Brain stimulation is increasingly used to modulate neural activity, with applications ranging from basic neuroscience to clinical interventions in epilepsy, depression, Parkinson’s disease, and disorders of consciousness. Yet one major challenge remains: the same stimulation can sometimes produce different effects depending on when it is delivered. This suggests that the brain is not a passive target, but a dynamical system whose response depends on its ongoing internal state.
In this work, we show that phase-dependent stimulation responses are shaped by the brain’s dynamic functional connectivity — the moment-to-moment pattern of interactions between brain regions. In other words, the local phase of the stimulated area is not enough to predict the effect of stimulation. The response also depends on the current whole-brain network state: which regions are functionally coupled, how strongly they interact, and how information is transiently routed across the network.
Using whole-brain computational modeling, the study demonstrates that identical stimulation pulses delivered at comparable phases can produce different outcomes depending on the ongoing dynamic functional connectivity state. Conversely, the same stimulation site may be more or less effective depending on the transient network configuration in which it is embedded. The brain is therefore not just an oscillator to be pushed at the right moment; it is a changing communication network whose current state shapes the consequences of any perturbation.
This provides an important refinement for adaptive and closed-loop brain stimulation. Optimizing stimulation may require more than choosing the right target and the right phase. It may also require monitoring the brain’s ongoing functional connectivity state and delivering stimulation when the network is configured in a way that supports the desired response.
A useful analogy is not simply “pushing a swing at the right phase.” It is more like pushing one swing in a playground where many swings are coupled together by moving ropes. The effect of the push depends on the phase of the swing, but also on how it is currently coupled to all the others.
This study therefore shifts the focus from phase-dependent stimulation alone to network-state-dependent phase response. It suggests that future stimulation protocols should be state-aware: not only phase-locked, but also connectivity-informed.
To know more:
- Stulz, S. B., Castro, S., Gutkin, B., Gilson, M., & Battaglia, D. (2026). Phase-dependent stimulation response is shaped by the brain’s dynamic functional connectivity. Network Neuroscience, 10, 475–507. https://doi.org/10.1162/NETN.a.548.