JoVE Journal > Medicine
Summary
Abstract
Introduction
Protocol
Results
Discussion
Disclosures
Acknowledgements
Materials
References
자동 번역
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의학

治療抵抗性大うつ病性障害の治療薬としてdmPFC-のrTMSをMRIガイド

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

反復経頭蓋磁気刺激（のrTMS）は、間接的な焦点皮質刺激の形です。のrTMSは、ターゲット脳領域を刺激する頭蓋骨を貫通する短い、焦点電磁界パルスを採用しています。のrTMSことにより領域の皮質の興奮性の増加または減少が1を刺激し、シナプスの長期増強および長期抑圧のメカニズムに係合するように考えられています。一般的に、のrTMSパルス周波数は、その効果を決定する：より低い周波数は阻害であるが、より高い周波数の刺激は、興奮性になる傾向があります。 4 –非侵襲的刺激手順も広く一時'皮質病変」を誘発し、一時的に所望の皮質領域2の機能を無効にすることによって、神経行動の関係または機能的領域を確立する原因のプローブとして使用されています。

治療のrTMSは通常D一度適用、複数の刺激セッションを伴いますaily数週間にわたって、大うつ病性障害（MDD）5、障害6摂食、および強迫性障害7を含む、様々な障害を治療することができます。 MDDのためのrTMSは、医学的に難治性の患者のための潜在的な選択肢であり、臨床医は、非侵襲的に標的とし、直接うつ病の病因や病態生理に関与する皮質領域の興奮性を変更することができます。 MDD-のrTMSのための従来の皮質のターゲットは、背外側前頭前野（DLPFC）8です。しかし、神経画像、病変、および刺激研究からの収束の証拠はMDD 9のための潜在的に重要な治療標的と考え、行動の自己調節に欠損を特徴とする他の精神疾患の様々な、感情的な等の背内側前頭前皮質（dmPFC）を識別する状態10。 dmPFCは感情的な規制11、行動規制12,13における一貫した活性化の領域です。ザdmPFCはまた、14の神経化学15の構造、およびMDDにおける機能16の異常と関連しています

ここで説明した大うつ病性障害の治療薬として、左右dmPFCへのrTMSを案内され、磁気共鳴画像（MRI）の20セッション（4週間）のための手順です。従来の10Hzのプロトコルは、30分かけて適用することに加えて、断続シータバースト刺激プロトコル（TBS）を6分間かけて5セッション17 Hzで50 Hzのトリプレットバーストを適用する、議論されています。両方のプロトコルは、TBSのプロトコルは非常に短いセッション18を使用して、同等の効果を達成する可能性を有する、興奮性であると考えられています。両方のプロトコルでは、解剖学的MRI画像などの臨床評価はのrTMSの前に取得されています。ニューロはdmPFCの解剖学的変動性を考慮してのrTMSの位置を最適化するために、解剖学的スキャンを使用しています。比較的新しい120°-angled流体冷却式のrTMSコイルは、米国でありました深い正中線皮質構​​造を刺激するために、編。最後に、のrTMS強度滴定は、従来のDLPFC刺激と比較して、患者がdmPFC刺激に関連した高い痛みのレベルに慣らすことができることを確実にするためのrTMSセッションの最初の週にわたって使用されました。

Protocol

この研究は、大学健康ネットワークで研究倫理委員会によって承認されました。 1.対象の選択将来の患者の初期評価を行います。評価する精神科医によって確立され包含基準は、薬剤の少なくとも1適切な裁判に耐性があり、現在のうつ病エピソードの存在、およびMDDの診断と精神疾患の統計マニュアル、第5版、（DSM-5）診断を含め。標準化されたミニメンタルス…

Representative Results

前作では、HAMD 17は 10ヘルツdmPFC-のrTMS。 表1に、治療前および治療 ​​後HAMD以前に公開された症例27で17得点の治療応答の尺度として使用しました。すべての被験者のうち、前処理HAMD 17スコアが有意12.58.2後のrTMS（T 22 = 6.54、P <0.0001）27に4331パーセント減少している21.66.9ました。 HAMD 17≤7の寛解基準を使用して、23の被験…

Discussion

ここでは、MRIガイドdmPFC-のrTMSは、治療抵抗性のMDDのために適用しました。一般的には、このサイトでのrTMSは十分に適応滴定を使用して管理された刺激の部位での軽度の頭皮の不快感や痛みに、忍容性が良好でした。 HAMD 17とBDI-IIによって測定されるようなオープンラベル試験およびチャートのレビューでは、10 Hzからシータバースト刺激の両方がうつ病重症度の有意な改善をもたら?…

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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