotion regulation, we tested the efficacy of cognitive regulation after stress exposure. Participants first underwent fear-conditioning, where they learned that one stimulus (CS+) predicted an aversive outcome but another predicted a neutral outcome (CS−). Cognitive regulation training directly followed where participants were taught to regulate fear responses to the aversive stimulus. The next day, participants underwent an acute stress induction or a control task before repeating the fear-conditioning task using these newly acquired regulation skills. Skin conductance served as an index of fear arousal, and salivary α-amylase and cortisol concentrations were assayed as neuroendocrine markers of stress response. Although groups showed no differences in fear arousal during initial fear learning, nonstressed participants demonstrated robust fear reduction following regulation training, whereas stressed participants showed no such reduction. Our results suggest that stress markedly impairs the cognitive regulation of emotion and highlights critical limitations of this technique to control affective responses under stress.

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Extinction training during reconsolidation has been shown to persistently diminish conditioned fear responses across species. We investigated in humans if older fear memories can benefit similarly. Using a Pavlovian fear conditioning paradigm we compared standard extinction and extinction after memory reactivation 1 d or 7 d following acquisition. Participants who underwent extinction during reconsolidation showed no evidence of fear recovery, whereas fear responses returned in participants who underwent standard extinction. We observed this effect in young and old fear memories. Extending the beneficial use of reconsolidation to older fear memories in humans is promising for therapeutic applications.[Supplemental material is available for this article.]Learning to predict threat from cues in the environment is adaptive. In order to remain adaptive, however, the memory of the association between a neutral cue and a threat cue, as well as the elicited fear response or defensive behavior, needs to be flexibly modified as situations change. The standard approach to modify fear is extinction or exposure training in which a new, safe association is learned, leading to a gradually diminished fear expression. With extinction, however, fear might return because the original fear memory is not significantly altered and must be inhibited to express the new extinction memory (Bouton 2004). It has been suggested that the inability to consistently inhibit fear memories following extinction or exposure may be a factor in the maladaptive expression of fear in anxiety, trauma, or stress-related disorders, such as post-traumatic stress disorder (PTSD) (Rauch et al. 2006). The potentially temporary nature of extinction or exposure training led to the search for strategies to more persistently alter fear memories, which renewed interest in the post-retrieval memory process of reconsolidation. Reconsolidation is a restabilization process triggered by the retrieval of the original memory (Duvarci and Nader 2004). Interventions that interfere with reconsolidation can persistently alter the expression of fear memories (Nader et al. 2000;Schiller et al. 2010). However, to derive a viable therapeutic technique based on disrupting reconsolidation, it is critical that both recently formed and older fear memories can be altered. Since memories of trauma are often formed long before treatment opportunities are available, it is important to characterize the effectiveness of reconsolidation for older memories. To date, there is little evidence in humans demonstrating the efficacy of targeting reconsolidation to diminish the expression of fear memories .1 d old. The goal of the present study was to start to bridge this gap by targeting reconsolidation in 7-d-old fear memories.Two primary techniques have been used to target the reconsolidation of fear memories: pharmacological and behavioral. These studies have examined fear memories using Pavlovian fear conditioning, in which an aversive unconditioned stimulus (UCS) is paired with a neutral co...

In a dynamic environment, sources of threat or safety can unexpectedly change, requiring the flexible updating of stimulus-outcome associations that promote adaptive behavior. However, aversive contexts in which we are required to update predictions of threat are often marked by stress. Acute stress is thought to reduce behavioral flexibility, yet its influence on the modulation of aversive value has not been well characterized. Given that stress exposure is a prominent risk factor for anxiety and trauma-related disorders marked by persistent, inflexible responses to threat, here we examined how acute stress affects the flexible updating of threat responses. Participants completed an aversive learning task, in which one stimulus was probabilistically associated with an electric shock, while the other stimulus signaled safety. A day later, participants underwent an acute stress or control manipulation before completing a reversal learning task during which the original stimulus-outcome contingencies switched. Skin conductance and neuroendocrine responses provided indices of sympathetic arousal and stress responses, respectively. Despite equivalent initial learning, stressed participants showed marked impairments in reversal learning relative to controls. Additionally, reversal learning deficits across participants were related to heightened levels of alpha-amylase, a marker of noradrenergic activity. Finally, fitting arousal data to a computational reinforcement learning model revealed that stress-induced reversal learning deficits emerged from stress-specific changes in the weight assigned to prediction error signals, disrupting the adaptive adjustment of learning rates. Our findings provide insight into how stress renders individuals less sensitive to changes in aversive reinforcement and have implications for understanding clinical conditions marked by stress-related psychopathology.

Fear learning and regulation is a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ability to flexibly regulate fear responses that are acquired through Pavlovian fear conditioning. Our primary aim is to explore the impact of stress on fear regulation in humans. Given this, we focus on techniques where stress has been linked to alterations of fear regulation in humans (extinction and emotion regulation), and briefly discuss other techniques (avoidance and reconsolidation) where the impact of stress or stress hormones have been mainly explored in animal models. These investigations reveal that acute stress may impair the persistent inhibition of fear, presumably by altering prefrontal cortex function. Characterizing the effects of stress on fear regulation is critical for understanding the boundaries within which existing regulation strategies are viable in everyday life and can better inform treatment options for those who suffer from anxiety and stress-related psychopathology.