High-frequency neuromodulation improves obsessive-compulsive behavior.

Nearly one billion people worldwide suffer from obsessive-compulsive behaviors1,2, yet our mechanistic understanding of these behaviors is incomplete, and effective therapeutics are unavailable. An emerging perspective characterizes obsessive-compulsive behaviors as maladaptive habit learning3,4, which may be associated with abnormal beta-gamma neurophysiology of the orbitofrontal-striatal circuitry during reward processing5,6. We target the orbitofrontal cortex with alternating current, personalized to the intrinsic beta-gamma frequency of the reward network, and show rapid, reversible, frequency-specific modulation of reward- but not punishment-guided choice behavior and learning, driven by increased exploration in the setting of an actor-critic architecture. Next, we demonstrate that chronic application of the procedure over 5 days robustly attenuates obsessive-compulsive behavior in a non-clinical population for 3 months, with the largest benefits for individuals with more severe symptoms. Finally, we show that convergent mechanisms underlie modulation of reward learning and reduction of obsessive-compulsive symptoms. The results contribute to neurophysiological theories of reward, learning and obsessive-compulsive behavior, suggest a unifying functional role of rhythms in the beta-gamma range, and set the groundwork for the development of personalized circuit-based therapeutics for related disorders.