Kilohertz Transcranial Magnetic Perturbation (kTMP): A New Non-invasive Method to Modulate Cortical Excitability

Non-invasive brain stimulation (NIBS) provides a method for safely perturbing brain activity, and has been employed in basic research to test hypotheses concerning brainbehavior relationships with increasing translational applications. We introduce and evaluate a novel subthreshold NIBS method: kilohertz transcranial magnetic perturbation (kTMP). kTMP is a magnetic induction method that delivers continuous kHz-frequency cortical electric fields (E-fields) which may be amplitude-modulated to potentially mimic electrical activity at endogenous frequencies. We used TMS to compare the amplitude of motor-evoked potentials (MEPs) in a hand muscle before and after kTMP. In Experiment 1, we applied kTMP for 10 min over motor cortex to induce an E-field amplitude of approximately 2.0 V/m, comparing the effects of waveforms at frequencies of 2.0, 3.5, or 5.0 kHz. In Experiments 2 and 3 we used two forms of amplitude-modulated kTMP with a carrier frequency at 3.5 kHz and modulation frequencies of either 20 or 140 Hz. The only percept associated with kTMP was an auditory tone, making kTMP amenable for doubleblind experimentation. Relative to sham stimulation, non-modulated kTMP at 2.0 and 3.5 kHz resulted in an increase in cortical excitability, with Experiments 2 and 3 providing a replication of this effect for the 3.5 kHz condition. Although amplitude-modulated kTMP increased MEP amplitude compared to sham, no enhancement was found compared to non-modulated kTMP. kTMP opens a new experimental NIBS space inducing relatively large amplitude subthreshold E-fields able to increase cortical excitability with minimal sensation.