AbstractThe amygdala, orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) form a crucial part of the emotion circuit, yet their emotion induced responses and interactions have been poorly investigated with direct intracranial recordings. Such high-fidelity signals can uncover precise spectral dynamics and frequency differences in valence processing allowing novel insights on neuromodulation. Here, leveraging the unique spatio-temporal advantages of intracranial electroencephalography (iEEG) from a cohort of 35 patients with intractable epilepsy (with 71 contacts in amygdala, 31 in OFC and 43 in mPFC), we assessed the spectral dynamics and interactions between the amygdala, OFC and mPFC during an emotional picture viewing task. Task induced activity showed greater broadband gamma activity in the negative condition compared to positive condition in all the three regions. Similarly, beta activity was increased in the negative condition in the amygdala and OFC while decreased in mPFC. Furthermore, beta activity of amygdala showed significant negative association with valence ratings. Critically, model-based computational analyses revealed unidirectional connectivity from mPFC to the amygdala and bidirectional communication between OFC-amygdala and OFC-mPFC. Our findings provide direct neurophysiological evidence for a much-posited model of top-down influence of mPFC over amygdala and a bidirectional influence between OFC and the amygdala. Altogether, in a relatively large sample size with human intracranial neuronal recordings, we highlight valence-dependent spectral dynamics and dyadic coupling within the amygdala-mPFC-OFC network with implications for potential targeted neuromodulation in emotion processing.