Phase-dependent Closed-loop TMS

Transcranial magnetic stimulation (TMS) is a tool to modulate brain activity. However, brain states are constantly changing. So, if we want to use TMS optimally (either in research or in clinical application) we need to take the current activity of the brain into account. For this we can use a closed-loop approach, which means that we read out brain activity and adjust our brain stimulation according to the brain activity that we analyzed.

One method that is great for closed-loop approaches is electroencephalography (EEG) as it has a fantastic temporal resolution. There are different things that EEG tells us about brain activity. One interesting aspect is the phase of a neural oscillation. The motor cortex for example, is driven by brain oscillations in the mu and beta range. So, in this study we use closed-loop TMS-EEG to investigate the effects of brain oscillation phase on brain excitability. 


We used a closed-loop algorithm previously published by Shirinpour et al. (2020), referred to as estimated temporal prediction (ETP). ETP uses resting-state EEG data to estimate inter-peak intervals between oscillations. During real-time application this is used to predict the next peak, falling phase, trough or rising phase.

To measure cortical excitability 600 motor-evoked potentials (150 per phase) were recorded. Two sessions were performed investigating different brain rhythms: sensorimotor mu (8-13 Hz) and beta (13-30 Hz) oscillations


Average results of 20 volunteers showed that the excitability of the primary motor cortex depends on both phase and frequency of an oscillation. For the Mu rhythm excitability was highest for the rising phase, whereas for the Beta rhythm it was highest for the falling phase.

Control analyses showed that these results were not confounded by harmonic brain activity, or the source of the oscillations.


Closed-loop TMS offers a great opportunity to adjust stimulation parameters to each individual. We read out everyone's unique brain state and adjust the stimulation accordingly. In this study we show that this is important because excitability of the brain fluctuates over time. The brain is more or less susceptive to outside stimulation depending on both the phase and the frequency of brain oscillations. 


Wischnewski, Haigh, Shirinpour, Alekseichuk & Opitz (2022). The phase of sensorimotor mu and beta oscillations has the opposite effect on corticospinal excitability. Brain Stimulation, 15(5), 1093-1100.