State-specific modulation of mood using intracranial electrical stimulation of the orbitofrontal cortex

Background: Orbitofrontal cortex (OFC) is a promising target for intracranial electrical stimulation (iES) aimed at improving mood states. However, knowledge gaps remain regarding the underlying neural mechanisms of iES effects, such as the effect of the OFC target in comparison with other emotional network targets, the impact of brain state at the time of stimulation, and the neural response induced by iES at both local and network scales. Objective: Our study aims to address the neural mechanisms underlying the effects of iES in improving mood states. Methods: We conducted a study in 24 epilepsy patients who received iES through implanted electrodes in the emotional network and compared the effects of iES on multiple targets in the emotional network. Results: We found that only iES applied to the orbitofrontal cortex (OFC) led to mood improvement and changes in neural activity. We also observed that iES to the OFC suppressed the delta-theta power when the brain was in a low mood state. Moreover, the iES to the OFC decreased delta-theta power and increased gamma power at local regions within the emotional network, and enhanced the information flow through the frequency domain among regions within the emotional network. Conclusions: These findings provide insight into the neural correlates of iES-induced mood improvement and support the potential of iES as a therapeutic intervention for mood disorders.