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27th May 2022
Changes in brain connectivity during treatment for depression with transcranial magnetic stimulation (TMS) and which improve symptom scores can be seen during an MRI scan. This was the key finding of a study by a team of researchers from Canada and the US.
Depression affects an estimated 3.8% of the world’s population and a 2022 meta-analysis found the point prevalence of major depression to be 8%. Repetitive transcranial magnetic stimulation (TMS) is a non-invasive technique which uses magnetic pulses to influence the excitability and connection strength of the cortical neurons and has been used as a treatment modality for major depression. It involves placing an electromagnetic coil on the scalp and delivery of a brief pulsatile magnetic field that depolarises cortical neurons. Treatment with TMS has been shown to be effective for reducing suicidal ideation and in alleviating depression. The treatment is normally applied to the left or right dorsolateral prefrontal cortex (DLPFC) although use on either side appears to be equally effective. The mode of action for TMS remains uncertain although the effects of TMS on brain activity that can now be studied by combining it with neuroimaging methods such as functional magnetic resonance imaging. In a 2020 study combining TMS with MRI imaging, researchers observed how the magnetic stimulation induced lasting connectivity and excitability changes such that after treatment, the DLPFC appeared better able to engage in top-down control of the amygdala.
However, the particular changes in brain connectivity affected by TMS among those with major depression are unknown. For the present study, the team wanted to visualise these changes with MRI but also determine whether such changes led to a clinical response in patients with major depression. They recruited adults with major, treatment-resistant depression and performed an open-label trial of TMS. The team initially acquired MRI scans without TMS and compared these to scans when TMS was delivered. The treatment was applied to the right DLPFC once daily for a period of 4 weeks. The TMS-induced changes were assessed by pairwise comparison between the MRI scan with and without TMS. Depression symptoms were assessed using the Montgomery-Asberg Depression rating scale (MADRS) which was measured at baseline and at the end of the study.
Transcranial magnetic stimulation and depression
A total of 38 patients with a mean age of 41.8 years (68% female) were included in the study.
When comparing the two scans, the researchers observed 43 edges that were changed after use of TMS with a preponderance of inter-hemispheric functional connectivity. As the changes were absent from the baseline MRI scan, these were indicative of the response to TMS and hence an index of short-term macro-scale neuroplasticity. The observed TMS-induced changes were short-lived and the authors suggested that repeated stimulation might be necessary to induce long-lasting connectivity effects.
More importantly however, the observed were associated with an improvement in depression symptom scores, with a drop in MADRS of 10.87.
The authors concluded that the observed TMS-induced effect on connectivity may index macro-level neuroplasticity changes and which might be indicative of an individual’s response to TMS treatment. They called for further studies to assess the generalisability of these findings and their relevance to connectivity changes after repeated TMS therapy.
Ge R et al. Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial Am J Psychiatry 2022