Figure 5

A schematic of the rationale for the translation of VNS into a clinical PTSD therapy based on preclinical observations. (A) Preclinical studies often use extinction of conditioned fear as a model of exposure therapy for PTSD. Fear (freezing) is evoked by presentations of the conditioned sound (CS) previously paired with a footshock. Delivering VNS during (Dur.) CS presentation only or continuously (Cont.) throughout the extinction session are equally effective at enhancing fear extinction in rats. (B) Since trauma cues are often complex, overlapping, and multimodal, clinical delivery of VNS during PTSD therapy is more complicated than it is in animal models. For example, therapists cannot readily control the intensity and duration of the recalled memories that drive distress. As a result, it may not be possible to deliver precisely paired VNS in exposure therapy as performed in preclinical studies in rodents. Our preclinical studies suggest that it may not be necessary to precisely time VNS delivery to occur only during peak recall of trauma reminders. We propose that VNS delivered continuously throughout imaginal exposure conducted by a therapist, in vivo exposure to trauma reminders, and homework assignments to listen to recorded therapy sessions may improve the effectiveness of prolonged exposure therapy.