New MRI technique tracks brain activity at millisecond scale

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A A new approach to magnetic resonance imaging could allow neuroscientists to noninvasively track the propagation of brain signals at the millisecond scale, according to a study published yesterday (October 13) in Science.

The technique, which its creators call “direct imaging of neural activity” (DIANA), uses existing magnetic resonance imaging (MRI) technology to take a series of rapid partial images, then combines those images to create a high resolution image of which parts of the brain are active when.

DIANA has so far only been tested in anesthetized mice, and the underlying mechanisms are not entirely clear, notes Matthew Self, a neuroscientist at the Netherlands Institute for Neuroscience who was not involved in the work. . But provided it can be replicated in other labs, the method could represent a “major breakthrough” in brain imaging, he says.

“This would be the first technique capable of noninvasively measuring neural activity with high spatial and temporal resolution,” Self says. “I really want to try it.”

The researchers who spoke The scientist already say they are excited about the potential of the new technique.

MRI technology uses magnetic fields and radio waves to produce detailed images of tissue. Its use is based on the fact that different materials have distinct magnetic properties, allowing a scanner to distinguish between different tissues or monitor changes in tissues over time.

Researchers have long used a version of this technology, known as blood oxygen level-dependent functional MRI (BOLD fMRI), to study how the human brain works. This method detects changes in blood flow to particular regions of the brain as a proxy for neural activity.

BOLD fMRI can localize activity to a millimeter or less of brain tissue. But the temporal resolution of the technique is less impressive. Changes in blood flow occur within seconds, much slower than the millisecond time scale of neural signals. fMRI images often show an entire neural pathway active at once, when in reality a neural signal is propagating from one part of the pathway to the next.

See “Which neurons go to sleep first in humans? fMRI can tell”

Other noninvasive techniques that directly measure electrical activity, such as electroencephalography (EEG) and magnetoencephalography (MEG), are much better at identifying the timing of neural firing, but much worse in terms of spatial resolution. .

In the new study, Jang-Yeon Park, a biomedical engineer at Sungkyunkwan University in South Korea, and his colleagues proposed a new way to tackle the problem. Rather than taking full images of a particular cross-section of the brain every few seconds, as in conventional fMRI, he and his colleagues tuned their MRI equipment to gather sequences of much smaller partial frames at very short intervals – just a few milliseconds apart. They could then stitch these partial images together to get a full view of that cross-section of the brain at every moment.

To see if they could identify a signal of brain activity with this approach, the researchers fed anesthetized mice into the MRI scanner and then lightly zapped the animals’ whisker pads with an electric current. They found that the images produced by their technique registered some kind of signal in the somatosensory cortex – the part of the mouse brain that detects whisker stimulation – within about 25 milliseconds after the zap.

Exploring this further, they discovered that the “DIANA signal” shifts over time. It appeared in a region of the brain called the thalamus about 10 milliseconds after the whisker zap, moved to one section of the somatosensory cortex about 25 milliseconds, then popped up in another part of the somatosensory cortex a few milliseconds later.

A bigger puzzle is what DIANA detects, exactly.

By taking measurements of the same brain area with invasive techniques such as electrophysiology and optogenetics, the team showed that their DIANA signal actually tracked the spread of neural activity in response to whisker stimulation.

Peter Bandettini, a neuroscientist and physicist at the National Institute of Mental Health (NIMH) who was not involved in the study, calls the team’s work “incredibly compelling.” Several teams have tried to increase the temporal resolution of MRI before, he adds, but few have gone that far to back up their claims. The paper included a “tour de force of experimentation” to show that the technique did indeed track the propagation of neural signals.

Park tells The scientist that he’s not sure why researchers haven’t reported this effect before, given that it doesn’t require any particularly special equipment, but says it’s likely people just haven’t thought of it create images in this way. Bandettini notes that hacking an MRI machine to take rapid partial images like DIANA requires a significant amount of expertise and the belief that it might reveal something interesting.

A bigger puzzle is what DIANA detects, exactly. Park and colleagues show in their study that BOLD effects are unlikely to be responsible and instead suggest that their method records changes in the membrane potential of firing neurons, possibly via fluctuations in water quantity. on the surface of the membrane or via cell swelling. It’s a possibility, says Self, but overall, “the mechanism isn’t very clear. . . . I think this needs to be demonstrated in future studies.

In its current form, DIANA has some limitations, notes Park, who is named co-inventor on a patent related to the method. Because of the way it stitches together snapshots of the whole brain by combining partial images taken at different times, the technique is likely to be susceptible to so-called motion artifacts – disturbances caused by the movement of the head of the animal between shots. This could present difficulties in translating DIANA into awake animals or people.

The signal that DIANA picks up is also relatively weak — about an order of magnitude smaller than that of BOLD fMRI, Bandettini notes. The groups would need relatively sophisticated MRI equipment to be able to mimic the team’s approach, as well as an experimental protocol that included repeated tasks or stimulations to allow results from multiple scans to be averaged. , he said. “You need lots of repetitions of the same thing and very, very precise resolution.”

However, researchers who spoke to The scientist already say they are excited about the potential of the new technique. Bandettini points to another of the team’s experiments that suggests DIANA may be able to distinguish between excitatory and inhibitory neural signals, which is difficult even with invasive techniques such as electrophysiology. “It’s super exciting. This would open up a whole realm of understanding how the brain interacts.

Self, who studies visual processing, says he knows of several groups that are already trying to get DIANA to work in people. Although the technique still may not offer the single-cell resolution achievable with some invasive technologies, there are far-reaching implications if it works in other labs, he says. “In principle, it could be introduced into humans, perhaps it could even be used in patient studies – it could open up a whole world of research into understanding the brain in health and disease.”

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