A Case for Translation From the Clinic to the Laboratory.

Laboratory procedures have been used for decades as analogues for clinical processes with the goal of improving our understanding of psychological treatments for emotional disorders and identifying strategies to make treatments more effective. This research has often focused on translation from the laboratory to the clinic. Although this approach has notable successes, it has not been seamless. There are many examples of strategies that work in the laboratory that fail to lead to improved outcomes when applied clinically. One possible reason for this gap between experimental and clinical research is a failure to focus on translation from the clinic to the laboratory. Here, we discuss potential benefits of translation from the clinic to the laboratory and provide examples of how this might be implemented. We first consider two well-established laboratory analogues (extinction and cognitive reappraisal), identify critical aspects of the related clinical procedures (exposure and cognitive restructuring) that are missing from these analogues, and propose variations to better capture the clinical process. Second, we discuss two clinical procedures that have more recently been brought into the laboratory (eye-movement desensitization and reprocessing and imagery rescripting). We conclude by highlighting potential implications of this proposed shift in focus for translational research.

Defensive freezing and its relation to approach-avoidance decision-making under threat.

Successful responding to acutely threatening situations requires adequate approach-avoidance decisions. However, it is unclear how threat-induced states-like freezing-related bradycardia-impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach-avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia (high-vs-low threat) interacted with subjective value, depending on the action-context (passive-vs-active). Specifically, in action-contexts incongruent with participants' intrinsic action-tendencies, stronger bradycardia related to diminished effects of subjective value on choice across participants. These findings illustrate the relevance of testing approach-avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach-avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporating internal psychophysiological states and external action-contexts into models of approach-avoidance decision-making.

A cognitively demanding working-memory intervention enhances extinction Research article.

Improving extinction learning has the potential to optimize psychotherapy for persistent anxiety-related disorders. Recent findings show that extinction learning can be improved with a cognitively demanding eye-movement intervention. It is, however, unclear whether [1] any cognitively-demanding task can enhance extinction, or whether it is limited to eye movements, and [2] the effectiveness of such an intervention can be enhanced by increasing cognitive load. Participants (n = 102, n = 75 included in the final sample) completed a Pavlovian threat conditioning paradigm across two days. One group underwent standard extinction (Control), a second group underwent extinction paired with a 1-back working memory task (Low-Load), and a third group underwent extinction paired with a 2-back working memory task (High-Load). We found that the conditioned response during extinction was reduced for both the Low-Load and the High-Load groups compared to the Control group. This reduction persisted during recovery the following day when no working memory task was executed. Finally, we found that within the High-Load group, participants with lower accuracy scores on the 2-back task (i.e., for who the task was more difficult) had a stronger reduction in the conditioned response. We did not observe this relationship within the Low-Load group. Our findings suggest that cognitive load induced by a working memory intervention embedded during extinction reduces persistent threat responses.

Eye-Movement Intervention Enhances Extinction via Amygdala Deactivation.

Improving extinction learning is essential to optimize psychotherapy for persistent fear-related disorders. In two independent studies (both n = 24), we found that goal-directed eye movements activate a dorsal frontoparietal network and transiently deactivate the amygdala (η p2 = 0.17). Connectivity analyses revealed that this downregulation potentially engages a ventromedial prefrontal pathway known to be involved in cognitive regulation of emotion. Critically, when eye movements followed memory reactivation during extinction learning, it reduced spontaneous fear recovery 24 h later (η p2 = 0.21). Stronger amygdala deactivation furthermore predicted a stronger reduction in subsequent fear recovery after reinstatement (r = 0.39). In conclusion, we show that extinction learning can be improved with a noninvasive eye-movement intervention that triggers a transient suppression of the amygdala. Our finding that another task which taxes working memory leads to a similar amygdala suppression furthermore indicates that this effect is likely not specific to eye movements, which is in line with a large body of behavioral studies. This study contributes to the understanding of a widely used treatment for traumatic symptoms by providing a parsimonious account for how working-memory tasks and goal-directed eye movements can enhance extinction-based psychotherapy, namely through neural circuits (e.g., amygdala deactivation) similar to those that support cognitive control of emotion.SIGNIFICANCE STATEMENT Fear-related disorders represent a significant burden on individual sufferers and society. There is a high need to optimize treatment, in particular via noninvasive means. One potentially effective intervention is execution of eye movements following trauma recall. However, a neurobiological understanding of how eye movements reduce traumatic symptoms is lacking. We demonstrate that goal-directed eye-movements, like working-memory tasks, deactivate the amygdala, the core neural substrate of fear learning. Effective connectivity analyses revealed amygdala deactivation potentially engaged dorsolateral and ventromedial prefrontal pathways. When applied during safety learning, this deactivation predicts a reduction in later fear recovery. These findings provide a parsimonious and mechanistic account of how behavioral manipulations taxing working memory and suppressing amygdala activity can alter retention of emotional memories.