Over the past two decades the most important revolution in human brain research took place due to the availability of non-invasive imaging methods allowing to evaluate the structure and function of the brain. Structural imaging using magnetic resonance imaging (MRI) allows us to assess structural changes that occur as the brain develops when we are young and deteriorate as we age. When disease processes attack the brain, atrophy or other structural changes occurs at a rapid rate. MRI allows us to precisely assess these changes. Further, it is now possible to measure the activity of brain cells using functional MRI (fMRI). Brain cells compute and communicate using electrical signals. This activity requires oxygen, the brain’s energy source, and the intricate and precise supply of oxygen to the brain can be measured with fMRI, providing us a map of brain activity.
Our aims and research methodology
In the lab we seek to understand the relation between the brain’s structure and function in health and disease. We aspire to understand how brain structure and activity give rise to various aspects of behavior. To that end, we use fMRI in humans and mice to understand the basic principles of brain function as well as detect brain regions that are not working normally, follow them carefully and try novel first-in-class therapeutic approaches to alleviate brain disorders.
We measure activity in multiple brain systems simultaneously, looking at the interactions between regions of the brain. We attempt to characterize changes in activity that can be used to identify populations or individuals at risk. Namely, we look for changes that precede and predict diseases. In doing so we open a time window for prevention and/or early therapeutic intervention programs that may benefit people that seem to be on a trajectory to develop a brain disorder.
Why do we use mice?
Although using MRI in humans allows us to develop approaches to diagnose brain malfunction, it is not sufficient to help us understand the underlying mechanisms of the biological processes in health and disease. This is because MRI and other tools available to use in humans are too crude to measure pathological changes (for example, deficiency in proteins the brain needs for normal function or toxins killing brain cells). In order to understand what goes wrong we need the tools of cellular biology. Such tools can only be used in animals. Currently, the lab mouse is the primary animal used in biomedical research. Studying mice we can figure out the biological mechanisms in detail. Moreover, many findings from studies concerning the mouse brain (but not all) give us insight about brain structure and function of all mammals and particularly to humans.
In summary, our approach is to first diagnose disruptions or pathologies in humans using fMRI. Then, using fMRI in mice that we engineered to have the pathology of neurodegenerative diseases or that are old, we are testing whether they show the same phenomenology found in humans. For the phenomena that are well replicated, we now use systems neuroscience tools (electrophysiology, cellular imaging, pharmacology, etc) to develop therapeutic targets and test them.
Impact and applications
We aspire to advance both the field of medicine and neuroscience. Our hope is that the research conducted in our lab will:
(1) Advance the understanding of the causal chain of events that take place in the brain, from genes to behavior.
(2) Help find and define specific signatures of various brain pathologies and thus will enable a diagnosis that relies more objective tests rather than on reported symptoms.
(3) Enable an early diagnosis and opportunity for prevention and more meaningful intervention programs.
If you are interested in learning more about our research or join the team, contact Dr. Itamar Kahn.