Medical NeuroDelta: Ambulant Neuromonitoring for Prevention and Treatment of Brain Disease

Brain disorders have a disastrous influence on people’s lives, but they are notoriously hard to study and difficult to treat.

For example, migraine, which is characterized by repeated attacks of severe headache, is difficult to investigate in patients, because it is impossible to predict when an attack will strike. When patients are asked to go to the hospital to investigate their brain disorder, they will often notice they do not get an attack. This happens because the hospital setting is so different from the patient’s natural environment. “In order to better understand the disease, it is important that the patient’s brain activity can be measured over a longer period of time in their home environment, preferably using a non-invasive method,” says Arn van den Maagdenberg, professor of molecular and functional neurogenetics at LUMC.

The same holds for autism, a developmental disorder that starts in young children. “Autism is caused by a disturbed interaction between the cerebellum and cerebrum. People with autism have problems with social interaction and they show repetitive behavior. We need better means to monitor how the brain deteriorates in autism,” says Chris de Zeeuw, professor and head of the Department of Neuroscience at Erasmus MC. 

Observing patients in their home environment

In this Medical Neurodelta program, researchers focus primarily on autism and migraine – two disorders with widespread brain dysfunction. For both disorders, it is important to observe patients in their home environments to understand why disease worsens over time or how attacks begin. A non-invasive method would provide a much wider time window in which brain activity can be studied, giving doctors and scientists extremely valuable insights.

Wireless long-term neuromonitoring systems 

The Medical Neurodelta program focuses on the development of wireless long-term neuromonitoring systems to register brain activity. Bio-electronics, acoustrodes and optrodes in combination with artificial intelligence and machine-learning will be applied for diagnosis and treatment.

The new system should not only monitor brain activity, but it should also modulate brain activity. Advances in light probes and ultra- sound, made at TUDelft, make this feasible. In Rotterdam, within CUBE, Medical Neurodelta researchers have already started to
use high-frequency ultrasound to measure the activity in large parts of the brain; within the project, they will use low frequencies to stimulate specific brain areas to correct brain activity. According to professor De Zeeuw, ultrasound would also allow monitoring throughout the day in the home environment, which would be unique in the world. Compared with MRI, for example, this would be much easier – it would not be possible to place an MRI scanner in a patient’s house.

Testing in mice

In the program, ways to monitor and modulate brain activity will be first tested in mice, paving the way for clinical applications in humans. Testing in mice is already being done, but these experiments are conducted in non-natural settings.

Professor De Zeeuw asks: “If you investigate autism with mice housed in isolation, how can you see the effects of an intervention?” In this new study, researchers will make use of their recently developed FlashTrack system, in which individual mice can move freely and can be easily identified within a group. Using this system, several mice can be put together and followed over time.

Collaboration

In this consortium, Erasmus MC, TU Delft and LUMC are collaborating. According to professor Van den Maagdenberg,
the Medical Delta area is small enough that there is a regular crossover and large enough to incorporate different expertise and make real progressing. It is a unique opportunity to create added value.

In other projects within the overall Medical Neurodelta program, other brain diseases, such as epilepsy and brain dysfunction in infants, are also being investigated. The same technology can be applied to investigate these disorders.