Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

Summary

The present protocol describes the application of repetitive transcranial magnetic stimulation (rTMS), where a subregion of the dorsolateral prefrontal cortex (DLPFC) with the strongest functional anticorrelation with the subgenual anterior cingulate cortex (sgACC) was located as the stimulation target under the assistance of a fMRI-based neuronavigation system.

Abstract

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe neuromodulation technique that immediately changes brain activity. Despite its wide application in the treatment for MDD, the treatment response remains different among individuals, which may be attributable to the inaccurate positioning of the stimulation target. Our study aims to examine whether the functional magnetic resonance imaging (fMRI)-assisted positioning improves the efficacy of rTMS in treating depression. We intend to identify and stimulate the subregion of dorsolateral prefrontal cortex (DLPFC) in MDD with strongest anti-correlation with the subgenual anterior cingulate cortex (sgACC), and to conduct a comparative investigation of this novel method and the traditional 5-cm rule. To achieve more precise stimulation, both methods were applied under the guidance of neuronavigation system. We expected that the TMS treatment with individualized positioning based on resting state functional connectivity may show better clinical efficacy than the 5-cm method.

Introduction

Major depressive disorder (MDD) is characterized by significant and persistent depression, and in more severe cases, patients can encounter hallucinations and/or delusions^1,2. Compared with the general population, the risk of suicide among MDD patients is approximately 20 times higher³. While medication is currently the most used treatment for MDD, 30% - 50% of the patients lack adequate response to antidepressants⁴. For the responders, the symptom improvement tends to appear after a relatively long latent period and is accompanied by side effects. Psychotherapy,....

Protocol

Inform all participants about the study and ask them to sign the informed consent form prior to the start of the study. The present protocol was approved by the Research Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University.

NOTE: In this double-blind study, patients with depression were randomly divided into two groups. In the experimental group, stimulation targets are located by the DLPFC-sgACC-based individualized location method (Please see 3.3 for detailed description). The targets of the control group are obtained by the average 5-cm method (i.e. (-41, 16, 54))²².

Results

ROI-wise FC analysis should show that sgACC is significantly anti-correlated with DLPFC, in which the strongest negative correlation is the stimulus target to be chosen. Significant anti-correlation between the sgACC-DLPFC functional connectivity and the treatment response should be found in the correlation analysis³³.

The current protocol is based on an innovative TMS targeting method that no previous studies have applied. Here we present results from an fMRI-guided TM.......

Discussion

The sgACC is responsible for emotional processing and plays an important role in stress regulation^16,17,18. A study suggests that targeting on a subregion of DLPFC that shows strongest functional anti-connectivity with sgACC (6, 16, -10) may enhance the antidepressant effect²⁵. Therefore, precisely locating this target is the critical step of this protocol. Before the stimulation, the borders of the brain.......

Materials

Name	Company	Catalog Number	Comments
3T Philips Achieva MRI scanner	Philips
Harvard/Oxford cortical template	http://www.cma.mgh.harva rd.edu/
MATLAB	MathWorks
SPM12	http://www.fil.ion.ucl.ac.uk/spm
The Visor2 system	ANT Neuro		The Visor2 software, the optical tracking system, tracking tools and calibration board are part of the visor2 system.
TMS device	Magstim, Carmarthenshire, UK