39 Frequency dependent emotion differentiation and directional coupling in amygdala, orbitofrontal and medial prefrontal cortex network with intracranial recordings

Objectives/Aims The amygdala, orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) form a crucial part of the emotion circuit and their dysfunction is implicated in affective disorders attested by numerous functional magnetic resonance (fMRI) studies. However, the precise nature of emotion induced spectral responses and interactions amongst this circuitry have not been investigated with direct human intracranial recordings which may enable new knowledge for neuromodulation and translational benefits. Methods We acquired intracranial electroencephalography (iEEG) data from a cohort of 35 patients with intractable epilepsy, who underwent an emotional picture viewing task localising 71 contacts in the amygdala, 31 in OFC and 43 in mPFC. We first quantified high frequency activity (30–140 Hz) responses and subsequently assessed the lower frequency spectral dynamics. Finally, we investigated connectivity between these regions, with a hierarchical approach using functional undirected connectivity (coherence), functional direct connectivity (spectral granger causality) and model based-effective connectivity (dynamic causal modelling – DCM). Results Emotional stimuli induced high frequency responses in the amygdala, but which were remarkably absent in the OFC and mPFC. All three regions showed valence dependent differences in lower frequencies in theta (amygdala), alpha (OFC) and beta. In particular, beta activity was increased to negative relative to positive stimuli in both the amygdala and OFC with the opposite direction of effect was observed in the mPFC. Functional connectivity analyses showed predominant bi-directional coupling in low frequency (<12 Hz) range. Ultimately, effective connectivity analyses revealed unidirectional connectivity from mPFC to the amygdala and bidirectional communication between OFC-amygdala and OFC-mPFC. Conclusions Our findings demonstrate a complex orchestration of emotion induced spectral responses, in the amygdala, OFC and mPFC differentiating valence conditions. We demonstrate for the first time using direct intracranial recordings evidence for a top-down influence of mPFC over the amygdala and bidirectional connectivity between the OFC and the amygdala coupling during emotional processing, thus extending the current account of prefrontal-amygdala interaction. Future work could build on this and explore dynamic modulations and the effects of stimulation between these nodes and circuit with implications for neuromodulation targets for affective pathologies.