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Abstract
Introduction
Protocol
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Medicine

MRI-guidata dmPFC-rTMS come Trattamento di trattamento resistente Disturbo Depressivo Maggiore

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

Ripetitiva stimolazione magnetica transcranica (rTMS) è una forma di stimolazione corticale focale indiretta. rTMS impiega brevi focali impulsi di campo elettromagnetico, che penetrano il cranio per stimolare regioni cerebrali bersaglio. rTMS è pensato per impegnare i meccanismi di sinaptica potenziamento a lungo termine e depressione a lungo termine, aumentando o diminuendo l'eccitabilità corticale della regione stimolata 1. In generale, la frequenza degli impulsi rTMS determina i suoi effetti: stimolazione maggiore frequenza tende ad essere eccitatorio, mentre la frequenza più bassa è inibitorio. Procedure di stimolazione non invasivi sono anche ampiamente utilizzati come sonda di causalità per indurre temporanei lesioni corticali ", e stabilire relazioni neurale di comportamento o regioni funzionali disattivando temporaneamente la funzione di una regione corticale desiderato 2-4.

Terapeutico rTMS coinvolge molteplici sedute di stimolazione, applicati di solito una volta dAily per diverse settimane, per il trattamento di una serie di disturbi, tra cui il disturbo depressivo maggiore (MDD) 5, disturbi alimentari 6, e il disturbo ossessivo-compulsivo 7. rTMS per MDD è un potenziale opzione per i pazienti medicalmente refrattari, e consente al medico di indirizzare in modo non invasivo e alterare l'eccitabilità di una regione corticale direttamente coinvolto con eziologia depressivo o fisiopatologia. Il target corticale convenzionale per MDD-rTMS è la corteccia prefrontale dorsolaterale (DLPFC) 8. Tuttavia, le prove convergenti da neuroimaging, lesioni, e gli studi di stimolazione identifica la corteccia prefrontale dorsomediale (dmPFC) come potenzialmente importante obiettivo terapeutico per MDD 9 e una varietà di altri disturbi psichiatrici caratterizzati da deficit di autoregolamentazione di pensieri, comportamenti, ed emozionale afferma 10. Il dmPFC è una regione di attivazione coerente nella regolazione emozionale 11, regolazione del comportamento 12,13. IldmPFC è anche associato con neurochimico 14, 15 strutturale e funzionali 16 anomalie nella MDD

Descritto qui è la procedura per 20 sessioni (4 settimane) di risonanza magnetica (MRI) guidato rTMS al dmPFC bilateralmente, come trattamento per il disturbo depressivo maggiore. Oltre a un protocollo 10 Hz convenzionale applicato sopra 30 min, un protocollo di stimolazione theta raffica intermittente (TBS) è discusso, che applica 50 Hz tripletta raffica a 5 Hz in un 6 min sessione di 17. Entrambi i protocolli sono pensati per essere eccitatoria, con il protocollo TBS avere il potenziale per raggiungere effetti comparabili con una sessione molto più breve 18. In entrambi i protocolli, risonanza magnetica anatomiche e valutazioni cliniche vengono acquisiti prima di rTMS. Neuronavigazione utilizza le scansioni anatomiche per spiegare la variabilità anatomica di dmPFC e ottimizzare la posizione di rTMS. Una relativamente nuova bobina 120 ° rTMS liquido raffreddato -angled era anche noied al fine di stimolare strutture corticali più profonda della linea mediana. Infine, rTMS intensità titolazione è stata utilizzata nel corso della prima settimana di sessioni rTMS al fine di garantire che i pazienti potrebbero abituarsi ai livelli di dolore più elevati associati con la stimolazione dmPFC rispetto alla stimolazione DLPFC convenzionale.

Protocol

Questo studio è stato approvato dal Comitato Etico di ricerca presso la University Health Network. 1. Fatte salve Selezione Condurre una valutazione iniziale su un paziente prospettico. I criteri di inclusione comprendevano la presenza di un episodio depressivo corrente che è resistente ad almeno 1 di sperimentazione sufficiente di farmaci, e un Manuale Diagnostico e Statistico dei Disturbi Mentali, Fifth Edition (DSM-5) diagnosi di MDD come stabilito dallo psichiatra valutando …

Representative Results

In un lavoro precedente, HAMD 17 è stato utilizzato come misura della risposta al trattamento per La Tabella 1 mostra 10 Hz dmPFC-rTMS. I pre e post-trattamento Hamd 17 colonne in una serie di casi in precedenza pubblicato 27. Tra tutti i soggetti, pretrattamento Hamd 17 punteggio 21.66.9 che significativamente diminuita del 4.331% al 12.58.2 post-rTMS (t 22 = 6.54, p <0,0001) 27. Utilizzando un criterio di remissione di Hamd 17<…

Discussion

Qui, MRI-guidata dmPFC-rTMS è stato applicato per il trattamento resistente MDD. In generale, rTMS in questo sito è stato ben tollerato, con lieve disagio del cuoio capelluto e dolore nel sito di stimolazione che è stato gestito adeguatamente con la titolazione di adattamento. Negli studi in aperto e una revisione delle cartelle, sia 10 Hz e theta stimolazione scoppiare determinato miglioramenti significativi nella gravità depressivo come misurato dal Hamd 17 e BDI-II.

Ci sono…

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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