Electronics and methods for multi-locus transcranial magnetic stimulation

Heikki Sinisalo

Electronics and methods for multi-locus transcranial magnetic stimulation

Julkaisun otsikon käännös: Elektroniikan ja metodien kehitys monikohteiselle transkraniaaliselle magneettistimulaatiolle

Heikki Sinisalo

Neurotieteen ja lääketieteellisen tekniikan laitos

Tutkimustuotos: Doctoral Thesis › Collection of Articles

Abstrakti

Aivosairaudet ovat kasvava huolenaihe ihmiskunnalle, sillä ne johtavat elämänlaadun heikkenemiseen sekä jopa biljoonien eurojen vuosittaisiin taloudellisiin kustannuksiin. Ongelman ratkaisemiseksi tarvitaan uusia menetelmiä, jotka tarjoavat tehokkaampaa ja nopeampaa hoitoa sekä auttavat ymmärtämään aivosairauksia ja aivojen toimintaa paremmin. Yksi tällainen menetelmä on transkraniaalinen magneettistimulaatio (TMS). TMS perustuu voimakkaan virtapulssin ajamiseen pään päälle asetetun stimulaatiokelan läpi, mikä indusoi sähkökentän aivokuorelle aktivoiden hermosoluja. TMS:ää käytetään masennuksen, migreenin ja pakko-oireisen häiriön hoitoon sekä aivokirurgiaa edeltävissä kartoitusmenetelmissä. Menetelmän suurin rajoitus on ollut sen kyky aktivoida vain yhtä aivokuoren kohtaa kerrallaan, vaikka aivojen toiminnan tiedetään riippuvan eri aivoalueiden keskinäisestä vuorovaikutuksesta. Lisäksi menetelmän tehokkuus voi vaihdella sen mukaan, miten hyvin paras stimuloitava paikka aivoissa löydetään. Monikohteinen TMS (mTMS) tarjoaa ratkaisun esitettyihin ongelmiin. Yhden stimulaatiokelan sijasta mTMS-laitteistossa on useita stimulaatiokeloja omine sähkökenttäprofiileineen. Antamalla erivahvuisia pulsseja näistä keloista yhtä aikaa sähkökenttä voidaan muokata aktivoimaan tiettyjä aivokuoren kohtia ilman fyysistä kelan siirtämistä. Tämä sallii useamman aivokuoren kohteen stimuloinnin lyhyellä aikavälillä, mahdollistaen samalla algoritmipohjaisten ja käyttäjästä riippumattomien kohdistusmenetelmien kehittämisen. Tämä väitöskirja koostuu johdannon lisäksi kuudesta julkaisusta ja keskittyy mTMS-laitteiston ja sen menetelmien kehittämiseen edistäen teknologian laajempaa käyttöä ja lopulta kaupallistamista. Osatyössä 1 kehitettiin ja validoitiin kuutta kelaa tukeva mTMS-laite sekä viisikelainen kelasto. Järjestelmällä kyetään kohdistamaan stimulaatio 3 cm halkaisijaltaan olevan alueen sisällä mahdollistaen tarkan aktivaation läheisissä aivokuoren alueissa. Tällä laitteistolla voidaan lisäksi automatisoida protokollia esimerkiksi aivokuoren toiminnalliseen kartoitukseen tai optimaalisen stimulaatiopaikan löytämiseen. Osatyössä 2 kuvataan magneettikuvauksen (MRI) kanssa yhteensopiva mTMS-laite ja kaksikelainen kelasto, jotka mahdollistavat esikliiniset tutkimukset. Yhdistelmän käyttö voi antaa arvokasta tietoa aivoaktivaation dynamiikasta sekä terveissä että sairastuneissa aivoissa. Osatyössä 3 tutkittiin mTMS-pulssien antamista pulssinleveysmodulaatiotekniikalla, joka mahdollistaa peräkkäisten pulssien kohdistamisen eri aivokuoren alueille millisekuntiluokan viiveillä. Vaikka sähkökentät käyttäytyvät monimutkaisesti, aivojen aktivaatio on samankaltaista kuin perinteisillä pulsseilla, mahdollistaen aivojen verkostovuorovaikutusten tutkimisen. Osatyössä 4 mTMS-laiteteknologiaa jatkokehitettiin täyttämään lääketieteellisten laitteiden määräykset. Tällainen laite asennettiin Saksan Tübingenissä sairaalakäyttöön. Osatyössä 5 esitellään mTMS-teknologiaa, sen mahdollisuuksia sekä mahdollisia haasteita. Osatyössä 6 käsitellään TMS:n periaatteita, sen käyttöä ja erilaisia validointimittauksia. Tämä väitöskirjatyö johti kehittyneiden mTMS-järjestelmien rakentamiseen, jotka kykenevät aktivoimaan erillisiä aivokuoren kohtia millisekuntiluokan viiveillä. Tämä kehitys on merkittävä harppaus kohti aivoverkostojen vuorovaikutuksia tutkivia työkaluja.

Julkaisun otsikon käännös	Elektroniikan ja metodien kehitys monikohteiselle transkraniaaliselle magneettistimulaatiolle
Alkuperäiskieli	Englanti
Pätevyys	Tohtorintutkinto
Myöntävä instituutio	Aalto-yliopisto
Ohjaaja	Hämäläinen, Matti, Vastuuprofessori Ilmoniemi, Risto, Ohjaaja Nieminen, Jaakko, Ohjaaja Souza, Victor, Ohjaaja
Kustantaja	Aalto University
Painoksen ISBN	978-952-64-2588-7
Sähköinen ISBN	978-952-64-2587-0
Tila	Julkaistu - 2025
OKM-julkaisutyyppi	G5 Artikkeliväitöskirja

Tutkimusalat

TMS
mTMS
elektroniikka
monikelajärjestelmä
pulssinleveysmodulaatio
ei-invasiivinen aivostimulaatio

Pääsy asiakirjaan

http://urn.fi/URN:ISBN:978-952-64-2587-0

Science-IT
Hakala, M. (Manager)
Perustieteiden korkeakoulu
Laitteistot/tilat: Facility

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@phdthesis{8bb6b594d74c4f4cb2ff01cc09fa0cdd,

title = "Electronics and methods for multi-locus transcranial magnetic stimulation",

abstract = "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{\textquoteright}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.",

keywords = "TMS, mTMS, electronics, coil array, pulse-width modulation, non-invasive brain stimulation, TMS, mTMS, elektroniikka, monikelaj{\"a}rjestelm{\"a}, pulssinleveysmodulaatio, ei-invasiivinen aivostimulaatio, TMS, mTMS, electronics, coil array, pulse-width modulation, non-invasive brain stimulation",

author = "Heikki Sinisalo",

year = "2025",

language = "English",

isbn = "978-952-64-2588-7",

series = "Aalto University publication series Doctoral Theses",

publisher = "Aalto University",

number = "112",

address = "Finland",

school = "Aalto University",

}

TY - BOOK

T1 - Electronics and methods for multi-locus transcranial magnetic stimulation

AU - Sinisalo, Heikki

PY - 2025

Y1 - 2025

N2 - 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.

AB - 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.

KW - TMS

KW - mTMS

KW - electronics

KW - coil array

KW - pulse-width modulation

KW - non-invasive brain stimulation

KW - TMS

KW - mTMS

KW - elektroniikka

KW - monikelajärjestelmä

KW - pulssinleveysmodulaatio

KW - ei-invasiivinen aivostimulaatio

KW - TMS

KW - mTMS

KW - electronics

KW - coil array

KW - pulse-width modulation

KW - non-invasive brain stimulation

M3 - Doctoral Thesis

SN - 978-952-64-2588-7

T3 - Aalto University publication series Doctoral Theses

PB - Aalto University

ER -

Electronics and methods for multi-locus transcranial magnetic stimulation

Abstrakti

Tutkimusalat

Pääsy asiakirjaan

Sormenjälki

Laitteet

Science-IT

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