Insights into the thalamus could improve understanding of brain dysfunction and its therapies
The thalamus functions as the brain’s communication center: it transmits information from the sensory organs and other parts of the brain to its destination. Despite its important role, it is far from fully understood. Scientists from the Max Planck Institute for Biological Cybernetics in Tübingen have now investigated the relationship between the thalamus and other areas of the brain. Their statistical analyzes allow them to assign the respective tasks to different parts of the thalamus. The results could contribute to the development of more targeted therapies for diseases such as Parkinson’s disease or epilepsy.
Deep in the human brain lies an area that can be compared to a large airport: the thalamus. It receives and distributes signals from the sense organs and throughout the brain. For example, all visual sensations first enter the thalamus, from where they are then sent to areas of the brain for further processing – much like people traveling from different cities and destinations often have to transfer at the same major airport. However, our knowledge of which parts of the thalamus play a role in which brain functions is still very patchy.
A research team from the Max Planck Institute for Biological Cybernetics has now begun to fill these gaps and map the thalamus. Many subunits of the thalamus have been shown to share their tasks with each other. “We call this phenomenon functional multiplicity,” explains Vinod Kumar, lead author of the study. “You can compare it to how a CPU works. Whether you’re running a game or an office application on your computer – everything has to be processed in the CPU – and the CPU doesn’t care what program is running; performs the calculation for the application that needs it at the moment.”
But the flexibility of the thalamus goes even further: it is also involved in higher brain functions. The bandwidth of these higher brain functions is large: the thalamus plays a role in everything from working memory to decision making and impulse control. More often, these higher functions are associated with the cerebral cortex, the outer layer of the brain that developed relatively late in evolution in humans and other mammals. “What we found about the transmission nuclei in the visual thalamus is consistent with recent observations in the animal literature,” comments Kumar. “But it was remarkable that I could observe it in humans.
Statistical analysis of 3.5 million brain scans
The researchers reached their results by statistically analyzing 3.5 million brain scans from 730 subjects from the Human Connectome Project research database. Images were created using functional magnetic resonance imaging (fMRI). With this non-invasive method, the activity of neurons is visualized indirectly by determining the proportions of oxygenated and deoxygenated blood. Because active neurons require a blood supply, this method can be used to create an image in which active areas of the brain light up while relatively inactive areas remain dark. Even when the subject is not performing a task, important connections in the brain can be seen on these so-called functional resting MRIs. The researchers supplemented their analyzes with data from more than 14,000 fMRI studies in which subjects were asked to perform tasks during scans.
A key success factor was the team’s question – which parts of the thalamus are associated with which tasks? – has already been answered in detail for the cerebral cortex. Therefore, the connections between different areas of the thalamus and the cerebral cortex revealed in the fMRI scans made it possible to draw conclusions about the tasks of the areas of the thalamus. For example, strong connections from a certain region of the thalamus to a pain-processing network in the cerebral cortex indicate that this region of the thalamus is associated with pain.
A wide range of possible clinical applications
New insights into the functioning of the thalamus could become relevant for many clinical applications in the future. Injuries to the thalamus are the cause of a whole range of diseases, including sensory perception disorders, memory problems, Parkinson’s disease, epilepsy and hand tremors. Neurosurgeons already treat such diseases with so-called deep brain stimulation. Some areas of the brain in the thalamus are electrically stimulated, for example, to relieve the symptoms of Parkinson’s or drug-resistant epilepsy.
Other potential clinical applications include transcranial direct current stimulation and transcranial magnetic stimulation, both non-invasive methods used to treat a variety of neurological and mental disorders. “Thanks to our new understanding of the functional multiplicity in the thalamic nuclei, we can interpret clinical disorders,” says Kumar. “For example, we could better understand why a patient with Parkinson’s disease suffers from certain side effects when treated with deep brain stimulation in the thalamus.” He hopes this knowledge will help better target such interventions in ways that maximize their effects and reduce their side effects.