The role of pulse shape in motor cortex transcranial magnetic stimulation using full-sine stimuli

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than fullsine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the halfsegment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS

PLUSPULS: A transcranial magnetic stimulator with extended pulse protocols

Transcranial magnetic stimulation (TMS) is increasingly applied in basic neuroscience while its field of usage for diagnosing and treating various neurological diseases broadens steadily. A TMS device generates a current pulse in the reach of several thousand ampére to produce a magnetic pulse which induces an electric field around neurons. This electric field, if high enough to depolarize the neuron membrane, generates an action potential at the neuron which travels down the neurons connected to it. The PLUSPULS TMS generates this magnetic pulse by pre-charging a pulse capacitor C with the voltage VC0 and connecting it with a stimulation coil L. The oscillation of the resonance circuit is cut off after one period and is called a biphasic pulse. PLUSPULS is a high frequency stimulator with inter stimulus intervals (ISI) down to 1ms which enables different pulse protocols as paired pulse or quadri theta burst stimulation. A GUI on PC allows a flexible control of PLUSPULS with varying amplitudes and ISI in one burst. The modular hardware and the control via GUI on PC allows for an easier adjustment on requirements to come. The article provides design considerations, hardware, firmware and software to reconstruct a modular biphasic TMS with enhanced charging network to enable extended pulse protocols

The role of pulse shape in motor cortex transcranial magnetic stimulation using full-sine stimuli

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than fullsine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the halfsegment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS

The role of pulse shape in motor cortex transcranial magnetic stimulation using full-sine stimuli

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than full-sine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the half-segment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior-anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS

The role of pulse shape in motor cortex transcranial magnetic stimulation using full-sine stimuli

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than fullsine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the halfsegment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS

Quadri-Pulse Theta Burst Stimulation using Ultra-High Frequency Bursts - A New Protocol to Induce Changes in Cortico-Spinal Excitability in Human Motor Cortex.

Patterned transcranial magnetic stimulation (TMS) such as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS) can induce changes in cortico-spinal excitability, commonly referred to as long-term potentiation (LTP)-like and long-term depression (LTD)-like effects in human motor cortex (M1). Here, we aimed to test the plasticity-inducing capabilities of a novel protocol that merged TBS and QPS. 360 bursts of quadri-pulse TBS (qTBS) were continuously given to M1 at 90% of active motor threshold (1440 full-sine pulses). In a first experiment, stimulation frequency of each burst was set to 666 Hz to mimic the rhythmicity of the descending cortico-spinal volleys that are elicited by TMS (i.e., I-wave periodicity). In a second experiment, burst frequency was set to 200 Hz to maximize postsynaptic Ca2+ influx using a temporal pattern unrelated to I-wave periodicity. The second phase of sinusoidal TMS pulses elicited either a posterior-anterior (PA) or anterior-posterior (AP) directed current in M1. Motor evoked potentials (MEPs) were recorded before and after qTBS to probe changes in cortico-spinal excitability. PA-qTBS at 666 Hz caused a decrease in PA-MEP amplitudes, whereas AP-qTBS at 666 Hz induced an increase in mean AP-MEP amplitudes. At a burst frequency of 200 Hz, PA-qTBS and AP-qTBS produced an increase in cortico-spinal excitability outlasting for at least 60 minutes in PA- and AP-MEP amplitudes, respectively. Continuous qTBS at 666 Hz or 200 Hz can induce lasting changes in cortico-spinal excitability. Induced current direction in the brain appears to be relevant when qTBS targets I-wave periodicity, corroborating that high-fidelity spike timing mechanisms are critical for inducing bi-directional plasticity in human M1

Transcranial magnetic stimulation with a half-sine wave pulse elicits direction-specific effects in human motor cortex

<p>Abstract</p> <p>Background</p> <p>Transcranial magnetic stimulation (TMS) commonly uses so-called monophasic pulses where the initial rapidly changing current flow is followed by a critically dampened return current. It has been shown that a monophasic TMS pulse preferentially excites different cortical circuits in the human motor hand area (M1-HAND), if the induced tissue current has a posterior-to-anterior (PA) or anterior-to-posterior (AP) direction. Here we tested whether similar direction-specific effects could be elicited in M1-HAND using TMS pulses with a half-sine wave configuration.</p> <p>Results</p> <p>In 10 young participants, we applied half-sine pulses to the right M1-HAND which elicited PA or AP currents with respect to the orientation of the central sulcus.</p> <p>Measurements of the motor evoked potential (MEP) revealed that PA half-sine stimulation resulted in lower resting motor threshold (RMT) than AP stimulation. When stimulus intensity (SI) was gradually increased as percentage of maximal stimulator output, the stimulus–response curve (SRC) of MEP amplitude showed a leftward shift for PA as opposed to AP half-sine stimulation. Further, MEP latencies were approximately 1 ms shorter for PA relative to AP half-sine stimulation across the entire SI range tested. When adjusting SI to the respective RMT of PA and AP stimulation, the direction-specific differences in MEP latencies persisted, while the gain function of MEP amplitudes was comparable for PA and AP stimulation.</p> <p>Conclusions</p> <p>Using half-sine pulse configuration, single-pulse TMS elicits consistent direction-specific effects in M1-HAND that are similar to TMS with monophasic pulses. The longer MEP latency for AP half-sine stimulation suggests that PA and AP half-sine stimulation preferentially activates different sets of cortical neurons that are involved in the generation of different corticospinal descending volleys.</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

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