Intact Animal Studies

Most recently, we published a method of stimulating intact brain circuits using transcranial pulsed ultrasound. The basic approach we developed for transmitting pulsed ultrasound through the skin and skull into the intact brains of rodents is shown at right.
We found that transcranial US is capable of safely and reliably stimulating in vivo brain circuits, such as the motor cortex and intact hippocampus of mice. We further found transcranial pulsed ultrasound for intact brain circuit stimulation has a lateral spatial resolution of approximately two millimeters and does not require exogenous factors or surgical invasion. This spatial resolution is approximately five times better than other more conventional noninvasive brain stimulation methods like TMS.  

The movie below illustrates the stimulation of intact motor cortex using transcranial pulsed ultrasound. In the movie, a "yellow" LED flashes to indicate the delivery of a pulsed ultrasound waveform to the motor cortex. Depending on the location of stimulation, different movements can be triggered using pulsed ultrasound. The method is entirely noninvasive in mice and causes no cell death, no damage to cerebrovasculature, no damage to cellular ultrastructure, and no behavioral impairments.

In our recent study, we also aimed to determine if trancranial pulsed US can be used to stimulate subcortical brain circuits in intact mice. To address this issue, we focused our attention on the intact mouse hippocampus. The hippocampus is a brain region involved in certain cognitive processes like learning and memory. Moreover, brain wave activity patterns in the hippocampus, such as gamma oscillations and sharp-wave ripples are known to underlie an animals awareness and ability to learn and retain information. Data from experiments designed to test the influence of transcranial pulsed ultrasound on intact hippocampal activity are shown at left. We found that transcranial ultrasound can be used to remotely stimulate the hippocampus while triggering natural activity patterns or gamma oscillations and sharp-wave ripples. We further found that ultrasound can stimulate the production of the neurotrophin BDNF, which is one of the most potent regulators of brain plasticity. Beyond direct brain stimulation uses, these data strongly support the use of pulsed ultrasound in cognitive enhancement therapies to modify learning and memory processes.

Based on our study demonstrating that trancranial pulsed US is capable of stimulating intact brain circuits, one can begin to imagine a vast number of applications where this method might enable us to better understand and manipulate brain function.

Y. Tufail et al., 2010. Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron 66(5), 681-694. PDF