Neuromodulation of risk preferences encoded in human orbitofrontal cortex activity

Human behavior presents a natural range of variation beyond which extreme behavior appears, often as a hallmark of psychiatric conditions. for example, risk preferences, which naturally range from risk-seeking to risk-averse, are characteristically affected in multiple pathologies, e.g. increased risk-taking in gambling disorders. Despite its basic and translational importance, how underlying brain activity reflects and determines behavioral variation is mostly unknown, in part due to the difficulty of directly examining neural activity in decision-relevant brain areas from cohorts of subjects with varying preferences. To address this, we combined human intracranial recordings (n=15 patients) from the orbitofrontal cortex (OFC), a key brain region in economic decision-making, with risky decision-making tasks and computational modeling. We observed significant behavioral variation in risk preferences, which was strongly correlated with low-frequency (delta-theta) oscillatory coherence in OFC. Low-frequency oscillatory phase was coupled to high-frequency activity amplitude, providing a potential neurophysiological mechanism for integrating preferences with trial-by-trial risk computations. Finally, targeted OFC electrical stimulation caused significantly decreased risk-taking behavior and faster reaction times without impairing overall decision-making. These results show a neural correlate for inter-individual variation in decision-making preferences and provide proof-of-principle evidence for modulation of risk-taking behavior through OFC-targeted neurostimulation, paving the way for developing neuromodulatory interventions for pathologies characterized by heightened risk-seeking, such as addiction and gambling disorders.