Causal effects of prefrontal transcranial magnetic stimulation on dopamine-mediated reinforcement learning in healthy adults

Abstract

Background: 10-Hz repetitive transcranial magnetic stimulation (rTMS) to the left dorsal lateral prefrontal cortex (DLPFC) has been shown to increase dopaminergic activity in the dorsal striatum, a region strongly implicated in reinforcement learning. However, the behavioural influence of this effect remains largely unknown. Objective: Here, we tested the causal effects of rTMS on behavioral and computational characteristics of reinforcement learning. Methods: 40 healthy individuals were randomized into Active and Sham rTMS groups. Each participant underwent one 10-Hz rTMS session (1500 pulses) in which stimulation was applied over the left DLPFC using a robotic arm. Participants then completed a reinforcement learning task sensitive to striatal dopamine functioning. Participants trial-to-trial training choices were modelled using a reinforcement learning model (Q-learning) that calculates separate learning rates associated with positive and negative reward prediction errors. Results: Subjects receiving Active TMS exhibited an increased reward rate (number of correct responses per second of task activity) compared to the Sham rTMS group. Computationally, the Active rTMS group displayed a higher learning rate for correct trials (αG) compared to incorrect trials (αL). Finally, when tested with novel pairs of stimuli, the Active group displayed extremely fast reaction times, and a trend towards a higher reward rate. Conclusions: The present study provided specific behavioral and computational accounts of altered striatal-mediated reinforcement learning induced by a proposed increase of dopamine activity by 10-Hz rTMS to the left DLPFC. Together, these findings bolster the use of TMS to target neurocognitive disturbances attributed to the dysregulation of dopaminergic-striatal circuits.