Brain circuit-mapping technique developed to probe Parkinson's disease tremors

Stanford University bioengineer and neuroscientist Jin Hyung Lee has developed a new brain mapping technique to reveal circuitry, or neural pathways, behind Parkinson's disease tremors.

Lee, who trained as an electrical engineer before becoming a brain researcher, has adapted that idea that if a piece of electronics isn't working, troubleshooting the problem often involves probing the flow of electricity through the various components of the circuit to locate any faulty parts.

One hallmark of Parkinson's disease are uncontrollable tremors, believed to be caused by malfunctions in the neural pathways that control motion.

Neuroscientists know that different regions of the brain are constantly forming circuits to carry out tasks, whether motion or speech. However, prior to Lee's technique, researchers had no way to show how activating a specific type of neuron might cause a specific circuit to form in the whole brain.

Described her work in this week's issue of Neuron, Lee's circuit-mapping approach combines two experimental tools with a computational method.

The first experimental tool is optogenetics, which modifies specific types of neurons - the basic working parts of the brain - so they can be turned on in response to light.

The second experimental tool is called functional MRI, or fMRI, which measures blood flow in the brain. Increased blood flow is associated with increased activity.

Using optogenetics to turn on a specific type of neuron, and fMRI to observe how other regions of the brain responded, Lee then used a computational analysis to map the entire, specific neural circuit and also determine its function.

"Electrical engineers try to figure out how individual components affect the overall circuit to guide repairs," Lee said.

Testing her approach on rats, Lee probed two different types of neurons known to be involved in Parkinson's disease although it wasn't known exactly how.

Her team found that one type of neuron activated a pathway that called for greater motion while the other activated a signal for less motion. The team then designed a computational approach to draw circuit diagrams that underlie these neuron-specific brain circuit functions.

"This is the first time anyone has shown how different neuron types form distinct whole brain circuits with opposite outcomes," Lee was quoted as saying in a news release from Stanford.

Lee said the findings should help to improve treatments for Parkinson's disease.

More broadly speaking, she thinks that optogenetic fMRI combined with computational modeling gives researchers a new way to reverse-engineer the functions of the many different types of neurons in the brain and the bafflingly diverse array of neural circuits formed to carry out different commands.

source: Xinhua