A series of mouse-brain maps shows faster responses to visual stimuli than can be imaged with standard fMRI.Credit: P. T. Toi et al./Science
Tweaking a workhorse neuroscience technique makes it map a mouse’s brain activity faster than ever before.
A twist on functional magnetic resonance imaging (fMRI) offers a multi-fold improvement in its time sensitivity, better enabling it to unveil the fine-scale dynamics underlying mental processes. Researchers published the results on 13 October in Science1.
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A standard fMRI technique measures brain activity indirectly, by tracking increases in blood flow in regions where neurons are suddenly consuming more oxygen. This signal, though, can lag behind neuronal activity by 1 second, which dampens time sensitivity — the speedy cells take mere milliseconds to send messages to one another.
Jang-Yeon Park, an MRI physicist at Sungkyunkwan University in Suwon, South Korea, set out to enhance fMRI’s temporal precision by collecting data on a shorter time scale — every 5 milliseconds, about 8 times faster than what the standard technique can capture. He and his colleagues accomplished this by changing the software of a high-intensity MRI scanner and applying frequent, repetitive stimulation to animals they were testing. This suppressed the slower-paced blood oxygenation signal, making it possible to observe faster-paced brain activity. The researchers named their technique direct imaging of neuronal activity, or DIANA.
Quick change
In the study, an anaesthetized mouse inside an MRI scanner received a minor electric shock to its face every 200 milliseconds. Every 5 milliseconds — in sync with the stimulus — the machine scanned one tiny region of the mouse’s brain. The scanner moved on to a new area after the next electric shock. After the software stitched everything together, the process produced an image of one full slice of the brain from a head-on view, capturing neuronal activity over a 200-millisecond time period. (Spatial resolution was 0.22 millimetres, which is standard for high-intensity MRI.)
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During the scan, the facial stimulation activated a part of the brain that processes sensory inputs, causing the region to light up with a signal. The researchers found that this ‘DIANA response’ happened at the same time that neurons fired off signals, or ‘spiked’, as measured separately, using a surgically inserted probe. Furthermore, the team was able to trace the DIANA signal through a brain circuit as neurons sequentially triggered each other.
It is not entirely clear what causes the DIANA response, however. When neurons send messages, they swell and the surrounding water molecules get rearranged. These water alterations might be picked up as a signal (MRI machines usually detect signals from the hydrogen atoms in water molecules). Further experiments showed that the DIANA response was correlated with the time it took for ions to rush inside neurons, an event that changes their voltage, ultimately making them spike and send messages. Park and his colleagues therefore propose that the DIANA signal arises from multiple neurons changing their intracellular voltage.
Details to come
Although the team hasn’t confirmed what biological phenomenon is behind the response, experts aren’t concerned.
“The data itself shows that regardless of the mechanism, this is an MRI change that is tightly linked to spiking activity in the brain,” says Ravi Menon, a physicist and neuroscientist at Western University in London, Canada. “I think that’s probably the most important thing to start with — details can come later.”
Ben Inglis, a physicist at the University of California, Berkeley, agrees. The signal could be an effect of blood circulation, he says, but ultimately, the source doesn’t matter because the response is so fast — and therefore useful.
The biggest 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 every time. But a person who is awake might grow bored of or used to the repetition, Menon says, altering that response. Furthermore, complex mental processes such as emotional reactions or decision-making can influence brain activity for long periods and would be difficult to trigger in a reproducible way with quick, repetitive stimuli, Inglis says.
Nevertheless, the research team is excited to see others implement the DIANA method. Study co-author Jeehyun Kwag, an electrophysiologist at Seoul National University in Korea, thinks that looking at the brain’s connectivity both functionally and structurally at the same time will change the field.
“That will answer many unresolved problems in neuroscience,” she says.
