Electronics and methods for multi-locus transcranial magnetic stimulation

Brain disorders are a growing concern for society, causing reduced quality of life and trillions of euros in yearly economic costs. This calls for new methods that provide improved therapy based on better understanding not only of the illnesses but also the functioning of the brain. One such method is transcranial magnetic stimulation (TMS). In TMS, an electric field is induced in the cortical surface by driving a strong pulse of current through a stimulation coil placed on the head, eliciting local, non-invasive activation of the brain. TMS is used to treat depression, migraine, and obsessive-compulsive disorder, as well as in pre-surgical mapping procedures. However, a major limitation of TMS has been its ability to target only a single cortical site at a time, whereas the healthy operation of the brain depends on the proper interaction between connected areas. In addition, the expertise of the operator can affect the outcomes of TMS, as, e.g., finding the best stimulation site still, to a degree, depends on the operator’s interpretation. Recently, multi-locus TMS (mTMS) has been introduced as a new solution to mitigate these issues. Instead of a single stimulation coil, mTMS relies on a stacked array of coils with overlapping, coilspecific electric field profiles. By firing several of these coils at once with different currents, the electric field in the cortex can be adjusted to accurately deliver the stimulation to specific cortical targets without physical coil movement. This overcomes the limitation of single-site stimulation only, while also presenting an opportunity for algorithmic, user-independent targeting. The work carried out in this Thesis, presented in six publications, focused on developing, implementing, and advancing the hardware and methods of mTMS, paving the way towards its commercialization. In Publication 1, an mTMS device supporting up to six coils and a five-coil array were developed and verified. The system is capable of targeting the stimulation inside a 3-centimeter-diameter area, allowing rapid and accurate delivery of stimuli to adjacent cortical areas as well as automation of protocols such as functional mapping of the cortex, or finding the optimal site of stimulation. In Publication 2, a magnetic resonance imaging (MRI)-compatible mTMS device and a two-coil array were developed, allowing pre-clinical studies with interleaved mTMS and functional imaging in an ultra-high-field scanner. This combination could provide valuable information about the dynamics of cortical and subcortical activation in the healthy and the diseased brain. In Publication 3, mTMS was combined with pulse-width modulation to enable delivery of successive stimuli to distinct cortical areas with millisecond-range intervals. Although the required stimulus waveforms are temporally complex, the elicited activation is like that from conventional stimuli, allowing the study of network interactions of the brain. In Publication 4, mTMS device technology was further developed to comply with medical-device regulations, and such a device was deployed in Germany for hospital use, enabling the study of patient populations by experts in the field. In Publication 5, the concept of mTMS, its future directions, and possible challenges were explored and disseminated. Publication 6 discusses the principles of TMS, its use, and various validation measurements to characterize the device output. This Thesis culminated in the development of advanced mTMS systems capable of targeting distinct cortical sites at millisecond-scale intervals, marking significant progress towards accessible tools for the study of network interactions of the brain.