Predicting rTMS Treatment Outcomes in Major Depression Using EEG

Post by Ewina Pun

What is depression and how can rTMS help?

Depression is a common mental disorder and a major contributor to suicide. It is estimated that over 300 million people suffer from depression globally, equivalent to 4.4% of the world’s population. Major depressive disorder (MDD) is diagnosed with symptoms such as depressed mood, loss of interest and enjoyment, fatigue, disturbed sleep, and change in appetite. While anti-depressant medication and psychotherapy are available forms of treatment, about 30% of people are resistant to these standard therapies. Recently, researchers found that some people with treatment-resistant MDD respond to repetitive transcranial magnetic stimulation (rTMS), a type of noninvasive neuromodulation where repeated electromagnetic pulses are applied outside of the skull to induce changes in functional networks in the brain.

TMS has been shown to be clinically effective in treating neuropsychiatric disorders and typically involves weeks of repeated sessions for improvement to take place. During each visit, patients receive TMS stimulations at a targeted brain area, where the device sends pulses by inducing a magnetic field from a magnetic coil. Stimulations at the left dorsolateral prefrontal cortex (DLPFC) at 5-10Hz elicit an excitatory effect, while at the right DLPFC at 1Hz elicits an inhibitory effect on neural circuitry related to emotion regulation. rTMS can affect brain regions not only at the stimulation site but also others not directly under the coil. About 50% of patients receiving rTMS treatment show improvement in depression symptoms, however, it’s difficult to predict who may benefit from rTMS.

How can we predict positive treatment outcomes?

To better understand the neural mechanism of how rTMS elicits changes in network connectivity associated with clinical improvement, researchers have used electroencephalography (EEG) to identify biomarkers. Recent work suggests that EEG ‘microstates’ may help delineate subtypes of depression. EEG microstates are recurring transient voltage topographies characterized within resting-state brain networks (common patterns of fluctuations in brain activity that can be found while someone is simply resting). Microstates are likely generated by repeated co-activation of large-scale networks between brain areas.

Four to six of these canonical microstate topographies are found consistently across participants, and recent papers have identified microstates characterizing MDD. For example, the proportion and occurrence of some microstates is significantly different in MDD compared to healthy controls. By measuring changes between resting state EEG before and after rTMS treatment, researchers have revealed that there are selective changes in microstates, specifically in MDD patients who responded to treatment (and not in non-responders). Changes in some microstates are believed to correlate with changes in resting state brain networks associated with depression that are elicited by TMS, such as the cognitive control network and default mode network. While further investigation is required, microstates analysis can potentially serve as biological markers for early response in MDD patients and therefore predict future clinical outcomes prior to committing to the weeks-long rTMS treatment.

What’s the takeaway?

People with depression experience a range of symptoms with varying severity and duration. Its underlying etiology can also be heterogeneous. Therefore, predicting which treatments work best for which patients is critical for effective treatment. rTMS is a viable alternative therapy for some antidepressant-resistant patients. EEG helps researchers identify biomarkers related to positive rTMS outcomes and study the underlying mechanisms of these outcomes in different depression subtypes. The combination of TMS-EEG is a promising tool to optimize the process of treatment for MDD and provide better treatment for patients sooner.

References +

Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organization. (2017).

Guse et al. Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: a systematic review. Journal of Neural Transmission. (2010).

P. B. Fitzgerald et al., Accelerated repetitive transcranial magnetic stimulation in the treatment of depression. Neuropsychopharmacology. (2018).

M. Murphy et al. Abnormalities in electroencephalographic microstates are state and trait markers of major depressive disorder. Neuropsychopharmacology (2020).

D. Yan et al. Prediction of Clinical Outcomes with EEG Microstate in Patients with Major Depressive Disorder. Front. Psychiatry. (2021).

M. C. Gold et al. Large-scale EEG neural network changes in response to therapeutic TMS. Brain Stimulation. (2022).