Circuit dynamics of approach-avoidance conflict in humans.

Debilitating anxiety is pervasive in the modern world. Choices to approach or avoid are common in everyday life and excessive avoidance is a cardinal feature of anxiety disorders. Here, we used intracranial EEG to define a distributed prefrontal-limbic circuit supporting approach and avoidance. Presurgical epilepsy patients (n=20) performed a continuous-choice, approach-avoidance conflict decision-making task inspired by the arcade game Pac-Man, where patients trade-off harvesting rewards against potential losses from attack by the ghost. As patients approached increasing rewards and threats, we found evidence of a limbic circuit mediated by increased theta power in the hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), that drops rapidly during avoidance. Theta band connectivity within this circuit and with the lateral prefrontal cortex increases during approach and falls during avoidance, and amygdala and lateral frontal activity granger-caused the theta oscillations in both the OFC and ACC. Importantly, the degree of network connectivity predicted how long patients approach, with enhanced network synchronicity extending approach times. Finally, when threat is imminent, the system dynamically switches to a sustained increase in high-frequency activity (70-150Hz) in the middle frontal gyrus (MFG), tracking the degree of threat. The results provide evidence for a distributed prefrontal-limbic circuit, mediated by theta oscillations and high frequency activity, underlying approach-avoidance conflict in humans.