Light shows fMRI works as advertised

Optogenetic method validates assumption underlying brain imaging technique

A quick flash of light has confirmed the key assumption justifying the use of functional magnetic resonance imaging to reveal the inner workings of living brains. In a study appearing online May 16 in Nature, researchers used light to activate nerve cells and then saw the telltale fMRI signal, demonstrating that nerve cell activity is indeed responsible for the colorful splotches appearing on fMRI images. The new technique, called optogenetic fMRI, may lead to a much deeper understanding of how information travels through the brain.

These results “put the fMRI field on firm footing,” by showing unambiguously that neuron activity can cause the fMRI signal, says study coauthor Karl Deisseroth of Stanford University.

One of the most common versions of fMRI doesn’t directly measure the activity of nerve cells, or neurons, in the brain (SN: 12/19/09, p. 16). Instead, the typical method, called BOLD (for blood oxygen level-dependent), tallies slight changes in oxygen levels in the blood that surrounds neurons. Presumably, as neurons become active, they need more energy and consume more oxygen. These tiny fluctuations in oxygen serve as a proxy for brain activity. But direct evidence for this causal relationship has been lacking.

Deisseroth and colleagues used a technique pioneered in their lab called optogenetics, in which light-responsive molecules are used to control particular cells (SN: 1/30/10, p. 18). To directly test the relationship between neuron activity and BOLD signal, the researchers inserted a molecule that responds to a pulse of blue light into neurons in the motor cortex of rats. Under normal conditions, these neurons activate and send the “go” signal when the rat wants to move a leg. With the addition of the light-responsive molecule, these neurons also fire when a pulse of blue light strikes. Armed with the ability to activate select groups of neurons at will, Deisseroth and colleagues could play with the switch and see when BOLD signals were made.

Anesthetized rats with the optogenetic blue-light switches were placed in an fMRI machine. Sure enough, when the neurons were turned on with a pulse of blue light, the researchers detected a strong BOLD signal emanating from the motor cortex neurons’ neighborhood. The BOLD signals were exactly what was expected. “It was very compelling and reassuring,” Deisseroth says. “Everyone can breathe a sigh of relief.”

Neuroscientist Aniruddha Das of Columbia University calls the results very clean and says the new study provides a clearer picture of what BOLD signals actually mean. “There are lots of questions that have been raised about patterns in brain activity,” Das says, and this new optogenetic technique could help answer some of them.

Das cautions that just because specific neuronal activity can cause BOLD signals doesn’t mean that it’s the only thing that does. Some of Das’ studies have found that seemingly unrelated signals arising from elsewhere in the brain can cause strong BOLD signals also.

Deisseroth adds that there may be many intermediate steps between neuronal excitation and the ultimate BOLD signal, including activity from other kinds of neurons that dampens signals, glia cells and other unexpected blood flow changes. “We’re certainly not saying that other processes don’t contribute to these signals,” he says. “We’re saying that driving these excitatory neurons kicks it off.”

In additional experiments, the team activated neurons in one region of the brain and measured BOLD signals in a distant but connected region. The ability to initiate and follow this kind of neuronal cross talk offers a promising tool for mapping how information moves through the brain, Deisseroth says. Figuring out how regions of the brain interact with each other may be the key to understanding psychiatric disorders.

“A true, deep understanding of disorders will require a global view,” Deisseroth says.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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