Based on a new study, a group of British scientists has developed a new understanding of the mechanisms by which transcranial magnetic stimulation (TMS) relieves severe depression. TMS is often used as an alternative treatment to electroconvulsive therapy (ECT), but knowledge of how it works is still limited. Understanding its mechanism of action may open the door to better and more targeted treatment. Currently, TMS produces its effects by sending magnetic pulses to the patient’s frontal area. Similar to ECT, TMS appears to have a “resetting” effect on the brain, but is simpler to use than ECT because it requires no anesthesia and has relatively few side effects. For this reason, it is increasingly used in the treatment of depression. However, similar to ECT, TMS is a relatively “blunt” treatment, and its mechanism of action is poorly understood by scientists. Today’s new study shows that targeted magnetic pulses can lead to changes in biochemistry and connectivity across the brain. In this placebo-controlled study, researchers from the University of Nottingham recruited 27 healthy volunteers and applied magnetic resonance (MRI)-guided intermittent theta-pulse transcranial magnetic stimulation (iTBS) to the subjects’ dorsolateral prefrontal cortex (DLPFC). This is the first time that MRI-guided TMS pulses have been used to observe changes in individual brain networks and brain chemistry. Using the same MRI scanning equipment, the researchers were able to determine subtle changes in brain function due to the magnetic pulses, and by using magnetic resonance spectroscopy, they were also able to identify changes in brain chemistry. We found that a single TMS treatment changed the connectivity of a large network of brain regions, especially the right anterior insula (rAI), which is critical for depression,” said lead researcher Dr. Sarina Iwabuchi. We also found that TMS altered the concentration of neurotransmitters in the brain, such as GABA, which is also strongly associated with the onset of depression.” The results showed that: ★ the negative effect of DLPFC on rAL was significantly attenuated after iTBS treatment (p = 0.043), and GABA levels were similarly significantly reduced (p = 0.041); ★ the absolute change in frontal insula junctional function caused by iTBS was significantly correlated with the absolute change in GABA levels (p = 0.002). The study abstract states, “By inhibiting the effect of DLPFC on rAL, iTBS has a direct effect on the effective connectivity between DLPFC and rAI, a functional change that may be mediated by changes in GABA levels in prefrontal brain regions.” ”This means that for the first time we understand the direct effects of TMS on the brain. If we can see for ourselves the changes triggered by the treatment, then the treatment will be smarter. It also means that we can better tailor the treatment to each patient’s specific situation. In other words, this therapy promises to be an individualized treatment for depression.” ”This study in healthy volunteers shows that individualized treatments are feasible and can indeed lead to changes in the brain. The next step is to actually apply the treatment to depressed patients in a clinical trial setting; in fact, that trial is already underway in Noningham. These are the first steps towards individualized treatment.” Professor Catherine Harmer of the University of Oxford commented on the study on behalf of the ECNP: “These are exciting findings in terms of understanding how targeted magnetic stimulation works in the brain and exerts its antidepressant effects; TMS technology is still evolving and its efficacy for depression still needs further validation and optimization. Such experimental medical studies are necessary to improve the individualization of antidepressant treatments.” Credit: Scientists show how magnetic pulses change the brain in treatment for depressed patients: may open door to individualised treatment. media Release: European College of Neuropsychopharmacology (ECNP).