Eye-Movement Intervention Enhances Extinction via Amygdala Deactivation

Abstract

Improving extinction learning is essential to optimize psychotherapy for persistent fear-related disorders. In two independent studies (both = 24), we found that goal-directed eye movements activate a dorsal frontoparietal network and transiently deactivate the amygdala (η = 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 = 0.21). Stronger amygdala deactivation furthermore predicted a stronger reduction in subsequent fear recovery after reinstatement ( = 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. 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.

Implicit but not explicit extinction to threat‐conditioned stimulus prevents spontaneous recovery of threat‐potentiated startle responses in humans

“…However, the fact that participants needed to hold their answer for a couple of seconds might have comprised some cognitive demand during image presentation. It has been recently reported that working memory load during extinction can suppressed amygdala activity and subsequently reduce recovery of threat responses (Voogd, Neville, Roelofs, Fernández, & Hermans, 2018). However, the cognitive demand in this task (i.e., 27 s of a 2N-Back task and goal-directed eye-movements) further exceeds the one required for our detention task.…”

A cognitively demanding working-memory intervention enhances extinction

“…Interestingly, amygdala inhibition is also found when participants perform a working memory task (Cousijn et al, 2010;de Voogd et al, 2018b;Qin et al, 2009) or play a computer game of Tetris (Price et al, 2013). Furthermore, greater decreases in BOLD-signal in the amygdala are observed when the cognitive load increases (de Voogd et al, 2018a).…”

“…One way extinction learning may be improved is through an eye movement intervention (de Voogd et al, 2018b). This idea is based on the notion that goal-directed eye movements form an important part of eye movement desensitization and reprocessing (EMDR).…”

“…Eye movements are central to EMDR, but there has been a debate as to whether they play a role in the therapeutic outcome above standard extinction (Devilly, 2002;Rogers and Silver, 2002). It was recently found that persistent threat responses were reduced when goal-directed eye movements were embedded during extinction learning, compared to standard extinction when no additional task was executed (de Voogd et al, 2018b), suggesting a benefit of eye movements above standard extinction. The notion that the execution of goal-directed eye movements during extinction learning can reduce persistent threat responses has also recently been found in animal models (Baek et al, 2019).…”

“…During extinction, the amygdala is inhibited by the ventromedial prefrontal cortex (vmPFC), leading to a reduction in the expression of threat responses (Milad and Quirk, 2012). Interestingly, a decrease in blood oxygenation leveldependent (BOLD) signal, measured with functional Magnetic Resonance Imaging (fMRI) is observed during the execution of goal-directed eye movements (de Voogd et al, 2018b). It could therefore be the case that an additional inhibition of the amygdala during extinction, via an eye movement intervention, can strengthen extinction.…”