BackgroundTranscranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer.ObjectiveTo develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region.MethodsWe designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand.ResultsThe transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum.ConclusionThe developed mTMS system enables electronically targeted brain stimulation within a cortical region.

Brain stimulation

10.1016/j.brs.2021.11.014

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Design, construction, and deployment of a multi-locus transcranial magnetic stimulation system for clinical use

Research Square (Research Square) (2025)

Heikki Sinisalo Olli‐Pekka Kahilakoski Victor H. Souza Aino E. Nieminen Robin Rantala

Abstract Background:Transcranial magnetic stimulation (TMS) is an established method for noninvasive brain stimulation, used for investigating and treating brain disorders. Recently, multi-locus TMS (mTMS) has expanded the capabilities of TMS by employing an array of overlapping stimulation coils, enabling delivery of stimulation pulses at different cortical locations without physical coil movement. We aimed to design, construct, and deploy an mTMS device and a five-coil array for clinical environment, emphasizing safety of the system. Methods: Our mTMS device is controlled by a field-programmable gate array (FPGA). The power electronics comprises five stimulation channels, each consisting of a high-voltage capacitor connected to a pulse circuit, controlling a single coil in the array. The device contains custom-designed circuit boards, with functions such as monitoring the system state, reporting errors, and delivering pulses. Our design utilizes redundancy in both hardware and firmware to ensure robust operation and safety. We performed an automated motor mapping test to verify the electronic targeting capabilities of the device. Results: We constructed the mTMS device and deployed it to the Hertie Institute for Clinical Brain Research (Tübingen, Germany). Compared to our earlier prototype, the new design improves patient and operator safety. The motor mapping test confirmed that our device can accurately target stimulation pulses in the cortex. Significance:mTMS or other similar technologies are currently not available for hospital use. The present device and its installation are major steps toward establishing multicoil TMS as an accessible clinical tool for investigation and treatment of the brain.

10.21203/rs.3.rs-5979885/v1

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Electric-field guided neuronavigation: validation in human experiments using TMS

Brain stimulation (2025)

Ana M. Soto Renan H. Matsuda Olli‐Pekka Kahilakoski Tuomas Mylläri Kalle Jyrkinen

Neuronavigation

10.1016/j.brs.2024.12.922

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The impulse noise of TMS inside a 3 T and 9.4 T MRI

Brain stimulation (2021)

Mikko Nyrhinen Victor H. Souza Juuso T. Korhonen Heikki Sinisalo Jaakko Paasonen

Abstract The operation of a transcranial magnetic stimulation (TMS) coil produces high-intensity impulse sounds. In TMS, a magnetic field is generated by a short-duration pulse in the range of thousands of amperes in the coil. When placed in a strong magnetic field, such as inside an magnetic resonance imaging (MRI) bore, the interaction of the magnetic field and the current in the TMS coil can cause strong forces on the coil casing. The strengths of these forces depend on the coil orientation in the main magnetic field (B0). Part of the energy in this process is dissipated in the form of acoustic noise. To conduct concurrent TMS and functional MRI (fMRI) safely, the sound pressure levels (SPLs) generated by the TMS coil must be quantitatively characterized. Measuring the SPLs of fast and loud impulse sounds accurately in the presence of static and gradient magnetic fields is challenging. In this study, we present a method for such measurements and report the SPLs of two commercial MRI-compatible TMS systems inside a 3T MRI scanner and of a prototype multi-channel TMS (mTMS) system inside a 9.4T small-animal MRI scanner. The mTMS coil allows for changing the direction of the electric field (E-field) without physically moving the TMS coil. We measured the acoustic noise generated by the TMS coils with different E-field orientations relative to the B0 field at different stimulation intensities and locations. The measurements were compared to the sound level measured outside the MRI room. SPLs and spectrum of the click sounds changed depending on coil and induced E-field orientation compared to the B0 field. SPLs exceeding the safety limit of 140 dB(C) was measured with all the devices. Our study provide is an important step towards the safety operation of concurrent TMS-fMRI respecting the auditory limits of small animals and humans. Keywords: TMS, mTMS, fMRI, acoustic noise

Coil noise

Search coil

10.1016/j.brs.2021.10.060

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Which direction should I go? A quest for understanding the effect of TMS stimulus orientation on evoked responses

Brain stimulation (2023)

Victor Souza Tuomas P. Mutanen Jaakko O. Nieminen Aino Nieminen Heikki Sinisalo

Stimulus (psychology)

10.1016/j.brs.2023.01.173

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Self-driving TMS: the future is now!

Brain stimulation (2023)

Dubravko Kičić Risto J. Ilmoniemi Jaakko O. Nieminen Aino Nieminen Lari M. Koponen

Symposium title: Multichannel TMS: from the concept to approaches and applications Symposium description: The idea of Multichannel Transcranial Magnetic Stimulation (mTMS) was presented for the first time by Risto Ilmoniemi and Ferdinando Grandori in their patent application in 1993 more than 29 years ago. In their disclosed patent application that became public in 1996, the authors already showed images of the linear combinations of E-fields calculated for an array of sensors. Those ideas were explained further in a publication in 1998 from Ruohonen and Ilmoniemi describing how the stimulating field can be shaped and targeted without the coils themselves being moved by properly choosing the required driving $currents for each coil. This unique capability of the mTMS can open many possibilities that cannot be achieved with the standard 1-channel systems: (i) multi-locus stimulation of the brain, either simultaneous or sequential, (ii) correcting stimulation site after movements of a subject or (iii) fast mapping of motor cortex with no coil movement. Many years after the idea was originally presented, several groups are implementing different systems to enable multichannel TMS on the human brain and provide new tools that can revolutionize the use of TMS in research and clinical applications. In this Symposium we will briefly present the different approaches chosen by three different groups, their most important advances, and applications. The topics will cover mTMS instrumentation including coil and stimulator design, electronic targeting and computational neuronavigation, as well as integration with neuroimaging modalities such as electroencephalography (EEG) and functional MRI (fMRI). Abstract The efficacy of transcranial magnetic stimulation (TMS) protocols depends crucially on technical factors such as targeting accuracy (MRI-based anatomical personalization, and the numerical accuracy of the calculation of the induced electric field in the brain), repeatability of targeting (positioning and re-positioning of the coil), and head movement tracking (coil fixation systems, head fixation, and movement prevention). Unfortunately, human operators introduce significant systematic errors, which degrades clinical outcomes and/or diminishes the power of research results. Imagine a future in which all these steps could be automated and operator free. In fact, that future is now, as we demonstrate a “self-driving” robotized multi-locus TMS system that autonomously adjusts the stimulation sequence, minimizing the need for a human operator in the protocol. With our novel design of multi-coil transducers, power electronics, robotics, advanced neuronavigation, and closed-loop operation, we are delivering game-changing accuracy, reliability, and repeatability to both research and clinical TMS protocols. Research Category and Technology and Methods Translational Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: mTMS, Closed-loop, Brain Networks, Robotic TMS

Brain stimulation

10.1016/j.brs.2023.01.062

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Modulating brain networks in space and time: Multi-locus transcranial magnetic stimulation

Clinical Neurophysiology (2023)

Heikki Sinisalo Ilkka Rissanen Olli‐Pekka Kahilakoski Victor H. Souza Timo Tommila

10.1016/j.clinph.2023.12.007

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Electronic targeting of brain stimulation: design and validation of a 5-coil multi-locus TMS transducer

Brain stimulation (2021)

Victor H. Souza Mikko Malmi Jaakko O. Nieminen Matti Stenroos Heikki Sinisalo

Abstract Conventional transcranial magnetic stimulation (TMS) systems rely on the manual or robotic positioning of the stimulation coil over the scalp. This inherently slow process restricts the development of neuromodulation protocols engaging with structural and functional brain networks at the time scale of neuronal information flow (milliseconds). To overcome this limitation, we designed, built, and validated the first 5-coil multi-locus TMS (mTMS) transducer for fast electronic control of the peak electric field (E-field) location and orientation on the cortex. The coil windings were designed with a minimum-energy optimization algorithm. We tested multiple transducer dimensions, number of winding turns, stacking order, and the area under the coil where stimulation location can be controlled. Coils were manufactured using Litz wire in 3D-printed square formers (26-mm total thickness and 300-mm side length). For each coil, we recorded the induced E-field distribution in a spherical cortex model with a robotic TMS characterizer. The E-field distributions were combined in an optimization algorithm to compute the required intensity in each channel for electronically shifting the locus and orientation of the maximum E-field. Stimulation pulses were delivered by a custom-made mTMS power electronics. The 5-coil mTMS transducer consists of two four-leaf clover coils at 45° apart, two figure-of-eight coils at 90° apart, and one round coil stacked on top of each other from closest to furthest from the head. We have demonstrated that the electronic control of the E-field can be performed within a 30-mm-diameter circular region below the transducer center. The 5-coil transducer delivers consecutive stimuli to multiple locations and orientations faster (within milliseconds) and more precisely (within a millimeter) than a human or a robot can do when physically moving a conventional TMS coil. This work provides the technology for novel stimulation paradigms to interact with the real-time dynamics of brain networks. Keywords: multi-locus TMS, coil design, automated brain stimulation, closed-loop stimulation

Neuromodulation

10.1016/j.brs.2021.10.550

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