Overnight fasting facilitates safety learning by changing the neurophysiological response to relief from threat omission

Excessive avoidance and slow extinction of fear are hallmarks of anxiety disorders. We have previously found that overnight fasting diminishes excessive avoidance and speeds up fear extinction by decreasing subjective relief during threat omissions. Since relief tracks the reward prediction error signal that governs safety learning, we hypothesized that these effects of fasting might be linked to a decreased activation in brain regions related to reward prediction error processing. Hence, we replicated our previous study in a 3T-MRI scanner. Overnight fasting increased effective avoidance and sped up fear extinction learning. During extinction, the fasting group showed lower activations in the ventromedial prefrontal cortex and nucleus accumbens in response to threat omissions signaled by a safe cue. Nucleus accumbens activations were modulated by relief in the control group. This study provides support for overnight fasting as an adjunct to treatments for anxiety, but the effects should be investigated in anxious patients.