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Summary
Abstract
Introduction
Protocol
Results
Discussion
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Acknowledgements
Materials
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Automatic Translation
Medicine

Guiada por MRI dmPFC-EMTr como um tratamento para o Transtorno Depressivo Maior resistente ao tratamento

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

A estimulação magnética transcraniana repetitiva (EMTr) é uma forma de estimulação cortical focal indireta. EMTr emprega breves, focais pulsos de campo eletromagnético que penetram no crânio para estimular regiões alvo do cérebro. rTMS é pensado para envolver os mecanismos de potenciação de longo prazo sináptica e depressão a longo prazo, aumentando assim ou diminuindo a excitabilidade cortical da região estimulada 1. Geralmente, a frequência de pulso EMTr determina seus efeitos: maior estimulação frequência tende a ser excitatórios, enquanto menor freqüência é inibidora. Procedimentos estimuladores não-invasivos são também amplamente utilizado como uma sonda causal para induzir lesões corticais '' temporários, e estabelecer relações neural-comportamento ou regiões funcionais, desativando temporariamente a função de uma região cortical desejado 2-4.

Terapêutico EMTr envolve múltiplas sessões de estimulação, usualmente aplicados uma vez dAily longo de várias semanas, para tratar uma variedade de doenças, incluindo transtorno depressivo maior (MDD) 5, 6 distúrbios alimentares e transtorno obsessivo-compulsivo 7. rTMS para MDD é uma opção potencial para os pacientes clinicamente refractários, e permite que o clínico para alvejar de forma não invasiva e alterar a excitabilidade de uma região cortical directamente envolvido com etiologia depressivo ou patofisiologia. O alvo cortical convencional para MDD-EMTr é o córtex pré-frontal dorsolateral (CPFDL) 8. No entanto, evidências convergentes de neuroimagem, lesão, e os estudos de estimulação identifica o córtex pré-frontal dorsomedial (dmPFC) como um alvo terapêutico potencialmente importante para MDD 9 e uma variedade de outros transtornos psiquiátricos caracterizados por déficits na auto-regulação dos pensamentos, comportamentos, e emocional 10 estados. O dmPFC é uma região de activação consistente na regulação emocional 11, regulação comportamental 12,13. OdmPFC também está associada com neuroquímica 14, 15 estruturais, funcionais e 16 anormalidades na MDD

Descrito aqui é o procedimento para 20 sessões (4 semanas) de ressonância magnética (MRI) guiada EMTr para o dmPFC bilateralmente, como um tratamento para o transtorno depressivo maior. Além de um protocolo convencional de 10 Hz aplicado ao longo de 30 min, um protocolo de estimulação de explosão teta intermitente (TBS) é discutido, que se aplica 50 Hz tripleto estouros de 5 Hz ao longo de uma sessão de 17 minutos 6. Ambos os protocolos estão pensados ​​para serem excitatórios, com o protocolo TBS tendo o potencial para atingir efeitos comparáveis ​​usando uma sessão de 18 muito mais curto. Em ambos os protocolos, ressonâncias magnéticas anatômicas, bem como avaliações clínicas são adquiridos antes da EMTr. Neuronavegação usa os scans anatômicas para explicar a variabilidade anatômica da dmPFC e otimizar a localização da EMTr. Uma relativamente nova bobina de 120 ° EMTr refrigerado a fluidos -angled também nos foied, a fim de estimular a linha média mais profundo estruturas corticais. Finalmente, a rTMS titulação intensidade foi utilizada durante a primeira semana de sessões rTMS para assegurar que os pacientes poderiam habituar para os níveis mais elevados de dor associados com estimulação dmPFC em relação ao estímulo DLPFC convencional.

Protocol

Este estudo foi aprovado pelo Conselho de Ética em Pesquisa da University Health Network. Seleção 1. Assunto Realizar uma avaliação inicial em um paciente em potencial. Os critérios de inclusão a presença de um episódio depressivo atual que é resistente a pelo menos um julgamento adequado de medicação, e um Manual Diagnóstico e Estatístico de Transtornos Mentais, Fifth Edition, (DSM-5) diagnóstico de MDD como estabelecido pelo psiquiatra avaliação . Confirmar o di…

Representative Results

Em trabalhos anteriores, HAMD 17 foi usado como uma medida da resposta ao tratamento para 10 Hz dmPFC-EMTr. A Tabela 1 apresenta os pré e pós-tratamento HAMD 17 pontuações em uma série de casos publicada anteriormente 27. Entre todos os assuntos, o pré-tratamento HAMD 17 pontuação foi 21.66.9 que diminuiu significativamente em 4331% a 12.58.2 pós-EMTr (t 22 = 6,54, p <0,0001) 27. Usando um critério de remissão de 17</su…

Discussion

Aqui, guiada por MRI dmPFC-EMTr foi aplicada para o tratamento resistente à TDM. Em geral, a EMTr neste local foi bem tolerada, com desconforto no couro cabeludo leve e dor no local da estimulação que foi adequadamente gerenciados usando titulação adaptativa. Em ensaios abertos e uma revisão de prontuários, ambos de 10 Hz e theta estimulação explosão resultou em melhorias significativas na severidade depressiva medida pelo HAMD 17 e BDI-II.

Existem dois passos críticos …

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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