Initially, they measured nerve cells’ activity in the visual cortex, an area in the back of the brain that’s activated by visual stimuli, in response to flashes of light aimed at the rats’ eyes. Focusing the ultrasound beam on that brain area, they watched electrical activity there plunge while the beam was being transmitted, then recover within about 10 seconds after the device was shut off. This drop-off in the visual cortex’s electrical activity, which is what you’d expect from the release of an anesthetic there, grew more pronounced with increasing ultrasound intensity, and didn’t occur at all when the rats had been injected instead with drug-free nanoparticles.
In contrast, activity in the motor cortex, a brain area not involved in vision, in response to light flashes directed at the rats’ eyes was not diminished when ultrasound was applied there. But ultrasound targeting the lateral geniculate nucleus, a brain area that relays visual information to the visual cortex, did reduce electrical activity in the visual cortex. This showed that propofol release in one brain structure can produce secondary effects in another, distant region receiving inputs from that structure.
Brainwide metabolic response
Next, Airan’s team monitored the brainwide metabolic response to focused ultrasound by using positron emission tomography to measure brainwide uptake of a radioactive analog of glucose — glucose is the brain’s chief energy source — in the rats. When the injected nanoparticles were blanks, there was no effect in ultrasound-exposed areas. But with propofol-loaded nanoparticles, the metabolism dropped, meaning there was reduced neural activity in these ultrasound-exposed regions. This inhibition increased with increasing ultrasound intensity. Cranking the ultrasound level high enough also triggered selectively diminished activity in distant brain regions known to receive inputs from the ultrasound-exposed area.
“We hope to use this technology to noninvasively predict the results of excising or inactivating a particular small volume of brain tissue in patients slated for neurosurgery,” said Airan. “Will inactivating or removing that small piece of tissue achieve the desired effect — for example, stopping epileptic seizure activity? Will it cause any unexpected side effects?”
Other study co-authors are postdoctoral scholar Qian Zhong, PhD, and medical student Daivik Vyas.