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


A range of neurostimulation modalities exists that are used to either treat neurological or psychiatric diseases, or to modulate brain function for scientific research purposes.


Non-invasive neurotimulation modalities

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are examples of non-invasive brain stimulation techniques. TMS is based on magnetic induction and is applied by a coil that is placed over the scalp. The alternating magnetic field of a TMS coil causes induction currents in the underlying brain tissue, which influence neural information processing. In tDCS, a weak current is sent through the brain using large, spongy, electrodes.


Invasive neurotimulation modalities

In addition to these non-invasive neurostimulation methods, also invasive neurostimulation techniques exitst, in which electrodes are placed within the body during a surgical procedure. The best-known invasive neurostimulation modality is deep brain stimulation (DBS), in which an electrode is implanted within the basal ganglia.

In conventional DBS, the brain is continuously being stimulated. In responsive neurostimulation (RNS), however, the brain is only stimulated when a certain event, e.g. abnormal brain activity, is detected. The stimulation is applied via a pulse generator that is placed under the left clavicle or in the abdominal cavity.

Vagus nerve stimulation (VNS) and trigeminal nerve stimulation (TNS) are methods to stimulate the brain indirectly, i.e. via a cranial nerve. Both have an invasive and a non-invasive version. In invasive VNS, an electrode is wound around the vagus nerve in the neck, whereas in non-invasive transcutanous (“across the skin”) VNS (tVNS), an electrode is placed within the ear to stimulate a specific peripheral branch of the vagus nerve. Also the trigeminal nerve can be stimulated invasively by subcutaneously implanted electrodes (“under the skin”; sTNS) and non-invasively (external, eTNS), using an electrode patch attached to the forehead.

Mechanisms of action

These various neurostimulation methods don’t work equally well in every subject, and the exact stimulation parameters are typically based on clinical experience rather than an in-depth understanding of how exactly they influence neuronal information processing. Within the Neu3CA program, we aim to increase our understanding of the mechanisms of action of neurostimulation to increase their effectiveness (maximum benefit, minimal side effect) and applicability (e.g. improved efficiency of non-invasive versions). Especially the LCEN3 lab of Ghent University is an important partner here, with a large translational research line, all the way from fundamental animal experiments all the way to daily clinical care for a large group of (mostly) epilepsy patients.

real-time fMRI neurofeedback

The neuromodulation modality that is mostly studied within our program is real-time fMRI neurofeedback, although we also work on neurofeedback based on functional near-infrared spectroscopy (fNIRS).

Functional MRI is based on the BOLD contrast (blood oxygen level dependent). Effectively this means that if we record a series of fMRI images (e.g. one image every 2 seconds), the gray value of each image element goes up and down in accordance with brain activity-related changes in blood perfusion. Effectively this means that fMRI provides a non-invasive window on brain activity.


Real-time fMRI neurofeedback principle: ongoing brain activity is compared to a desired brain activity pattern and the subject receives feedback on to what extent his/her brain activity already resembles this desired brain state.

In real-time fMRI neurofeedback, fMRI data is continually acquired and analyzed while the test subject is still in the scanner. A metric of brain activity is then presented to the subject. Thus, this person is made aware of his/her ongoing brain processes and can be trained to modulate them. In depression patients, for example, certain regions of the brain are too low in activity, and rt-fMRI-NF has been used to train these subjects, and symptoms improve.

Within the Neu3CA program, we aim to use rt-fMRI-NF to assess and train brain networks that mediate cognition. Having trained a subject using the high spatial precession (resolution) of fMRI, we aim to prolong the training effect with portable neurofeedback modalities, such as fNIRS.