In this study, a statistically significant decrease in HAMD-17 score was observed in subjects treated with the sTMS device compared to sham. These results indicate that a sub-threshold alternating sinusoidal magnetic field generated in the alpha frequency range can have therapeutic efficacy in patients with MDD. The sub-threshold alternating electrical field in the brain generated by the sTMS device would not actively depolarize neurons, but instead may influence neurons to fire at the induced frequency by modulating the threshold potential required for depolarization. These results support the hypothesis that a sinusoidal magnetic field applied at or near the IAF has a significant effect on brain function, possibly through entrainment of oscillations to the frequency of stimulation. This may help reset cortical oscillators, promote synaptic plasticity, and change brain function and patients’ mood through a mechanism similar to conventional rTMS systems .
The results of this study need to be interpreted within the context of several limitations. In the present study, clinical improvement was seen during the 4 weeks of treatment. It is not clear, however, that this is necessarily the optimal length of treatment. Subjects were contacted informally by telephone 4 weeks after the completion of the study to ensure there were no latent adverse effects, but no long-term clinical data was obtained. We would anticipate future studies to evaluate possible long-term effects of sTMS.
Our study found that the subjects treated at the IAF showed improvement that was numerically, but not statistically significantly greater, than subjects treated at an active random-frequency in the alpha range. These data suggest that there may be an advantage to matching the IAF, but neither prove nor disprove the hypothesis. One reason for this finding may be that the bandwidth of influence is large enough that any frequency in the alpha band may have an effect. This may also be a contributing factor to the efficacy of standard rTMS, which delivers treatment at a fixed 10 Hz, in the center of the alpha band. In a future clinical trial, it would be beneficial to compare the results of matching the IAF to an active device set to a more remote frequency, such as one in the beta or theta band.
The sTMS device used in this study was designed primarily to deliver stimulation at a specific frequency or set of frequencies. Other design decisions were made on a practical basis to make it feasible to build a first-generation sTMS device that could operate reliably in a multi-site clinical trial. Three rotating magnets were chosen to deliver treatment broadly over the midline region; it is possible that a different number of magnets in the same or different locations might match or exceed the efficacy seen in this study. As is evident in Figure 1, the rotating magnets are 180 degrees out of phase with each other. This creates the same phase relationship in the electric field generated in the brain. The relationship between the magnets was not chosen due to any perceived benefit of opposite phases. Instead, this relationship between magnets allowed for a smaller motor required to turn the magnets. Additional research into the benefits of different phase relationships would be valuable.
This study aimed to examine only the safety and efficacy of sTMS treatment. Future studies should also examine the effects of sTMS on various biological metrics, such as alpha power, frequency selectivity, blood flow, or EEG coherence. In the present study, both active groups (fixed and random frequency) had a positive effect on symptoms. Future studies should go further to establish clearly which technique achieves the most significant response. The present findings suggest that the sTMS device can be an efficacious treatment for MDD, and supports the conduct of a larger, definitive clinical trial.