My research: The brain, the most complicated structure in the universe

Do you remember from your biology course, what a synapse is? Actually, we are still trying to understand it, so if you already forget, no worries. It has been estimated that the number of possible connections (synapses) that could be formed in our brain is higher than the number of the atoms in the universe! While our brain is this complex, a simplified view is necessary to understand its functions and to be able to develop treatments for devastating neurological diseases.

The main research focus of my laboratory is to investigate the changes in the brain structure after an injury. Upon a brain injury, for example due to a traffic or sports accident, the brain region that is exposed to the direct injury is damaged and mostly degenerates itself. This can be considered as hitting one side of our car to the wall while we are parking. The impact site will be destroyed while the rest of the car remains physically unaffected. However, when we follow brain injury patients at the clinic over years and decades, we observe degeneration of the brain far away from the lesion side. This spreading of degeneration in the brain eventually results in long-term complications including early onset of dementia such as Alzheimer’s and Parkinson’s disease or neuropsychiatric disorder such as schizophrenia and depression. We are familiar with Muhammed Ali, who got Parkinson’s disease at the age of 42, due to the head injuries he was exposed to during boxing. On the other hand, we also know various American Football players having psychiatric problems, committing suicide or being heavily depressed, again due to head injuries they receive during their professional career. All these long-term complications that are observed over years to decades in humans after brain injuries imply that their brain structure continuously changes. How does this happen? How does damage at one corner of the brain physically spread to the rest of it? What are the mechanisms driving this spread? My research group is now trying to address these important questions.

Mild brain injuries occur often in children when they play. We mostly ignore such small injuries in children. However, it is possible that they are the cause of complications such as ADHD (Attention deficit hyperactivity disorder) and epilepsy seen later in life.

One way to study brain function in health and disease is to visualize its structure and activity with imaging techniques. Most of us probably have seen MRI (magnetic resonance imaging) pictures showing the general structure of the brain. They help doctors to identify brain regions with abnormalities, such as a tumor or degenerating tissue. However, the zoom ability of MRI is very low and usually can only show the large changes, not the details. We can imagine this as the satellite view over a city. If there is a fire in a particular region, the satellite view will help us to determine which building is on fire. However, this view will be insufficient to resolve the source of the problem, whether it started at an electricity connection, gas pipe, or someone’s cigarette bud, which was not extinguished. Similarly, while MRI pictures can show the overall brain structure, they cannot resolve sufficient details to see the cellular mechanisms that can cause dementia and psychiatric diseases. To overcome this limitation, my group develops novel imaging techniques to observe detailed structures in the brain and help to identify the source of brain diseases. An important limitation of brain imaging is that the light cannot penetrate deep into brain structures, because it is blocked by opaque tissue -such as skull- at the surface. One way to light up the deep brain structures for visualization is to make them transparent. In recent years, we developed methods to render the brain transparent to be able to ‘look inside’ the brain. This is similar to making the buildings transparent via glass constructions from top to bottom. Now, using the satellites with high zoom features, one can see through the buildings and identify the source of a possible fire, because now we are able to zoom and image every detail of the building. We call this method 3DISCO. You can see some examples of such transparent organs at the following link: http://youtu.be/cyHNHJ2eHYs