Noninvasive Suppression of Responses to Threat Using Focused Ultrasonic Waves

The processing of threat- and fear-related responses is known to involve the amygdala and the bed nucleus of the stria terminalis. Malignant activity in these nuclei is associated with several important disorders, including generalized anxiety disorder and post-traumatic stress disorder. A noninvasive approach to modulate these deep brain circuits could provide novel treatment options for these disorders, but current noninvasive approaches cannot access these targets directly. This study modulates these nuclei using transcranial low-intensity focused ultrasound in nonhuman primates. The ultrasound was delivered into these circuits prior to an emotional stimulus (neutral, submissive, or threatening monkey faces or snake images) while measuring the system's autonomic response using pupil size. We found that the neuromodulation substantially reduced the pupillary responses to threat images. The effect was specific to threat face images and specific to focused ultrasound; it was not observed for other types of images or for unfocused or no-ultrasound. Thus, focused ultrasound targeting fear circuits can suppress responses to threat images. This approach could be developed into noninvasive treatments of disorders that affect these circuits.