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Summary
Abstract
Introduction
Protocol
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Medicina

MR-guided dmPFC-rTMS som en behandling for behandling-resistent depression

Published: August 11, 2015
doi:
10.3791/53129
, , , , , ,
1Institute of Medical Sciences,University of Toronto, 2MRI-Guided rTMS Clinic,University Health Network, 3Department of Psychiatry,University Health Network, 4Toronto Western Research Institute,University Health Network, 5Department of Psychiatry,University of Toronto, 6Faculty of Arts and Science,University of Toronto, 7Temerty Centre for Therapeutic Brain Intervention,Centre for Addiction and Mental Health

Summary

Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

Abstract

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.

Introduction

Gentagne transkraniel magnetisk stimulation (rTMS) er en form for indirekte omdrejningspunkt kortikal stimulation. rTMS beskæftiger korte, fokale elektromagnetiske felt pulser som trænger kraniet for at stimulere target hjerneområder. rTMS menes at engagere mekanismerne i synaptisk langtidspotensering og langsigtet depression, og derved øge eller sænke den kortikale ophidselse af regionen stimuleret 1. Generelt er rTMS pulsfrekvensen bestemmer dens virkninger: højere frekvens stimulation tendens til at være excitatorisk, mens lavere frekvens er inhiberende. Ikke-invasive stimulerende procedurer også meget anvendt som en kausal sonde til at fremkalde midlertidige 'kortikale læsioner «, og etablere neurale-adfærd relationer eller funktionelle regioner ved midlertidigt at deaktivere funktionen af et ønsket kortikale region 2 – 4.

Terapeutisk rTMS omfatter flere stimulation sessioner, der normalt anvendes, når daily over flere uger, til behandling af en række lidelser, herunder depression (MDD) 5, spiseforstyrrelser 6 og obsessiv-kompulsiv sygdom 7. rTMS for MDD er en potentiel mulighed for medicinsk refraktære patienter, og gør det muligt for klinikeren at ikke-invasivt målrette og ændre ophidselse af en cortical området direkte involveret med depressive ætiologi eller patofysiologi. Den konventionelle kortikale mål for MDD-rTMS er dorsolaterale præfrontale cortex (DLPFC) 8. Men konvergerende beviser fra neuroimaging, læsion, og stimulation undersøgelser identificerer dorsomedial præfrontale cortex (dmPFC) som en potentielt vigtig terapeutisk mål for MDD 9 og en række andre psykiatriske lidelser kendetegnet ved underskud i selvregulering af tanker, adfærd og følelsesmæssige hedder 10. Den dmPFC er en region i sammenhængende aktivering i følelsesmæssig regel 11, adfærdsregulering 12,13. DendmPFC er også forbundet med neurokemiske 14, strukturel 15, og funktionelle 16 abnormiteter i MDD

Beskrevet her er proceduren for 20 sessioner (4 uger) af magnetisk resonans imaging (MRI) guidede rTMS til dmPFC bilateralt, som en behandling for depression. Ud over en konventionel 10 Hz protokol anvendes over 30 min, er en intermitterende theta burst stimuleringsprotokol (TBS) diskuteret, som gælder 50 Hz triplet strømstød ved 5 Hz over 6 min session 17. Begge protokoller menes at være excitatoriske, med TBS-protokollen, der har potentiale til at opnå sammenlignelige effekter ved hjælp af en meget kortere session 18. I begge protokoller er anatomiske MRIs samt kliniske vurderinger erhvervet før rTMS. Neuronavigation anvender de anatomiske scanninger for at redegøre for anatomiske variabilitet dmPFC og optimere placeringen af ​​rTMS. En forholdsvis ny 120 ° -overvågningsmønster væske-kølet rTMS coil var også osed for at stimulere dybere midterlinjen kortikale strukturer. Endelig blev rTMS intensitet titrering anvendes i den første uge af rTMS sessioner for at sikre, at patienterne kunne vænne til de højere smerte der er forbundet med dmPFC stimulering sammenlignet med konventionelle DLPFC stimulering.

Protocol

Denne undersøgelse blev godkendt af Research Ethics Board ved University Health Network. 1. Med forbehold Selection Foretage en indledende vurdering af en potentiel patient. Inklusionskriterierne omfattede tilstedeværelsen af ​​en aktuel depressiv episode, der er resistent over for mindst 1 tilstrækkelig forsøg med medicin, og en Diagnostiske og Statistiske håndbog for psykiske forstyrrelser, femte udgave, (DSM-5) diagnosticering af MDD som fastsat af en vurdering psykiat…

Representative Results

I tidligere arbejde blev Hamd 17 anvendt som et mål for behandling respons for 10 Hz dmPFC-rTMS. Tabel 1 viser de før og efter behandling hamd 17 scorer i en tidligere offentliggjort sag serie 27. Blandt alle fag, forbehandling hamd 17 score var 21.66.9 der væsentligt faldt med 4331% til 12.58.2 post-rTMS (t 22 = 6,54, p <0,0001) 27. Ved hjælp af en eftergivelse kriterium Hamd 17 ≤7, 8 af 23 forsøgspersoner hjemvist e…

Discussion

Her blev MRI-guidede dmPFC-rTMS anvendes til behandling-resistent depression. Generelt blev rTMS på dette websted veltolereret, med mild hovedbund ubehag og smerter på det sted, stimulering, der var tilstrækkeligt styres ved hjælp af adaptiv titrering. I open-label forsøg og et diagram gennemgang, både 10 Hz og theta brast stimulation resulterede i signifikante forbedringer i depressive sværhedsgrad målt ved Hamd 17 og BDI-II.

Der er to kritiske trin værd at bemærke i pr…

Divulgazioni

The authors have nothing to disclose.

Acknowledgements

The authors wish to thank Aisha Dar, Vanathy Niranjan, and Dr. Umar Dar for technical assistance with rTMS delivery and data collection. The authors also wish to acknowledge the generous support of the Toronto General and Western Hospital Foundation, the Buchan Family Foundation, and the Ontario Brain Institute in funding this work.

Materials

3T GE Signa HDx Scanner GE n/a
Visor 2.0 Neuronavigation System ANT Neuro n/a
MagPro R30 Stimulator MagVenture n/a
Cool-DB80 Coil MagVenture n/a
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Tags

MRI-guidedDmPFC-rTMSTreatment-resistantMajor Depressive DisorderNeuronavigation3D Head ModelStimulation TargetHamilton Rating Scale For DepressionBeck Depression Index IIDouble-cone CoilResting Motor ThresholdStimulation Parameters
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Citazione di questo articolo
Dunlop, K., Gaprielian, P., Blumberger, D., Daskalakis, Z. J., Kennedy, S. H., Giacobbe, P., Downar, J. MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder. J. Vis. Exp. (102), e53129, doi:10.3791/53129 (2015).
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