Intracranial recordings of amygdala and orbitofrontal cortex reveal temporal response and directed connectivity...

Understanding social cues, such as facial expressions, is critical to social functioning. Facial emotion processing is impaired in many neuropsychiatric disorders, including epilepsy, and can diminish patients' quality of life. The amygdala and orbitofrontal cortex (OFC) are critical for this ability, but their interactions remain unknown, partly due to the limited spatiotemporal resolution of current neuroimaging methods. We addressed this gap by using intracranial electroencephalography (iEEG) to directly record the amygdala, medial OFC (mOFC), and lateral OFC (lOFC) in 25 patients with drug-resistant epilepsy while they completed an implicit facial emotion processing task. We sought to characterize local high gamma (70-150) responses and theta band (4-7) connectivity patterns within this circuit. Viewing emotional compared to neutral faces evoked rapid amygdala activation to fearful expressions, followed by happy, but not to sad, suggesting that the amygdala responds more to the arousal level of facial emotion than valence. The mOFC exhibited latent, less prolonged responses to facial emotion, and activity in both OFC subregions predicted behavioral performance. Directed functional connectivity analyses revealed a robust pattern of bottom-up theta-band connectivity from the amygdala to the mOFC and bidirectional connectivity between the mOFC and lOFC supporting low-frequency communication as a key mechanism for coordinating emotion processing across fronto-limbic circuits.