Chinese researchers have wagged the tail of an unconscious mouse using only ultrasound directed at its brain, in an experiment that could lead to new therapies for a range of diseases in humans that cause uncontrollable movement such as palsy.
In the experiment carried out at a Shenzhen laboratory operated by the Chinese Academy of Sciences, a mouse was anaesthetised and its head delicately held in place in rods on a small platform. An ultrasound transducer pressing down on its skull generated an acoustic pulse 300 milliseconds every three seconds at 5 Megahertz, a frequency four times higher than what was been used in previous attempts.
By focusing the beam of sound on a specific region of the brain, researchers were able trigger a swiping motion in the tail. The mouse’s whiskers also raised simultaneously. An electromyography or EMG machine detected a surge of neural activity each time the high frequency sound was applied.
“This is a strange phenomenon,” said Qiu Weibao, a scientist involved in the research. “We are still scratching our heads because nobody knows exactly what has happened, or why the brain obeys so precisely to sound commands.”
Ultrasound had been widely used in the medical sector, mostly for diagnostic purposes such as pregnancy examinations. But the experiment showed promise as a new therapy to cure brain-related diseases, according to researchers.
“One possible area of application is the treatment of essential tremor”, a common disorder of the nervous system that causes involuntary shaking. Scientists are still trying to understand exactly what causes the condition which affects about four out of 100 people over the age of 40.
Ultrasound waves, Qiu suspected, might give the brain cells something similar to a “massage”. The mechanical movements might stimulate the generation of neurological signals or the release of certain chemicals that would not have occurred in natural conditions, but whether the hunch was correct or not remained would be known only through further studies.
Scientists increasingly believe that brain activities might, to a substantial extent, stem from mechanical movements of brain cells. A separate study by scientists in Shanghai this month suggested that the “feel-good” effect of marijuana could be largely the result of a “push” generated by the cannabis molecule on neurons.
“We are also seeking potential applications to treat eye conditions. Some eye diseases occur on the retina, where there is a concentration of a large number of neurons. The potential of the technology is huge,” Qiu added.
Over the decades, numerous types of brain therapies had been developed, including the use of chemicals or electric shocks. But nearly all have side effects. Using electric shock treatment required inserting metal rods into the patient’s brain to stimulate certain areas, as the electric currents could not penetrate the skull.
Ultrasound brain treatment is an emerging technology that has attracted increasing research attention in recent years, but previous attempts were limited to 1MHz or below. At a low frequency, the sound waves were dispersed over a wider area of the brain, making precise application impossible. But the higher the frequency, the more difficult it becomes for the sounds waves to penetrate deep into the brain.
The researchers overcame the problem and their equipment can send sound waves to a depth of more than 10cm inside the skull.
One major concern was safety. The researchers examined brain samples from mice receiving extensive treatments, and could find no sign of physical damage such as tissue bleeding or cell necrosis. But the temperature of the brain cells in the treated zone increased 1.6 degrees Celsius, which was more than what was seen by using lower frequencies.
Qiu said many technical problems remained and extensive clinical trials would have to be conducted before the ultrasound beam could be used on humans.
The experiment, detailed in a paper in the journal Scientific Reports in April, was only one of several projects underway at Qiu’s lab.
He and his colleagues are embarking on more challenging tasks, such as controlling mouses’ behaviour while the animals are fully conscious.
They were also planning to conduct experiments on monkeys, whose brain structure shares many similarities to humans.