Rapid MRI scans capture brain activity in mice

Rapid MRI scans capture brain activity in mice

Series of mouse brain maps showing DIANA responses to visual stimuli

A series of mouse-brain maps show faster responses to visual stimuli than can be imaged by standard fMRI.Credit: PT Toi etc/science

Modifying a workhorse neuroscience technique makes it possible to map a rat’s brain activity faster than ever before.

An evolution of functional magnetic resonance imaging (fMRI) offers a multi-fold improvement in its time sensitivity, better enabling it to uncover the fine-scale dynamics underlying mental processes. The researchers published the results on October 13 science1.

A standard fMRI technique measures brain activity indirectly, tracking increases in blood flow in areas where neurons suddenly receive more oxygen. This signal, however, can lag the neuronal activity by 1 second, which reduces time sensitivity – fast cells take milliseconds to send messages to each other.

Jang-Yeon Park, an MRI physicist at Sungkyunkwan University in Suwon, South Korea, set out to increase the temporal precision of fMRI to track neuronal activity on the order of milliseconds. He and his colleagues accomplished this by modifying the software of a high-intensity MRI scanner to acquire data every 5 milliseconds—about 8 times faster than standard techniques can capture—and applying frequent, repetitive stimuli to the animals they tested. It suppresses slow-moving blood oxygenation signals, making it possible to observe fast-moving brain activity. The researchers named their technique direct imaging of neuronal activity, or DIANA.

rapid change

In the study, an anesthetized mouse inside an MRI scanner received a small electric shock to its face every 200 milliseconds. Between shocks, the machine acquires data from a tiny region of the mouse’s brain every 5 milliseconds. After the next electric shock it was moved to a new area. After the software stitches everything together, the process creates a head-on image of a full slice of the brain by capturing neuronal activity in a 200-millisecond period. (Spatial resolution was 0.22 mm, ideal for high-intensity MRI.)

During the scan, facial stimulation activates a part of the brain that processes sensory inputs, causing the area to light up with a signal. The researchers found that this ‘Diana response’ occurred at the same time as the neuron stopped signaling, or ‘spiked’ – activity that was measured separately, using surgically inserted probes. Furthermore, the team was able to detect Diana signals through brain circuits as groups of neurons triggered each other in sequence.

It’s not entirely clear what causes DIANA’s reaction, though. When neurons send messages, they swell and the surrounding water molecules rearrange. These water changes can be taken as a signal (MRI machines usually detect signals from hydrogen atoms in water molecules). Further experiments showed that the Diana response was correlated with the time it takes for ions to rush inside neurons, an event that changes their voltage, ultimately causing them to spike and send messages. Park and his colleagues therefore propose that Diana signals from multiple neurons to change their voltage.

Details to come

Although the team has not confirmed any biological phenomenon behind the reaction, experts are not concerned.

“The data itself shows that regardless of the mechanism, it is an MRI change that is strongly associated with spiking activity in the brain,” said Ravi Menon, a physicist and neuroscientist at Western University in London, Canada. “I think it’s probably the most important thing to start with — the details can come later.”

Ben Inglis, a physicist at the University of California, Berkeley, agrees. The signal could be the effect of blood circulation, he says, but ultimately, the source doesn’t matter because the response is so fast — and therefore useful.

The big question now is whether the new data-acquisition method can be applied to human fMRI scans. The Diana method assumes that repeated stimuli, such as flashing lights, will affect the brain in the same way each time. But a person who is awake can become bored or habituated to repetition, Menon says, changing that response. Additionally, complex mental processes such as emotional reactions or decision-making can affect brain activity for long periods of time and would be difficult to trigger in a reproducible way with rapid, repetitive stimulation, Inglis said.

Still, the research team is excited to see others implement the DIANA method. Study co-author Jeehyun Kwag, an electrophysiologist at Seoul National University in South Korea, thinks looking at brain connectivity functionally and structurally at the same time will change the field.

“It will answer many unsolved problems in neuroscience,” she says.

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