Abstract
Low frequency ultrasound (<1 MHz) has been demonstrated to be a promising approach for non-invasive neuro-stimulation. However, the focal width is limited to be half centimeter scale. Minimizing the stimulation region with higher frequency ultrasound will provide a great opportunity to expand its application. This study first time examines the feasibility of using high frequency (5 MHz) ultrasound to achieve neuro-stimulation in brain, and verifies the anatomical specificity of neuro-stimulation in vivo. 1 MHz and 5 MHz ultrasound stimulation were evaluated in the same group of mice. Electromyography (EMG) collected from tail muscles together with the motion response videos were analyzed for evaluating the stimulation effects. Our results indicate that 5 MHz ultrasound can successfully achieve neuro-stimulation. The equivalent diameter (ED) of the stimulation region with 5 MHz ultrasound (0.29 ± 0.08 mm) is significantly smaller than that with 1 MHz (0.83 ± 0.11 mm). The response latency of 5 MHz ultrasound (45 ± 31 ms) is also shorter than that of 1 MHz ultrasound (208 ± 111 ms). Consequently, high frequency (5 MHz) ultrasound can successfully activate the brain circuits in mice. It provides a smaller stimulation region, which offers improved anatomical specificity for neuro-stimulation in a non-invasive manner.
Highlights
Neuro-stimulation methods have been applied enormously in the neuroscience community due to their therapeutic utility for the treatment of neurologic and psychiatric diseases
One is for 1 MHz, − 3 dB focal width, the other one is for 5 MHz, − 3 dB focal width. (d) Coronal section of a mouse brain, left side marked by two semi-ellipses which present 1 MHz, − 3 dB sonication region and 5 MHz, − 3 dB sonication region. (e) Simulation results of
In contrast with other neuro-stimulation methods, ultrasound offers a number of advantages, such as non-invasive procedure, MRI compatibility, and synchronous monitoring, etc
Summary
Neuro-stimulation methods have been applied enormously in the neuroscience community due to their therapeutic utility for the treatment of neurologic and psychiatric diseases. TDCS achieves the neural stimulation by transmitting electrical current to activate target regions in the brain[8,9]. The spatial resolution of both tDCS and TMS are noticeably worse than those invasive methods They are difficult for specific activation of neuronal cells in a small region. The stimulated area in the brain is hard to be located, as the focal region of low frequency ultrasound is relatively large. It is a critical case, especially for the small animals such as mice due to their small brain size. The values of equivalent diameter (ED), which describes the size of effective stimulation region, and response latency are significantly smaller than those using 1 MHz ultrasound
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