New NMR technology narrows the time scale for tracking brain activity

According to a study published yesterday (Oct.
13) in the journal Science, a new method of magnetic resonance imaging allows neuroscientists to non-invasively track the propagation
of brain signals on millisecond timescales.

The technique, dubbed Direct Imaging of Neuronal Activity (DIANA) by its inventors, uses existing magnetic resonance imaging (MRI) techniques to take a series of fast-firing local images, which are then combined to produce a high-resolution image showing which parts of the brain are active
and when.

Matthew Self, a neuroscientist at the Netherlands Institute for Neuroscience, notes that so far, DIANA has only been tested on anesthetized mice, and the underlying mechanisms are not fully understood
.
He was not involved in the study
.
But if it can be replicated in other labs, he said, the method could represent a "major advance" in brain imaging
.

Self explains: "This will be the first technique
capable of noninvasively measuring neural activity at high spatial and temporal resolution.
I really want to try it
.

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

Researchers have long used a version of this technique, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI), to study how the human brain works
.
This method detects changes in blood flow in specific areas of the brain as agents of
neuronal activity.

BOLD functional magnetic resonance imaging can precision activity down to a millimeter or smaller brain tissue
.
But the temporal resolution of the technology is
less impressive.
Changes in blood flow occur in seconds, much slower than the millisecond timescale for neuronal signals
.
Images of functional magnetic resonance imaging often show that the entire neural pathway is active at the same time, in fact, one nerve signal travels from one part of the pathway to another
.

Other non-invasive techniques that directly measure EEG activity, such as electroencephalography (EEG) and magnetoencephalography (MEG), are much better at pinpointing the timing of neuronal 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 propose a new way to
solve this problem.
Instead of imaging a specific section of the brain completely every few seconds, as is the case with traditional functional magnetic resonance imaging, he and his colleagues set up their MRI device to collect smaller partial sequences
of images at extremely short intervals (just a few milliseconds apart).
They were then able to stitch these parts of the image together to get a complete view
of the cross-section of the brain at each point in time.

To see if they could identify any signals of brain activity with this method, the researchers placed anesthetized mice into an MRI scanner and then gently stimulated the animals' whisker pads
with an electric current.
They found that for about 25 milliseconds after the shock, the images produced by their technique recorded some kind of signal
in the somatosensory cortex, the part of the mouse brain that perceives whisker stimuli.

DIGGING FURTHER, THEY FOUND THAT THE "DIANA SIGNAL" ACTUALLY MOVES
OVER TIME.
About 10 milliseconds after the whisker hits, it appears in an area of the brain called the thalamus, moving to one part of the somatosensory cortex in about 25 milliseconds, and a few milliseconds later in
another part of the somatosensory cortex.

By measuring the same brain region using invasive techniques such as electrophysiology and optogenetics, the team showed that their DIANA signal was actually tracking the propagation of neuronal activity in response to the
muster-needed stimulus.

Peter Bandettini, a neuroscientist and physicist at the National Institute of Mental Health (NIMH) who was not involved in the study, called the team's work "very compelling.
"
He added that several teams have tried to improve the temporal resolution of MRI before, but few have made such a big effort to support their claims
.
The paper includes a "masterpiece of experimentation" to prove that the technique is indeed tracking the propagation
of neuronal signals.

The bigger mystery is exactly what
DIANA detected.
Park and his colleagues show in their study that the BOLD effect is unlikely to be the cause, and instead they believe their approach is by recording changes in the membrane potential of firing neurons, possibly through fluctuations in membrane surface moisture or through cell swelling
.
Self says it's a possibility, but in general, "the mechanism is not very clear .
I think this needs to be confirmed
in future studies.
”

Park noted that DIANA has some limitations
in its current form.
Park is a co-inventor of a patent for the method
.
Due to the way the technology stitches together parts of images taken at different times, it is likely to be affected by so-called moving artefacts, that is, interference
caused by animals moving their heads between shots.
This can present some challenges
in translating DIANA to awake animals or humans.

Bandettini noted that the signal received by DIANA was also relatively weak, about an order of magnitude
smaller than BOLD fMRI.
He said the team needed relatively sophisticated NMR equipment to mimic the team's approach, as well as an experimental protocol that included repetitive tasks or stimulation to achieve averaging results
across multiple scans.
"You need to repeat the same thing many times, and very, very precise resolution
.
"

Bandettini points to another experiment by the team, which suggests that DIANA may be able to distinguish between excitatory and inhibitory neuronal signals — something that even invasive techniques like electrophysiology can challenge
.
"It's super exciting
.
This will open up a whole new field
of understanding how brains interact.
”

Self, who studies visual processing, said he knows of several groups that are already experimenting with applying DIANA to humans
.
While the technique still doesn't provide the single-cell resolution that some invasive techniques can achieve, it could have wide-ranging implications
if it could work in other labs, he said.
"In principle, it could be applied to humans, or even to patient studies — it could open up a whole world
of research that understands brain health and disease.
"