By Matthew Chin

Since the early 1990s, functional magnetic resonance imaging (fMRI) has been used to give insight to the inner workings of the brain.

This powerful tool has been used in numerous research studies, starting in medicine and science, but has even branched out into social and cultural topics, such as views of food or religious beliefs.

A special type of MRI, an fMRI measures the blood and oxygenation level in the brain (BOLD). Areas of heightened blood oxygenation level are correlated with brain activity. The vivid contrasting colors of the brain scan imagery show that there is activity in areas of the brain, but are these BOLD signals directly caused by the activity of neurons? More specifically, which neuronal element can trigger the BOLD response? These topics have been controversial in the field.

Now, research lead by Jin Hyung Lee, an assistant professor of electrical engineering at the UCLA Henry Samueli School of Engineering and Applied Science sheds light on this topic with a powerful new imaging tool.

By using optogenetics, (ofMRI) a novel technology that allows genetically specified neurons to be activated through light, the researchers now show that very specific neuronal elements can be triggered and monitored. The group introduced two genes into rat brain cells called excitatory neurons. One of the genes uses a fluorescent jellyfish protein gene to show where the cells responded. The other was a gene from an alga that reacts to light.

Using a light source to stimulate the excitatory neurons, the group looked for the resulting response of the brain, which showed similar response shape to that generated using traditional fMRI.

“This technology shows that BOLD signal can be generated causally by excitatory neurons,” Lee said. “And also, it gives you a new platform to analyze and debug your brain circuit.”

Lee’s research has shown that ofMRI has the potential to be a far more powerful and precise neuroimaging tool – one that can discern the brain’s specific internal structure, wiring, and function in much greater detail than currently available. The research was published in the journal Nature in June.

Traditionally, fMRI were used to monitor effects caused by sensory stimulus – for example, by showing a picture then watching the brain’s reactions, or more directly by using electrodes to stimulate regions of the brain. But those could not selectively stimulate based on cell types or wiring topology of the brain, making it difficult to understand how the different regions are related.

Lee’s research demonstrated the capability of the new ofMRI technology with two different types of specificity.

First they showed that ofMRI can reveal responses caused by cell body location and genetic cell type specific stimulation. These experiments were also verified using electrode readings at the motor cortex and thalamus. The ofMRI response very closely mirrored the electrophysiological measurements at both regions.

Some brain cells have fibers, called axons, that connect to other regions of the brain, and even other parts of the body, much like wiring does for a classical electrical circuit. In another experiment, the researchers selectively stimulated excitatory neurons with cell body in the motor cortex and axonal fibers in the thalamus by shining light to the axonal fibers. This experiment showed that such specific stimulation also gives rise to robust ofMRI signal.

“This shows we can achieve a triple layer of unprecedented specificity – genetic identity, cell body location, and wiring.” Lee said.

For future research, Lee is working in several areas that will continue to bridge engineering and biomedical imaging to enable advanced applications for medical research.

“We’re working on further improving this technology to have more capability,” Lee said. “At the same time, we’re also working on figuring out brain circuitry associated with neuropsychiatric disease and also looking to apply findings to help cure those diseases.”

Lee also holds faculty appointments in psychology and biobehavioral sciences, and radiology, both in the UCLA David Geffen School of Medicine. This contributes important aspects in leading her interdisciplinary research to success.