Introduction: Reward learning plays a critical role in shaping adaptive behavior, as it helps organisms, including humans, learn from the outcomes of their actions to ensure evolutionary success (O’Doherty et al., 2017). This process is governed by a frontostriatal network that drives reward-guided actions, with the medial orbitofrontal cortex (OFC)-nucleus accumbens (NAc) being a key circuit in this network (Averbeck & Costa, 2017; Lee et al., 2012; Niv, 2009; O’Doherty et al., 2017). However, there is currently a limited understanding of the brain mechanisms that are causal in implementing this behavior in humans.

Methods: We combine the transcranial temporal interference stimulation (tTIS), behavioural data, and functional magnetic resonance imaging (fMRI) to investigate the causal role of the OFC and the NAc separately and their interaction mechanisms in reward learning. We used tTIS to modulate either the OFC or NAc to identify the intrinsic reward-related beta-gamma frequency while participants performed reinforcement learning tasks. Additionally, we employed reinforcement learning models to investigate potential computational mechanisms underlying the effects of neuromodulation.

 Results: The present study demonstrates for the first time that either OFC or NAc tTIS can disrupt reward learning and noninvasively modulate activity of NAc-OFC circuit in humans. Specifically, tTIS applied on either the OFC or NAc disrupted reward-but not punishment-guided behavior by reducing weight to positive feedback within a reinforcement learning framework This behavioral disruption was linked to alterations in the activity of the NAc-OFC circuitFurthermore, we provided evidence that NAc regulated OFC during rewarding learning. NAc tTIS modulated reward prediction error-related activity both in the NAc and OFC and functional connection between these areas. Conversely, OFC tTIS only affected activity in OFC but not in NAc

 Conclusions: Our results provide causal evidence that disrupted OFC-NAc circuit can negatively impact reward-guided behavior and support the idea that reward-relevant signals are first managed by the NAc, the output of which regulates gradual learning mechanisms in the OFC. Our study indicates that tTIS can noninvasively induce specific, focal and functional modulation of deep brain circuit involved in reward learning, thereby facilitating investigations into causal relationships between deep brain activity and behavior, as well as the interactive mechanisms within these circuits.

Dr. Zhengde Wei is an Associate Professor in the Department of Psychology at the University of Science and Technology of China. He is the Secretary of the Drug Addiction Psychotherapy Committee of the Asian Society of Drug Abuse Research and a Board Member of the Social Cognitive Science Branch of the Chinese Cognitive Science Society. His research interests primarily focus on two areas: (1) using neuroimaging techniques to study cognitive impairments and neural mechanisms related to mental disorders, as well as developing novel intervention techniques for these conditions; (2) exploring the impact of emerging technologies on human cognition and psychology through experimental psychology and neuroimaging techniques. He has published SCI papers in high-impact academic journals such as Advanced Science, Translational Psychiatry, Journal of Behavioral Addiction, Neuroimage, and Science.