Modelling and validating an enhanced transcranial magnetic stimulator for neuroscience and clinical therapies

Thesis

Transcranial magnetic stimulation (TMS) is a non-invasive technique for stimulating the nervous system. Conventional TMS devices are limited to a small set of predefined pulse shapes. Recent technological developments in TMS devices using switching circuits have allowed more control over the TMS parameters. Our group has introduced a new TMS device, the programmable TMS (pTMS), which uses pulse-width modulation (PWM) to rapidly switch between voltage levels, allowing the approximation of pulses of arbitrary shape.

In the first part of this thesis, I validated the PWM method by using computational modelling to compare the neuronal response to stimuli generated by the pTMS device and by a conventional transcranial magnetic stimulator. The computational models predicted highly correlated activation thresholds for both stimulator types, showing that the pTMS can approximate existing pulses.

Second, I validated the model and the pTMS by assessing the comparability of the effects of PWM and conventional pulses on motor evoked potentials in a first-in-human validation study. Resting motor thresholds showed a strong correlation between the stimulation pulses, with a consistently lower threshold for the PWM pulses, corroborating the results of the computational model. No significant differences in other motor response measures were found between the pulse types.

Third, I exploited the capabilities of the pTMS device by designing and conducting an in-human study where I investigated a previously unfeasible stimulation pattern, monophasic theta burst stimulation (TBS). Comparing the effects of monophasic TBS with conventional biphasic TBS on corticospinal excitability, the monophasic pulses induced larger plasticity effects than biphasic pulses and than an anatomical control.

Finally, I explored the sources of variability of resting motor thresholds in a large data set collected across TMS clinics, in particular investigating the effects of time of day. The results indicated that the majority of the observed differences in thresholds across the day were due to differences between clinics, highlighting the need to control for and standardise methods across clinics.

In summary, this thesis demonstrates and validates the capabilities of the programmable TMS device, to firstly mimic the stimulation effects of conventional stimulators but importantly to also expand the parameter set to new stimulation protocols with the potential to have stronger effects on the stimulated neurons, and investigates the origins of variance in clinical practice.

Authors: Wendt, K

• DOI: 10.5287/ora-ko1rajrrd
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: neuromodulation; Transcranial Magnetic Stimulation; MEPs; bioelectronics; Motor Evoked Potentials; TMS
• Subjects: Biomedical engineering; Brain stimulation