Neuromodulation involves neurostimulation, i.e. direct or indirect electrical stimulation of brain tissue, and neuromodulation, which involves other methods to influence brain states (e.g. neurofeedback).


Neurostimulation is the electrical or magnetic stimulation of nerve tissue. This provides a targeted and reversible means to treat brain diseases. Within the Neu3CA research program, especially transcranial magnetic stimulation (TMS) and vagal nerve stimulation (VNS) are studied.

In TMS, a coil is held over the scalp, which is driven by an alternating current. The resulting magnetic field induces an electric field that influences the membrane potential of the underlying neurons. Depending on the exact stimulation protocol, neuronal excitability can hereby either be increased or decreased.


Epileptic seizures may be triggered by a patch of overexcitable brain cortex called the epileptic focus. A potential application of TMS is to reduce the excitability of the epileptic focus, with the goal of lowering the changes of having a seizure.

Even though TMS is successfully applied in the clinic, the underlying neurophysiological mechanisms are largely unknown. For example, why do the neurons respond differently to different stimulation frequencies (reduced excitability for pulse repetition frequencies below around 5 Hz, increased excitability above 20 Hz)? And why is TMS more effective in some subjects compared to others?

Within the Neu3CA brain research program we investigate several of these questions. For example, we model how TMS exactly couples into the brain, and look into what direct brain effects are triggered where. We also investigate how these local effects may distribute over the brain network using neurophsyiological models of brain networks and information on global brain connectivity derived from functional MRI and/or tractography.

Furthermore, we look into how these stimulations may lead to (transient) changes in brain network organization, and try to link our findings with behavioral/clinical changes.

VNS is a neurostimulation modality in which the vagal nerve is stimulated, which is a cranial nerve that runs through the neck. It provides an indirect means to stimulate the brain, where amongst others it leads to the release of nor-adrenaline in specific brain structures. Nor-adrenaline has seizure-suppresive effects, and thus VNS can be used as an alternative epilepsy treatment.

However, also in VNS the exact neurophysiological working mechanism is unknown. Therefore, the effectiveness of VNS in limited (only in 13 of the patients implanted with a VNS device, seizure reduction is more then 50%). Furthermore, nor-adrenaline also plays a role in neuroplasticity, i.e. the ability of the brain to adapt. VNS may thus potentially also be used to improve learning or otherwise facilitate changes in the brain network. Within the Neu3CA program, we look into how VNS exactly influences the brain, and how we may use this knowledge to improve the treatment of seizures and/or to restore cognitive levels in patients with epilepsy.