Transcranial Magnetic Stimulation #2

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Transcranial magnetic stimulation – also known as TMS –  uses focused magnetic pulses to improve brain activity. TMS induces changes in activity of nerve cells by applying rapidly changing or repetitive magnetic fields. Thus, TMS is also called repetitive TMS (rTMS).

Transcranial magnetic stimulation is a clinically meaningful and effective treatment of depression (major depressive disorder) (Lefaucheur et al., 2014; McClintock et al., 2017). The treatment is non-invasive, and does not require anesthesia. TMS is a drug-free alternative to antidepressant medication, and is offered to patients either not responding to their medication or who cannot tolerate the side effects. 

The largest clinical trial using rTMS for treatment of depression shows that 49% of patients who previously failed to receive improvement from prior antidepressant medication responded to treatment, and 32% received remission, meaning they were no longer clinically depressed (Blumberger et al., 2018). TMS has been marketed and approved for this purpose for almost a decade in both Europe and the USA and is covered by insurance (McClintock et al., 2017).

Why is TMS effective in treating depression?

The most common symptoms of depression is the presence of empty, sad or irritable mood in combination with both cognitive and somatic changes that can significantly affect the individual’s capacity to function (Downar, Blumberger, Daskalakis, 2016). These behavioral and functional consequences of depression are due to alterations in brain activity. In depression, a whole distributed network of brain areas is affected. The cardinal idea of applying TMS for treatment of depression is to precisely target the areas of the brain involved in treatment-resistant depression. The part of the brain that is being stimulated is located to the left side of the brain, specifically the dorso-lateral prefrontal cortex, or in short Left-DLPFC. This cortical area is the prime target for CE and FDA approved TMS treatment, as it is a focal point connecting all the different brain areas that are involved in the pathology of depression (Anderson, Hoy, Daskalakis, & Fitzgerald, 2016; Tik et al., 2017). Insurance will often cover TMS if the patient is treatment resistant, meaning that anti-depressants from two different medication classes have failed to resolve symptoms.

Depression treatment without systemic side effects 

The Left-DLPFC is responsible for:

• Coordinating and adjusting complex behavior
• Controlling impulses
• Displaying appropriate emotional reactions
• Manifesting personality
• Focusing attention
• Considering and prioritizing competing and simultaneous information
• Ignoring external distractions

• Complex planning
• Assessing options and choosing a course of behavior
• Deferring certain immediate gratifications in order to obtain greater long-term benefits
• The left half of pre-frontal cortex is involved in establishing positive feelings
• The right half is involved in establishing negative feelings

Thus, stimulating at the focal point and modulating its activity will consequently modulate the activity in other areas of the brain, and thereby transcranial magnetic stimulation  is selectively improving overall brain activity (Chen et al., 2013; Liston et al., 2014). Or in other words, TMS enhances entire brain networks, alleviating depression and the behavioral and cognitive symptoms, without any of the systemic side effects often associated with medication.

References

Anderson, R. J., Hoy, K. E., Daskalakis, Z. J., & Fitzgerald, P. B. (2016). Repetitive transcranial magnetic stimulation for treatment resistant depression: Re-establishing connections. Clin Neurophysiol, 127(11), 3394-3405. doi:10.1016/j.clinph.2016.08.015
Association, A. P. (2013). Diagnostic and Statistical Manual og Mental Disorders (DSM-5): American Psychiatric Association Publishing.
Blumberger, D., Vila-Rodriguez, F., Thorpe, K. E., Feffer, K., Noda, Y., Giacobbe, P., . . . Downar, J. (2018). Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. The Lancet, April 28, 2018, volume 391, Issue 10131, p1683-1692.
Chen, A. C., Oathes, D. J., Chang, C., Bradley, T., Zhou, Z. W., Williams, L. M., . . . Etkin, A. (2013). Causal interactions between fronto-parietal central executive and default-mode networks in humans. Proc Natl Acad Sci U S A, 110(49), 19944-19949. doi:10.1073/pnas.1311772110
Downar, J., Blumberger, D. M., & Daskalakis, Z. J. (2016). The Neural Crossroads of Psychiatric Illness: An Emerging Target for Brain Stimulation. Trends Cogn Sci, 20(2), 107-120. doi:10.1016/j.tics.2015.10.007
Lefaucheur, J. P., Andre-Obadia, N., Antal, A., Ayache, S. S., Baeken, C., Benninger, D. H., . . . Garcia-Larrea, L. (2014). Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol, 125(11), 2150-2206. doi:10.1016/j.clinph.2014.05.021
Liston, C., Chen, A. C., Zebley, B. D., Drysdale, A. T., Gordon, R., Leuchter, B., . . . Dubin, M. J. (2014). Default mode network mechanisms of transcranial magnetic stimulation in depression. Biol Psychiatry, 76(7), 517-526. doi:10.1016/j.biopsych.2014.01.023
McClintock, S. M., Reti, I. M., Carpenter, L. L., McDonald, W. M., Dubin, M., Taylor, S. F., . . . Treatments. (2017). Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. J Clin Psychiatry. doi:10.4088/JCP.16cs10905
Tik, M., Hoffmann, A., Sladky, R., Tomova, L., Hummer, A., Navarro de Lara, L., . . . Windischberger, C. (2017). Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity. Neuroimage, 162, 289-296. doi:10.1016/j.neuroimage.2017.09.022