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Abstract
Introduction
Protocol
Results
Discussion
Disclosures
Acknowledgements
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Medicine

MR-guidad dmPFC-rTMS som en behandling för behandlingsresistent egentlig 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

Upprepad transkraniell magnetisk stimulering (rTMS) är en form av indirekt fokal kortikal stimulering. rTMS använder korta, bränn elektromagnetiska fältpulser som tränger skallen att stimulera mål hjärnregioner. rTMS tros ingripa mekanismerna för synaptiska långsiktig potentiering och långvarig depression, därmed öka eller minska det kortikala retbarhet av regionen stimulerade en. I allmänhet bestämmer rTMS pulsfrekvens dess effekter: högre frekvens stimulering tenderar att vara excitatoriska, medan lägre frekvens är hämmande. Icke-invasiva stimulerande rutiner används också allmänt som ett orsaks sond för att orsaka temporära "kortikala skador", och etablera neural-beteende relationer eller funktionella regioner genom att tillfälligt inaktivera funktionen hos en önskad kortikal region 2-4.

Terapeutisk rTMS involverar flera stimuleringssessioner, som vanligen används när dAily under flera veckor, för att behandla en rad olika sjukdomar, inklusive egentlig depression (MDD) 5, ätstörningar 6, och tvångssyndrom 7. rTMS för MDD är en potentiell alternativ för medicinskt eldfasta patienter, och gör det möjligt för läkaren att icke-invasivt rikta och ändra retbarhet av en kortikal regionen direkt involverad med depressiv etiologi eller patofysiologi. Den konventionella kortikala mål för MDD-rTMS är dorsolaterala prefrontala cortex (DLPFC) 8. Men konvergerande bevis från neuroradiologiska, skada, och stimuleringsstudier identifierar dorsomediala prefrontala cortex (dmPFC) som en potentiellt viktig terapeutisk mål för MDD 9 och en mängd andra psykiska sjukdomar som kännetecknas av underskott i självreglering tankar, beteenden och emotionell påstår 10. Den dmPFC är en region av konsekvent aktivering i emotionell reglering 11, beteende reglering 12,13. DendmPFC är också förknippat med neurokemiska 14, strukturella 15 och funktionella 16 avvikelser i MDD

Beskrivs här är förfarandet för 20 sessioner (4 veckor) av magnetisk resonanstomografi (MRT) guidade rTMS till dmPFC bilateralt, som en behandling för egentlig depression. Förutom en konventionell 10 Hz protokoll applicerat över 30 minuter, är ett intermittent theta skurstimuleringsprotokoll (TBS) diskuterats, som gäller 50 Hz triplett pulser på 5 Hz över en 6 minuters session 17. Båda protokollen tros vara excitatoriska, med TBS-protokollet har potential att uppnå liknande effekter med hjälp av en mycket kortare session 18. I båda protokollen är anatomiska MRI samt kliniska bedömningar förvärvats före rTMS. Neuro använder anatomiska skannar att ta hänsyn till anatomiska variationer i dmPFC och optimera placeringen av rTMS. En relativt ny 120 ° -angled vätskekylda rTMS spole var också ossed för att stimulera djupare mittlinjen kortikala strukturer. Slutligen rTMS intensitet titrering används under den första veckan i rTMS sessioner för att säkerställa att patienter kan vänja till de högre smärtnivåer i samband med dmPFC stimulering jämfört med konventionell DLPFC stimulering.

Protocol

Denna studie har godkänts av Forskningsetiska styrelsen vid University Health Network. 1. Om inte annat val Genomföra en första bedömning på en blivande patient. Inklusionskriterierna inbegrep förekomsten av en aktuell depression som är resistent mot minst 1 adekvat prövning av läkemedel, och en Diagnostic and Statistical Manual of Mental Disorders, femte upplagan, (DSM-5) diagnosen MDD som fastställts av bedömning av psykiater . Bekräfta diagnosen med en standardisera…

Representative Results

I tidigare arbete, var HAMD 17 som ett mått på behandlingssvar för Tabell 1 visar de före och efter behandling HAMD 17 poäng i en tidigare publicerad fallserier 27 10 Hz dmPFC-rTMS.. Bland alla ämnen, förbehandling HAMD 17 poäng var 21.66.9 som väsentligt minskade med 4331% till 12.58.2 efter rTMS (t 22 = 6,54, p <0,0001) 27. Med hjälp av en eftergift kriterium HAMD 17 ≤7, 8 av 23 försökspersoner efterges efter…

Discussion

Här var MRI-guidade dmPFC-rTMS tillämpas för behandlingsresistent MDD. I allmänhet tolererades väl rTMS på denna webbplats, med mild hårbotten obehag och smärta på platsen för stimulering som var tillräckligt hanteras med adaptiv titrering. I öppna studier och ett diagram översyn, både 10 Hz och theta skurstimuleringen resulterade i signifikanta förbättringar av depressiv svårighetsgrad mätt med HAMD 17 och BDI-II.

Det finns två viktiga steg värt att notera i r…

Disclosures

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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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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