In a study published in Nature, a Stanford University-led team has shown that fMRI signals based on elevated levels of oxygenated blood in specific parts of the brain can be caused by activation of local excitatory neurons.

In the past, for example, researchers could only assume that when they showed subjects a picture of someone they knew, a stronger fMRI signal measured using the blood oxygenation level-dependent (BOLD) technique in a part of the brain that possibly deals with face recognition was caused by the excitation of neurons, rather than some other factor.

The key experiment involved turning on genetically engineered excitatory neurons in an experimental group of rats in the presence of blue light delivered via a fiber optic cable. The researchers then anesthetized the rats and looked at their brains with fMRI. They found that exciting these defined neurons with the optogenetic light produced the same kind of signals that researchers see in traditional fMRI BOLD experiments — with the same complex patterns and timing. In the control group of rats, which were not genetically altered, no such signals occurred. This showed that true neural excitation indeed produces positive fMRI BOLD signals.

To see what else this new understanding of optogenetically enhanced fMRI BOLD might yield, the team took the research a few steps further: they found that they could use optogenetics to produce activity in specific kinds of cells in neural circuits, and then read out the far-reaching effects with fMRI BOLD over a substantial distance in the brain.

In one experiment, for example, the team could see how activity they stimulated in the thalamus, a key relay center deep in the brain, could affect circuits stretching into the somatosensory cortex, a surface brain region important in processing sensation.

Because researchers have published more than 250,000 papers using or building upon the BOLD technique, clarifying its true meaning is very important, said senior author Karl Deisseroth, MD PhD, associate professor of bioengineering and of psychiatry and behavioral sciences.

“We can now ask what the true impact of a cell type is on global activity in the brain of a living mammal,” Deisseroth said. “A key to scientific inquiry is developing tools that allow us to intervene and experiment with brain circuits — engineering a reversible gain or loss of function — rather than simple observation of correlations. This points to new approaches for understanding and treatment.”

The findings suggest that fMRI can now be used to study the brain-wide impact of changes in neural circuitry, such as ones that may underlie many neurological and psychiatric diseases.

More info: Stanford University School of Medicine and Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

Also see: Control of cell movement with light accomplished in living organisms