Frontotemporal network engagement by human intracranial stimulation in limbic hubs

Frontotemporal circuits in the human brain play an important role in cognitive and affective processing. Neuromodulation therapies delivered to certain key hubs within these circuits are being used with increasing frequency to treat a host of neuropsychiatric disorders, but the detailed neurophysiological effects of stimulation are largely unknown. Here, we performed intracranial recordings across frontotemporal networks while delivering electrical stimulation to two well-established white matter hubs involved in cognitive regulation. We demonstrate a frontotemporal circuit consisting of the amygdala, lateral orbitofrontal cortex, and ventromedial prefrontal cortex in which gamma oscillations are differentially modulated depending on the target stimulated. We additionally highlight the heterogeneity in neural responses to stimulation across human subjects in other corticolimbic regions and demonstrate the capacity for further tuning of neural activity using current-steered stimulation. Our findings indicate a potential neurophysiological mechanism for the dissociable therapeutic effects seen across targets for neuromodulation and implications for future efforts in personalized, network-guided neurostimulation.