Photo Credits : University of British Columbia Faculty of Medicine

rTMS (repetitive transcranial magnetic stimulation) has become a popular treatment option for patients suffering from depression, including those with major depressive disorder (MDD) who have not responded to other treatments. However, there is still much to learn about the mechanism of action of rTMS and whether there is a way to predict who will benefit from the treatment. 

A recent study led by Fidel Vila-Rodriguez, M.D., Ph.D., at the University of British Columbia, and BC Schizophrenia Society Board member, aimed to investigate the therapeutic action of rTMS and its relation to plasticity. The team recruited 52 patients with treatment-resistant MDD for a trial to measure the impact of a 4-week course of rTMS therapy. Of these, 38 patients underwent a separate inquiry involving having a single rTMS session conducted prior to the beginning of the treatment course. These patients received this initial rTMS session while inside a scanner that generates functional MRI images of brain activity in real-time. 

The researchers found that rTMS stimulation of the right DLPFC (dorsolateral prefrontal cortex) “induced widespread acute alterations in functional connectivity,” and that these changes “predicted clinical outcome after a 4-week course of rTMS treatment.” Broadly speaking, altering plasticity means changing the strength of connections between brain regions, making them stronger or weaker. If rTMS acts by altering neuroplasticity, this would support an important theory of what causes depression. 

The team made several interesting observations in addition to this conclusion. They found “widespread connectivity changes even in [brain] regions with no known functional or anatomical connections” with the site targeted in the treatments, the DLPFC. This suggests that one of the reasons for rTMS’s effectiveness in depression is its ability to change connectivity at the “macro level,” i.e., in widely dispersed sites across the brain that may be involved in different ways in depression’s varied symptoms. 

Moreover, the connectivity changes observed were reductions in baseline connectivity, not increases. It was also interesting that the connectivity changes seen after an initial rTMS session, while significant, were not long-lasting. This suggests that repeated stimulation sessions, longer sessions, or sessions delivering a larger number of magnetic pulses, are needed to generate clinical improvement in rTMS therapy. 

Finally, the team commented on the predictive value of functional connectivity changes they observed after the first rTMS session. There was an association between the level of connectivity changes in that first session and treatment response after a 4-week course of therapy. Those patients with the most pronounced changes in the initial session tended to get more benefit from the full course of treatment. For this reason, the team proposes that the preliminary fMRI readout of how rTMS changes plasticity in the brain might be used as an indicator of an individual patient’s capacity to respond to a full course of therapy. 

In conclusion, this study sheds light on the therapeutic action of rTMS in treatment resistant MDD patients and its relation to plasticity. The results suggest that rTMS has the potential to influence brain functional organization beyond that predicted by the DLPFC’s already known connectivity pattern. The preliminary fMRI readout of how rTMS changes plasticity in the brain might be used as an indicator of an individual patient’s capacity to respond to a full course of therapy. While further studies are needed to replicate these findings, this research provides an important clue to the effectiveness of rTMS and its potential to help those suffering from depression. 

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