rTMS Targeted with MRI Based Neuro-Navigation in Treatment-Resistant Depression


Efficacy of rTMS for treatment resistant depression isn’t impressive to say the least. The results of studies show little clinical relevance of the efficacy compared to sham rTMS, many studies have reported limited effect sizes or response rates.

A recent study tried to address one of the main concerns that could be responsible for the lack of efficacy namely the way in which the rTMS treatment
is targeted over the Dorsolateral Prefrontal Cortex (DLPFC). The localization is done with “the 5 cm measure”, this involves the localization of the motor cortical site for optimal stimulation of a hand muscle, usually the abductor pollicis brevis, and then measurement 5 cm anteriorly along the scalp surface. This traditional method for targeting the DLPFC with rTMS may be suboptimal, potentially explaining the modest therapeutic effects of rTMS.

In this study the neuro-navigational method was used. This method generally involves localization of the scalp position that corresponds to a brain site identified on an MRI scan from an individual subject.

How was this study done?

we conducted a randomized double blind trial comparing left prefrontal rTMS localized either using the 5 cm method or a navigational technique. We hypothesized that the targeted rTMS would result in a greater therapeutic efficacy in major depressive disorder (MDD) compared with the ‘5 cm’ method. We utilized an ‘offline’ navigational technique to localize the site of DLPFC in the experimental group and compared this with the 5 cm localization method.

Fifty-one patients with treatment-resistant depression were randomized to receive a 3-week course (with a potential 1-week extension) of high-frequency (10 Hz) left-sided rTMS. Thirty trains (5 s duration) were applied daily 5 days per week at 100% of the resting motor threshold. Treatment was targeted with either the standard 5 cm technique (n=27) or using a neuro-navigational approach (n=24). This involved localizing the scalp location that corresponds to a specific site at the junction of Brodmann areas 46 and 9 in the DLPFC based on each individual subject’s MRI scan

The efficacy of rTMS with a structural MRI-based neuro-navigational procedure can have the capacity to improve response to the rTMS treatment in TRD. Other such as altering stimulation frequency
increasing dose, and the use of a neuro-navigationally guided rTMS based on pretreatment positron emission tomography (PET) scans did not improve efficacy.

At least a MRI is needed for this neuro-navigational method and:

The miniBIRD is quite inexpensive and the MRIreg and MRIcro software available as freeware. These are also relatively easy to use with training.

From this research it is hard to tell whether rTMS is efficacious for TRD since the results may have been confounded by non-specific effects given that we have not included a sham control group.
I hope this method might improve efficacy, what do you think?

Paul B Fitzgerald, Kate Hoy, Susan McQueen, Jerome J Maller, Sally Herring, Rebecca Segrave, Michael Bailey, Greg Been, Jayashri Kulkarni, Zafiris J Daskalakis (2009). A Randomized Trial of rTMS Targeted with MRI Based Neuro-Navigation in Treatment-Resistant Depression Neuropsychopharmacology DOI: 10.1038/npp.2008.233