Transcranial magnetic stimulation of the prefrontal cortex in awake nonhuman primates evokes a polysynaptic neck muscle response that reflects oculomotor activity at the time of stimulation.

Transcranial magnetic stimulation (TMS) has emerged as an important technique in cognitive neuroscience, permitting causal inferences about the contribution of a given brain area to behavior. Despite widespread use, exactly how TMS influences neural activity throughout an interconnected network, and how such influences ultimately change behavior, remain unclear. The oculomotor system of nonhuman primates (NHPs) offers a potential animal model to bridge this gap. Here, based on results suggesting that neck muscle activity provides a sensitive indicator of oculomotor activation, we show that single pulses of TMS over the frontal eye fields (FEFs) in awake NHPs evoked rapid (within ∼25 ms) and fairly consistent (∼50-75% of all trials) expression of a contralateral head-turning synergy. This neck muscle response resembled that evoked by subsaccadic electrical microstimulation of the FEF. Systematic variation in TMS location revealed that this response could also be evoked from the dorsolateral prefrontal cortex (dlPFC). Combining TMS with an oculomotor task revealed state dependency, with TMS evoking larger neck muscle responses when the stimulated area was actively engaged. Together, these results advance the suitability of the NHP oculomotor system as an animal model for TMS. The polysynaptic neck muscle response evoked by TMS of the prefrontal cortex is a quantifiable trial-by-trial reflection of oculomotor activation, comparable to the monosynaptic motor-evoked potential evoked by TMS of primary motor cortex. Our results also speak to a role for both the FEF and dlPFC in head orienting, presumably via subcortical connections with the superior colliculus.