Waveforms applied by the flexTMS device.

<p>Depicted are recorded waveforms used in the four experiments (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115247#s2" target="_blank"><i>Methods</i></a>). Traces show coil current waveform (black traces) and the induced voltage of the search coil (light blue traces). The search coil output voltage is proportional to the induced electric field. All pulse shapes were measured at 25% MSO. (A, B, C) Shown are recorded pulses for the half-sine, full-sine, and monophasic waveforms used in Expt. 1. These waveforms are commonly used in TMS. (D) Depicted is the two segment waveform consisting of two concatenated PA-oriented half-sines used in Expt. 2. (E) In Expt. 3a, the amplitude of a given half-segment of the full-sine pulse was modified. In the shown pulse waveform, the second half-segment was reduced to 50% of the unaltered AP-PA pulse. (F) In Expt. 3b, the duration of a given half-segment of the full-sine pulse was modified. In the illustrated pulse waveform, the second half-segment of the AP-PA pulse was shortened to 60 µs. (G) The symmetrically prolonged full-sine pulses probed in Expt. 4 induce an electric field waveform where the opposite phases are temporally separated.</p

Full-sine waveforms have lower RMT than pulses with two half-sine segments of identical current orientation.

<p>(A) TMS pulse waveforms used for this experiment. Pulses of 160 µs duration were designed with two identical half-segments (termed AP/AP and PA/PA) to investigate the influence of pulse duration. (B) Depicted is mean RMT (n = 9) for full-sine stimuli (AP/PA and PA/AP) and concatenated stimuli with two identical half-sines (PA/PA and AP/AP). (C) For comparison, mean RMT is displayed for 80 µs half-sine stimuli (n = 10). Note that RMT was not lower for pulses with two concatenated half-sine half-segments (PA/PA and AP/AP; duration 160 µs) compared with the respective single half-sine pulses (duration 80 µs). Data are means, error bars represent sem. *<i>P</i><0.05, Student’s paired <i>t</i> test.</p

Comparison of the three different TMS waveforms using a single stimulation device.

<p>(A) The three commonly used TMS waveforms. The flexTMS device allows application of half-sine, full-sine and monophasic pulses. Bold lines indicate the coil current <i>I</i>, gray lines represent the induced electric field <i>E</i>. The monophasic pulse is truncated at 400 µs for display purposes. All waveform pictograms in this and the following figures are simplified for illustration (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115247#pone-0115247-g002" target="_blank">Fig. 2</a> for recorded waveform traces). (B) Mean RMT for the three different waveforms applied with the same stimulator. RMT was significantly lower when probed with full-sine pulses, indicating higher effectiveness of this waveform to elicit a motor response. (C) MEPs evoked with half-sine, full-sine, and monophasic stimuli from a representative participant. Traces are averages of 10 trials each and were recorded using stimulation intensity (SI) of 120% of RMT. (D) Stimulus-response curves for half-sine, full-sine (biphasic), and monophasic stimuli. Depicted is the mean MEP amplitude as a function of SI for each waveform. Stimulus-response curves were recorded at intensities referenced relative to individual RMT. (E) Mean amplitude and latency of MEPs recorded using SI of 120% of RMT for the three different waveforms. Data are from n = 10 participants, error bars represent sem. *<i>P</i><0.05, Student’s paired <i>t</i> test.</p

Longer full-sine pulses are characterized by lower RMT.

<p>Symmetrically prolonged full-sine (biphasic) waveforms impact on RMT. Pulses of 200 and 240 µs duration were compared with the unaltered 160 µs full-sine waveform. (A) Examples of waveforms used for Experiment 4. Note the middle phase of the electric field waveform <i>E</i> (gray lines) is identical for these pulses. The three phases of the induced electric field are temporally separated. (B) RMT probed with full-sine pulses of 160 µs, 200 µs, and 240 µs total duration. RMT was significantly lower for longer pulse duration. Data are means (n = 10), error bars represent sem. **<i>P</i><0.01, Student’s paired <i>t</i> test.</p

Experimental design.

<p>The study consisted of four experiments. The flexTMS stimulator allowed a comparison of the three conventional TMS waveforms applied by a single stimulation device (Expt. 1). We probed resting motor threshold (RMT), MEP amplitude, and stimulus-response-curves (SRC). In experiment 2, full-sine TMS pulses were compared with waveforms consisting of two concatenated half-sine pulses of identical current orientation. Expt. 3 examined how modifications of a given half-segment of the full-sine pulse impact on RMT. Changes in amplitude (Expt. 3a) and duration (Expt. 3b) of a given half-segment were tested separately. The duration of full-sine pulses was extended covering a longer range in experiment 4. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115247#s2" target="_blank"><i>Methods</i></a> for a detailed description of experimental procedures.</p

Changing half-segment amplitude of the full-sine pulse differentially influences RMT.

<p>To test if the half-segments inducing AP or PA current in M1-HAND differentially influences RMT, the amplitude of either the first or second half-segment of the full-sine pulse was altered for both current orientations separately. (A) Examples of waveforms used for this experiment. Coil current amplitude <i>I</i> was reduced to 75%, 50%, or 25% for a given half-segment. Pulse amplitudes in percent refer to amplitude of the first or second half-segment of the unaltered full-sine waveform (i.e. 100%/100% relative amplitude, illustrated by dashed lines). (B) Amplitude variation of the first half-segment of the AP/PA pulse resulted in minor changes of RMT. (C) Reduction of the second half-segment’s amplitude of the AP/PA pulse produced a significant increase in RMT already at 75% relative pulse segment amplitude. (D) Amplitude variation of the first segment of the PA/AP pulse led to a strong increase in RMT. (E) Amplitude variation of the second segment of the PA/AP pulse resulted in small changes of RMT. Data are means (n = 10), error bars represent sem. *<i>P</i><0.05, one-sample <i>t</i> test on data normalized to the unaltered reference pulses.</p

The influence of changing the amplitude or duration of one segment of the full-sine waveform depends on current orientation.

(a)<p>Pulse segment amplitude is referenced relative to the unaltered full-sine pulses (i.e. 100%/100% relative amplitude).</p>(b)<p>RMT data were normalized to the unaltered reference pulses for statistical analysis because RMT was significantly different between AP-PA and PA-AP oriented full-sine pulses (cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115247#pone-0115247-g005" target="_blank">Figs. 5</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115247#pone-0115247-g006" target="_blank">6</a>).</p>(c)<p>Current direction refers to induced current in M1-HAND.</p>(d)<p>P-values refer to results of post-hoc Student’s paired <i>t</i> tests between current orientations of the pulse (AP-PA vs. PA-AP).</p>(e)<p>In experiment 3b, duration of a given half-segment was shortened or prolonged, resulting in total pulse durations of 140 or 180 µs, respectively.</p><p>The influence of changing the amplitude or duration of one segment of the full-sine waveform depends on current orientation.</p

Results of three-way rmANOVAs conducted for experiment 3.

<p>Results of three-way rmANOVAs conducted for experiment 3.</p