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Neuroscience

Måling og manipulation funktionelt specifikke neurale veje i det menneskelige motorsystem med tværkraniel magnetisk stimulation

Published: February 23, 2020
doi:
10.3791/60706
, , , ,
1School of Kinesiology, Brain Behavior Laboratory,University of Michigan

Summary

Denne artikel beskriver nye tilgange til at måle og styrke funktionelt specifikke neurale veje med transkraniel magnetisk stimulation. Disse avancerede noninvasive hjernestimulationsmetoder kan give nye muligheder for forståelse af hjerneadfærdsrelationer og udvikling af nye behandlingsformer til behandling af hjernesygdomme.

Abstract

Forståelse interaktioner mellem hjernen områder er vigtigt for studiet af målrettet adfærd. Funktionel neuroimaging af hjernen smuligheder har givet vigtig indsigt i grundlæggende processer i hjernen som kognition, læring, og motorkontrol. Men denne tilgang kan ikke give årsagssammenhæng evidens for inddragelse af hjernen områder af interesse. Transkraniel magnetisk stimulation (TMS) er et kraftfuldt, noninvasive værktøj til at studere den menneskelige hjerne, der kan overvinde denne begrænsning ved forbigående at ændre hjerneaktivitet. Her fremhæver vi de seneste fremskridt ved hjælp af en parret-puls, dual-site TMS metode med to spoler, der kausal sonder kortico-kortikale interaktioner i det menneskelige motorsystem i forskellige opgave sammenhænge. Derudover beskriver vi en Dual-site TMS protokol baseret på kortikal parret associative stimulation (cPAS), der forbigående øger synaptisk effektivitet i to indbyrdes forbundne hjerneområder ved at anvende gentagne par kortikale stimuli med to spoler. Disse metoder kan give en bedre forståelse af de mekanismer, der ligger til grund for kognitiv-motorisk funktion samt et nyt perspektiv på at manipulere specifikke neurale veje på en målrettet måde at modulere hjernen kredsløb og forbedre adfærd. Denne tilgang kan vise sig at være et effektivt redskab til at udvikle mere avancerede modeller af hjerne-adfærd relationer og forbedre diagnose og behandling af mange neurologiske og psykiatriske lidelser.

Introduction

Noninvasive hjerne stimulation er en lovende vurdering værktøj og behandling for mange neurologiske lidelser, såsom Parkinsons sygdom, Alzheimers sygdom, og slagtilfælde1,2,3,4. Der er akkumulerende beviser for forholdet mellem adfærdsmæssige manifestationer af neurologiske sygdomme og abnormiteter i kortikal ophidselse, neuroplasticitet, kortico-kortikale og kortico-subkortikale tilslutningsmuligheder5,6. Derfor kan grundlæggende viden om hjernennetværk dynamik og plasticitet i neurologiske tilstande give uvurderlig indsigt i sygdomsdiagnose, progression, og reaktion på terapi. Funktionel magnetisk resonans imaging(fMR) er et nyttigt værktøj til at forstå de komplekse relationer mellem hjerne og adfærd i både sunde og syge hjernenetværk og har potentiale til at forbedre behandlingen baseret på et netværk perspektiv7,8,9. Men, fMR er korrelationsmæssig karakter og kan ikke give en årsagssammenhæng mellem hjernefunktion og adfærd, eller manipulere funktionelle tilslutningsmuligheder for at genoprette unormale neurale kredsløb forbundet med adfærdsmæssige funktionsnedsættelser hos patienter10,11,12. Transkraniel magnetisk stimulation (TMS) kan både kausal måle og modulere menneskelige hjernefunktion og adfærd i sundhed og sygdom3,13,14,15.

TMS er en sikker, noninvasive metode til at stimulere den menneskelige hjerne16,17og kan bruges til at fremkalde og måle plasticitet18. Denne metode kan fremme vores forståelse af kausalrelationer mellem individuelle hjerneområder og adfærd10,11,12,19og deres specifikke funktionelle interaktioner med andre noder i et hjernenetværk20,21,22,23. Til dato har de fleste undersøgelser fokuseret på det menneskelige motorsystem, da TMS til håndområdet af den motoriske cortex (M1) kan producere motor fremkaldte potentialer (MEP’er) som fysiologiske udlæsninger for ændringer i forbindelse med motorisk adfærd24, så undersøgelse af forskellige hæmmende og excitatoriske kredsløb på systemniveau i den menneskelige hjerne25. Nylige fremskridt ved hjælp af en konditioneringtest TMS tilgang med to spoler viser, at det er muligt at måle funktionelle interaktioner mellem forskellige kortikale områder. I motorsystemet viser TositeTMS-eksperimenter, at input fra kortikale områder, der er forbundet med M1, kan ændre sig med opgavekrav, alder eller sygdom14,26. Skelsættende arbejde af Ferbert og kolleger har konstateret, at anvende en konditionering stimulus til M1 forud for en test stimulus af den anden M1 kan resultere i hæmning af MEP amplitude, et fænomen kendt som kort interval interumisk hæmning (SIHI)28. En række TMS-undersøgelser ved hjælp af denne fremgangsmåde har også vist, at M1 er stærkt forbundet med den kontralaterale M1, ventrale præmotoriske cortex (PMv), dorsale præmotoriske cortex (PMd), supplerende motorområde (SMA), pre-SMA, primær sensorisk cortex (S1), dorsolateral præfrontal cortex (DLPFC) og posterior parietal cortex (PPC) i hvile27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42. Interessant, effekten af stimulation fra disse kortikale områder på motor kortikal ophidselse er anatomisk, tidsmæssigt, og funktionelt specifikke for den igangværende hjerneaktivitet under udarbejdelsen af en bevægelse (tilstand- og kontekstafhængig43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,69). Men, meget få undersøgelser ved hjælp af dual-site TMS har karakteriseret mønstre af funktionelle kortico-kortikale tilslutningsmuligheder med motoriske og kognitive funktionsnedsættelser hos patienter med hjernesygdomme70,71,72. Dette giver mulighed for at udvikle nye metoder til vurdering og behandling af motoriske og kognitive forstyrrelser.

Ved hjælp af denne teknik, det er også blevet konstateret, at gentagne par kortikale TMS anvendes på kortikale områder forbundet med M1 såsom kontralaterale M168,69,70, PMv76,77,78, SMA71, og PPC80,81,82 kan fremkalde ændringer i synaptisk effektivitet i specifikke neurale veje baseret på Hebbian princippet om associativ plasticitet83 ,84,85,86 og forbedre adfærdsmæssige ydeevne72,73,74. Stadig, få undersøgelser har brugt denne tilgang til at studere kredsløb og plasticitet dysfunktion i neurologiske lidelser2,75,76,77,78,79,80,81,82,83,84,90,91,92, 93,94,95,96. Det er stadig at blive vist, om en styrkelse af funktionelt specifikke neurale veje med TMS kan genoprette aktiviteten i dysfunktionelle kredsløb, eller om den potentielle styrkelse af intakt kredsløb kan øge modstandsdygtigheden97 i hjernen netværk støtte motoriske og kognitive funktion i hele levetiden og i sygdom. Manglen på grundlæggende forståelse af de neurale mekanismer, der ligger til grund for neurologiske lidelser og virkninger af stimulation på indbyrdes forbundne dysfunktionelle hjernenetværk, begrænser den nuværende behandling.

På trods af sin evne, TMS er endnu ikke blevet en standard del af armamentarium af neurovidenskab og kliniske værktøjer til at forstå hjerne-adfærd relationer, patosysiologi af hjernesygdomme, og effektiviteten af behandlingen. Derfor, at realisere sit potentiale og støtte sin store anvendelse, standardisering TMS metoder er vigtigt, fordi det er mere tilbøjelige til at øge stringens af fremtidige TMS eksperimenter og reproducerbarhed på tværs af uafhængige laboratorier. I denne artikel beskrives, hvordan TMS kan bruges til både at måle og manipulere funktionelle interaktioner. Her beskriver vi denne teknik i motorsystemet (f.eks. parieto-motorvej44) ved at måle TMS-baserede outputforanstaltninger (f.eks. mep’er), hvor metoden bedst forstås. Det er dog vigtigt at bemærke, at denne protokol også kan tilpasses til at målrette funktionel kobling af andre subkortikale85, cerebellar86,87, og kortikale områder. 73,74,88 Desuden kan neuroimaging teknikker som EEG89,90,91 og fMRI92,93 anvendes til at vurdere de TMS-inducerede ændringer i aktivitet og konnektivitet26,94. Vi slutter med at foreslå, at undersøgelsen af den funktionelle inddragelse af kredsløbsniveau kortikale tilslutningsmuligheder med disse TMS metoder i både sundhed og sygdom gør det muligt at udvikle målrettede diagnoser og innovative behandlingsformer baseret på mere avancerede netværksmodeller af hjerne-adfærd relationer.

Protocol

Følgende tre TMS-metoder er beskrevet nedenfor. For det første er to metoder beskrevet til at måle kortico-kortikale tilslutningsmuligheder ved hjælp af dual-site transkraniel magnetisk stimulation (dsTMS), mens deltagerne er enten 1) i hvile (hviletilstand) eller 2) udfører en objekt-rettet reach-to-grasp bevægelse ( opgaveafhængig). For det andet beskrives en kortikal parret associativ stimulationsmetode (cPAS) for at modulere samspillet mellem to hjerneområder på en kontrolleret måde ved at parre kortikale s…

Representative Results

Figur 5 viser størrelsen af et eksempel på et eksempel på et parlamentsmedlemmers respons, der fremkaldes i FDI-musklen af TMS for en ukonditioneret teststimuli (TS alene til M1, blå spor) eller konditionerede stimuli fra PPC (CS-TS, rødt spor), mens deltageren var i hvile (øverste panel) eller planlagde en målrettet gribehandling mod et objekt (nederste panel). I hvile udøver PPC en hæmmende indflydelse på ipsilateral M1, som det fremgår af faldet i MEP amplitudes forstærket af …

Discussion

Den dual-site TMS metode, der er beskrevet her kan anvendes til at undersøge funktionelle interaktioner mellem forskellige kortikale områder forbundet med den primære motoriske cortex, mens en deltager er i hvile eller planlægger en målrettet handling. Mens hjernebilleddannelse er korreleret, grundlæggende viden fra dual-site TMS metoder kan afsløre kausal hjerne-adfærd relationer forbundet med ændringer i kortico-kortikale kredsløb. Desuden kan kortikal parret associativ stimulation med to TMS-spoler, der anve…

Disclosures

The authors have nothing to disclose.

Acknowledgements

Dette arbejde blev støttet af University of Michigan: MCubed Scholars Program og School of Kinesiology.

Materials

Alpha B.I. D50 coil (coated) Magstim 50mm coil
BrainSight 2.0 Software Rogue Research Neuronavigation software
BrainSight frameless Stereotactic System Rogue Research Neuronavigation equiptment
D702 Coil Magstim 70mm coil
Discovery MR750 General Electric 3.0T MRI machine
Disposable Earplugs 3M Foam earplugs
ECG Electrodes 30mm x 24mm Coviden-Kendall H124SG Disposable electrodes
Four Channel Isolated Amplifier Intronix Technologies Corporation 2024F EMG amplifier
gGAMMAcap g.tec Medical Engineering EEG head cap
Micro1401-3 Cambridge Electronic Design Scientific data recorder and processing machine
Nuprep Skin Prep Gel Weaver and Company Skin prep abrasive gel
Signal v.7 Cambridge Electronic Design Data acquisition and analysis software
The Magstim BiStim2 Magstim Transcranial magnetic stimulator (two 2002 units)
DOWNLOAD MATERIALS LIST

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Transcranial Magnetic StimulationTMSNon-invasive Brain StimulationMotor SystemBrain CircuitsBrain ExcitabilityBrain ConnectivityNeurological DisordersPsychiatric DisordersMotor CortexM1NeuronavigationEMGElectromyographyPrecentral Gyrus

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Goldenkoff, E. R., Mashni, A., Michon, K. J., Lavis, H., Vesia, M. Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation. J. Vis. Exp. (156), e60706, doi:10.3791/60706 (2020).
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