Bursts of Low-intensity Ultrasound Make Neurons Fire.

Neuroscientists are well accustomed to making neurons fire artificially by shocking them and doping them. Indeed it's the backbone of most neurological therapies. Now, it seems, we can do it with just sound.

Bioengineers at Arizona State University published an article in Neuron today (it's free online) in which they demonstrate the ability to stimulate neuronal action potentials (electrical impulses) by applying bursts of low-intensity ultrasound to the mouse brain. Other people have shown that this is possible to do in brain tissue, but the Arizona lab claims to be the first to make it work through the skull in a live animal.

If such a technique is to become therapeutically viable it will have fierce competition from another stimulation strategy that excites neurons through the skull with either direct current or electromagnetic induction (called tDCS and rTMS respectively). These two approaches have spawned a veritable deluge of research, raising hopes of alleviating migraine pain, depression, and attention deficit disorder, to name just a few. Despite a lot of encouraging results, rTMS and tDCS have pretty terrible spatial resolution and this is precisely where ultrasonic stimulation may be able to compete and contribute.

In the experiments published today, the researchers looked at spatial resolution in two different ways. First they stimulated areas of the brain that control movement and found that they could isolate specific muscles. Point pulses of ultrasound at one part of the motor cortex and the paw twitches, move it slightly and the tail jerks. This alone is more precision than has been shown with electrical stimulation. (There's a link to a movie for those who can stomach research on restrained mice).

But the group went further and analyzed the biochemistry of the brains to see exactly what parts of the tissue had been stimulated. Their results suggest that ultrasound can be used at a resolution that is about 5 times better than rTMS. They also estimate that they could successfully use 0.5 MHz of ultrasound to stimulate brain regions that are 1 millimeter wide and less.

However, it's not as clean as all that. The sound waves seem to reflect in some instances and can stimulate the tissue unpredictably.

As of yet, there is no solid hypothesis to explain how the ultrasonic waves cause neurons to fire. The most convincing theory is that it produces enough mechanical stress on ion channels to open them. Normally these channels remain gated until the electrical potential across the neuron's membrane changes enough to fling them suddenly open and initiate the cascade effect we call an action potential.

Whatever the mechanism, the side effects on the cell seem to be minimal. Basic tests for cellular death showed no increases after applying the ultrasound.

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