Transcranial magnetic stimulation (TMS) of the primary motor hand area (M1-HAND) can induce multiple descending corticospinal volleys which can be recorded from the upper spinal cord using invasive techniques
[1, 2]. These descending volleys are caused by either direct or indirect activation of fast-conducting pyramidal tract neurons that connect monosynaptically to spinal motoneurons
. According to their latency, these waves have consequently been termed direct waves (D-waves) and early or late indirect waves (I-waves)
. Early and late I-waves are thought to be generated transsynaptically by TMS-induced excitation of different intracortical circuits projecting onto the corticospinal neurons.
The recruitment pattern of these multiple descending volleys is not fixed but rather depends on the intensity of the TMS pulse and the direction of the current that is induced in M1-HAND
. If the coil is positioned over M1-HAND in a way that the main current in M1-HAND runs in a sagittal direction, TMS can be used to preferentially recruit different sets of I-waves. At stimulus intensities that are just suprathreshold for evoking a motor evoked potential (MEP), a single monophasic TMS pulse that induces a posterior-anterior (PA) current in the M1-HAND leads to preferential recruitment of early I-waves (I1)
[5, 6]. If the induced current has an anterior-posterior (AP) direction, later I-waves (I3) are primarily recruited
[5, 6]. Since early and late I-waves are thought to be generated by different intracortical circuits, it has been concluded that different sets of intracortical neurons are excited in the motor cortex when inverting the current direction of a monophasic stimulus from PA to AP or vice versa
The pattern of evoked descending volleys also depends on the configuration of the TMS pulse
. An asymmetric “monophasic” pulse is mostly used when studying the physiology of human M1-HAND with single-pulse TMS, while a “biphasic” pulse configuration is commonly used for repetitive TMS
. The first phase of the “monophasic” pulse produces a strong initial current flow which lasts less than 100 μs, while the second phase produces a critically dampened return current lasting several 100 μs. Since only the first phase of the stimulus produces a current flow in the stimulated brain which is strong enough to elicit action potentials, monophasic single-pulse TMS are well-suited to investigate direction-specific effects of TMS on the excitation of corticospinal output neurons
[7, 10]. For biphasic TMS pulses – that were not investigated in the present study -, the direction of the current is reversed twice. Since the phase of the biphasic pulse is rapidly reversed, all current components induced by the different phases of the biphasic TMS pulse contribute to electrical cortex stimulation. In contrast to monophasic TMS, the tissue current induced by the second (reversal) phase is physiologically more effective than the current induced by the initial current phase when using a biphasic TMS pulse
[11, 12]. These differences between monophasic and biphasic TMS pulses also explain why different pulse configurations excite partly different sets of cortical axons when using the same coil orientation
Like (asymmetric) monophasic pulses, a half-sine TMS pulse only induces a tissue current that flows in one direction without current reversal. Thus, single-pulse TMS using a half-sine pulse configuration should be suited to study direction-specific effects of TMS in the intact human M1-HAND. However, a previous TMS study failed to demonstrate any statistically significant direction-specific differences in MEP amplitude, latency or cortical motor threshold for AP versus PA currents when using a half-sine pulse configuration
. In the present study, we re-examined the question whether TMS pulses having a half-sine wave configuration can be used to examine direction-specific effects of TMS of the M1-HAND. Significant direction specific effects of half-sine pulses have not been shown so far and they might offer new opportunities to study direction specific effects of TMS and, prospectively, motivate to install plasticity inducing protocols that combine AP and PA oriented half-sine stimuli. This was possible by using a TMS device that was able to generate isolated negative and positive half-sine waves (P-Stim 160 stimulator, Mag & More GmbH, Munich, Germany). It was achieved by installing a second antiparallel connected thyristor (semiconductor switch) allowing the regulation of both polarities. Using either AP or PA stimulation with respect to the central sulcus, we assessed the direction-specific properties of the half-sine wave configuration on resting motor threshold (RMT), MEP amplitude and MEP latency without changing coil position. MEPs were recorded at rest from the left abductor pollicis brevis muscle (APB). Our basic assumption was that switching the current direction would result in a preferential activation of cortical circuits involved in the generation of early or late cortical I-waves. Hence, we expected RMT to be consistently lower, MEP amplitudes to be significantly higher, and MEP latencies to be consistently shorter for half-sine wave stimulation inducing a PA as opposed to an AP current in M1-HAND. The direction-specific effects on MEP amplitudes and latencies were assessed across a wide range of stimulus intensities which enabled us to construct stimulus–response curves (SRCs) for both, MEP amplitude and latency. SRCs (often referred to as input–output curve or recruitment curve) were obtained with and without adjustment for differences in RMT.