A New Window Into the Active Brain: Measuring TMS Effects as They Happen

How does this new method compare with what has been used historically?

Transcranial magnetic stimulation (TMS) is a non-invasive treatment that uses magnetic pulses applied to the scalp to stimulate brain regions involved in mood regulation. Up until now, researchers could study the effects of TMS either by measuring indirect changes in brain activity through blood flow, or by measuring brain chemistry before and after stimulation. While blood flow changes can be measured immediately, they do not directly reflect brain chemistry, and pre- and post-treatment measurements cannot capture what happens during stimulation itself. Our new method, using standard Magnetic Resonance Imaging (MRI) hardware, allows us to directly measure brain chemistry in real time while TMS is being delivered, providing a more direct and complete understanding of its biological effects. 

What motivated this research? 

TMS is an effective and widely used treatment for depression, particularly for people who do not respond to medications. However, we still do not fully understand how it works at the biological level. While previous studies could measure changes in brain activity through blood flow, they could not directly measure the brain’s chemical response during stimulation. We developed this method to better understand the real-time chemical effects of TMS, with the goal of improving treatments and helping guide more personalized and effective care for patients with depression. 

What was the most important finding of this study, in your opinion? 

The most important finding is that we were able to directly measure real-time changes in brain chemistry while TMS was being delivered. Depression disrupts how brain cells communicate, and TMS is thought to alleviate symptoms by restoring healthy brain activity.  This study shows, for the first time, that TMS produces real-time chemical changes in the human brain, helping us better understand how this treatment works. 

How does this change service delivery in the future? 

This method could help clinicians better understand why some people respond to TMS while others do not. In the future, it may allow us to tailor treatments based on each patient’s brain chemistry, improving effectiveness and reducing trial-and-error. It could also help researchers develop improved stimulation protocols and accelerate the development of new brain-based treatments. 

Any next steps? 

The next step is to study this method in larger groups of persons with depression to confirm these findings and ensure they are reliable. We also plan to further refine and optimize the technique to improve its precision and sensitivity. This will help us better understand how TMS affects brain chemistry, neurotransmitter concentrations, and move closer to using these measurements to guide and personalize treatment. 

What is the major take home message for the public? 

This study shows that TMS produces immediate and measurable changes in brain chemistry. For the first time, we can directly observe the brain’s chemical response to stimulation as it happens, rather than relying on indirect measures like blood flow. This brings us closer to understanding how TMS works and may help improve and personalize treatments for people living with depression. 

Are there any other Departmental faculty or learners you'd like to mention? 

Maria Vasileiadi, a post-doctoral fellow supervised by Dr. Sean Nestor, led this work. Dr. Jamie Near, PhD, a biomedical engineer from Sunnybrook Research Institute, was a key collaborator. We would also like to thank our co-investigators who also helped support this work: Peter Truong, Benjamin Davidson, Christopher Pople, Clement Hamani, Peter Giacobbe, Nir Lipsman, and Martin Tik.