Why does the brain’s stress system remain stuck in overdrive for some people? Researchers at the Netherlands Institute for Neuroscience (NIN) and Maastricht UMC are joining forces to find the answer. By combining fundamental neuroscience with clinical research, they aim to better understand how the brain regulates stress and lay the groundwork for new treatments for conditions such as post-traumatic stress disorder (PTSD) and anxiety disorders.
The brain’s alarm system
Everyone is familiar with the body’s automatic response to danger: your heart rate increases, your muscles tense, and your body prepares to fight, flee, or freeze. In people with stress-related or anxiety disorders, however, this alarm system often remains activated even when there is no immediate threat.
At the heart of the project is a tiny structure deep within the brainstem called the periaqueductal gray (PAG).”The PAG is essentially the control center for our defensive responses,” says neurobiologist Alexander Heimel.”But because it is so small and located deep within the brain, we are looking for the brain regions that regulate the PAG instead. These regions may be much better suited as targets for teaching people to better control their stress responses.”
From the laboratory to the clinic
To achieve this, the researchers are combining two complementary approaches. In Amsterdam, they use advanced techniques in mice to identify the brain circuits involved in fear and stress. Colleagues in Maastricht then investigate whether the same networks are involved in humans using ultra-high-field 7 Tesla MRI scanners. Ultimately, they aim to test whether people can learn to consciously influence these brain regions through neurofeedback.
During neurofeedback training, participants receive real-time feedback about their own brain activity while undergoing a functional MRI scan. They then gradually learn how to influence activity in those specific brain regions.”
A unique collaboration
The close integration of fundamental neuroscience and clinical psychiatry is what makes this project unique. “There are relatively few projects in which fundamental animal research and psychiatry work this closely together,” says Heimel. “This allows us to translate fundamental discoveries into potential clinical applications much more quickly.”
Psychiatrist David Linden believes this close collaboration is one of the project’s greatest strengths. “To develop new treatments, you first need a thorough understanding of the brain networks you want to influence. By combining fundamental neuroscience and human research from the very beginning, we are building a much stronger foundation for future therapies.”
The project also has an educational mission. The researchers intend to integrate the knowledge gained into the training of psychiatrists, psychologists, and early-career researchers. “It is important that future mental health professionals not only know how to treat patients, but also understand the brain circuits that underlie fear and stress,” says Linden. “This fundamental knowledge helps us better understand our patients and supports the development of new therapies.”
This project is one of two selected research projects funded through a new collaboration between the Netherlands Institute for Neuroscience (NIN) and Dutch psychiatrists . The program promotes close collaboration between fundamental neuroscientists and clinicians to improve our understanding of the biological basis of psychiatric disorders, helping fundamental discoveries find their way more rapidly into clinical practice.