Der Effekt der Pulsweite auf die kortikale Erregbarkeit hervorgerufen durch 5-Hz-cTMS

Repetitive Transcranial Magnetic Stimulation (rTMS) is known as an important diagnostic and therapeutic clinical tool, for example in treatment of depression. Here, we wanted to optimize stimulation parameters in order to reduce failures in clinical application. For this reason we examined the effect of variable pulse widths on cortical excitability elicited by 5 Hz controllable pulse transcranial magnetic stimulation (cTMS) on healthy subjects, stimulating in a standard block design with bidirectional pulses. We hypothesised that wider pulses will generate longer lasting excitability increases when applied to the motor cortex as compared to shorter pulse width. To measure cortical excitability we applied suprathreshold TMS to the M1. Motor evoked potentials (MEPs) were recorded by electromyography (EMG) from the first dorsal interosseus muscle (FDI). The TMS coil was placed over the motor cortex area targeting the cortical representation of the FDI. Each session consisted of three phases: premeasurement, intervention by subthreshold 5-Hz-cTMS and postmeasurement. First, resting motor threshold (RMT) was determined. Suprathreshold MEPs targeting a peak-to-peak amplitude of 1 mV were recorded for premeasurement. For intervention we used a new transcranial magnetic stimulator (Rogue Research, Canada) and applied 1200 pulses in six blocks with a frequency of 5 Hz. The stimulation parameters were varied randomized for each session as described below. During postmeasurement we recorded suprathreshold MEPs with the same TMS intensity used for baseline determination every five minutes for 30 minutes overall in order to see an effect of the intervention. 14 healthy subjects participated in the first part of the study. Here we investigated the parameters of stimulation direction (anterior-posterior and posterior-anterior) combined with a pulse width of either 60/80 µs, 60/100 µs or 60/ 120 µs for each session at a stimulation intensity of 80% of RMT. For a second part of the study 15 healthy subjects were investigated. The stimulation intensity was set at 90% of RMT, and an AP current direction was generated. Here we investigated the TMS with pulse widths of 63/120 µs and 60/80 µs. There were no significant effects in the first part of the study. A current direction of AP seemed to be more effective for stimulation. RMT was lower for PA directed current flow as compared to the AP direction. Moreover, RMT was lower for wider pulses in comparison to shorter pulse widths. The analysis of the second part of the study showed a significant effect of stimulation, showing that applying cTMS at an intensity of 90% of RMT can induce an elevation of cortical excitability, measurable for a minimum of 30 minutes after intervention is completed. A trend of wider pulses being more effective than shorter pulses could be observed, using a stimulation intensity of 90 % RMT. A stimulation intensity of 90% of RMT occured to be a limit for subthreshold 5- Hz- cTMS intervention to the M1 since higher intensities bear a risk of inducing adverse events and lead to excessive coil heating. An intensity of 80% of RMT could not produce any significant effects at all. For future studies the investigation of effectiveness of TMS application with even wider pulses could be of interest. To predict a therapeutic effect the application of 5-Hz-cTMS in a block-design to the prefrontal dorsolateral cortex of patients with diagnosed depression seems to be interesting. It would be desirable to establish TMS further in a clinical context for it is a painless non-invasive stimulation method and could reduce failure in therapy since it unlikely leads to adverse events compared to drug therapy and electroconvulsive therapy