An illustration of the practical constraints of tES and kTMP in frequency and amplitude space.

Solid lines represent the dependency of the electric field amplitude upon frequency and amplitude of the electric current supplied to the electrodes (A) or coil (B). Calculations are based on for a typical 5 × 7 cm tES electrode montage or figure-of-eight TMS/kTMP coil. Left vertical axis represents estimated scalp E-field amplitude while the right vertical axis represents the estimated motor cortex E-field amplitude. Shaded zones represent regions of the perturbation space constrained by practical considerations. Both methods are constrained by the scalp E-field magnitude, which at high values may result in discomfort due to peripheral nerve stimulation (gray shading). The gray dashed function depicts the dependence of scalp stimulation threshold upon frequency [14]. Note the substantial difference in the cortical E-field range that can be delivered tolerably for tES and kTMP. Illustrated here are approximate levels of discomfort for sustained waveforms (tES and kTMP) as opposed to pulsed methods (e.g., TMS). Note that magnetic induction methods such as kTMP (or TMS) are additionally constrained by high energetic costs (purple shading) required to generate E-fields of sufficient magnitude to influence neuronal states at low frequencies.

Experimental protocol and hardware.

A. Timing of each experimental session. After determining the participant’s resting motor threshold (rMT), TMS assessment blocks were conducted before (Pre) and after (Post) kTMP stimulation (active or sham). B. The same coil was driven by either the TMS current source or the kTMP current source. TMS pulses were recorded in an auxiliary channel of the EMG and triggered the neuronavigation system to record the coordinates of the coil in 3-D space.

Waveforms, spectra and conditions for the three kTMP experiments.

A commonly used form of amplitude modulation is E(t) = E0[a + m sin(2πfm t)] sin(2πfc t). The constants fc, fm, and E0 refer to the carrier frequency, modulation frequency and the E-field amplitude (cortical E-field) respectively. Left column, Waveforms: ENM, EAM1 and EAM2 refer to the non-modulated waveform and the two forms of amplitude modulation tested. Black lines indicate the modulation frequency. Center column, Spectrum: Carrier frequency and sidebands for the corresponding waveforms. Note the absence of power at the modulated frequency (fm). Right column, Waveform parameters and characteristics for each experiment. fb refers to the burst repetition frequency.

Replication of post-stimulation change in cortical excitability for sham and non-modulated 3.5 kHz kTMP stimulation.

A. Change in MEP amplitude measured with single pulse TMS following sham stimulation (left) and kTMP stimulation at 3.5 kHz (right). Dots denote values for individual subjects, bars— mean values, and whiskers—standard error. MEP change post-intervention did not significantly differ across experiments for sham and 3.5 kHz. B. Change in MEP amplitude for the three post kTMP blocks for the 3.5 kHz condition (mean ± standard error).

Post-stimulation changes in cortical excitability as measured by single-pulse TMS for all conditions.

Percent change in MEP amplitude following sham and active kHz stimulation, relative to baseline. Dots denote values for individual subjects, bars—mean values, and whiskers—standard error. Note that the data for the Sham and non-modulated 3.5 kHz conditions are combined across the three experiments. * p < .05, ** p < .01, *** p < .001.

Post-stimulation change in cortical excitability as measured by single-pulse TMS across the three post-kTMP blocks.

Percent change in MEP amplitude following sham and active kHz stimulation, relative to baseline for the three post blocks (error bars represent standard error). The data for the Sham and non-modulated 3.5 kHz conditions are combined across the three experiments.

kTMP did not produce any change in measures of short intracortical inhibition or intracortical facilitation.

Data are plotted as the ratio of the paired-pulse MEP amplitude over the single pulse MEP amplitude, with an inter-pulse interval of 3 ms for SICI and 10 ms for ICF. Each pair of bars shows this ratio for pre-kTMP (averaged over two probe blocks) and post-kTMP (averaged over three probe blocks).

kTMP stimulation is not associated with any subjective experience.

Mean ratings (SE in parenthesis) combined across Exp 2 and Exp 3 on a 0-to-10 scale in response to questions assessing annoyance, pain, and awareness of finger movement. For TMS, the survey was administered after the second baseline probe block; for kTMP, the survey was administered after kTMP stimulation.