Hebbian learning of stimulus-response associations using transcranial magnetic stimulation

Classical conditioning states that the systematic co-occurrence of a neutral stimulus with an unconditioned stimulus can cause the neutral stimulus to, over time, evoke the same response as the unconditioned stimulus. On a neural level, Hebbian learning suggests that this type of learning occurs through changes in synaptic plasticity when two neurons are simultaneously active, resulting in increased connectivity between them. Inspired by learning theories, we here investigated whether the mere co-activation of visual stimuli and stimulation of the primary motor cortex using transcranial magnetic stimulation (TMS) would result in stimulus-response associations that can impact future behaviour. During a learning phase, we repeatedly paired the presentation of a specific colour (but not other colours) with a TMS pulse over the motor cortex. Next, participants performed a two-alternative forced choice task where they had to categorize simple shapes and we studied whether the shapes task-irrelevant colour (and its potentially associated involuntary motor activity) affected the required motor response. Participants showed more errors on incongruent trials for stimuli that were previously paired with high intensity TMS pulses, but only when tested on the same day. Using a drift diffusion model for conflict tasks, we further demonstrate that this interference occurred early, and gradually increased as a function of associated TMS intensity. Taken together, our findings show that the human brain can learn stimulus-response associations using externally induced motor cortex stimulation.