Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modulating endogenous oscillations in humans. The current standard method for rTMS defines the stimulation intensity based on the evoked liminal response in the visual or motor system (e.g., resting motor threshold). The key limitation of the current approach is that the magnitude of the resulting electric field remains elusive. A better characterization of the electric field strength induced by a given rTMS protocol is necessary in order to improve the understanding of the neural mechanisms of rTMS. In this study we used a novel approach, in which individualized prospective computational modeling of the induced electric field guided the choice of stimulation intensity. We consistently found that rhythmic rTMS protocols increased neural synchronization in the posterior alpha frequency band when measured simultaneously with scalp electroencephalography. We observed this effect already at electric field strengths of roughly half the lowest conventional field strength, which is 80% of the resting motor threshold. We conclude that rTMS can induce immediate electrophysiological effects at much weaker electric field strengths than previously thought. Neurons and neural assemblies in the mammalian brain temporally synchronize their activity leading to the emergence of macroscopic network oscillations 1. Network oscillations are rhythmic patterns of neural activity that are maintained in all physiologically occurring brain states 2. They are crucial for intact neuropsychological functioning and are frequently disrupted in neurological or psychiatric diseases 3. However, neurons also respond to both endogenous and exogenous electric fields 4. Non-invasive electrical brain stimulation (NIBS) methods, such as repetitive transcranial magnetic stimulation (rTMS), are promising techniques for modulating endogenous oscillations 5. Many NIBS studies employ oscillating electric fields because it is believed that these exogenous oscillations can modulate the phase or the power of endogenous oscillations 6. The two crucial properties of rTMS-generated periodic electric fields are its frequency and its magnitude. Whereas the frequency of the electric field is clearly defined, its magnitude in the brain is defined only indirectly. Most studies choose to set the stimulation intensity using the near threshold approach. This approach defines the stimulation intensity as a percentage of the threshold intensity required to induce a liminal response in the motor or visual cortex 7. Although the near threshold approach utilizes individualized stimulation intensities, the properties of the rTMS-induced electric field, including its strength, can differ substantially within and across individuals. For example, this approach cannot account for differences in the cortical folding pattern and the cortex-scalp distance between motor and non-motor areas 8. However, it is crucial to account for these known anatomical effects because the induced electric field strength plays an...

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Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modulating endogenous oscillations in humans. The current standard dosing method for rTMS defines the electric field strength only indirectly. A better characterization of the electric field strength induced by a given rTMS protocol is necessary in order to improve the understanding of the neural mechanisms of rTMS. In this study we used a novel approach, in which individualized prospective computational modeling of the induced electric field guided the choice of stimulation intensity. We consistently found that rhythmic rTMS protocols increased neural synchronization in the posterior alpha frequency band when measured simultaneously with scalp electroencephalography. We observed this effect already at electric field strengths of roughly half the lowest conventional dose, which is 80% of the resting motor threshold. We conclude that rTMS can induce immediate electrophysiological effects at much weaker electric field strengths than previously thought.

No abstract