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Summary
Abstract
Introduction
Protocol
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Medicina

MRI-geleide dmPFC-rTMS als een behandeling voor de behandeling-resistente Depressieve stoornis

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

Repetitieve transcraniële magnetische stimulatie (rTMS) is een vorm van indirecte focale corticale stimulatie. rTMS telt korte, brandpunt elektromagnetische veld pulsen die de schedel te doelwit gebieden van de hersenen te stimuleren door te dringen. rTMS wordt gedacht dat de mechanismen van synaptische langetermijnpotentiëring lange termijn depressie aangrijpen, waardoor het verhogen of verlagen van de corticale exciteerbaarheid van de regio gestimuleerde 1. In het algemeen, de rTMS pulsfrequentie bepaalt de effecten: hogere frequentie stimulatie neigt exciterend zijn, terwijl lagere frequentie remmend. Niet-invasieve stimulerende procedures worden ook veel gebruikt als een causale probe tijdelijke 'corticale letsels' induceren en neurale gedragsrelaties of functionele regio vast aan de functie van een gewenst corticale gebied 2 tijdelijk uit – 4.

Therapeutische rTMS stimulatie bestaat uit meerdere sessies, een keer d meestal toegepastAily gedurende een aantal weken, aan een verscheidenheid van aandoeningen, waaronder depressieve stoornis (MDD) 5, eetstoornissen 6, en obsessief-compulsieve stoornis 7. rTMS voor MDD is een mogelijke optie voor medisch refractaire patiënten, en kan de arts niet-invasief richten en exciteerbaarheid in een corticaal gebied direct met depressieve etiologie en pathofysiologie te wijzigen. De conventionele corticale doelstelling voor MDD-rTMS is de dorsolaterale prefrontale cortex (DLPFC) 8. Echter, convergerende aanwijzingen uit neuroimaging, letsel en stimulatie studies worden de dorsomediale prefrontale cortex (dmPFC) als een potentieel belangrijk therapeutisch doel voor MDD 9 en verschillende andere psychiatrische stoornissen gekenmerkt door tekorten in zelfregulering gedachten, gedrag en emotionele stelt 10. De dmPFC is een regio van consistente activering in emotionele regulering 11, behavioral regulering 12,13. DedmPFC is ook geassocieerd met neurochemische 14, 15 structurele en functionele abnormaliteiten 16 in MDD

Hier beschreven procedure moet 20 sessies (4 weken) van magnetic resonance imaging (MRI) geleid rTMS de dmPFC bilateraal, voor de behandeling van depressieve stoornissen. Naast conventionele 10 Hz protocol toegepast over 30 min, wordt een intermitterende theta burst stimuleringsprotocol (TBS) besproken, waarbij 50 Hz triplet zijn bursts op 5 Hz over een 6 min zitting 17. Beide protocollen worden gedacht exciterend zijn, met TBS protocol waarin zich potentieel vergelijkbare effecten met een veel kortere sessie 18 bereiken. In beide protocollen, zijn anatomische MRI's evenals de klinische evaluaties voorafgaand aan rTMS verworven. Neuronavigatie gebruikt de anatomische scans om rekening te houden anatomische variabiliteit van dmPFC en optimaliseren van de locatie van rTMS. Een relatief nieuwe 120 ° -angled-vloeistof gekoelde rTMS spoel was ook onsed om dieper middellijn corticale structuren te stimuleren. Tenslotte werd rTMS intensiteit titratie gebruikt over de eerste week van rTMS sessies zodat patiënten kunnen wennen aan de hogere niveaus van pijn geassocieerd met dmPFC stimulatie vergeleken met conventionele DLPFC stimulatie.

Protocol

Deze studie werd goedgekeurd door de Research Ethics Board aan de Universiteit Health Network. 1. Onder Selection Voeren een initiële beoordeling van een potentiële patiënt. De criteria opname inclusief de aanwezigheid van een huidige depressieve episode die resistent is tegen ten minste 1 adequate proef van medicatie en een Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) diagnose van MDD zoals vastgesteld door het beoordelen van psychiater . Beves…

Representative Results

In eerdere werk, HAMD 17 werd gebruikt als maat voor de respons op de behandeling voor 10 Hz dmPFC-rTMS. Tabel 1 toont de pre- en post-behandeling hamd 17 scores in een eerder gepubliceerde case series 27. Van alle onderwerpen, voorbehandeling HAMD 17 score was 21.66.9 die aanzienlijk gedaald met 4.331% tot 12.58.2 post-rTMS (t 22 = 6,54, p <0,0001) 27. Met behulp van een remissie criterium HAMD 17 ≤7, 8 van de 23 proefper…

Discussion

Hier, MRI-geleide dmPFC-rTMS werd toegepast voor de behandeling-resistente MDD. Over het algemeen werd rTMS op deze site goed verdragen mild hoofdhuid ongemak en pijn op de plaats van stimulatie die toereikend was beheerd middels adaptieve titratie. In open-label trials en een grafiek beoordeling, zowel 10 Hz en theta burst stimulatie geleid tot significante verbeteringen in depressieve ernst zoals gemeten door de HAMD 17 en BDI-II.

Er zijn twee belangrijke stappen vermeldenswaard…

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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